Clinical Chemistry 2

Week 11- Parathyroid Gland Part 2 and 3

THYROID GLAND organ is the thyroid. The thyroid gland will
produce thyroid hormone.
 Butterfly-shaped gland  Once the concentration of T4 (thyroid hormone)
 Consists of two lobes connected by isthmus reaches its maximum or normal concentration,
 Pyramidal lobe the production of TSH and TRH are now
o Normal anatomic variant arising from the inhibited.
isthmus
o It is seen as a third thyroid lobe
o Present in 10-30% of the population
 By 11 weeks of gestation, the gland begins to
produce measurable amounts of hormones
 Follicle – is the fundamental unit of the thyroid
gland
 Follicle has 2 types of cells:
o Follicular cells – secretory (T4 and T3)
o Parafollicular cells or C cells –
calcitonin
 Thyroglobulin – acts as a preformed matrix
(inside the thyroid gland in between the follicles)
containing tyrosyl groups which are the
glycoproteins; stored in the follicular colloid of
the thyroid gland

Biosynthesis of Thyroid Hormones:

 Iodine is the most important element in the

biosynthesis of thyroid hormone
 Protein bound hormones are metabolically
inactive
 FT3 and FT4 – are the physiologically active
portions of the thyroid hormones
 Reverse T3 – produced by removal of one
iodine from the inner ring of T4; metabolically
inactive; product of T4 metabolism
Hypothalamic-Pituitary-Thyroid Axis:
Thyroid Hormone Production:
 The neuroendocrine system that regulates the
production and secretion of thyroid hormones
 The thyroid is regulated by another gland
located in the brain. The pituitary is regulated in
part by thyroid hormone that is circulating in the
blood (feedback).
 The pituitary produces the TSH which direct the
thyroid to produce thyroid hormones. If there’s
an increase of thyroid hormones in the
bloodstream/plasma, it will inhibit the production
of TSH. (Feedback mechanism)
 This pituitary gland is also regulated by the
hypothalamus which is found in the brain. Once
the hypothalamus detects stimulus (ex:
decreased thyroid hormone), it will produce  Iodide trap comes from exogenous source.
thyroid-releasing hormone (TRH). The target Once it is absorbed in the GIT, it is in iodide
organ is the pituitary gland which will produce form. Trapping happens in the thyroid follicle.
thyroid-stimulating hormone (TSH). The target
 Clinical Chemistry 2
Week 11- Parathyroid Gland Part 2 and 3
 Iodide is taken up and then converted into iodine  Better indicator of recovery from hyperthyroidism
(oxidation/organification)  then condensed into as well as the recognition of recurrence of
tyrosine residues (tyrosine- found in hyperthyroidism
thyroglobulin)
 Oxidation – Iodide undergoes oxidation and is
converted into iodine. Iodine is condensed into
tyrosine residue (seen in the thyroglobulin)
 Organification – iodine combines with tyrosine
 The reaction results in either mono-iodinated Tetraiodothyronine (T4):
tyrosine or di-iodinated tyrosine (product)
 These newly formed iodothyroglobulin forms one  Although it is not metabolically active, but it is
of the most important constituents on the colloid the principal secretory product
material present in the follicle of the thyroid unit.  Can be converted into T3 in the liver and kidney
Other synthetic reaction that is closely linked to  Major fraction of organic iodine in the circulation
organification is the coupling.  A prohormone for T3 production
 Coupling – Di-iodinated tyrosine molecule  All circulating T4 originates in the thyroid gland
coupled together (most common) or one mono-  The amount of serum T4 is a good indicator of
iodinated tyrosine and one di-iodinated tyrosine the thyroid secretory rate
to form thyroxine or tetraiodothyronine (T4)  Elevated thyroxine causes inhibition of TSH
 Tetraiodothyronine (T4) – 2 di-iodinated secretory
tyrosine
 Triiodothyronine (T3) – one mono-iodinated Thyroid Hormone Binding Proteins:
tyrosine and one di-iodinated tyrosine
Thyroxine-binding globulin
 From the perspective formation of thyroid
hormone, the major coupling reaction is the  Principal protein for the transport of T3 and T4
diiodotyrosine coupling to produce T4. Although  Transport 70-75% of total T4
T3 is more biologically active than T4, the major  Affinity for T3 is lower than T4
production of T3 occurs outside the thyroid
gland. The majority of T3 is produced by the Thyroxine-binding prealbumin (transthyretin)
peripheral conversion of T4 in a deiodination
 Transports 15-20% of total T4
reaction involving specific enzyme which
removes one iodine from the outer ring of T4.  T3 has no affinity for prealbumin
 T3 and T4 released from the thyroid by Thyroxine-binding albumin
proteolysis reach the blood stream where they
are bound to thyroid hormone binding proteins.  Transport T3
The major thyroid hormone binding protein is the  Transport 10% of T4
thyroxine binding globulin which accounts
about 75% of the bound hormone. DISORDERS ASSOCIATED WITH THYROID GLAND

