7 - Endocrinology
7 - Endocrinology
7 - Endocrinology
Practice file
Editing file
Done by :
● Ghada Alothman
● Raghad Soaeed
● Albandari Alanazi
● Hamad Almousa
● Nouf Alsubaie
Lecture Quiz
Resources
Lecture Quiz
Lecture
Table Quiz
of content
Lecture Quiz
Pituitary disorders 10 4
Thyroid disorders 11 8
Parathyroid disorders 10 13
Adrenal disorders 10 18
Obesity 5 22
Hyperlipidemia 10 25
Diabetes type 1 9 29
Diabetes type 2 11 32
Diabetes complications 12 36
General endocrinology 6 41
Lecture
Pituitary
Lecture Quiz
disorders
Quiz
Q1 (500Best): A 33-year-old man complains of a tingling sensation in his hands for several months which
occasionally awakens him during sleep. The patient has noticed he has gained weight and no longer wears
his wedding ring as it has become too tight. You notice the patient is sweating while speaking to you and
has quite a large jaw, furrowed tongue and large hands. His blood pressure reading is 142/91 mmHg. The
most appropriate investigation would be:
Explanation: The glucose tolerance test (B) is diagnostic in patients with suspected acromegaly, many of whom will appear diabetic. Growth hormone (GH) levels
(C) can be raised during periods of stress and for most of the time remain <1mU/L. A raised GH level is therefore not sufficient to diagnose acromegaly though low or
undetectable levels can exclude this diagnosis. An MRI scan (A) is the best modality to reveal a pituitary adenoma secreting GH, however this investigation should always
follow an abnormal glucose tolerance test reading. Hyperprolactinaemia (E) is commonly associated in acromegaly patients as the pituitary adenoma often co-secretes
GH and prolactin and is useful to measure in a confirmed diagnosis of acromegaly and especially if a patient presents with symptoms of elevated prolactin. Thyroid
function tests (D) would not be correct in this case. Although the patient does show some symptoms of hypothyroidism, such as weight gain and carpal tunnel syndrome,
patients tend not to have elevated blood pressure and increased sweating which would be a feature in hyperthyroidism.
Q2 (500Best): A 19-year-old woman presents with concerns about changes to her facial appearance, in
particular her nose and jaw seem quite large, she is also quite sweaty and despite using antiperspirants is
finding it difficult to control and is afraid of embarrassment at university. A glucose tolerance test is
performed and found to be raised. The most appropriate management would be:
A. Trans-sphenoidal surgery
B. Octreotide
C. Bromocriptine
D. Pituitary radiotherapy
E. Pegvisomant
Explanation: Left untreated, acromegaly patients succumb to cardiovascular related morbidities, such as hypertension and heart failure, as well as an increased
incidence of colon cancer. Trans-sphenoidal surgery (A) is first line therapy and is particularly effective against microadenomas. Pituitary radiotherapy (D) usually follows
unsuccessful surgery, it is also more useful as an adjunct to other medical treatments as response to radiotherapy alone is often slow. Octreotide (B) is a somatostatin
receptor agonist which is effective in reducing growth hormone levels and are often used for short-term treatment, but are not definitively used as first-line therapy.
Bromocriptine (C) is a dopamine agonist and is primarily used to reduce the size of tumours before more definitive treatment such as surgery. This is useful since high GH
levels are a poor prognostic markers prior to surgery. Pegvisomant (E) is a GH antagonist and is effective in lowering IGF-1 levels rather than GH or tumour size. They are
used in patients refractory to surgical, radiotherapy and somatostatin therapy.
Q3 (500Best):A 49-year-old man presents with a history of difficulty sleeping. He reports feeling
increasingly tired and general weakness which he attributes to his poor sleep pattern. Additionally, the
patient has noticed he has gained weight and sweats very easily. On examination, the patient has coarse
facial features. The most likely diagnosis is:
A. Hyperthyroidism
B. Cushing’s disease
C. Acromegaly
D. Hypothyroidism
E. Diabetes
Explanation: Acromegaly (C) is most commonly due to a pituitary tumour usually identified on MRI scan, patients most frequently present with changes in appearance
followed by visual defects and headaches. Sleep apnoea is often a common complaint among patients due to weight gain. Other manifestations include large hands and
feet, hirsutism, prominent and coarse facial features, carpal tunnel syndrome, hypertension, diabetes and heart failure among others. The glucose tolerance test is
diagnostic for suspected acromegaly, GH levels can be measured directly, although elevated findings are not sufficient for diagnosis. Hyperthryoidism (A) produces
symptoms that are usually secondary to an elevation in metabolic rate, such symptoms include diarrhoea, goitre, sweating and intolerance to the temperature whereby
the patient consistently feels hot irrespective of the true environmental temperature. Sleep apnoea is not usually a complaint among patients since they often lose
weight despite an increased appetite. Cushing’s disease (B) results from a pituitary tumour producing excess ACTH, the excess cortisol levels result in symptoms such as
striae, bruising, thin skin, weight gain (particularly in the abdominal region) and often a dorsocervical fat pad (buffalo hump). Hypothyroidism (D) features include
tiredness, depression, cold intolerance, constipation and weight gain. Patients do not tend to sweat more and the disease does not coarsen facial features. In diabetes
(E), patients’ symptoms often result in weight loss though in type 2 diabetes they may suffer from sleep apnoea due to their high BMI.
Explanation: This patient is most likely suffering from hyperprolactinaemia, which is most commonly caused by a prolactinoma which is a pituitary adenoma causing
stalk compression or hypothyroidism. Prolactin levels (E) must first be measured in order to confirm the diagnosis before more invasive tests are used to determine the
cause. An MRI scan (C) is the most definitive investigation in this patient as the patient’s complaint of headaches alongside the rest of the history point towards a
pituitary tumour. Prolactin levels above 1000mU/L also strongly suggest this. A CT scan (B) is not able to reveal pituitary masses as readily as MRI scans can and also
involve considerable radiation levels which are especially important in sensitive areas such as the brain. In large lesions, a lateral skull x-ray (A) can reveal fossa
enlargement, lesions are often also discovered incidentally, however lateral skull x-rays are rarely used as definitive investigation. Thyroid function tests (D) are
important to conduct as they can also cause hyperprolactinaemia; however, as the patient does not have features of thyroid disease they are not first line.
Q5 (500Best): A 37-year-old man presents with symptoms of an acute headache, vomiting, malaise and
visual disturbance. A neurological examination reveals a bitemporal superior quadrantanopia. A CT scan
shows a hyperdense area within the pituitary gland. The most likely diagnosis is:
A. Kallman syndrome
B. Septo-optic dysplasia
C. Sheehan’s syndrome
D. Empty sella syndrome
E. Pituitary apoplexy
Explanation: Pituitary apoplexy (E) is characterized by a sudden headache, vomiting, visual disturbances and hormonal dysfunction. The cause is most commonly due to
the abrupt growth of a pituitary adenoma or pituitary infarction. The headache in apoplexy is usually very abrupt and can be mistaken for a subarachnoid haemorrhage,
although usually not as severe. The presentation can be unilateral or generalized. Visual defects are most commonly of the superior quadrant bitemporally. Visual
disturbances, such as loss of vision and opthalmoplegia affecting cranial nerves III, IV and VI, help differentiate apoplexy from other intracranial pathology.
Hypopituitarism can also follow an apoplexy although this is dependent on degree of damage and often patients present feeling very tired or nauseous. Kallman
syndrome (A) is characterized by gonadotrophin deficiency and congenital anosmia. Septo-optic dysplasia (B) is a congenital disorder characterized by the triad of optic
nerve hypoplasia, hypopituitarism and forebrain abnormalities. The empty sella syndrome (D) is the observation of absent pituitary tissue within the sella turcica
observed on imaging, however pituitary function is normal due to ectopic or unusual position of pituitary tissue within the sella fossa. Sheehan syndrome (C) is also
called postpartum hypopituitarism and is most commonly a rare complication of pregnancy. Patient’s present with agalactorrhoea, amenorrhoea and hypothyroidism
after pregnancy.
Q6 (500Best): A 38-year-old woman presents to clinic complaining of changes in her appearance and
weight gain. She has recently been through a divorce and attributed her weight gain to this. However,
despite going to the gym her clothes are still tight, especially around her waist, her face seems puffy and
flushed. The most likely diagnosis is:
A. Hyperthyroidism
B. Cushing’s disease
C. Acromegaly
D. Hypothyroidism
E. Diabetes
Explanation: Acromegaly (C) is most commonly due to a pituitary tumour, usually identified on MRI scan. Patients most frequently present with changes in appearance
followed by visual defects and headaches. Sleep apnoea, due to weight gain, is often a common complaint among patients. Other manifestations include large hands
and feet, hirsutism, prominent and coarse facial features, carpal tunnel syndrome, hypertension, diabetes and heart failure, among others. The glucose tolerance test is
diagnostic for suspected acromegaly, GH levels can be measured directly, although elevated findings are not sufficient for diagnosis. Hyperthyroidism (A) produces
symptoms that are usually secondary to an elevation in metabolic rate, such symptoms include diarrhoea, goitre, sweating and intolerance to the temperature, whereby
the patient consistently feels hot irrespective of the true environmental temperature. Sleep apnoea is not usually a complaint among patients since they often lose
weight despite an increased appetite. Cushing’s disease (B) results from a pituitary tumour producing excess ACTH, excess cortisol levels result in symptoms such as
striae, bruising, thin skin, weight gain, particularly abdominally, and often a dorsocervical fat pad (buffalo hump). Hypothyroidism (D) features include tiredness,
depression, cold intolerance, constipation and weight gain. Patients do not tend to sweat more and the disease does not coarsen facial features. In diabetes (E) patients,
symptoms often result in weight loss although in type 2 diabetes they may suffer from sleep apnoea due to their high BMI.
A. Serum osmolality
B. Fasting plasma glucose
C. Urinary electrolytes
D. Magnetic resonance imaging (MRI) scan of the head
E. Water deprivation test
Explanation: This patient is likely to be suffering from psychogenic polydipsia. The water deprivation test (E) is the most appropriate investigation to confirm this
diagnosis. In a normal patient, the serum osmolality remains within the normal range (275–295 mOsm/kg), while the urine osmolality rises to >600 mOsm/kg as water is
reabsorbed. In diabetes insipidus, the serum osmolality is elevated with no compensatory concentration of urine osmolality. If the patient responds to desmopressin,
this confirms cranial DI rather than nephrogenic DI, hence a water deprivation test is the most appropriate answer. An MRI scan (D) is most appropriate for investigating a
pituitary tumour. This commonly presents with visual field impairment and symptoms of elevated prolactin not seen in this patient. The fasting plasma glucose (B)
would be appropriate for investigating a patient with suspected diabetes mellitus, however this is often accompanied by weight loss. Serum osmolality (A) would be
useful in gauging how serious the patient’s degree of dehydration is, but would not be diagnostic. Urinary electrolytes (C) and fasting plasma glucose would be useful in
gauging the severity of the patient’s clinical state, but would not confirm the diagnosis.
Q8 (500Best): A 69-year-old man presents with confusion. His carers state that over the last month he has
become increasingly lethargic, irritable and confused. Despite maintaining a good appetite, he has lost
10kg in the last month. Blood results are as follows:
The most likely diagnosis is:
A. Hypothyroidism
B. Dilutional hyponatraemia
C. Addison’s disease
D. Acute tubulointerstitial nephritis
E. Syndrome of inappropriate anti-diuretic hormone (SIADH)
Explanation:The syndrome of inappropriate anti-diuretic hormone (E) (SIADH) is due to inappropriately elevated levels of ADH which leads to the retention of water. The
syndrome is therefore characterized by reduced serum sodium levels (hyponatraemia) and reduced serum osmolality, while urine osmolality and urine sodium levels are
elevated. Patients are also euvolaemic without signs of oedema. In patients suffering from heart failure, liver failure or the nephrotic syndrome, the reduced circulatory
volume acts as a stimulus for the ADH secretion. Despite the patient being in a hypo-osmolar state, ADH secretion is increased causing hyponatraemia, however such
patients will be hypervolaemic as in dilutional hyponatraemia (B) due to fluid overload. The SIADH can arise from an inappropriate source of ADH such as tumours both
in and out of the pituitary or failure in the feedback mechanism. Hypothyroidism (A) and Addison’s disease (C) can also cause the SIADH, however the above patient does
not exhibit any of the other signs of these diseases such as weight gain and hypotension, respectively. Acute tubulointerstitial nephritis (D) affects the tubules or
interstitium of the kidney and most commonly arises due to hypersensitivity reactions from medications such as non-steroidal anti-inflammatory drugs (NSAIDs).
Patients usually present with fever, arthralgia and renal failure.
Q9 (500Best): A 45-year-old Asian man is diagnosed with Cushing’s disease in India. He undergoes a
bilateral adrenalectomy and recovers well from the operation. On his return to the UK one year later, he
complains of a constant dull headache, peripheral visual disturbances and increasing pigmentation of the
skin creases of both hands. The most likely diagnosis is:
Explanation: Nelson syndrome (C) occurs in patients who undergo bilateral adrenalectomies, the loss of negative feedback over time causes a macroadenoma to form in
the pituitary which secretes adrenocorticotropin (ACTH). A spectrum of symptoms may arise due to the effects of serum ACTH, as well as the deficiency in other pituitary
hormones. An ectopic tumour secreting ACTH (A) can produce similar symptoms, however they usually originate from oat cell of small cell lung carcinomas which are
associated with weight loss rather than headaches and visual disturbances. Iatrogenic steroid side effects (E) would cause symptoms imitating cortisol excess such as
striae, bruising, thin skin and weight gain. A prolactinoma (B) can cause some of the symptoms the patient complains of, such as headache and visual disturbances, due
to impingement upon surrounding structures. However, symptoms in males does not involve hyperpigmentation and usually include loss of libido, impotence and
gynaecomastia. Addison’s disease (D) causes similar symptoms described in the question stem, however the cause of adrenal function loss is due to autoimmune action
or infection.
(A) Adrenal CT
(B) Adrenal MRI
(C) Cosyntropin stimulation test
(D) Pituitary MRI
Explanation: The most appropriate next diagnostic test for this patient is pituitary MRI. She has biochemical features of adrenocorticotropic hormone (ACTH)-dependent
Cushing syndrome (hypercortisolism and elevated ACTH). The cause of the ACTH hypersecretion is either a pituitary adenoma or an ectopic source, such as a carcinoid
tumor. In this patient, partial suppression was achieved with high-dose dexamethasone, which suggests an ACTH-secreting pituitary microadenoma. High-dose
dexamethasone is usually not successful in suppressing ACTH production from an ectopic source. However, there are exceptions, so caution must be exercised in
interpretation. In such instances, expert consultation is highly recommended.
Adrenal imaging is indicated if the hypercortisolism is ACTH independent (hypercortisolism and normal or low ACTH level). In patients with hypercortisolism associated
with suppressed ACTH secretion, a CT scan of the adrenal glands often shows a tumor (adenoma or carcinoma). However, this patient's ACTH level was elevated and
adrenal imaging is not indicated with either a CT or MRI scan.
The cosyntropin stimulation test is used to determine the adrenal reserve by measuring the response to a standard dose of synthetic adrenocorticotropic hormone. The
test does not detect Cushing syndrome but, rather, adrenal insufficiency and is therefore not indicated for this patient.
Answers: Q10: D
Lecture
Thyroid Quiz
disorders
Lecture Quiz
Q1 (500Best): A 33-year-old obese woman complains of tiredness. She has recently given birth to a healthy
baby boy and is enjoying being a mother. However, she is becoming more reliant on her partner for
support as she always feels exhausted and often becomes depressed. The patient has a poor appetite and
often does not finish her meals, despite this she has gained 5 kg in the last 2 weeks. The most likely
diagnosis is:
A. Postpartum depression
B. Eating disorder
C. Hyperthyroidism
D. Hypothyroidism
E. Occult malignancy
Explanation: Hypothyroidism (D) is a common disease with a higher prevalence in females and is usually a primary disorder affecting the thyroid gland itself. Thyroid
hormones control the metabolic rate in many tissues, underactivity produces symptoms which are often insidious. These include tiredness, depression, cold intolerance,
constipation and weight gain. The main causes include iodine deficiency, autoimmune pathology such as Hashimoto’s thyroiditis and, in females who have recently
given birth, postpartum thyroiditis. Hyperthryoidism (C) results in an excess of thyroid hormones which inappropriately increases metabolic rate with symptoms such as
weight loss, increased sweating, restlessness and palpitations. A goitre can occur in both hypo- and hyperthyroidism. Postpartum depression (A) is often accompanied by
confusion and is characterized by low mood, anhedonia and anergia. Severely affected patients can have delusional thoughts about their newborn child, such as it being
evil, and even progress to thoughts of harming the child or suicidal ideation. Eating disorders (B), such as bulimia or anorexia nervosa, often result in drastic changes in
body weight resulting from psychological problems with self-image and include behaviours such as self-induced vomiting to avoid weight gain or binge eating. Most
malignancies (E) result in considerable weight loss though this is dependent on the type of cancer and often symptoms provide clues as to the location, e.g. neurological
problems.
Q2 (500Best): A 42-year-old woman presents with visual disturbances. She reports having double vision
which was intermittent initially but has now become much more frequent. In addition, she becomes
breathless very easily and experiences palpitations. On examination, raised, painless lesions are observed
on the front of her shins and finger clubbing. The most likely diagnosis is:
A. De Quervain’s thyroiditis
B. Thyroid storm
C. Phaeochromocytoma
D. Graves’ disease
E. Plummer’s disease
Explanation: Graves’ disease (D) is the most common cause of hyperthyroidism. The condition is due to IgG antibodies binding to the TSH receptor, this in turn causes
excess production of thyroid hormone. The antibodies also bind to other areas of the body such as the extraocular muscles leading to gaze abnormalities, the shins
causing raised lesions known as ‘pretibial myxoedema’ and rarely the fingers causing clubbing known as ‘thyroid acropachy’. These collective signs are only seen in
Graves’ disease, hence it is the only correct answer. De Quervain’s thyroiditis (A) is a transient thyroid state most likely due to a viral infection. The patient usually
complains of a fever and painful neck with some signs of hyperthyroidism, such as tachycardia, as well as raised ESR levels. A few weeks later, the patient suffers from
transient hypothyroid symptoms before returning to a euthyroid state. Phaeochromocytomas (C) are malignancies of the sympathetic nervous system, 90 per cent arise
in the adrenal medulla and produce excess catecholamines. The symptoms of a phaeochromocytoma are often similar to hyperthyroidism and include anxiety,
palpitations and headache. However, these symptoms are usually intermittent and the main risk to patients is from cardiovascular compromise. Plummer’s disease (E) is
a solitary nodule in the thyroid gland producing excess thyroid hormones. It is usually refractory to antithyroid treatment. A thyroid storm or crisis (B) is a rapid
deterioration in patients suffering from hyperthyroidism, often stimulated by a stressor such as infection. Patients present with acute-onset, severe tachycardia, distress
and hyperpyrexia.
Q3 (500Best): A 16-year-old girl presents to her GP complaining of a swelling in her neck which she has
noticed in the last 2 weeks. She has felt more irritable although this is often transient. On examination, a
diffuse swelling is palpated with no bruit on auscultation. The most likely diagnosis is:
A. Hyperthyroidism
B. Simple goitre
C. Riedel’s thyroiditis
D. Thyroid carcinoma
E. Thyroid cyst
Explanation: A simple goitre (B) is an idiopathic enlargement of the thyroid. Often the condition is associated with thyroid antibodies, but these do not cause any
symptoms. Riedel’s thyroiditis (C) is a rare inflammatory disease of the thyroid gland that is characterized by fibrosis of the thyroid gland and other structures in the
neck. It is often stony or woody on palpation and patients are usually asymptomatic. The patient does not have any features of hyperthyroidism (A) in which a thyroid
bruit can be present. A thyroid cyst or nodule (E) is usually harmless and is a fluid-filled swelling often presenting as a single compressible small lump rather than a
diffuse swelling. A full history and examination should always be conducted with ultrasound and fine needle examination to exclude malignancy. Thyroid cancer (D) is a
rare but important diagnosis, they often present as irregular thyroid nodules but can metastasize to the lung, brain, liver and bone. Papillary and follicular cancers
usually have good prognoses compared to medullary and anaplastic cancers.
A. Radioiodine scan
B. Thyroid stimulating hormone (TSH)
C. Total tetraiodothyronine level (T4)
D. Tri-iodothyronine level (T3)
E. Ultrasound scan of the neck
Explanation: This patient is suffering from hypothyroidism. The most appropriate firstline investigation is measurement of TSH (B) as this indicates if a primary disease
affecting the thyroid is present. In a patient with symptoms of hypothyroidism due to a primary disorder of the thyroid, the TSH would be elevated. Similarly, in
symptoms of hyperthyroidism due to a primary abnormality of the thyroid, the TSH would be depressed. The total tetraiodothyronine level (T4 ) (C) would be decreased
hypothyroidism and elevated in hyperthyroidism, but this could be due to abnormalities of TSH secretion or a primary disorder of the thyroid. Hyperthyroidism due to
elevated levels of tri-iodothyronine level (T3 ) (D) occurs much less commonly than T4 and hence is measured less often. A radioiodine scan (A) is useful for studying
causes of hyperthyroidism, such as Plummer’s disease. The patient in this question is suffering from symptoms of hypothyroidism. Ultrasound scan of the neck (E) is
most useful for differentiating between solid and cystic nodules; these usually do not alter thyroid function.
Q5 (500Best): A 58-year-old woman presents with an acutely painful neck, the patient has a fever, blood
pressure is 135/85 mmHg and heart rate 102 bpm. The patient explains the pain started 2 weeks ago and
has gradually become worse. She also notes palpitations particularly and believes she has lost weight. The
symptoms subside and the patient presents again complaining of intolerance to the cold temperatures.
The most likely diagnosis is:
Explanation: This patient is suffering from symptoms of hyperthyroidism (D) but with some atypical features that provide clues to the most accurate diagnosis. De
Quervain’s thyroiditis (C) causes a transient change in thyroid state usually due to a viral infection. The patient usually complains of a fever and painful neck with some
signs of hyperthyroidism, such as tachycardia, as well as raised ESR levels. This is due to thyroid hormone release as viral organisms infect the thyroid cells. Patients will
suffer hypothyroidism as thyroid hormone is depleted before becoming euthyroid again. Plummer’s disease (B) usually presents with a solitary nodule in the thyroid
gland producing excess thyroid hormones. Thyroid papillary (A) and follicular carcinoma (E) can present with all the features described in this case but are usually
painless and less often associated with fever. Apart from De Quervain’s thyroiditis, no other pathology swings from hyperthyroidism to hypothyroidism before returning
to a euthyroid state.
Q6 (pretest): A 24-year-old woman presents 6 months after the delivery of her first child, a healthy girl, for
evaluation of fatigue. She suspects that the fatigue is related to getting up at night to breastfeed her baby,
but she has also noticed cold intolerance and mild constipation. She recalls having a tremor and mild
palpitations for a few weeks, beginning 3 months after delivery. On examination, her BP is 126/84 and her
pulse rate is 56. The thyroid gland is 2 times normal in size and nontender. The rest of the physical
examination is normal. Laboratory studies reveal a free T4 level of 0.7 ng/ml (normal 0.9-2.4) and an
elevated TSH at 22 microU/mL (normal 0.4-4). What is the likely course of her illness?
Explanation: This patient requires no additional testing before levothyroxine therapy is initiated for her hypothyroidism. Hashimoto disease is the most common cause of
hypothyroidism, and confirmation of this diagnosis with measurement of TP antibody is not necessary. Measurement of PO antibody levels may be helpful in patients
with subclinical hypothyroidism (elevated thyroid-stimulating hormone [TSH] level but normal free thyroxine [Ta]). In these patients, increased titers of TPO antibody
confer an increased risk of hypothyroidism (~4% per year), which escalates as TSH levels rise above the reference range.
The radioactive iodine uptake (RAIU) test measures thyroid gland iodine uptake over a timed period, usually 24 hours. Patients with thyrotoxicosis typically have an
above- normal or high-normal RAIU, which is inappropriate in the context of a suppressed TSH level. In patients with thyroidit is or exposure to exogenous thyroid
hormone, the RAIU will be below normal (<5% at 24 hours). Radionuclide uptake scanning has no role in the evaluation of hypothyroidism.
Thyroglobulin, a glycoprotein integral in follicular storage of thyroid hormone, can be detected in serum. Thyroglobulin levels can be elevated in hyperthyroidism and
destructive thyroiditis. Intake of exogenous thyroid hormone generally suppresses thyroglobulin levels, which makes its measurement useful in patients with
thyrotoxicosis due to surreptitious use of thyroid hormone. Thyroglobulin is also an effective tumor marker in patients with papillary or follicular thyroid cancer after
thyroidectomy and radioactive iodine ablation therapy, because normal thyroid release of thyroglobulin should no longer be present. Measurement of thyroglobulin
levels has no role in the evaluation of hypothyroidism.
Q8 (MKSAP): A 42-year-old woman is evaluated for an asymmetric enlargement of her thyroid. She is
otherwise asymptomatic, and she has no risk factors for thyroid cancer. On physical examination, a
possible thyroid nodule is palpated on the left side. A complete blood count, routine serum chemistry
tests, and thyroid-stimulating hormone level (TSH) are normal. Ultrasound examination reveals a 2.2-cm
left-sided solid nodule.
What is the appropriate next step in the evaluation of this patient?
Explanation: The appropriate next step in the evaluation of this patient is a fine-needle aspiration of the thyroid nodule. The prevalence of palpable thyroid nodules is 4%
to 7%. The cancer risk for a thyroid nodule is 5% to 10%. Factors associated with increased cancer risk include extremes of age (<20 or >60 years), male sex, a history of
head or neck irradiation, a family history of thyroid cancer (especially medullary thyroid cancer), nodule size larger than 1 cm, rapid nodule growth, and hoarseness.
Fine-needle aspiration is a simple method of determining the presence of malignancy. Sensitivity is approximately 90% to 95%, with a false-negative rate of 1% to 11%.
Guidelines recommend biopsy of any nodule greater than 1 cm in diameter, and biopsy of smaller nodules should be considered in patients with cancer risk factors.
Limited laboratory testing is typically required in the evaluation of a thyroid nodule. Beyond a routine complete blood count and serum chemistry panel, the serum
thyroid-stimulating hormone (TSH) level should be measured, because the result will help guide the evaluation (autonomously functioning nodules and multinodular
goiters that suppress TSH levels are rarely malignant). Concomitant measurement of the serum free thyroxine (Ta) level is also reasonable if patients have thyroid-related
symptoms but unnecessary in an asymptomatic patient with a normal TSH level such as this patient.
Thyroglobulin, a glycoprotein integral in follicular storage of thyroid hormone, can be detected in serum of normal patients. Thyroglobulin levels can be elevated in
hyperthyroidism and destructive thyroiditis and is an excellent thyroid cancer marker in patients who have undergone thyroidectomy or radioactive iodine ablation. In
this patient with an intact thyroid gland, a thyroglobulin level measurement will not be helpful.
A thyroid scan and radioactive iodine uptake test are appropriate in the context of a suppressed serum TSH level because a toxic nodule or multinodular goiter may be
present. Because such hyperfunctional nodules rarely harbor cancer (<1%), their evaluation and management are far different. This patient does not have a suppressed
TSH, and a thyroid scan and radioactive iodine uptake test is not indicated.
Although surgery is sometimes considered for nodules larger than 4 cm in diameter, surgery has no role in this asymptomatic patient with a smaller nodule.
Explanation: The most appropriate next step is to recheck this patient's serum thyroid-stimulating hormone (TSH) level. Because a fetus depends on maternal thyroid
hormone for the first 10 to 12 weeks of gestation, the thyroid levels of pregnant women with hypothyroidism should be carefully monitored. Recent guidelines
recommend that TSH and total thyroxine (T4) levels be monitored throughout pregnancy because standard free Ta levels are not as accurate in pregnant patients. The
total T4 level should be kept stable at approximately 1.5 times the normal range, and the TSH level should be kept in the lower range of normal. This may require an
increase in their levothyroxine dosage of approximately 35% to 50% as early as the first trimester. Because of estrogen elevation during pregnancy, thyroid-binding
globulin (TBG) levels increase. However, without an increase in the dosage of levothyroxine, free Ta levels may decrease as more Ta becomes bound by TBG. After
delivery, TBG levels decrease, as do thyroid hormone requirements.
Although maternal iodine replacement has been successfully used in countries with prevalent iodine deficiency, its use in patients who are iodine sufficient can be
associated with catastrophic results, such as a fetal goiter (pharmacologic amounts of iodine blocks release of thyroid hormone). Because significant iodine deficiency in
the United States is rare, iodine therapy in pregnant U.S. women is not indicated.
Measurement of the free triiodothyronine (T3) level is not useful in the evaluation of hypothyroidism because T levels typically remain within the reference range until
the point of severe hypothyroidism. This pattern is unaltered by pregnancy.
Continuing the current management is inappropriate because undertreatment of maternal hypothyroidism can have a potentially negative effect on fetal neurocognitive
development.
Q10 (MKSAP): An 18-year-old woman is evaluated for tachycardia, nervousness, decreased exercise
tolerance, and weight loss of 6 months' duration. She has otherwise been healthy. Her sister has Graves
disease. She takes no medications. On physical examination, blood pressure is 128/78 mm Hg, pulse rate is
124/min, respiration rate is 16/min, and BMI is 19. There is no proptosis. An examination of the neck
reveals a smooth thyroid gland that is greater than 1.5 times the normal size. Cardiac examination reveals
regular tachycardia. Her lungs are clear to auscultation. Human chorionic gonadotropin Negative.
Thyroid-stimulating hormone <0.01 uU/mL (0.01 mU/L). Thyroxine (T4), free 5.5 ng/dL (71.0 pmol/L).
Trirodothyronine (T3), free 9.1 ng/L (14.0 pmol/L)
Which of the following is the most appropriate treatment for this patient?
(A) Atenolol
(B) Atenolol and met himazole
(C) Methimazole
(D) Radioactive iodine and methimazole
Explanation: The most appropriate medical regimen for this patient with Graves disease is atenolol and methimazole. Graves disease can present with either subclinical
or overt thyrotoxicosis. Physical examination may reveal tachycardia; an elevated systolic blood pressure with a widened pulse pressure; a palpable goiter, which is
classically smooth; a thyrotoxic stare due to lid retraction; proptosis; and, infrequently, an infiltrative dermopathy. To control her tachycardia, a -blocker, such as
atenolol, is indicated. Given the clinical and laboratory findings, this patient is also moderately hyperthyroid. To treat her hyperthyroidism, either methimazole or
propylthiouracil can be used.
Methimazole, which generally has fewer side effects and results in quicker achievement of the euthyroid state than propylthiouracil, is preferred in most patients.
Because of a presumed immunomodulatory effect, antithyroidal drugs result in drug-free remission rates of between 30% and 50% in patients with Graves disease who
are treated for year.
Atenolol alone would only address this patient's adrenergic symptoms and not reduce her thyroid hormone levels, and methimazole alone would not immediately
address her tachycardia.