Functions of Thyroid Hormones: Hyperthyroidism – refers to an excess of circulating

thyroid hormone
 Conserving energy (primary function)
Thyrotoxicosis:
 For tissue growth
 For development of the CNS  Is applied to a group of syndromes caused by
 Elevated heat production high levels of free thyroid hormones in the
 Increased oxygen consumption circulation
 TSH is low, FT4 is normal/increased but
Triiodothyronine (T3):
increased FT3 – T3 thyrotoxicosis / Plummer’s
 Most active thyroid hormonal activity disease
 Most biological active hormone produced by the Graves’ Disease (Diffuse Toxic Goiter):
thyroid gland
 Almost 80% is produced from the tissue  Most common cause of thyrotoxicosis
deiodination of T4 (liver and kidney)  Autoimmune disease
 The principal application of this hormone is in  It occurs 6x more commonly in women than in
diagnosing T3 thyrotoxicosis (Plummer’s men
disease)  Caused by Thyroid-stimulating
immunoglobulins (autoantibodies). It mimics
 Clinical Chemistry 2
Week 11- Parathyroid Gland Part 2 and 3
the function of the TSH (binds with thyroid  It is also caused by destruction or ablation of the
receptor to produce thyroid hormone) thyroid gland
 Caused by circulating antibodies to the TSH  Other causes: surgical removal of the gland;
receptor used of radioactive iodine for hyperthyroidism
 Features: exophthalmos (bulging eyes), pretibial treatment; radiation exposure; drugs such as
myxedema lithium

Hashimoto’s Disease (Chronic Autoimmune

Thyroiditis):

 Most common cause of primary hypothyroidism

 Caused by thyroid peroxidase antibody which
destroys the follicle cells
 The thyroid is replaced by a nest of lymphoid
tissue
 Associated with enlargement of the thyroid gland
(goiter)
 Method for testing: TPO antibody test = (+)
result

 Reidel’s Thyroiditis – the thyroid turns into a

woody or stony-hard mass
 Subclinical Hyperthyroidism – shows no
clinical symptoms but TSH level is low, and FT3
and FT4 normal (the patient is requested to back
to the hospital after weeks or months)

Secondary (Pituitary) Hyperthyroidism:

 Secondary – the origin is in the pituitary

 Increased TSH, FT4 and/or FT3

Subacute Granulomatous / Subacute Non-supportive

Thyroiditis / De Quervain’s Thyroiditis (Painful
Thyroiditis): Myxedema:

 Associated with neck pain, low-grade fever and  Describes the peculiar nonpitting swelling of the
swings in thyroid function tests skin
 Thyroidal peroxidase (TPO) antibodies are  The skin becomes infiltrated by
absent mucopolysaccharides
 ESR and thyroglobulin levels are elevated (due  Clinical feature: “puffy” face, weight gain, slow
to inflammation of the thyroid tissue) speech, eyebrows thinned, dry and yellow skin,
anemia
Hypothyroidism:  Myxedema coma – severe form of primary
hypothyroidism
 Develops whenever insufficient amounts of
thyroid hormone are available to tissues
 Treated with thyroid hormone replacement
therapy (levothyroxine)
 Symptoms:
o Cold intolerance
o Weight gain
o Dryness skin
o Mental dullness

Primary Hypothyroidism:

 Primarily due to deficiency of iodine

 Clinical Chemistry 2
Week 11- Parathyroid Gland Part 2 and 3
Cold intolerance Heat intolerance
Depression Infertility
Dry skin Irritability
Fatigue Muscle weakness
Forgetfulness Nervousness
Heavy menstrual periods Scant menstrual periods
Infertility Weight loss
Muscle aches Frequent bowel
movements
Weight gain Warm, moist plasms
Constipation Tremor of fingers
Brittle nails Soft nails