Radioactive iodine therapy preceded or followed by adjunctive therapy with an antithyroidal drug is occasionally used to treat Graves disease. The drug is given in an
attempt to decrease the risk of a transient worsening of the thyrotoxicosis after thyroid ablation. Because antithyroidal drugs render the thyroid radioresistant, they
must be stopped for several days before and after giving the radioactive iodine. Although an occasional patient becomes euthyroid after radioactive iodine
administration, the expected outcome is hypothyroidism, which typically occurs within 2 to 3 months of therapy, at which time thyroid hormone replacement therapy is
begun
(A) Methimazole
(B) Repeat measurement of TSH and free Ta levels
(C) Thyroid scan and 24-hour radioactive iodine uptake test
(D) Thyroid ultrasonography
Explanation: The best next management step is repeat measurement of the thyroid-stimulating hormone (TSH) and free thyroxine (T.) levels. Postpartum thyroiditis,
which occurs in approximately 5% of women in the United States within a few months of delivery, is a variant of painless thyroiditis. At presentation, patients may have
transient thyrotoxicosis alone, transient hypothyroidism alone, or thyrotoxicosis that is followed by hypothyroidism and then by recovery. This patient most likely has
postpartum thyroiditis that is now in the hypothyroid phase after a period of transient thyrotoxicosis. The hypothyroidism can be confirmed by remeasuring her TSH and
free T4 levels.
In this patient, the absence of a goiter and eye disease points away from Graves disease, as does the recent development of symptoms associated with hypothyroidism
Methimazole therapy is inappropriate for this patient because she most likely has hypothyroidism, not hyperthyroidism. If transient hypothyroidism is confirmed by a
high TSH level and low free Ta level, thyroid hormone replacement, not methimazole, can be considered for bothersome symptoms.
With postpartum thyroiditis, results of thyroid scans and radioactive iodine uptake tests will be low during the thyrotoxic phase and then become elevated during the
hypothyroid phase as the thyroid gland recovers and becomes very avid for iodine as stores are repleted. Before such testing can be advised, however, the results of
current thyroid function tests are required to assess the patient's thyroid hormone status and determine if scan results suggest Graves disease or, what is more likely,
recovery thyroiditis.
Ultrasound of the thyroid gland can be used to distinguish the high vascular flow of Graves disease from the low-flow pattern of autoimmune thyroiditis. A more direct
test of this patient's thyroid function, however, is measurement of the TSH and free T4 levels, which can quantify thyroid function and provide a baseline with which to
compare future thyroid function test results.
Answers: Q11: B
Lecture disorders
Parathyroid
Lecture Quiz
Quiz
Q1 (500Best): A 54-year-old woman presents to her GP complaining of a change in her breathing sound.
She first noticed numbness, particularly in her fingers and toes, three months ago but attributed this to
the cold weather. Her partner now reports hearing a high pitched, harsh sound while she is sleeping. Her
BMI is 27. While measuring blood pressure, you notice the patient’s wrist flexing. The most likely diagnosis
is:
Explanation: This patient exhibits many of the signs present in hypocalcaemia (B) including tingling in the fingers and toes and carpopedal spasm. In the latter, occlusion
of the brachial artery, which occurs when measuring blood pressure, causes muscle spasming of the hand and forearm (Trosseau’s sign). Other signs include facial
muscle twitching when the facial nerve is tapped on the same side (Chvostek’s sign), prolonged QT interval, hyperreflexia and stridor. Hypocalcaemia most commonly
arises due to renal failure. DiGeorge syndrome (C) is a congenital condition that arises due to an abnormality at chromosome 22q11 causing malformation of the third
and fourth pharyngeal arches. Patients present at a young age with cardiac abnormalities, abnormal facies, cleft palate and hypocalcaemia. Raynaud’s syndrome (E) is
characterized by triphasic changes in the peripheral digits, usually the fingers, stressors such as cold temperature causes arterial spasming which reduces the blood flow
to the end arteries. Patients will notice their fingers turn white, blue and then red as the blood flow returns. In mild disease, this can be associated with mild tingling
while severe disease can cause severe pain and even necrosis. Obstructive sleep apnoea (A) is a disorder of sleep that is characterized by loss of airway patency causing a
significant reduction in airflow despite constant breathing effort. This can occur for a number of reasons such as obesity, asthma and hypothyroidism. However, there are
not usually any underlying neurological signs. Guillain–Barré syndrome (D) is an immune-mediated disease which usually results following an infection such as
cytomegalovirus (CMV) and campylobacter causing a polyneuropathy. The demyelination typically occurs in a symmetrical ascending pattern starting with the distal
limbs. Paralysis of the respiratory muscles can occur, requiring emergency treatment, but there are no signs of hypocalcaemia as in the above patient.
Q2 (500Best): A 39-year-old man presents with a three-month history of depression. The patient recently
lost a family member and around the same period began to feel unwell with constipation and a depressed
mood. He has started taking analgesia for a sharp pain in his right lower back that often radiates towards
his front. The most appropriate investigation is:
Explanation: This patient appears to be suffering from symptoms of elevated calcium levels, these can include depression, constipation and renal stone formation
causing abdominal pain. The normal calcium homeostatic pathway is controlled by parathyroid hormone (PTH). When calcium levels fall, as in malnutrition, PTH levels
increase causing calcium reabsorption by the kidneys and the gastrointestinal system, while calcium stored in the bones is released. PTH malignancies are the most
common cause of elevated calcium, however the diagnosis of hypercalcaemia itself is only confirmed by measuring the serum calcium itself (D). PTH (A) levels would
then reveal whether the hypercalcaemia is due to hyperparathyroidism but are not appropriate before serum calcium measurements. Primary hyperparathyroidism
occurs due to parathyroid adenomas producing excess PTH. Secondary hyperparathyroidism is a compensatory increase in PTH in renal failure or vitamin D deficiency.
Tertiary hyperparathyroidism is autonomous PTH production after long-standing secondary hyperparathyroidism. An MRI scan (E) would not be appropriate without first
measuring blood levels of PTH if a PTH tumour were suspected. Although hyperthyroidism can cause hypercalcaemia, TSH (B) is not measured before serum calcium or
PTH. A colonoscopy (C) would be appropriate to investigate unexplained constipation, especially if a gastrointestinal (GI) malignancy were suspected alongside worrying
symptoms such as significant weight loss. Less invasive investigations such as blood tests should always be considered before more invasive investigations.
A- Primary hypoparathyroidism
B- Pseudohypoparathyroidism
C- Secondary hyperparathyroidism
D- Tertiary hyperparathyroidism
Explanation: This patient presents with features of severe chronic kidney disease (CKD) such as high creatinine, cutaneous excoriations due to uremia, anemia (pallor),
and a rugger-jersey spine. End-stage renal disease (ESRD) causes hyperphosphatemia due to decreased renal phosphate excretion and hypocalcemia due to decreased
renal vitamin D activation. Hypocalcemia is responsible for the muscle cramps seen here. Hypocalcemia would also stimulate the parathyroid glands to secrete PTH
(indicating secondary hyperparathyroidism), which results in bone pain with osteitis fibrosa cystica and a rugger-jersey spine (indicating renal osteodystrophy). ESRD is
the most frequent cause of secondary hyperparathyroidism.
Q4 (AMBOSS): A 46-year-old woman comes to the physician for a routine health examination. She was last
seen by a physician 3 years ago. She has been healthy aside from occasional mild flank pain. Her only
medication is a multivitamin. Her blood pressure is 132/88 mm Hg. Physical examination shows no
abnormalities. Serum studies showed, Subsequent serum studies show a repeat calcium of 11.2 mg/dL,
parathyroid hormone concentration of 890 pg/mL, and 25-hydroxyvitamin D of 48 ng/mL (N = 25–80). Her
24-hour urine calcium excretion is elevated. An abdominal ultrasound shows several small calculi in
bilateral kidneys. Further testing shows normal bone mineral density. Which of the following is the most
appropriate next step in management?
A- A
B- B
C- C
D- D
E- E
F- F
Explanation: In primary hyperparathyroidism, high levels of PTH increase serum calcium levels by increasing bone turnover and by increasing renal calcium reabsorption
from the distal convoluted tubule. Increased PTH would also cause hypophosphatemia by preventing phosphate reabsorption at the proximal convoluted tubule.
Increased bone turnover would be evident in serum by increased alkaline phosphatase levels. In advanced osteitis fibrosa cystica, large, cystic, vascular cavities with a
tumor-like appearance on x-ray and a brown color due to hemosiderin deposition ("brown tumors") can form in long bones. The most common cause of primary
hyperparathyroidism is a parathyroid adenoma
Q6 (AMBOSS): A 68-year-old man comes to the physician for a follow-up examination. He has type 2
diabetes mellitus, hypertension, and chronic kidney disease. Medications include insulin, metoprolol, and
atorvastatin. Physical examination shows pitting edema of both ankles. Serum creatinine concentration is
4.5 mg/dL. Which of the following sets of serum findings is most likely in this patient?
A- A
B- B
C- C
D- D
E- E
Explanation: CKD is associated with vitamin D deficiency due to decreased 1-alpha hydroxylase activity. By reducing intestinal absorption of calcium, vitamin D
deficiency also causes low calcium levels, which in turn stimulates the secretion of PTH, leading to secondary hyperparathyroidism. Although high levels of PTH normally
stimulate renal reabsorption of calcium and excretion of phosphate, phosphate excretion is impaired in CKD, resulting instead in hyperphosphatemia. Other laboratory
abnormalities in patients with CKD include hyperkalemia and metabolic acidosis.
A- Tertiary hyperparathyroidism
B- Senile osteoporosis
C- Secondary hyperparathyroidism
D- Postmenopausal osteoporosis
Explanation: Chronic kidney disease (CKD), which this patient suffers from, is the most frequent cause of secondary hyperparathyroidism (sHPT). In sHPT due to CKD,
decreased levels of serum calcium from impaired renal reabsorption and increased serum phosphate from impaired renal excretion cause reactive hyperplasia of the
parathyroid glands, increasing PTH secretion. Furthermore, kidney disease decreases biosynthesis of vitamin D, causing hypocalcemia and a further reactive increase in
PTH secretion. The lab values indicate that this patient has CKD and hypocalcemia, and likely also hyperphosphatemia given that she is taking sevelamer. Her CKD and
low calcium levels predispose her to bony fractures, such as a compression fracture of the L2 vertebra. This decreased bone mass as a result of another medical
condition is referred to as secondary osteoporosis.
Q8 (AMBOSS): A 65-year-old woman comes to the office for an annual health maintenance examination.
She feels well. Her medical history is significant for vasospastic angina controlled with diltiazem. She has
not had menses for 15 years. Her mother died of myocardial infarction at the age of 75 years. She has
smoked one pack of cigarettes daily for 30 years and drinks alcohol occasionally. Her other medications
are vitamin D and calcium supplements. The patient is 165 cm (5 ft 5 in) tall and weighs 52 kg (115 lb); BMI
is 19 kg/m2. Physical examination shows no abnormalities. Results of laboratory studies, including serum
calcium and creatinine concentrations, are within the reference ranges. Dual-energy x-ray absorptiometry
scan shows a T-score of -2.7 SD. Which of the following is the most appropriate next step in
pharmacotherapy?
A- Denosumab
B- Raloxifene
C- Teriparatide
D- Alendronate
E- No further pharmacotherapy is indicated at this time
Explanation: Oral bisphosphonates (e.g., alendronate, risedronate) are the preferred initial treatment in patients with osteoporosis because these drugs prevent bone
resorption by inhibiting osteoclasts and can significantly decrease the risk of fracture. Bisphosphonates should be taken in the morning and evening at least 30 minutes
before meals, with plenty of water, and the patient should maintain an upright position for at least 30 minutes following intake to prevent esophagitis. Other side effects
are osteonecrosis of the jaw and hypocalcemia. Contraindications to bisphosphonates include hypocalcemia, esophageal abnormalities, and decreased glomerular
filtration rate. In case of contraindications or unresponsiveness to bisphosphonates, medications such as parathyroid hormone analogs (teriparatide), selective estrogen
receptor modulators (raloxifene), or RANKL inhibitors (denosumab) may be used.
Sufficient intake of calcium and vitamin D is recommended as primary prevention and adjunct therapy for osteoporosis. Lifestyle modifications, such as physical activity
(e.g., strength and balance training) and avoidance of alcohol, tobacco, and glucocorticoids, should be encouraged.
Denosumab is indicated in patients with osteoporosis and impaired renal function or if the preferred initial treatment has failed. This patient's serum creatinine is
normal; therefore, another initial treatment is indicated.
Raloxifene can be used in patients with osteoporosis who have contraindications and/or in those who are unresponsive to the preferred initial treatment. Raloxifene may
also be used in patients with osteoporosis who require breast cancer prophylaxis. This patient has no family history of breast cancer. Furthermore, raloxifene increases
the risk of thromboembolic events, which is already elevated in this patient who smokes.
Teriparatide can be used in patients with osteoporosis who have contraindications and/or are unresponsive to the preferred initial treatment. Moreover, teriparatide can
be considered as an alternative for patients with osteoporosis and a high risk of fracture (e.g., T-score ≤ -3 SD, a history of severe and/or multiple fractures). However, this
patient has no history of fractures and a T-score of -2.7 SD.
A- Vitamin D deficiency
B- Destruction of parathyroid glands
C- Ectopic hormone production
D- Medication side effect
Explanation: This patient presents with hypocalcemia due to hypoparathyroidism, as indicated by the elevated phosphorus, normal alkaline phosphatase, and
symptoms of hypocalcemia in the setting of normal kidney function. Decreased parathyroid hormone (PTH) activity leads to decreased release of calcium and
phosphorus from the bone, as well as decreased calcium reabsorption and phosphorus secretion at the kidney. The most common cause of hypoparathyroidism in
adults is surgery (e.g., thyroidectomy, parathyroidectomy), which this patient has no history of. Instead, his hypoparathyroidism is most likely due to autoimmune
destruction of parathyroid glands (the second most common cause in adults). Other less common causes of hypoparathyroidism are congenital (e.g., DiGeorge
syndrome), infiltration of the parathyroid gland (e.g., hemochromatosis, granulomas), and radiation-induced destruction. Vitamin D deficiency can manifest with
symptoms of hypocalcemia; however, additional symptoms such as pathological fractures, bone pain, and muscle weakness would be expected. Additionally, this
patient's hyperphosphatemia shows that vitamin D-mediated absorption from the intestine remains intact. Moreover, the normal alkaline phosphatase indicates normal
osteoblast activity, making metabolic bone disease such as osteomalacia unlikely. Finally, this patient does not have any risk factors for vitamin D deficiency, including
low oral intake, malabsorption (e.g., chronic pancreatitis, celiac disease), or defective vitamin D metabolism (e.g., liver cirrhosis).
Q10 (AMBOSS): A 65-year-old woman comes to the physician because of a 4-month history of generalized
bone pain. She has a 25-year history of Crohn disease with multiple hospitalizations for acute
exacerbations, including a bowel obstruction last year. Current medications include mesalamine and
bisoprolol. She is 165 cm (5 ft 6 in) tall and weighs 53 kg (117 lb); her BMI is 19.5 kg/m2. Examination
shows a soft abdomen and pale conjunctivae. Neurological examination shows decreased vibratory
sensation over her lower extremities. Muscle strength is 4/5 in the distal groups and 3/5 in proximal
groups of the lower limbs. The pelvic bones are tender to palpation. An x-ray of the pelvis shows thin
cortices and multiple radiolucent bands that are perpendicular to the cortex and surrounded by a thin
sclerotic margin. Which of the following laboratory findings are most likely present in this patient?
A- A
B- B
C- C
D- D
E- E
F- F
Explanation: Severe vitamin D deficiency can lead to hypocalcemia and hypophosphatemia by decreasing the amount of calcium and phosphate absorption in the
intestine. As long as calcium levels are low, increased PTH secretion occurs in an attempt to maintain normal serum calcium levels (secondary hyperparathyroidism).
PTH releases calcium stored in bone into serum by increasing bone turnover, which the elevated ALP levels (a marker of bone turnover) indicate here. Increased PTH
levels also worsen hypophosphatemia by decreasing renal phosphate reabsorption.