Secondary Hypothyroidism: TEST OF THYROID FUNCTION

 Due to pituitary destruction or pituitary adenoma TRH Stimulation Test:

 T3 and T4 low levels
 It measures the relationship between the TRH
 TSH is also decreased
and TSH secretions
Tertiary Hypothyroidism:  Used to differentiate euthyroid and hyperthyroid
patients who both had undetectable TSH levels
 Due to hypothalamic disease  It may also be helpful in the detection of thyroid
 T3 and T4 low levels hormone resistance syndrome
 TSH is also decreased  It can also be used in distinguishing secondary
from tertiary hypothyroidism
Congenital Hypothyroidism (Cretinism):
 Result:
 Defects in the development or function of the o Excessive – primary
gland o Normal – tertiary
 Screening test: Total T4 – decreased o No response – secondary
 Confirmatory test: TSH – increased
TSH Test:
 Part of newborn screening
 The best laboratory test for identification of
Subclinical Hypothyroidism:
thyroid abnormalities
 T3 and T4 normal  The most clinically sensitive assay for the
 TSH is slightly increased detection of primary thyroid disorders
 Used to differentiate primary hypothyroidism
Increased TSH Decreased TSH from secondary hypothyroidism
Primary hypothyroidism Primary hyperthyroidism o Increased – primary
Hashimoto’s thyroiditis Secondary and tertiary o Decreased – secondary
hypothyroidism
Thyrotoxicosis due to Treated Graves’ disease  Result: 0.5 – 5.0 uU/mL
pituitary tumor Radioactive Iodine Uptake (RAIU):
TSH antibodies Euthyroid sick disease
Thyroid hormone Over replacement of  Used to measure the ability of the thyroid gland
resistance thyroid hormone in to trap iodine
hypothyroidism  Performed before radioactive iodine therapy.
They compute the dosage of the radioactive
iodine to be taken by the patient
Thyroid Dysfunction:
 Helpful in establishing the cause of
Hypothyroidism Hyperthyroidism hyperthyroidism
Dry, coarse hair Hair loss  High uptake indicates metabolically active gland
Loss of eyebrow hair Bulging eyes (active hormone production)
Puffy face Sweating
Enlarged thyroid (goiter) Enlarged thyroid (goiter) Thyroglobulin (Tg) Assay:
Slow heartbeat Rapid heartbeat
Arthritis Difficulty sleeping
 Clinical Chemistry 2
Week 11- Parathyroid Gland Part 2 and 3
 It is normally used as a post-operative marker of  Used to confirm results of FT3 or FT4 or
thyroid cancer abnormalities in the relationship of the total
 Used in monitoring the course of metastatic thyroxine and THBR
thyroid cancer  It is used to distinguish between hyperthyroidism
 Methods for testing: double-antibody RIA, causing high thyroxine levels and euthyroidism
ELISA, IRMA and immunochemiluminescent with increased binding by TBG and increased
assay thyroxine
 Increased level: hypothyroidism
Reverse T3 (rT3):
 Not routinely used
 Used to assess borderline or conflicting Fine Needle Aspiration:
laboratory results
 Helpful in determining thyroid status of patients  Most accurate tool in the evaluation of thyroid
with nonthyroidal illness (NTI) nodules (bukol)
 rT3 is produced by 5-deiodination of T4  To determine whether it’s cancerous, malignant,
or benign

Fine-needle aspiration of a thyroid nodule is the

Free Thyroxine Index (FT4I or T7): investigation of choice in a patient with a solitary nodule
of the thyroid, as it is very successful in obtaining cells
 It indirectly assesses the level of free T4 in blood
for cytological examination and thus in the diagnosis of
 It is based on the equilibrium relationship of thyroid carcinoma. It can usually be performed under
bound T4 and FT4 local anesthesia. This patient has a recurrent nodule
 Elevated in hyperthyroidism and decreased in after previous partial thyroidectomy for thyrotoxicosis.
hypothyroidism

TT 4 x T 3 U ( % )
FT 4 I = ∨¿
100
TT4 x THBR

 THBR – thyroid hormone binding ratio

Total T3 (TT3), Free T3 (FT3), Free T4 (TT4):

 FT4 test is used to differentiate drug induced

TSH elevation and hypothyroidism
 TT3 or FT3 is used to confirm hyperthyroidism

T3 Uptake Test:

 Measures the number of available binding sites

of the thyroxine binding proteins, most notably
TBG
 Elevated TBG results to decreased T3 uptake,
and vice versa
 Increased level: hyperthyroidism, euthyroid
patients, chronic liver disease
 Decreased level: hypothyroidism, oral
contraceptives, pregnancy, acute hepatitis

Thyroxine Binding Globulin (TBG) Test:

 Clinical Chemistry 2
Week 11- Parathyroid Gland Part 2 and 3
Parathyroid Hormone Activity of Parathyroid Hormone in Increasing
Calcium Concentration
 Calcium homeostasis
o Important aspect of parathyroid
hormone
 Maintaining balance to the concentration of
calcium intracellularly and extracellularly
 Organ physiology- responsible for control of the
calcium and how its disorders can cause
disease

 Parathyroid functions to regulate calcium levels

via its actions on 3 target organs:
o Bone
 Produced by parathyroid gland o Kidneys
 Parathyroid gland is located near the thyroid o Gastrointestinal Tract
capsule sometimes within the thyroid gland  Parathyroid hormone increases the resorption of
o May also be found outside their normal bone by stimulating osteoclast and promotes the
anatomic site between the hyoid bone in release of calcium and phosphate into the
the neck and the mediastinum circulation
 Most people has 4 parathyroid glands some  In the kidneys, parathyroid hormone acts to limit
have 8 or as few as 2 calcium excretion at the distal convoluted
 Smallest endocrine gland in the body tubules (DCT) via its active transport mechanism
 Secretes parathyroid hormone (PTH)-  Parathyroid hormone also inhibits phosphate
hypercalcemic hormone reabsorption and bicarbonate reabsorption
 PRIMARY ROLE: to prevent hypocalcemia  Parathyroid hormone and phosphatemia also
o Preserves calcium and phosphate w/in enhance the hydroxylation of 25- hydroxy
normal range vitamin D which is responsible for its indirect
effect of increasing intestinal calcium absorption
4 Ways on How Parathyroid Hormone Increase
Calcium Level Clinical Disorders
 Promotes bone resorption
 Increase renal reabsorption of calcium Primary hyperparathyroidism
 Stimulates conversion of inactive Vit D to  an enlargement of 1 or more parathyroid gland
activated Vit D3 causes over production of the hormone. It
 Indirectly stimulates intestinal absorption of causes high calcium levels in the blood which
can cause varieties of help problems. Surgery is
calcium
the most common treatment for primary
hyperparathyroidism
 Physiologic defect lies with the PT gland
 The most common cause of hypercalcemia
 Is due to the presence of a functioning adenoma
 Sporadic parathyroid adenoma- is the most
common for about 80-85% cause of
hyperparathyroidism
 Most prevalent in people 50-70 years old and
the prevalence is three time higher in females
than in males
 Lab results:
 Clinical Chemistry 2
Week 11- Parathyroid Gland Part 2 and 3
o Parathyroid hormone (PTH) is increased
o Due to abnormal increase in production Adrenal Gland
thus activation of all mechanisms so the
result of ionized calcium is also
increased. If there’s an increase serum
ionized calcium, excess calcium must be
excreted by the renal, thus
hypercalciuria happens

Secondary hyperparathyroidism
 Develops in response to decrease serum
calcium
 There is a diffuse hyperplasia of all 4 glands
 Causes: vitamin D deficiency and chronic renal
failure (causes increase excretion of calcium;  Adrenal glands are pyramid-shaped glands
Parathyroid gland response to the release to the located on top of the kidneys
decrease of calcium concentration in the serum  Composed of distinct but conjoined glands, tha
so it produces more parathyroid hormone out adrenal cortex (yellow) and inner adrenal
 Occurs in response to low blood calcium in the medulla (dark mahogany)
body. Over time, increased parathyroid hormone
levels occur
 Due to the response to this stimulus increased in
sizes of all 4 glands
 Lab results:
o Ionized calcium- decreased
o PTH- increased