Explanation: The patient appears to be suffering from cushingoid symptoms. After a history to exclude causes such as high-dose steroid intake, the main differential
diagnoses include an adrenal tumour, an ectopic tumour producing ACTH (Cushing’s syndrome) or a pituitary tumour (Cushing’s disease). Although a 24-hour urinary
free cortisol level measurement (E) does not confirm the exact diagnosis, it does indicate if there is a pathological excess of cortisol (levels can vary up to 700 nmol/L in
the morning to 280 nmol/L at midnight). A low dose (0.5 mg) dexamethasone test (A) involves measuring ACTH after dexamethasone administration. In Cushing’s disease
and syndrome, there is no suppression of ACTH. A highdose dexamethasone test (B) will differentiate between Cushing’s disease and Cushing’s syndrome since only in
the former is there suppressed ACTH production after high-dose dexamethasone administration. A CT scan (D) can be used to identify a pituitary tumour if requiring
surgical management. Urinary catecholamine (C) measurement is used in the diagnosis of a phaeochromocytoma, an adrenal tumour producing excess catecholamines
measurable in the urine. Differentiating an adrenal tumour producing excess cortisol can be done by administering metyrapone, an 11-β hydroxysteroid dehydrogenase
inhibitor, which effectively ceases adrenal cortisol production. If cortisol is still high it is due to an ectopic source, e.g. lung tumour.
Q2 (500Best): A 22-year-old woman complains of dizziness and feeling light-headed. She works in an office
and most frequently experiences this when standing up to visit the toilet. She has never fainted. The
patient has lost 5kg, but attributes this to eating more healthily. She has noticed a recent scar on the back
of her hand which has started to turn very dark. The most appropriate investigation is:
A. Synacthen test
B. Low-dose dexamethasone test
C. Cortisol measurement
D. Urinary free cortisol measurement
E. Abdominal ultrasound (US) scan
Explanation: This patient has Addison’s disease whereby the adrenal gland is destroyed, usually due to infection (TB) or autoimmunity. The reduced cortisol, aldosterone
and sex steroids produce a myriad of signs and symptoms, most importantly postural hypotension due to reduced aldosterone and increased pigmentation often in
palmar creases and newly formed scars. This latter sign is due to elevated melanocyte-stimulating hormone (MSH) which is derived from the POMC molecule which
breaks down into MSH and ACTH. Other symptoms include weight loss, malaise and vitiligo. The synachten test (A) involves giving an infusion of ACTH which would be
expected to cause an increase in measured cortisol. A short synacthen test confirms primary Addison’s disease, whereas ACTH deficiency or suppression by steroids can
be confirmed by doing a long synacthen test. Urinary free cortisol (D) and the low-dose dexamethasone test (B) is appropriate for investigating Cushing’s syndrome and
is not correct for this patient. A single cortisol measurement (C) is not very valuable for confirming diagnosis due to poor sensitivity and specificity, as well as the diurnal
nature of cortisol. A random measurement below 100 nmol/L during the day is more suggestive of Addison’s disease, while a value of >550 nmol/L makes the diagnosis
less likely. An abdominal US scan (E) would not be appropriate until less invasive blood tests which can confirm Addison’s had been conducted.
Q3 (500Best): A 47-year-old woman presents to clinic after being referred from her GP for consistently
elevated blood pressure. Her last reading was 147/93. The female does not report any symptoms but
recently lost her job and attributes the elevated reading to stress. Her blood tests are as follows:
The most appropriate investigation is:
A. CT scan
B. 24-hour ambulatory blood pressure
C. Abdominal ultrasound scan
D. Aldosterone–renin ratio
E. Glucose tolerance test
Explanation: The main differential in this patient is hyperaldosteronism arising from an adrenal tumour (Conn’s syndrome). The excess aldosterone causes hypertension,
elevated sodium reabsorption and potassium excretion. However, given the patient history, the elevated blood pressure could easily be due to the stress of having
blood pressure measured or the patient’s personal situation. A 24-hour ambulatory blood pressure measurement (B) is therefore the most appropriate
investigation to eliminate essential hypertension. Since the blood results are only mildly deranged and essential hypertension has not been eliminated, an
aldosterone–renin ratio (D), CT scan (A) or abdominal ultrasound (C) would not be the first-line investigations to consider. They would be useful to investigate Conn’s
syndrome if essential hypertension was excluded as a differential. A glucose tolerance test (E) is inappropriate in this case since the random glucose reading is not
abnormal and the patient is not suffering from symptoms suggestive of diabetes.
A. Phenoxybenzamine alone
B. Prolopanolol alone
C. Phenoxybenzamine followed by propanolol
D. Sodium nitroprusside
E. Propanolol followed by phenoxybenzamine
Explanation: Phaeochromocytomas are malignancies of the sympathetic tract, most commonly arising as tumours of the adrenal medulla. The excess catecholamines
put the patient at considerable risk of cardiovascular compromise, initial treatment must therefore protect against this with complete alpha and beta blockade (C).
Phenoxybenzamine (A) is a nonreversible alpha antagonist which acts to protect against the effects of hypertension. Propanolol (B) is a non-selective beta-blocker which
negates the increased heart contractility (inotropic effects) and heart rate (chronotropic effect). Alpha and beta blockade alone is not sufficient to protect the patient.
The alpha blockade by phenoxybenzamine must be started first before propanolol to prevent exacerbating the hypertension (E). Sodium nitroprusside (D) is a potent
vasodilator and is used during surgery when removing the adrenal tumour. Since severe hypertension can occur, sodium nitroprusside is used in this instance only.
Q5 (500Best): A 57-year-old woman, who has recently returned from a holiday in America, presents with
dull grey-brown patches in her mouth and the palms of her hand which she has noticed in the last week.
She has also noticed she gets very dizzy when rising from a seated position and is continually afraid of
fainting. The most likely diagnosis is:
A. Addison’s disease
B. SIADH
C. Conn’s syndrome
D. Waterhouse–Friderichsen syndrome
E. 17-hydroxylase deficiency
Explanation: This patient is suffering from Addison’s disease (A) whereby the adrenal gland is destroyed, usually due to infection (TB) or autoimmunity. The reduced
cortisol, aldosterone and sex steroids produce a myriad of signs and symptoms: most importantly, postural hypotension due to reduced aldosterone and increased
pigmentation often in palmar creases and newly formed scars. This latter sign is due to elevated MSH which is derived from the POMC molecule which breaks down into
MSH and ACTH. Other symptoms include weight loss, malaise, postural hypotension and vitiligo. The SIADH is due to inappropriately elevated levels of ADH (B) which
leads to the retention of water. The syndrome is therefore characterized by reduced serum sodium levels (hyponatraemia) and reduced serum osmolality, while urine
osmolality and urine sodium levels are elevated. Patients are also euvolaemic without signs of oedema. In patients suffering from heart failure, liver failure or the
nephrotic syndrome, the reduced circulatory volume acts as a stimulus for the ADH secretion. Conn’s syndrome (C) causes a significantly elevated level of aldosterone
secondary to an adrenal tumour. The Waterhouse–Friderichsen syndrome (D) is adrenal haemorrhage that most commonly occurs due to meningococcal infiltration.
Patients tend to present with abdominal pain, although symptoms of hypoadrenalism do occur and include fatigue, weakness, dizziness and vomiting. Symptoms of the
underlying disease process are also often present, such as fever. This condition tends to occur in younger patients and rarely affects adults. Patients therefore tend to be
fluid overloaded resulting in elevated blood pressure. 17-hydroxylase deficiency (E) is usually recognized around puberty, patients present with hypertension,
hypokalaemia and hypogonadism. The aldosterone synthesis pathway is overstimulated, while cortisol and sex steroid synthesis is reduced.
Q6 (pretest): A 58-year-old man is referred to your office after evaluation in the emergency room for
abdominal pain. The patient was diagnosed with gastritis, but a CT scan with contrast performed during
the workup of his pain revealed a 2-cm adrenal mass. The patient has no history of malignancy and denies
erectile dysfunction. Physical examination reveals a BP of 122/78 with no gynecomastia or evidence of
Cushing syndrome. His serum potassium is normal. What is the next step in determining whether this
patient’s adrenal mass should be resected?
Explanation: This patient has what is commonly referred to as an adrenal incidentaloma. If the mass is greater than 1 cm, the first step is to determine whether it is a
functioning or nonfunctioning tumor via measurement of serum metanephrines (pheochromocytoma) and dexamethasone suppressed cortisol (Cushing syndrome)
levels. As the patient has no history of malignancy, a CT-guided fine-needle aspiration is not required. The patient has normal BP and potassium; therefore, plasma
aldosterone/plasma renin ratio to evaluate primary hyperaldosteronism is not required. There are no signs of feminization or erectile dysfunction, so sex-steroid
measurement is not indicated. Unenhanced CT would be required after appropriate serum workup to determine true size and characteristics (Hounsfield units [HU]).
Malignant indicators include large-size (> 4-6 cm), irregular margins, soft tissue calcifications, tumor inhomogeneity, or high unenhanced CT attenuation values greater
than 10 HU. CT scans should be performed in 6 months and again in 1 year to ensure stability of the adrenal mass, but only after a functioning tumor has been excluded.
Explanation: Plasma-free metanephrine levels and overnight dexamethasone suppression test should be done next. The increasing use of imaging studies has revealed
many previously unrecognized, often asymptomatic adrenal masses (adrenal incidentalomas). Initial assessment should include a careful history and physical
examination to find any suggestion of malignant disease or clinical evidence of hormone hypersecretion. Most patients with metastatic cancer of the adrenal glands have
clinical evidence of disease elsewhere.
Imaging characteristics of the mass (size, CT attenuation, vascularity) can provide important clues. The risk of primary or metastatic cancer is nearly 2% for tumors less
than 4 cm in diameter but increases to 25% for tumors 6 cm or larger. Metastatic lesions to the adrenal glands tend to have a high CT attenuation (>20 Hounsfield units)
and are often bilateral. Primary adrenocortical carcinoma tends to be large with irregular borders and may include areas of necrosis. Pheochromocytoma, adrenal
carcinoma, and metastatic disease to the adrenal glands are often vascular, whereas benign adrenal adenomas are not highly vascular. Because overt clinical
manifestations are typically scant, screening tests are often necessary to identify potentially functioning adrenal incidentalomas secreting cortisol, aldosterone, or
catecholamines. Subclinical Cushing syndrome is the most common abnormality associated with adrenal incidentalomas. Because these patients have no symptoms or
physical findings of Cushing syndrome, the possibility of autonomous hypersecretion of glucocorticoids should be evaluated with an overnight dexamethasone
suppression test. Additionally, measurements of plasma catecholamines are reasonable screening tests to rule out pheochromocytoma, which can be asymptomatic or
associated with intermittent symptoms.
Adrenal incidentalomas are unlikely to secrete aldosterone, but patients should be screened for that possibility if they have hypertension or hypokalemia, both of which
are absent in this patient. Similarly, excess adrenal androgen production is rare, except when the mass represents adrenal cancer, and screening is not routinely
performed in the absence of clinical signs or symptoms of feminization in men or hyperandrogenism in women, which is also absent in this patient.
Q8 (MKSAP): A 43-year-old man is evaluated for drug-resistant hypertension. Hypertension was diagnosed
1 year ago and has been difficult to control despite maximum dosages of lisinopril, metoprolol, and
nifedipine. The patient reports feeling well. On physical examination, temperature is 36.5°C (97.7°F),
blood pressure is 146/92 mm Hg, pulse rate is 88/min, respiration rate is 17/min, and BMI is 27. Results of
the general physical examination and funduscopic examination are unremarkable.
Electrolytes: Sodium 143 meq/L (143 mmol/L). Potassium 3.3 meq/L (3.3 mmol/L).
Chloride 101 meq/L (101 mmol/L). Bicarbonate 33 meq/L (33 mmol/L). Creatinine 1.0 mg/dL (88.4 umol/L).
Spot urine potassium Inappropriately high
Urinalysis Normal
Which of the following is the most appropriate next diagnostic test?
Explanation: The most appropriate next diagnostic test is determination of the serum aldosterone to plasma renin activity ratio. This patient has drug-resistant
hypertension (uncontrolled hypertension on three drugs, including a diuretic), unprovoked hypokalemia, and probable metabolic alkalosis; he also has an
inappropriately high urine potassium level. In this setting, primary hyperaldosteronism is a very likely cause of his hypertension and hypokalemia, especially given his
age. The best screening test for primary hyperaldosteronism is a determination of the ratio of serum aldosterone (in ng/dL) to plasma renin activity (in ng/mL/min). A
ratio greater than 20, particularly when the serum aldosterone level is greater than 15 ng/dL (414 pmol/L), is consistent with the diagnosis of primary
hyperaldosteronism.
After biochemical confirmation of hyperaldosteronism, localization procedures are appropriate to differentiate aldosterone-producing adenomas, which are amenable
to surgical resection, from bilateral hyperplasia, which is medically treated. Given the high incidence of incidental adrenal lesions, however, imaging studies, such as CT
of the adrenal glands, should not be performed before biochemical testing that confirms the presence of hyperaldosteronism.
This patient does not fit the demographic or clinical profile of a patient with renovascular hypertension, and thus evaluating the renal arteries with digital subtraction
renal angiography is not indicated. Renovascular hypertension due to fibromuscular disease of the renal arteries usually presents in patients younger than 35 years, and
azotemia is rarely present. Atherosclerotic renovascular hypertension is more common in patients older than 55 years and is frequently associated with vascular disease
in other vessels; azotemia is often present. Other than sustained hypertension, this patient did not have any of other symptoms or signs suggestive of a
pheochromocytoma (palpitations, headache, tremor, diaphoresis). Therefore, screening for a pheochromocytoma with measurement of the plasma metanephrine and
normetanephrine levels is less likely to be helpful than is screening for hyperaldosteronism.
Explanation: The most appropriate next management step for this patient is an abdominal CT scan. She has the classic symptoms of pheochromocytoma-
-palpitations, sweating, headaches, and hypertension. Additionally, biochemical testing revealed increased plasma levels of catecholamines. Most pheochromocytomas
are located in the adrenal medulla, although some are extra-adrenal in origin. CT has sensitivities of 93% to 100% in detecting adrenal pheochromocytoma and
approximately 90% in detecting extra-adrenal catecholamine-secreting paragangliomas. MRI is as sensitive as CT in detecting adrenal pheochromocytomas and superior
to CT in detecting extra-adrenal catecholamine-secreting paragangliomas.
An adrenalectomy is appropriate only when a tumor is confirmed. An adrenalectomy would not be indicated if the source of the catecholamines were confirmed to be
extra-adrenal.
If an abdominal CT shows no masses, the next best localizing study would be a metaiodobenzylguanidine (MIBG) scan. MIBG scintigraphy is highly specific (99%) but less
sensitive (80%) than CT techniques. MIBG scintigraphy is generally reserved for patients with equivocal CT results, extra-adrenal catecholamine-secreting tumors, or
suspected malignancy.
Adrenal vein sampling is a technically difficult and hazardous procedure, especially in a patient with a pheochromocytoma. The availability of the highly specific and
sensitive MIBG scan should take precedence over this more hazardous procedure.
Q10 (MKSAP): A 65-year-old woman is evaluated for a 3-week history of fatigue, nausea, and poor
appetite. In the week before symptom onset, she had acute bronchitis with productive cough and fever.
The patient has a 2-year history of osteoarthritis of the knees that requires intra-articular corticosteroid
injections every 3 to 4 months; her last injection was 3 months ago. Her only other medication is
acetaminophen. On physical examination, the patient looks tired. Temperature is 37.5°C (99.5°F), blood
pressure is 112/58 mm Hg, pulse rate is 92/min, respiration rate is 17/min, and BMI is 32. The patient has
cushingoid features and central obesity. There are multiple ecchymoses on the upper and lower
extremities. Decreased axillary and pubic hair is noted. There is bony hypertrophy and small effusions of
the knees bilaterally but no evidence of warmth or erythema.
Adrenocorticotropic hormone (AM) Low normal
Cortisol (8 AM):
Initial measurement Low.
After cosyntropin stimulation Low normal.
Which of the following is the most likely cause of this patient's recent symptoms?
Explanation: This patient has central adrenal insufficiency secondary to exogenous corticosteroid use. Systemic corticosteroids are the most common cause of central
adrenal insufficiency, with supraphysiologic doses of exogenous corticosteroids causing disruption of hypothalamic/pituitary adrenocorticotropic hormone (ACTH)
production. Consequently, the adrenal cortex atrophies. When subsequently challenged by stress, the hypothalamus and pituitary gland are unable to stimulate
adequate adrenal production of cortisol. This central effect of exogenous corticosteroids can occur after only 3 weeks of suppressive therapy. The patient appears to
have developed Cushing syndrome as a result of chronic systemic exposure to the intra-articular injections of corticosteroids. Despite her cushingoid features, however,
she has clinical and biochemical evidence of adrenal insufficiency. Her low-normal serum ACTH level and her partial response to cosyntropin stimulation indicate that
she has central (secondary) adrenal insufficiency. Patients with adrenal insufficiency often decompensate during concurrent illnesses.
An adrenal adenoma could cause a suppressed ACTH level, cushingoid features, and central obesity, but her symptoms also suggest glucocorticoid deficiency.
Furthermore, an adrenal adenoma would cause an elevated, not suppressed, cortisol level.
A functioning pituitary adenoma might produce excessive ACTH, but in that case both the ACTH and cortisol levels would be elevated, not suppressed as they are in this
patient. A nonfunctioning pituitary adenoma might cause suppressed levels of ACTH and cortisol but there would be no signs of hypercortisolism, as seen in this patient.
Primary adrenal insufficiency (Addison disease) is typically associated with low cortisol production and elevated ACTH levels.
Q2 (AMBOSS): A 42-year-old woman comes to the physician for a routine health maintenance examination.
She has generalized fatigue and has had difficulties doing her household chores for the past 3 months. She
has eczema and gastroesophageal reflux disease. She has a history of using intravenous
methamphetamine in her youth but has not used illicit drugs in 23 years. Her medications include topical
clobetasol and pantoprazole. She is 160 cm (5 ft 3 in) tall and weighs 105 kg (231 lb); BMI is 42 kg/m2. Her
temperature is 37°C (98.6°F), pulse is 95/min, and blood pressure is 145/90 mm Hg. The lungs are clear to
auscultation. Cardiac examination shows no abnormalities. Pelvic examination shows a normal vagina
and cervix. Laboratory studies show:
Q4 (AMBOSS): A 43-year-old woman comes to the physician for an annual health maintenance
examination. On questioning, she has had excessive fatigue for the last month. A few weeks ago, she was
diagnosed with carpal tunnel syndrome for which she received a padded cast. She has mild persistent
asthma and anxiety disorder. She drinks 2–3 glasses of red wine per night and has smoked one pack of
cigarettes daily for 16 years. She is sexually active with her husband of 19 years. Menses occur at regular
28-day intervals and last 4–6 days. Her last menstrual period was 2 weeks ago. She works a desk job in
accounting and has recently been working long hours due to an upcoming company merger. Her father has
a history of a brain tumor. Current medications include alprazolam and a fluticasone-formoterol inhaler.
She is 160 cm (5 ft 3 in) tall and weighs 81.6 kg (180 lb); her BMI is 32 kg/m2. Her temperature is 37.2°C (99°
F), pulse is 92/min, and blood pressure is 128/80 mm Hg. Examination shows no abnormalities. Fasting
laboratory studies show:
Explanation: Insulin resistance and subsequent pancreatic β-cell dysfunction are the major pathophysiological mechanisms of type 2 diabetes mellitus. This patient
meets the criteria for obesity, a cardinal risk factor for type 2 diabetes mellitus. A fasting glucose level of ≥ 126 mg/dL is diagnostic of diabetes mellitus.
Answers: Q5: A
Lecture Quiz
Hyperlipidemia
Lecture Quiz
Q1 (MKSAP): A 50-year-old man is evaluated during a routine physical examination. He is asymptomatic,
has no medical problems, and takes no medications. He is a nonsmoker and drinks two alcoholic
beverages daily. His father, uncle, and a brother had myocardial infarctions bet ween the ages of 55 and 60
years. On physical examination, vital signs are normal. BMI is 28. On the skin examination, he has soft,
nontender, yellow plaques measuring between 0.5 and 1 cm on his upper eyelids. The remainder of the
physical examination results are normal.
Which of the diagnostic studies should be done next?
Explanation: The patient's skin lesions are xanthelasmas, which are the most common type of xanthomas. Xanthomas are the characteristic skin conditions associated
with primary (due to genetic defects) or secondary hyperlipidemias. Xanthomas are yellow, orange, reddish, or yellow-brown papules, plaques, or nodules. If the
infiltration is deep, the xanthoma may be nodular and have normal-appearing overlying skin. The type of xanthoma closely correlates with the type of lipoprotein that is
elevated. Xanthelasma is a type of xanthoma characterized by soft, nontender, nonpruritic plaques localized to the eyelids. Xanthelasma can occur without
hyperlipidemia, but is often associated with familial dyslipidemias. Other types of xanthomas include eruptive xanthomas, which present as clusters of erythematous
papules typically on the extensor surfaces. They are most often associated with extremely high (greater than 3000 mg/dL [33.9 mmol/L]) serum triglyceride levels.
Eruptive xanthomas regress with treatment of hypertriglyceridemia. Plane xanthomas are yellow-to-red plaques found in skin folds of the neck and trunk. They can be
associated with familial dyslipidemias and a variety of hematologic malignancies.
Tendon xanthomas are subcutaneous nodules occurring on the extensor tendons. They are associated with familial hypercholesterolemia.
Hypothyroidism is associated with elevated lipid levels and can be a cause of secondarv hyperlipidemias. However, hypothyroidism is not directly associated with the
formation of xanthomas and usually does not result in lipid levels high enough to cause xanthomas. An elevated serum ferritin suggests the diagnosis of
hemochromatosis, but hemochromatosis is not associated with xanthomas. Although liver chemistry tests may be abnormal in patients with extremely elevated lipid
levels and are important to monitor during lipid therapy with statins, they are not associated with xanthoma formation. Type 2 diabetes is often seen in association with
dyslipidemias, but abnormal glucose levels are not directly related to xanthoma formation.
Q2 (MKSAP): A 41-year-old man is evaluated for follow-up of a lipid profile obtained a month ago. He is a
smoker with a 15 pack-year history. He works in an office and does not regularly exercise. He does not
have hypertension and does not have a family history of premature coronary heart disease. On physical
examination, vital signs are normal. BMI is 38. His waist circumference is 94 cm (43 in). The remainder of
his physical examination results are normal. Serum glucose (fasting) 98 mg/dL (5.4 mmol/L).
Total cholesterol 188 mg/dL (4.8 mmol/L). HDL cholesterol 31 mg/dL (0.8 mmol/L).
LDL cholesterol 128 mg/dL (3.3 mmol/L). Triglycerides 145 mg/dL (1.6 mmol/L).
Which of the following is the most appropriate next management step?
Explanation: The most appropriate next management step is to recommend lifestyle modifications. In evaluating and managing low HDL cholesterol, it is important to
remember the primary target of therapy is LDL cholesterol. After LDL cholesterol has been evaluated and managed, non-HDL cholesterol is evaluated as a secondary
target in patients with elevated triglycerides. This patient has isolated low HDL cholesterol. Because of insufficient evidence of risk reduction from controlled trials, ATP
III has not set a specific goal for raising HDL cholesterol. In patients in whom the HDL cholesterol remains low despite use of stat ins or fibrates to treat high LDL or
non-HDL cholesterol, or in patients with isolated low HDL cholesterol such as this patient, the first management step is institution of lifestyle interventions, including
exercise, tobacco cessation, and weight management, because these interventions are capable of increasing the HDL cholesterol level.
The patient does not meet criteria for stat in therapy because his LDL cholesterol goal is 130 mg/dL (3.4 mmol/L) and his measured LDL cholesterol is 128 mg/dL (3.3
mmol/L). His LDL cholesterol goal is based on the presence of two cardiovascular risk factors: smoking and low HDL cholesterol. Fibrate therapy is not indicated to treat
his triglycerides because his non-HDL cholesterol, measured as total cholesterol-HDL cholesterol, is 157 mg/dL (4.0 mmol/L) and is below his target of 160 mg/dL (4.1
mmol/L)
The non-HDL cholesterol goal is calculated as 30 mg/dL (0.8 mmol/L) above the patient's LDL cholesterol goal. Fibrate therapy would be indicated if the patient had a
coronary heart disease equivalent such as diabetes or peripheral vascular disease, because fibrate therapy in this setting results in reduced mortality. Ultrasonography is
not needed to determine carotid intimal thickness, because such information will not modify therapeutic decisions.
Explanation: The best management for this patient is to repeat a fasting lipid level in the future. This patient has hyperlipidemia, defined by a total cholesterol level
above 200 mg/dL (5.2mmol/L). The LDL-cholesterol goal varies depending on the presence or absence of five major cardiovascular risk factors: cigarette smoking,
hypertension, older age (men≥45 years; women ≥55 years), low HDL-cholesterol level (<40 mg/dL [1.0 mmol/L]), and a family history of coronary artery disease (first
degree male relative <55 years;female relative <65 years).
In patients with zero or one risk factor, the LDL-cholesterol goal is below 160 mg/dL (4.1 mmol/L). This patient has no major risk factors. Because his current LDL-
cholesterol level is below 160 mg/dL (4.1 mmolL), no therapy is indicated. The U.S. Preventive Services Task Force (USPSTF) concluded that the optimal interval for
repeat screening is uncertain. It would be reasonable to repeat screening every 5 years, as recommended by the National Cholesterol Education Program, or select a
shorter interval if the lipid levels are close to the threshold for treatment, as in this patient.
Fibrate therapy would be indicated for hypertriglyceridemia (>200 mg/dL [2.3 mmol/L]) in the setting of elevated non-HDL-cholesterol levels, which is not present in this
patient.
Statin therapy would be appropriate for this patient with no risk factors if his LDL-cholesterol level were above 190 mg/dL (5.0 mmol/L) and would be optional if the level
were between 160 mg/dL and 190 mg/dL (4.1 and 5.0 mmol/L).
Lipoprotein(a) [Lp(a)] level determination is not recommended for routine practice. Lp(a) is associated with increased risk for CAD but does not appear to be an
independent predictor of risk of CAD
Q4 (MKSAP): A 60-year-old man with type 2 diabetes mellitus and hypertension visits the office to
establish medical care. His daily medications are metformin, lisinopril, amlodipine, and aspirin. On
physical examinat ion, blood pressure is 128/65 mm Hg and pulse is 76/min; BMI is 26. T he remaining
physical examinat ion findings are normal.
Cholesterol Total 215 mg/dL (5.6 mmol/L). HDL 39 mg/dL (1.0 mmol/L). LDL 145 mg/dL (3.8 mmol/L).
Triglycerides 185 mg/dL (2.1 mmol/L). Hemoglobin A1c 6.5%
Which of the following drugs should be initiated?
(A) Colestipol
(B) Ezetimibe
(C) Niacin
(D) Simvastat in
Explanation: The most appropriate therapy is initiation of a stat in, such as simvastatin. This patient has multiple risk factors for coronary artery disease, including
diabetes mellitus, hypertension, and hypercholesterolemia. Diabetes is a coronary artery disease equivalent risk factor, and patients with diabetes have the same
LDL-cholesterol goal as patients who have had a myocardial infarction, namely, below 100 mg/dL (2.6 mmol/L). A stat in is the first-line treatment for cholesterol
reduction. A 40-mg daily dose of simvast at in would likely reduce the LDL-cholesterol level by 30% and achieve the target goal.
Colestipol interrupts bile acid reabsorption and reduces LDL-cholesterol levels by 10% to 15%. It is often used as a second-line drug with statins because it acts
synergistically to induce LDL receptors. However, colestipol can interfere with the absorption of this patient's other medications and, for this reason, is not the best initial
management of his hyperlipidemia.
Although ezetimibe reduces LDL-cholesterol levels by reducing cholesterol absorption from the intestine, there are presently no clinical trial results showing that this
medication reduces cardiovascular disease events, in contrast to statins. Therefore, ezetimibe should be reserved as an adjunct to other cholesterol-lowering
medications if goal level is not achieved or for patients intolerant or allergic to other proven medications.
Niacin is an effective medication for modestly lowering LDL-cholesterol levels and increasing HDL-cholesterol levels but is often not tolerated because of its adverse
effects (nausea and flushing), particularly at the dosage needed to achieve adequate reduction of the LDL-cholesterol level. Niacin would be a poor choice for this patient
because it can cause glucose intolerance, potentially worsening his glucose control.
(A) Atorvastatin
(B) Orlistat
(C) Fenofibrate
(D) Ezetimibe
Explanation: While management of children and adolescents with hypertriglyceridemia mainly focuses on lifestyle modification (i.e., promoting a healthy diet, physical
activity, and weight loss), pharmacotherapy to reduce the risk of acute pancreatitis should be initiated in patients with triglyceride serum levels >1000 mg/dL and can be
considered for patients with serum levels of 400–1000 mg/dL. Fibrates, such as fenofibrate, are the most effective drug for lowering triglyceride serum levels and
therefore are the treatment of choice.
Causes of dyslipidemia in children and adolescents include an unhealthy diet (e.g., high in saturated fats), an underlying condition (e.g., obesity, type 2 diabetes
mellitus), and genetic defects. This patient's presentation with severe hypertriglyceridemia and a family history of dyslipidemia suggests a genetic disorder (e.g., familial
hypertriglyceridemia). While hypertriglyceridemia itself is not a strong risk factor for cardiovascular disease, affected patients commonly have other cardiovascular risk
factors (e.g., diabetes mellitus, obesity).
Q6 (AMBOSS): A 35-year-old man comes to the physician because of several episodes of crushing
substernal chest pain on exertion over the past 6 weeks. The pain occurs when he goes for his morning run
and disappears if he slows down to a walk. The patient is concerned because two of his uncles died of
myocardial infarction in their early 50s. Physical examination shows yellow plaques on both the palms.
Serum lipid studies showed, An ECG shows no abnormalities. Which of the following is the most likely
cause of this patient's symptoms?
Explanation: Type III familial hyperlipidemia (remnant hyperlipidemia) is caused by an autosomal recessive defect in apolipoprotein E (ApoE). ApoE normally mediates
the uptake of VLDL and chylomicron remnants into liver cells. Defective ApoE results in the reduced uptake of these lipids, which then causes hyperlipidemia and
chylomicronemia. Premature coronary artery disease and peripheral vascular disease due to accelerated atherosclerosis are common complications in such patients.
Q7 (AMBOSS): A 13-month-old boy is brought to the physician for a well-child examination. Physical
examination shows hepatosplenomegaly. A venous blood sample obtained for routine screening tests is
milky. After refrigeration, a creamy supernatant layer appears on top of the sample. Genetic analysis
shows a mutation in the apolipoprotein C-II gene (APOC2) on chromosome 19. This patient is at greatest
risk for developing which of the following complications?
Explanation: Patients with familial hyperchylomicronemia (type I dyslipidemia) have an increased risk of developing recurrent episodes of acute pancreatitis. These
patients typically have serum triglyceride concentrations > 880 mg/dL; the breakdown of these triglycerides by pancreatic lipases creates free fatty acids that directly
injure the pancreas and cause an autoinflammatory response. Additional manifestations of familial hyperchylomicronemia that can develop during childhood include
eruptive xanthomas, lipemia retinalis, and hepatosplenomegaly (due to chylomicron accumulation).
Explanation: Tendinous xanthomas indicate particularly high levels of LDL and are commonly associated with familial hypercholesterolemia, in which extremely
elevated circulating LDL occurs due to impaired LDL receptor signaling and breakdown. Other cutaneous manifestations of hyperlipidemia include xanthelasma, arcus
lipoides corneae, and non-tendinous xanthoma. Familial hypercholesterolemia is associated with premature complications of atherosclerosis, as illustrated by this
patient's maternal history of MI at an early age, and intensive lipid-lowering therapy with statins is vital in preventing cardiovascular complications.