Hypoparathyroidism
 Due to accidental injury to the parathyroid
glands (neck) during surgery- post surgical
cause
 Other cause: I) Radioactive treatment for
hyperthyroidism
o Very low magnesium level in the blood
o Autoimmune attack on the parathyroid  Has prime effects on blood pressure
glands
o DiGeorge syndrome Adrenal Cortex
o Familial hypoparathyroidism
 Individuals are unable to maintains calcium  The major site of steroid hormone production
concentration in blood without calcium  Cholesterol is the parent/main molecule of all
supplementation steroid hormones
 Calcium level <6mg/dL (1.5 mmol/L)  The secretion of adrenal glucocorticoids and
o Laryngeal stridor and tonic-clonic androgens is regulated by ACTH
seizures (Adrenocorticotropic Hormone), which is under
 Calcium level <8mg/dL (2.0 mmol/L) the control of the hypothalamic CRH
o Leads to tetany and altered (Corticotropin Releasing Hormone)
neuromuscular activity (chvostek’s sign  Mineralocorticoid secretion is controlled by the
and trousseau’s sign) RAS (Renin Angiotensin System)
 Chronic deficiency of calcium can lead to  Only the adrenal cortical mitochondria contain a
osteoporosis mixed function oxidase capable of converting
cholesterol to pregnenolone (precursor of all
hormone in the adrenal gland such as
aldosterone, cortisol, and sex hormones
testosterone and estrone)
 The cholesterol side chain enzyme contains
flavoproteins and cytochrome P40 SCC
 Clinical Chemistry 2
Week 11- Parathyroid Gland Part 2 and 3
rounded face, pink or purple stretch marks on
3 Layers of Adrenal Cortex the skin, high blood pressure, bone loss, on
occasion Type 2 diabetes, hyperglycemia,
 Zona glomerulosa (outermost layer)- 10% thinning of the skin, poor wound healing,
o Principal source of mineralocorticoid hypertension, decreased WBC (lymphocytes)
 Zona fasciculata (middlemost layer)- 75%
o Site of glucocorticoid production
 Zona reticularis (innermost layer)- 10%
o Produces androstenedione and DHEA
(dehydroepiandrosterone)

Cortisol

 Principal glucocorticoid
 Stimulates gluconeogenesis in the liver resulting
in hyperglycemia (anti-insulin effect)
 Synthesis is regulated by ACTH
 The only adrenal hormone that inhibit the
secretion of ACTH (when plasma cortisol levels
is elevated)
 Valuable therapeutic agent for rheumatoid
arthritis, SLE and multiple sclerosis
o Anti-inflammatory and
immunosuppressive actions
 Secretion is diurnal and is associated with a
person’s sleep-wake cycle Test For Hypercortisolism
 High levels in the morning (6-8am)
 Lowest at night (10pm to 12am)  24-hour urinary free cortisol test
 Serum, plasma, saliva and urine may be used; o Best screening test
blood sample for analysis should be drawn o 3 different collection sample
around 8am
 Overnight dexamethasone suppression test
 Increased urine free cortisol levels are sensitive o Normal: suppressed; abnormal: not
indicators of adrenal hyperfunction using 24-
suppressed
hour urine collection
 Low dose dexamethasone suppression test
o Confirmatory test
Urinary Metabolites Include
o Abnormal: not suppressed
 17-hydrocorticosteroid
ACTH Measurement
o Measured by porter-silber method
(positive result is yellow)
 Cushing’s syndrome (primary adrenal lesion)
o Reagent: phenyl hydrazine in H2SO4 +
o ↑ (increase) cortisol, ↓ (decrease) ACTH
alcohol
 Cushing’s disease (tertiary hypercortisolism
 17-ketogenic steroid
ACTH producing pituitary adenoma)
o Measured by Zimmerman Reaction
o ↑ (increase) cortisol, ↑ (increase) ACTH
(produces reddish purple reaction)
o Refers only to hypercortisolism
o Reagent: meta-dinitrobenzene
o Secondary to excess production of
o Oxidation procedure: Norymbersky
ACTH from a corticotroph pituitary
(using Na bismutate)
adenoma
o Secondary hypercortisolism
Clinical Disorders
o Due to excess production of
Hypercortisolism (Cushing’s Syndrome) hyperthalamic corticotropin releasing
 Caused primarily by excessive production of hormone (Tertiary hypercortisolism)
cortisol and ACTH
 Signs and symptoms: weight gain but thin High Dose Dexamethasone Suppression Test
extremities (“buffalo bump” in shoulders), a
 Clinical Chemistry 2
Week 11- Parathyroid Gland Part 2 and 3
 2mg dexamethasone every 6 hours for 2 days from tertiary adrenal insufficiency (increased
 Cushing’s syndrome ACTH response)
o Not suppressed (17-OH steroid and  Metyrapone (inhibitor of 11-B-hydroxylase) test
cortisol) is used as an alternative diagnostic or
 Cushing’s disease confirmatory test for secondary or tertiary
o Suppressed adrenal insufficiency (positive result is
decreased response- decreased ACTH)