Hereditary causes of hypertriglyceridemia include type I hyperlipidemia (hyperchylomicronemia), type III hyperlipoproteinemia, and type IV hyperlipidemia
(hypertriglyceridemia), none of which are associated with Achilles tendon xanthomas. Type I hyperlipidemia may present with eruptive xanthomas but would not
explain the premature atherosclerosis seen in this patient's mother. Type III hyperlipoproteinemia is associated with early atherosclerosis but the xanthomas are more
commonly found in the palmar creases, rather than the Achilles tendon xanthoma seen in this patient.
Q9 (AMBOSS): A 50-year-old man comes to the physician for his annual health maintenance examination.
The patient feels well. He has a history of hypertension, for which he currently takes lisinopril. He has
smoked a pack of cigarettes daily for 20 years. He drinks five to six beers on weekends. He is 181 cm tall (5
ft 11 in) and weighs 80 kg (176 lb); BMI is 25 kg/m2. His pulse is 75/min, respirations are 18/min, and blood
pressure is 140/85 mm Hg. Physical examination is unremarkable. Laboratory studies showed, In addition
to dietary and lifestyle modification, administration of which of the following agents is the most
appropriate next step in management?
Explanation: HMG-CoA reductase inhibitors, more commonly referred to as statins, are the first-line treatment for dyslipidemia. According to the 2018 AHA/ACC
guidelines, adults ≤ 75 years of age should be started on statin therapy if they have concomitant clinical ASCVD, an LDL-cholesterol concentration ≥ 190 mg/dL, and/or an
estimated 10-year ASCVD risk ≥ 7.5%; adults age 40–75 with diabetes mellitus should also be started on statin therapy. This patient has a calculated LDL level of 191
mg/dL, which is an indication for statin therapy. Statins are the most effective drug for reducing LDL levels and also improving HDL and triglyceride levels. The treatment
goal should be an LDL level < 130 mg/dL.
Q10 (pretest): A 32-year-old, overweight, diabetic woman is found to have a triglyceride level greater than
1000 mg/dL. Family history is positive for diabetes, pancreatitis, and premature coronary artery disease.
TSH is normal. You advise the patient to follow a low-fat diabetic diet, to exercise regularly and to avoid
alcohol. What medication would be most appropriate to start at this time?
A. High-dose rosuvastatin
B. Nicotinic acid
C. Low-dose atorvastatin
D. High-dose fenofibrate
E. Over-the-counter fish oil
Explanation: A normal triglyceride (TG) level is below 150 mg/dL. A moderate to high triglyceride level is between 150 to 499 mg/dL, and over 500 is considered very high.
Obesity increases TG levels by causing increased hepatic VLDL production. In diabetes, insulin insufficiency leads to decreased lipoprotein lipase activity and
impairment of VLDL catabolism. In addition, this patient may have familial hypertriglyceridemia or familial combined hyperlipidemia. All such patients should be
advised to follow a low-fat diet. Because of the risk of acute pancreatitis with such high levels of TG, medication should be instituted as well. Patients with levels over 500
should be started on a fibrate such as fenofibrate or gemfibrozil.
While potent statins such as rosuvastatin and atorvastatin decrease TG modestly, they are second-line agents in this situation. Nicotinic acid also reduces TG levels but
often elevates the blood glucose level in diabetics. Fish oil in high doses can lower the TG level but not as effectively as fenofibrate or gemfibrozil.
Q2 (500Best): A 29-year-old man presents to his GP complaining of being constantly thirsty, tired and
visiting the toilet more often than usual during the last 4 days. He has noticed his clothes have become
more baggy and he now needs to tighten his belt. His parents both have diabetes requiring insulin
therapy. A fasting plasma glucose result is most likely to be:
A. 9.0 mmol/L
B. 6.0 mmol/L
C. 16.3 mmol/L
D. 5.0 mmol/L
E. 3.0 mmol/L
Explanation: Diabetes symptoms with polyuria, polydipsia and weight loss occur due to the osmotic diuresis that results from elevated blood glucose. In symptomatic patients, a single
abnormal glucose reading is adequate and this may be a fasting plasma glucose ≥7.0 mmol/L or a random plasma glucose of ≥11.1 mmol/L, hence the most appropriate answer is (A) while
answer (C) is most likely to occur in a patient with significant symptoms with a random plasma glucose measurement. Asymptomatic patients require two abnormal readings, such as two
fasting or two random plasma glucose measurements ≥7.0 mmol/L. Answer (D) is within the normal fasting plasma glucose range (3.9–5.5 mmol/L), while answer (E) is hypoglycaemia. Answer
(B) is mildly impaired fasting plasma glucose which is unlikely in a patient who is symptomatic.
Q3 (MKSAP): A 20-year-old woman is brought to the emergency department by her college roommate. The
patient is lethargic with rapid respirations. Her roommate reports that the patient has had a cough, fever,
and chills for the 3 days. She has a 12-year history of type 1 diabetes mellitus. During the previous 24
hours, the patient has had poor oral intake and has not taken her insulin. Today she developed abdominal
pain, nausea, and vomiting. On physical examination, the patient is lethargic but arousable. Temperature
is 35.5°C (96.0°F), blood pressure is 90/68 mm Hg, pulse rate is 120/min, and respiration rate is
28/min and deep. The cardiopulmonary examination is normal. Bowel sounds are diminished but present.
Palpation elicits generalized tenderness, but no peritoneal signs are present. Other than lethargy, the
neurologic examination is normal.
Which the following tests will establish the diagnosis?
(A) Serum glucose and electrolytes and urine ketones
(B) Serum glucose and potassium, complete blood count, and urinalysis
(C) Serum glucose, electrolytes, and ketones and arterial blood gases
(D) Serum glucose, phosphate, and potassium and arterial blood gases
(E) Serum ketones and carbon dioxide, complete blood count, and urine ketones
Explanation: This patient has diabetic ketoacidosis (DKA), and the tests to establish the diagnosis are serum glucose, electrolytes, and ketones and arterial blood gases. The most life-
threatening acute complication of diabetes is DKA, which mostly affects patients with type 1 diabetes and is sometimes its presenting manifestation. At presentation, patients with DKA usually
report a several-day history of polyuria, polydipsia, and blurred vision, culminating in nausea, vomiting, abdominal pain, dyspnea, and altered mental status. Physical examination typically
reveals deep, labored breathing (Kussmaul respirations), a fruity odor to the breath (from acetone), poor skin turgor, tachycardia, and hypotension. This complication can occur as a result of
precipitating acute stresses such as infections (influenza, pneumonia, or gastroenteritis) or acute myocardial infarction; in patients with insulin pumps, when a technical interruption of insulin
infusion occurs; and in patients who are nonadherent to their medication regimen. In almost all instances, DKA is entirely preventable if patients practice regular glucose monitoring and
understand the need for increased insulin doses during acute stress events. The diagnosis of DKA is based on a blood glucose level less than 250 mg/dL (13.9 mmolL), anion gap metabolic
acidosis (arterial pH <7.30), a serum carbon dioxide level less than 15 meg/L (15 mmol/L), and positive serum or urine ketone concentrations.
A. Insulin resistance
B. Insulin deficiency
C. Elevated thyroxine levels
D. Inadequate ADH secretion
E. Inadequate ADH secretion
Explanation: Absolute insulin deficiency is the underlying pathology of type 1 diabetes mellitus, caused by an autoimmune-mediated destruction of pancreatic β cells. The resulting elevation of
blood glucose levels lead to a range of symptoms, typically including polyuria, nocturia, polydipsia, and increased appetite. Nonspecific symptoms of fatigue, weight loss, and an increased
tendency to infections (e.g., skin infections, UTIs) are also common. The symptoms usually develop within days to a few weeks, or manifest suddenly with diabetic ketoacidosis. While glucosuria
detected via urine dipstick is suggestive of diabetes mellitus, the diagnosis is confirmed through an oral glucose tolerance test or a random blood glucose level ≥ 200 mg/dL.
Q5 (AMBOSS): A 22-year-old woman with type 1 diabetes mellitus and mild asthma comes to the physician
for a follow-up examination. She has had several episodes of sweating, dizziness, and nausea in the past 2
months that occur during the day and always resolve after she drinks orange juice. She is adherent to her
diet and insulin regimen. The physician recommends lowering her insulin dose in certain situations. This
recommendation is most important in which of the following situations?
Explanation: This patient should be advised to lower her insulin dose before exercise because exertion can cause hypoglycemia by increasing insulin sensitivity (resulting in a reduced need for
exogenous insulin) and by increasing insulin-independent glucose uptake. Higher sensitivity to insulin increases glycolysis and reduces gluconeogenesis. The patient should also be advised to
closely monitor her blood glucose before, during, and after exercise to watch out for symptoms of hypoglycemia.
Q6 (AMBOSS): A 19-year-old woman comes to the physician for a follow-up examination. She has a history
of type 1 diabetes mellitus and is adherent with her medications. After reviewing the patient's recent
blood sugar levels, the physician changes the patient's antidiabetic regimen by changing the dosage of an
insulin that does not produce an observable peak in serum insulin concentration. The dosage of which of
the following types of insulin was most likely changed in this patient's medication regimen?
A. Insulin glargine
B. Insulin glulisine
C. Regular insulin
D. Insulin lispro
E. NPH insulin
Explanation: Insulin glargine is a basal, long-acting, peakless insulin that is nearly identical to human insulin. It can be used in basal-bolus insulin regimens and as basal supported oral therapy.
After subcutaneous administration, glargine precipitates in the tissue and forms hexamers, which delay absorption and prolongs the duration of action. Long-acting insulins are usually
administered once daily.
Q8 (AMBOSS): A 25-year-old man comes to the physician for a 2-month history of abdominal discomfort,
fatigue, and increased urinary frequency, especially at night. He has also noticed that despite eating more
often he has lost 14-lbs (6-kg). He has a congenital solitary kidney and a history of Hashimoto thyroiditis,
for which he takes levothyroxine. He has smoked two packs of cigarettes daily for 10 years. BMI is 18
kg/m2. His temperature is 36.7°C (98.1°F), pulse is 80/min, and blood pressure is 110/60 mm Hg. Physical
examination is unremarkable. Serum studies show an osmolality of 305 mOsm/L and bicarbonate of 17
mEq/L. Urinalysis shows clear-colored urine with no organisms. Which of the following is most likely to be
helpful in establishing the diagnosis?
A. Ultrasonography of the thyroid gland
B. Serum glucose
C. Water deprivation test
D. Serum creatinine
E. Digital rectal examination
Explanation: A single random serum glucose level of ≥ 200 mg/dL is sufficient for the diagnosis of diabetes mellitus in a patient with other classic signs of the disease
(e.g., polyuria, dehydration, weight loss). Alternatively, a fasting plasma glucose ≥ 126 mg/dL, oral glucose tolerance test ≥ 200 mg/dL, or hemoglobin A1C ≥ 6.5 % are
also diagnostic of diabetes mellitus. This patient's young age, history of autoimmune disease, evidence of acidosis, and weight loss are suggestive of type 1 diabetes
mellitus, which is caused by autoimmune destruction of pancreatic beta cells.
Q9 (AMBOSS): A previously healthy 15-year-old girl is brought to the physician by her parents for lethargy,
increased thirst, and urinary frequency for 10 days. She is 173 cm (5 ft 8 in) tall and weighs 54 kg (120 lb);
BMI is 18 kg/m2. Physical examination shows no abnormalities. Her serum glucose concentration is 224
mg/dL. A urine dipstick is positive for ketone bodies. Which of the following is most likely involved in the
pathogenesis of this patient's condition?
A. Expression of human leukocyte antigen subtype A3
B. Complement-mediated destruction of insulin receptors
C. Pancreatic islet amyloid polypeptide deposition
D. T-cell infiltration of pancreatic islets
Explanation: In patients with type 1 diabetes mellitus, infiltration of autoreactive CD4 and CD8 positive T cells into the pancreatic islets leads to the progressive
destruction of insulin-producing β cells, which ultimately results in insulin deficiency. The immune system is thought to be activated by one or more environmental
triggers (e.g., a viral infection, dietary factors) in genetically susceptible individuals. The loss of functioning β cells continues over months to years; symptoms usually
manifest once 80–90% of β cells have been destroyed.
Explanation: Type 2 diabetes symptoms are usually well recognized, as in this patient, with polyuria and weight loss occurring due to the osmotic diuresis that results
from elevated blood glucose. In subacute presentations, more subtle signs include lethargy and opportunistic infections, such as Candida, causing pruritus vulvae in
females or penile inflammation (balantis) in males. The criteria for diabetes diagnosis depends on the clinical presentation. In symptomatic patients, a single abnormal
glucose reading is adequate and this may be a fasting plasma glucose ≥7.0 mmol/L or as in this case a random plasma glucose (C) of ≥11.1 mmol/L. In asymptomatic
presentations, two abnormal readings are required, e.g. two fasting plasma glucose ≥7.0 mmol/L or two random plasma values ≥11.1 mmol/L. Water deprivation (D) is
useful in investigating polydipsia for conditions such as diabetes insipidus. An oral glucose tolerance test (A) is only used for borderline cases or diagnosis of gestational
diabetes. Other investigations, such as triglyceride (E), cholesterol and glycated haemoglobin (B), can be conducted after diagnosis to monitor the progress of the
condition and used as potential risk factors for other conditions.
Q2 (500best): A 50-year-old Asian man is referred to the diabetes clinic after presenting with polyuria and
polydipsia. He has a BMI of 30, a blood pressure measurement of 137/88 and a fasting plasma glucose of
7.7 mmol/L. The most appropriate first-line treatment is:
Explanation: The initial management of type 2 diabetes (T2DM) should begin with lifestyle changes (A) which involve obtaining a dietary history, physical exercise per
week and other factors such as a smoking history. Expert clinical advice may then be offered with the help of a registered dietician, regular exercise encouraged and
smoking cessation encouraged. The aim should be to normalize blood glucose, blood pressure and lipid levels. Unfortunately, T2DM becomes progressively worse with
time until eventually exogenous insulin replacement is required. Metformin (E) is particularly proficient in lowering serum glucose and should be used in
overweight/obese patients with particular difficulty in controlling glucose levels. Insulin secretagogues (B) (sulphonylureas and rapid-acting insulin secretagogues, such
as nateglinide and repaglinide) are particularly effective in controlling HbA1 c levels and improving cardiovascular outcomes. They should be used as first-line treatment
if patients are not overweight and require rapid glucose control due to hyperglycaemic symptoms. Patients unable to maintain or achieve adequate glucose control may
use sulphonylureas as second-line therapy. Exenatide (C) and thiazolidinediones (D) tend to be considered following lifestyle, metformin and sulphonylurea action to
control HbA1 c levels.
Q3 (500Best): A 49-year-old man has recently been diagnosed with type 2 diabetes and is being carefully
monitored. He has been advised to maintain a healthier diet and lifestyle, he attends a follow-up clinic and
claims to have been following the diet stringently since his last appointment three months ago. The most
appropriate investigation is:
Explanation: Glycated haemoglobin (D) reflects the level of blood glucose due to glucose attachment to red blood cells non-enzymatically. Since red blood cells have a
half-life of 120 days, they will reflect the glucose level of the patient for approximately three months. Measuring the random plasma glucose (A) and fasting glucose (B)
will show the state of glucose control at the instant of measurement, but provides no information about the degree of control the patient has over a longer period of
time. Patients may therefore fast closer to the date of their appointments despite poor compliance. Similarly, urine dipstick (C) can only reflect the control of glucose
homeostasis at the instance of measurement, it is also only appropriate as a screening measurement and must be quantified with blood tests. Weight measurement (E)
would be useful to measure to record the change in BMI over time; however, it provides no information to the state of diabetes control.
Q5 (pretest): A 50-year-old woman is 5 ft 7 in tall and weighs 185 lb. There is a family history of diabetes
mellitus. Fasting blood glucose (FBG) is 160 mg/dL and 155 mg/dL on two occasions. HgA1c is 7.8%. You
educate the patient on medical nutrition therapy. She returns for reevaluation in 8 weeks. She states she
has followed diet and exercise recommendations, but her FBG remains between 130 and 140 and HgA1C is
7.3%. She is asymptomatic, and physical examination shows no abnormalities. Which of the following is
the treatment of choice?
A. Thiazolidinediones such as pioglitazone
B. Encourage compliance with medical nutrition therapy
C. Insulin glargine at bedtime
D. Metformin
E. Glipizide
Explanation: The classification of diabetes mellitus has changed to emphasize the process that leads to hyperglycemia. Type 2 DM is a group of heterogeneous disorders
characterized by insulin resistance, impaired secretion of insulin, and increased glucose production. In this type 2 patient, the first intervention, medical nutrition
therapy, failed to achieve the goal HgA1c of less than 7.0%. Medical nutrition therapy (MNT) is a term now used to describe the best possible coordination of calorie
intake, weight loss, and exercise. It emphasizes modification of risk factors for hypertension and hyperlipidemia, not just weight loss and calorie restriction. Blood
glucose control should be evaluated after 4 to 6 weeks and additional therapy should be added; therefore, continued observation is not the best option. Metformin is
considered first-line therapy in that it promotes mild weight loss, has known efficacy and side-effect profile, and is available as a generic with very low cost.
Thiazolidinediones (“glitazones”), sulfonylureas, and insulin are considered second-line or add-on therapy for most patients with type 2 DM.
Q6 (MKSAP): A 48-year-old man comes to the office for a routine physical examination. The patient is
asymptomatic but overweight. Although he has no pertinent personal medical history, he has a strong
family history of diabetes mellitus. He currently takes no medications. Results of physical examination are
normal, except for a BMI of 29. Results of routine laboratory studies show a fasting plasma glucose level of
158 mg/dL (8.8 mmol/L). These results are confirmed 2 days later.
Which of the following terms best describes his current glycemic status?
A. Impaired fasting glucose
B. Impaired glucose tolerance
C. Metabolic syndrome
D. Type 2 diabetes mellitus
Explanation: This patient has type 2 diabetes mellit us. The diagnosis of diabetes mellit us can be established by a fasting plasma glucose level of at least 126 mg/dL (7.0 mmol/L), a random plasma glucose level of at least 200
mg/dL (11.1 mmol/L) and symptoms of hyperglycemia (for example, polyuria, polydipsia, or blurred vision), or a 2-hour oral glucose tolerance test (OGTT) result of at least 200 mg/dL (11.1 mmol/L). In 2010, the American
Diabetes Association endorsed a hemoglobin A1 value of 6.5% of greater as diagnostic of diabetes.Impaired fasting glucose, impaired glucose tolerance, or both mark the transition from normal glucose tolerance to type 2
diabetes mellitus. Impaired fasting glucose is diagnosed when the fasting plasma glucose level is in the range of 100 to 125 mg/dL (5.6 to 6.9 mmolL), and impaired glucose tolerance an analogous prediabetic state--iS
diagnosed when the plasma glucose level at the 2-hour mark of an OGTT is 140 to 199 mg/dL (7.8 to 11.0 mmol/L). For a diagnosis of the metabolic syndrome to be made, information about the patient's blood pressure
(≥130/85 mm Hg), lipid levels (triglyceride level ≥150 mg/dL [1.7 mmol/L]; HDL-cholesterol <40 mg/dL in men [1.0 mmol/L]), fasting plasma glucose level (≥110 mg/dL [6.1 mmol/L]), and waist circumference (>40 in [>102 cm] in
men) is necessary. Insufficient data have been provided for this diagnosis.
A. Acarbose
B. Metformin
C. Ramipril
D. Rosiglitazone
E. Diet and exercise
Explanation: The most appropriate treatment for this patient is diet and exercise. She has impaired fasting glucose (IFG), defined as a fasting plasma glucose level in the
range of 100 to 125 mg/dL (5.6 to 6.9 mmol/L), and should begin a program of intensive lifestyle change, including 30 minutes of exercise most days of the week and a
calorie-restricted diet. to achieve weight reduction on the order of 7% of body weight.
Diet and exercise is the recommended approach for patients with either IFG or impaired glucose tolerance (IGT), the prediabetic states. The relative risk reduction (RRR)
in the incidence of diabetes in patients with IGT associated with intensive lifestyle change is 58%.
Pharmacologic therapy with glucose-lowering drugs is not indicated for this patient with isolated IFG. In pharmacologic studies of diabetes prevention, acarbose therapy
resulted in only a 25% RRR, which is inferior to that obtained with diet and exercise.
Met formin therapy is associated with an RRR of 31%, which is also inferior to the 58% RRR obtained with diet and exercise. Met formin therapy may be considered in
patients with both IFG and IGT, who constitute a higher risk group. This patient does not have IGT (fasting plasma glucose level of 140 to 199 mg/dL [7.7 to 11.0 mmol/L]
at the 2-hour mark of an oral glucose tolerance test) and so should not receive met formin.
Modulators of the renin-angiotensin axis, such as ramipril and other angiotensin-converting enzyme inhibitors, do not contribute to diabetes prevention
Rosiglitazone and pioglitazone have been associated with 62% and 81% RRRs, respectively, in the incidence of diabetes. These agents, however, are not endorsed for
rout < pharmacologic use in patients with prediabetes because of their costs and adverse effects, including edema, increased fracture risk in women, and possible
increased cardiovascular morbidity.
Q8 (MKSAP): An obese 44-year-old woman is evaluated for persistent hyperglycemia. For the past 3
months, she has followed a strict regimen of diet and exercise in an attempt to control her hyperglycemia.
Home blood glucose monitoring has shown preprandial levels between 120 and 160 mg/dL (6.7 and 8.9
mmol/L) and occasional postprandial levels exceeding 200 mg/dL (11.1 mmol/L). She takes no
medications. Vital signs and physical examination findings are normal, except for a BMI of 30. Laboratory
studies show a serum creatinine level of 0.8 mg/dL (70.7 umol/L); the urine is negative for
microalbuminuria.
Which of the following is the most appropriate treatment?
A. Begin exenatide
B. Begin glimepiride
C. Begin metformin
D. Begin pioglitazone
E. Continue the diet and exercise for an additional 3 months
Explanation: The most appropriate treatment for this patient is to begin metformin. Various oral and injectable agents are available for the initial management of type 2
diabetes, most of which reduce hyperglycemia to a similar degree. Because of its low cost, effectiveness, good tolerability, relative safety, favorable effects on body
weight, and absence of hypoglycemia as a side effect, met formin remains the best first-line agent available. Metformin is contraindicated in patients with renal
insufficiency (serum creatinine level >1.4 mg/dL [123.8 umol/L] for women and >1.5 mg/dL [132.6 umol/L] for men. For this patient, ongoing attempts at lifestyle change
are unlikely to reduce her blood glucose level further. Therefore, initiation of met formin therapy is most likely to improve her glycemic control.
Exenatide, an injectable agent, is only approved for use in combination regimens with oral agents and is inappropriate in most circumstances as monotherapy.
Glimepiride could be used but is associated with weight gain and the risk of hypoglycemia. Overall, it remains a less attractive choice than met formin in most patients,
including this one.
Pioglitazone is also available for monotherapy, but its side effects of weight gain, edema, increased peripheral bone fracture rates in women, and high cost make it less
attractive than met formin as a first-line therapy.
Explanation: Measurement of fasting blood glucose (FBG) concentration is routinely used to screen for diabetes mellitus. Although screening recommendations for
diabetes mellitus differ among expert groups, this 41-year-old patient with dyslipidemia and a BMI of 29 kg/m2 meets the screening criteria of both the United States
Preventive Services Task Force (USPSTF) and the American Diabetes Association (ADA). The USPSTF recommends screening individuals 35–70 years of age with a BMI ≥
25 kg/m2. The ADA recommends screening individuals with a BMI ≥ 25 kg/m2 who have at least one additional risk factor (e.g., physical inactivity, hypertension,
dyslipidemia, a first-degree relative with diabetes) and individuals ≥ 45 years of age who have no risk factors. Besides FBG, other tests used to screen for diabetes
mellitus include hemoglobin A1C (HbA1c) and the oral glucose tolerance test (OGTT). Each of the following findings can be used to establish a diagnosis of diabetes
mellitus: FBG ≥ 126 mg/dL, HbA1c ≥ 6.5%, and a 2-hour plasma glucose ≥ 200 mg/dL during an OGTT.
Q10 (AMBOSS): An 81-year-old man is admitted to the hospital due to acute decompensated heart failure.
He has type 2 diabetes mellitus, hypertension, coronary artery disease, and congestive heart failure.
Current medications include lisinopril, metformin, and low-dose aspirin. He has smoked one pack of
cigarettes daily for 45 years. His temperature is 37.6°C (99.7°F), pulse is 105/min and regular, respirations
are 21/min, and blood pressure is 103/64 mm Hg.
A. Begin hydrochlorothiazide therapy
B. Discontinue aspirin therapy
C. Discontinue metformin therapy
D. Begin norepinephrine therapy
E. Begin nitroprusside therapy
Explanation: Metformin is associated with an increased risk of life-threatening lactic acidosis in patients with predisposing conditions that reduce lactic acid clearance
(i.e., renal and/or hepatic insufficiency), increased lactic acid production (e.g., sepsis), or a combination of both (e.g., heart failure with low cardiac output). This patient's
renal insufficiency and heart failure with decreased cardiac output are both contraindications to metformin therapy, which should therefore be discontinued
immediately. Insulin should instead be used for inpatient glycemic control.
Q11 (AMBOSS): A 69-year-old man with type 2 diabetes mellitus comes to the physician for a follow-up
examination. His only medication is metformin. He has tried to lose weight for several years without
success. He is 168 cm (5 ft 6 in) tall and weighs 110 kg (243 lb); BMI is 39 kg/m2. His hemoglobin A1c is
8.5%. Which of the following is the most appropriate antidiabetic drug to address both this patient's
glucose control and weight?
A. Liraglutide
B. Sitagliptin
C. Glipizide
D. Miglitol
E. Rosiglitazone
Explanation: Liraglutide, which is a GLP-1 agonist, can facilitate weight loss and control hyperglycemia. Incretin-based therapeutic agents such as GLP-1 agonists also
have the additional benefit of carrying only a low risk of medication-induced hypoglycemia. Besides metformin and GLP-1 agonists, other drugs that can be used for
weight loss in diabetic patients include SGLT-2 inhibitors (e.g., dapagliflozin), orlistat, and pramlintide. However, orlistat does not cause glycemic control, which is
desired in this patient, and pramlintide is only used in combination with insulin therapy.
A. Autonomic neuropathy
B. Diabetic amyotrophy
C. Acute painful neuropathy
D. Symmetrical sensory neuropathy
E. Diabetic mononeuropathy
Explanation: Diabetic neuropathy is likely to occur through various pathways, occlusion of the vasa nervorum may explain mononeuropathies (E) that occur in isolation
and not symmetrically as in this patient. Diffuse symmetrical neuropathies produce more variable presentations and are likely to be due to metabolic damage. The build
up of sorbitol and fructose in Schwann cells due to hyperglycaemia is a popular theory. Symmetrical sensory neuropathy (D) is characterized by early loss of vibration,
pain and temperature sense in a glove and stocking pattern. In advanced disease, patients often lose their balance and complain of altered sensations. Painful
neuropathies (C) are less common and patients typically present with burning sensations or painful parasthesia of their feet, shins or thighs. Diabetic amyotrophy (B) is
characterized by painful wasting of the patients’ quadriceps muscles and is usually asymmetrical. Control of glucose levels over time usually resolves the condition.
Autonomic neuropathy (A) is rarely symptomatic, but can present with a number of different problems of the sympathetic and parasympathetic system. This includes
vagal neuropathy causing tachycardia at rest, gastroparesis which rarely can lead to vomiting, erectile dysfunction and atonic bladder.
Q2 (500Best): A 6-year-old girl presents to accident and emergency with severe abdominal pain, nausea
and vomiting. On examination, the patient is tachypnoeic, capillary refill is 3 seconds and she has a dry
tongue. While listening to the patient’s lungs, you detect a sweet odour from her breath. The most likely
diagnosis is:
A. Diabetic ketoacidosis
B. Non-ketotic hyperosmolar state
C. Gastroenteritis
D. Pancreatitis
E. Adrenal crisis
Explanation: In diabetic ketoacidosis (A), the body enters a catabolic state as it perceives a lack of energy stores. Ketones are produced from the breakdown of fat which
causes an acidotic state in the body. Patients commonly present with nausea, vomiting, dehydration and abdominal pain. The acidosis is partially compensated by
hyperventilation (Kussmaul respiration) and the sweet breath is acetone as the body tries to equilibrate the serum pH. A non-ketotic hyperosmolar state (B) usually
occurs in type 2 diabetes whereby the hyperglycaemic state causes a hyperosmolar state causing polyuria and dehydration which exacerbate the elevated glucose
concentration. Ketones are not responsible as there is a small presence of insulin inhibiting lipolysis. In an adrenal crisis (E), the adrenal gland is destroyed, usually due
to infection (TB) or autoimmunity. The reduced cortisol, aldosterone and sex steroids produce a myriad of signs and symptoms, most importantly postural hypotension
due to reduced aldosterone and increased pigmentation often in palmar creases and newly formed scars. This latter sign is due to elevated melanocyte-stimulating
hormone (MSH) which is derived from the POMC molecule which breaks down into MSH and ACTH. Other symptoms include weight loss, malaise and vitiligo.
Gastroenteritis (C) and pancreatitis (D) have more prominent symptoms of abdominal pain and do not usually feature acetone breath.
Q3 (500Best): A 29-year-old woman is found unconscious by her partner and rushed to accident and
emergency. She is a type 1 diabetic and has maintained excellent glucose control using insulin injections.
Blood biochemistry results demonstrate a moderately raised level of insulin, no detectable C-peptide and
very low blood glucose. Her partner mentions she is a lawyer and has been working particularly hard in
the last week, eating quick meals and occasionally missing meals. The most likely diagnosis is:
A. Hyperosmolar coma
B. Diabetic ketoacidosis
C. Insulin overdose
D. Hypoglycaemic coma
E. Autonomic neuropathy
Explanation: In this case, the most likely answer is a hypoglycaemic coma (D). The history indicates that the patient has been missing meals but adheres to her insulin
regime. The raised insulin level and absent C-peptide indicates no endogenous insulin production (which would produce insulin and C-peptide) but exogenous insulin.
The patient has therefore not eaten sufficiently to maintain an adequate glucose level despite taking a recommended dose of insulin. This differs from an insulin
overdose (C) where an excess level of insulin is injected causing an abnormally low glucose level. A diabetic ketoacidosis (B) occurs due to the body’s attempt to
compensate for the perceived lack of glycogen stores due to insulin deficiency. Therefore, by definition, serum insulin levels would be low or absent. A hyperosmolar
coma (A) affects type 2 diabetics whereby the hyperglycaemic state causes hyperosmolarity causing polyuria and dehydration. The glucose, however, is low in this case.
Diabetic neuropathy can cause a myriad of symptoms due to autonomic dysfunction (E) including urinary incontinence, constipation and postural hypotension.
However, there is usually a collection of such symptoms rather than an isolated event. Patients affected also tend to have poor diabetic control.
A. 180
B. 118
C. 139.2
D. 46.1
E. 28
Explanation: This patient is suffering from an episode of diabetic ketoacidosis; the accumulation of ketones causes a metabolic acid. Calculating the anion gap is useful,
narrowing the number of differentials that can cause a metabolic acidosis by showing whether it is due to the retention of H + and Cl − or due to other acids which can
help support the suspected diagnosis. The pH balance in the body is maintained by cations such as Na+ , K + and anions such as Cl− , HCO 3 − (there are other cations and
anions, but these are the main ones used in anion gap calculations). The anion gap is therefore calculated by ([Na+ ] + [K+ ]) − ([HCO3 − ] + [Cl− ]). The anion gap
calculation in this case is ([144]) + ([5]) − ([2.9]) − ([100]) giving 46.1 mmol/L (D). A normal anion gap is 10–18 mmol/L. A normal anion gap in an acidotic patient suggests
the retention of H+ /Cl − or the loss of Na+ /HCO3 − . This can be due to diarrhoea, renal tubular acidosis or hyperparathyroidism, among other causes. In a metabolic
acidosis with an elevated anion gap, as in this case, an unmeasured anion is present in increased quantities, such as lactate or ketones. Causes include lactic acidosis,
ketoacidosis and excess salicylates.
Q5 (MKSAP): A 48-year-old man is evaluated for mild blurring of his central vision bilaterally. He has had
type 1 diabetes mellitus for 24 years. The patient is referred for an immediate retinal examination, which
reveals macular edema and new neovascularization.
Which of the following is the most appropriate next management step?
A. Addition of aspirin
B. Addition of atorvastatin
C. Decrease in the insulin dosage
D. Retinal photocoagulation
Explanation: Panretinal photocoagulation is the most appropriate next step in management. Diabetic retinopathy is a well-recognized microvascular complication of
type 1 diabetes mellitus and is one of the leading causes of visual loss in adults in the United States. Diabetic retinopathy is classified as nonproliferative (with hard
exudates, microaneurysms, and minor hemorrhages), which is not associated with visual decline, and proliferative (with "cotton-wool spots" and neovascularization),
which is associated with loss of vision. Changes in retinal blood flow occur after several years of diabetes. These changes cause retinal ischemia, which in turn promotes
growth factors that stimulate proliferation of new blood vessels. This process leads to scarring and fibrosis. Fibrous tissue can put traction on the retina, which can cause
retinal detachment with resultant vision loss. New vessels can also become more permeable and leak serum, which causes macular edema. Tight glycemic control has
been shown to decrease the incidence and progression of retinopathy. Blood pressure reduction appears to exert as great a beneficial effect on retinopathy as glycemic
control. Once proliferative retinopathy or macular edema is established, vision can be preserved by appropriately timed laser photocoagulation.
Randomized clinical trials have detected no beneficial effect of aspirin on the incidence or progression of proliferative retinopathy or visual loss. At the same time, other
studies have not demonstrated harm to the optic system of patients who must take aspirin for cardiovascular protection.
Although lipid-lowering drugs, such as atorvastatin, have been associated in some studies with reduced rates of retinopathy, they cannot alter the course of established
retinopathy and are not indicated in this patient.
Abrupt rapid improvement in glycemic control has been associated with modest worsening of diabetic retinopathy in early studies, but there is no evidence that allowing
control to deteriorate by reducing the intake of insulin will improve retinopathy. This patient's glycemic control has been stable, so his insulin regimen should not be
changed.
Q7 (AMBOSS): A 53-year-old woman comes to the physician because of pain in her ankle. She twisted her
right ankle inward when walking on uneven ground the previous day. She describes the pain as 6 out of 10
in intensity. She is able to bear weight on the ankle and ambulate. Three weeks ago, she had an episode of
gastroenteritis that lasted for two days and resolved spontaneously. She has type 2 diabetes mellitus,
hypertension, and hyperlipidemia. Her father has type 2 diabetes mellitus and chronic renal failure. Her
mother has hypothyroidism and a history of alcohol abuse. The patient drinks 8–10 beers each week and
does not smoke or use illicit drugs. She adheres to a strict vegetarian diet. Current medications include
metformin, atorvastatin, and lisinopril. Her temperature is 36.9°C (98.4°F), heart rate is 84/min, and blood
pressure is 132/80 mm Hg. Examination of the right ankle shows edema along the lateral aspect. She has
pain with eversion and tenderness to palpation on the lateral malleolus. The foot is warm to touch and has
dry skin. Pedal pulses are palpable. She has decreased sensation to light touch on the plantar and dorsal
aspects of the big toe. She has full range of motion with 5/5 strength in flexion and extension of the big
toe. Laboratory studies show:
Which of the following is the most likely cause of the decreased sensation in this patient?
A- Microvascular damage
B- Vitamin B12 deficiency
C- Acute inflammatory demyelinating polyradiculopathy
D- Medication side effect
Explanation: This patient has a personal and family history of type 2 diabetes mellitus, as well as a hemoglobin A1c > 8%, which suggests that she has not received
adequate treatment for her condition. One of the major complications of long-standing undertreated diabetes mellitus is microvascular damage, which typically arises
5–10 years after disease onset and may manifest as diabetic nephropathy, retinopathy, or neuropathy. Diabetic sensory neuropathy presents with a progressive
symmetric loss of sensation in the peripheral nerves of the distal extremities, typically in a “stocking-glove” distribution. Patients may also report a burning sensation
(dysesthesia) in the affected areas. This patient's loss of sensation on the dorsal and plantar aspects of her right big toe are consistent with diabetic sensory neuropathy.
Furthermore, the preservation of motor function is also consistent with the diagnosis, as motor neuropathy is very rare in diabetes..
Q9 (AMBOSS): A 61-year-old man comes to the physician because of progressively worsening swelling of
his ankles. He says he has felt exhausted lately. Over the past 3 months, he has gained 5 kg (11 lb). He has
smoked one pack of cigarettes daily for 30 years. His pulse is 75/min and his blood pressure is 140/90 mm
Hg. Examination shows 2+ pitting edema in the lower extremities. Neurologic examination shows
diminished two-point discrimination in the fingers and toes. Laboratory studies show a hemoglobin A1c
concentration of 7.9% and a serum creatinine concentration of 1.9 mg/dL. A urine sample is noted to be
foamy. A biopsy specimen of the kidney is most likely to show which of the following?
A- Interstitial inflammation
B- Wire looping of capillaries
C- Nodular glomerulosclerosis
D- Immune complex deposition
Explanation: Nodular glomerulosclerosis with Kimmelstiel-Wilson nodules is pathognomonic of diabetic nephropathy, even though diffuse glomerulosclerosis is the
most common finding. Early antihypertensive treatment, e.g., with ACE inhibitors, can delay the progression of diabetic nephropathy. Antihyperglycemic therapy for this
patient should include lifestyle changes (i.e., weight reduction, increased physical activity, medical nutrition therapy), as well as monotherapy with metformin or insulin
therapy to target a hemoglobin A1c < 7%...
Q10 (AMBOSS): A 63-year-old woman comes to the emergency department because of a 1-day history of
progressive blurring and darkening of her vision in the right eye. Upon waking up in the morning, she
suddenly started seeing multiple dark streaks. She has migraines and type 2 diabetes mellitus diagnosed
at her last health maintenance examination 20 years ago. She has smoked one pack of cigarettes daily for
40 years. Her only medication is sumatriptan. Her vitals are within normal limits. Ophthalmologic
examination shows visual acuity of 20/40 in the left eye and 20/100 in the right eye. The fundus is
obscured and difficult to visualize on fundoscopic examination of the right eye. The red reflex is
diminished on the right. Which of the following is the most likely diagnosis?
A- Cataract
B- Retinal detachment
C- Vitreous hemorrhage
D- Central retinal artery occlusion
Explanation: Vitreous hemorrhage may occur secondary to proliferative diabetic retinopathy in which friable vessels in areas of neovascularization bleed, resulting in
sudden, painless loss of vision or visual obscuration with haze or floaters. This patient's fundus is difficult to visualize and examination demonstrates no red reflex in the
right eye, which is consistent with opacifying blood in the vitreous.
Q12 (AMBOSS): A 45-year-old woman comes to the physician because of early satiety and intermittent
nausea for 3 months. During this period she has also felt uncomfortably full after meals and has vomited
occasionally. She has not had retrosternal or epigastric pain. She has longstanding type 1 diabetes
mellitus, diabetic nephropathy, and generalized anxiety disorder. Current medications include insulin,
ramipril, and escitalopram. Vital signs are within normal limits. Examination shows dry mucous
membranes and mild epigastric tenderness. Her hemoglobin A1C concentration was 12.2% 3 weeks ago.
Which of the following drugs is most appropriate to treat this patient's current condition?
A- Omeprazole
B- Exenatide
C- Clarithromycin
D- Metoclopramide
Explanation: Metoclopramide therapy would benefit this diabetic patient with gastroparesis by inducing gastric contractions, promoting peristalsis, and increasing the
tone of the fundus. In addition, metoclopramide has antiemetic properties, making it the preferred first-line treatment for gastroparesis. Patients should be started on
the lowest possible dose and monitored closely for extrapyramidal side effects (e.g., acute dystonia). In addition, patients with diabetic gastroparesis should be
maintained on strict glycemic control to prevent further complications, and they should be advised to avoid eating large fatty meals and raw vegetables. Other drugs
used to treat gastroparesis include domperidone and erythromycin.
Q2 (pretest): A 25-year-old woman is admitted for hypertensive crisis. The patient’s urine drug screen is
negative. In the hospital, blood pressure is labile and responds poorly to antihypertensive therapy. The
patient complains of palpitations and apprehension. Her past medical history shows that she developed
hypertension during an operation for appendicitis at age 23. Hct: 49% (normal range 37%-48%)
WBC: 11,000/mm3 (4.3-10.8) Plasma glucose: 160 mg/dL (75-115) Plasma calcium: 11 mg/dL (9-10.5)
Which of the following is the most likely diagnosis?
a. Panic attack
b. Renal artery stenosis
c. Essential hypertension
d. Type 1 diabetes mellitus
e. Pheochromocytoma
Explanation: The patient has excessive growth of soft tissue that has resulted in coarsening of facial features, prognathism, and frontal bossing—all characteristic of
acromegaly. This growth hormone–secreting pituitary tumor will result in bitemporal hemianopsia when the tumor impinges on the optic chiasm, which lies just above the
sella turcica. Growth hormone– secreting tumors are the second commonest functioning pituitary tumors (second to prolactinomas). Serum IGF-1 (insulin-like growth
factor-1) level will be elevated and is usually the first diagnostic test. Since 40% of GH-producing tumors also produce prolactin, a prolactin level should be obtained as
well. Growth hormone secretion is pulsatile and a single GH level is often equivocal; the GH level must be suppressed (usually with glucose) to diagnose autonomous
overproduction.Dexamethasone suppression is used in the evaluation of Cushing syndrome, with partial suppressibility suggesting a pituitary cause, but this patient’s
presentation strongly suggests acromegaly, not Cushing syndrome. Once GH overproduction is documented, an MRI scan of the pituitary will show the size and extent of
the tumor (most are macroadenomas > 1 cm). The lateral skull film is insufficiently sensitive for this purpose. Growth hormone stimulation tests (insulin-induced
hypoglycemia, arginine plus GHRH) may be used to diagnose growth hormone deficiency, but would not be useful to diagnose GH overproduction, where a suppression
test should be used.
Explanation: The patient has excessive growth of soft tissue that has resulted in coarsening of facial features, prognathism, and frontal bossing—all characteristic of
acromegaly. This growth hormone–secreting pituitary tumor will result in bitemporal hemianopsia when the tumor impinges on the optic chiasm, which lies just above
the sella turcica. Growth hormone– secreting tumors are the second commonest functioning pituitary tumors (second to prolactinomas). Serum IGF-1 (insulin-like
growth factor-1) level will be elevated and is usually the first diagnostic test. Since 40% of GH-producing tumors also produce prolactin, a prolactin level should be
obtained as well. Growth hormone secretion is pulsatile and a single GH level is often equivocal; the GH level must be suppressed (usually with glucose) to diagnose
autonomous overproduction.Dexamethasone suppression is used in the evaluation of Cushing syndrome, with partial suppressibility suggesting a pituitary cause, but
this patient’s presentation strongly suggests acromegaly, not Cushing syndrome. Once GH overproduction is documented, an MRI scan of the pituitary will show the size
and extent of the tumor (most are macroadenomas > 1 cm). The lateral skull film is insufficiently sensitive for this purpose. Growth hormone stimulation tests
(insulin-induced hypoglycemia, arginine plus GHRH) may be used to diagnose growth hormone deficiency, but would not be useful to diagnose GH overproduction,
where a suppression test should be used.
Explanation: Iron overload should be considered among patients who present with any one or a combination of the following: hepatomegaly, weakness,
hyperpigmentation, atypical arthritis, diabetes, impotence, unexplained chronic abdominal pain, or cardiomyopathy. Diagnostic suspicion should be particularly high
when the family history is positive for similar clinical findings. The most frequent cause of iron overload is the common genetic disorder, idiopathic hemochromatosis.
Secondary iron storage problems can occur after multiple transfusions in a variety of anemias. The most practical screening test is the determination of serum iron,
transferrin saturation, and ferritin. Transferrin saturation greater than 50% in males or 45% in females suggests increased iron stores. Substantially elevated serum
ferritin levels confirm total body iron overload. Genetic screening is now used to assess which patients are at risk for severe fibrosis of the liver. Definitive diagnosis can
be established by liver biopsy. Determination of serum copper is needed when Wilson disease is the probable cause of hepatic abnormalities. Wilson disease does not
cause hypogonadism, heart failure, diabetes, or arthropathy. Chronic liver disease caused by hepatitis B would not account for the heart failure, hyperpigmentation, or
diabetes. Nocturnal penile tumescence and echocardiogram can confirm clinical findings but will not establish the underlying diagnosis.
Explanation: For the patient described, the markedly increased calcitonin level indicates the diagnosis of medullary carcinoma of the thyroid. In view of the family
history, the patient most likely has multiple endocrine neoplasia (MEN) type 2A, which includes medullary carcinoma of the thyroid gland, pheochromocytoma, and
parathyroid hyperplasia. Pheochromocytoma may exist without sustained hypertension, as indicated by excessive urinary catecholamines. Before thyroid surgery is
performed on this patient, a pheochromocytoma must be ruled out through urinary catecholamine determinations; the presence of such a tumor might expose him to a
hypertensive crisis during surgery. The serum calcium serves as a screening test for hyperparathyroidism. At surgery, the entire thyroid gland must be removed because
foci of parafollicular cell hyperplasia, a premalignant lesion, may be scattered throughout the gland. Successful removal of the medullary. carcinoma can be monitored
with serum calcitonin levels. Medullary carcinoma of the thyroid rarely metastases to the liver, so a liver scan would be unnecessary if liver enzymes are normal.
Thyroxine will be needed after surgery, but MEN type 2 is not associated with hypothyroidism. Radioactive iodine can be used to treat malignancies that arise from the
follicular cells of the thyroid; parafollicular cells, however, do not take up iodine and do not respond to radioactive iodine. Hyperparathyroidism, while unlikely in this
eucalcemic patient, is probably present in his brother.
Q6 (pretest): A 55-year-old woman with a history of severe depression and radical mastectomy for
carcinoma of the breast 1 year previously develops polyuria, nocturia, and excessive thirst. Laboratory
values are as follows:
Serum electrolytes: Na+ 149 mEq/L; K+ 3.6 mEq/L Serum calcium: 9.5 mg/dL
Blood glucose: 110 mg/dL
Blood urea nitrogen: 30 mg/dL
Urine osmolality: 150 mOsm/L
Which of the following is the most likely diagnosis?
A. Psychogenic polydipsia
B. Renal glycosuria
C. Hypercalciuria
D. Diabetes insipidus
E. Inappropriate antidiuretic hormone syndrome
Explanation: Metastatic tumors rarely cause diabetes insipidus, but of the tumors that cause it, carcinoma of the breast is by far the most common. In this patient, the
diagnosis of diabetes insipidus is suggested by hypernatremia and low-urine osmolality. To distinguish between central (ADH deficiency) and nephrogenic (peripheral
resistance to ADH action) diabetes insipidus, vasopressin (ADH by another name) is administered. If the urine osmolality rises and the urine output falls, the diagnosis is
central DI. There will be little response to vasopressin in nephrogenic DI.Psychogenic polydipsia is an unlikely diagnosis since serum sodium is usually mildly reduced in
this condition. Renal glycosuria would be expected to induce higher-urine osmolality than this patient has because of the osmotic effect of glucose. While
nephrocalcinosis secondary to hyper-calcemia may produce polyuria, hypercalciuria does not. Finally, the findings in inappropriate antidiuretic hormone syndrome are
the opposite of those observed in diabetes insipidus and thus are incompatible with the clinical picture in this patient.