Hypocortisolism Congenital Adrenal Hyperplasia (CAH)

 Primary hypocortisolism (Primary adrenal  Results from deficiency of enzymes such as 21-
insufficiency) hydroxylase (most common), 11-B-hydroxylase
o Due to decreased cortisol production- (2nd most common) and 3b-hydroxysteroid
90% destruction of the adrenal cortex; dehydrogenase-osemerase, necessary for the
aldosterone deficiency; excess ACTH synthesis of cortisol
release  Decreased plasma cortisol, increased ACTH
o Disorder: Addison’s disease levels and increased levels of androgens
(hypotension, hyponatremia,
hyperkalemia, hyperpigmentation and Aldosterone
darkening of the skin
o Lab test: ACTH stimulation test  The most potent mineralocorticoid (electro-
(Cosyntropin stimulation test) regulating hormone)
o Increase frequency in the evaluation and  A steroid hormone that helps regulate water and
the diagnosis of primary adrenal electrolytes (sodium and potassium and blood
insufficiency pressure
o A random cortisol level is checked  Acts on renal tubular epithelium to increase
retention of Na and excretion of K and H
before a 200microgram of injection of
cosyntropin and then 36-60 minutes  The synthesis of this hormone is primarily
later controlled by the renin-angiotensin system
o (+) result- delayed response to
Clinical Disorders
stimulation test/ decreased ACTH and
cortisol
Primary hyperaldosteronism (Conn’s disease)
Secondary and Tertiary hypocortisolism  Caused by aldosterone-secreting adrenal
adenoma
o Rare condition caused by over
 Also known as 2° and 3° adrenal insufficiency
production of aldosterone hormone that
 Is due to hypothalamic-pituitary insufficiency with
controls Na and K in the blood
loss of ACTH
o 33% cases are due adrenal adenoma
 No problem with mineralocorticoid (does not get
its stimulation from ACTH) secretion; absence of that produces aldosterone
hyperpigmentation o 66% cases are due to an enlargement of
 Lab test: ACTH stimulation test (Cosyntropin adrenal glands
stimulation test) o Common causes include adrenal cancer
 (+) result- delayed response to stimulation and inherited disorder or familial
test/decreased ACTH and cortisol hyperaldosteronism
 Symptoms: hypertension, hypokalemia, mild
Notes to Remember hypernatremia, and metabolic alkalosis

 24-hour urine free cortisol is the most sensitive Secondary hyperaldosteronism

and specific screening test for excess cortisol  Occurs as a result of excessive production of
production using HPLC (High Performance Lipid renin (main stimulus for the production of
Chromatography) or GC (Gas Chromatography) aldosterone)
with MS (Mass Spectrophotometry)
 Corticotropin-releasing hormone (CRH) Liddle’s syndrome (Pseudohyperaldosteronism)
stimulation test- differentiates secondary adrenal  Resembles 1° (primary) aldosteronism clinically,
insufficiency (decreased or no ACTH response) but aldosterone level is low and absence of
hypertension
 Clinical Chemistry 2
Week 11- Parathyroid Gland Part 2 and 3
 They circulate bound to steroid hormone binding
Barterr’s syndrome (bumetanide-sensitive chloride globulin (SHBG)
channel mutation)  Excessive production of androgens results in
 Elevated concentrations of aldosterone and virilization (pseudohermaphroditism)
renin  Excessive levels androgens can be confirmed by
measuring total and free testosterone and
Gitelman’s syndrome (thiazide-sensitive transporter DHEA-sulfate
mutation)
 Increased aldosterone Adrenal Medulla

Hypoaldosteronism  Composed primarily of chromatin cells that

secrete catecholamines
 Due to destruction of the adrenal glands and  L-tyrosine is the precursor of the catecholamines
deficiency of glucocorticoid  Norepinephrine and epinephrine are
 It is also associated with enzyme 21-hydroxylase metabolized by monoamine oxidase and
deficiency cathecol-0-methyl transferase to form
 Symptoms: hyperkalemia and metabolic acidosis metanephrines and VMA (Vanillylmandelic Acid)
 Test:  Ratio of norepinephrine to epinephrine in serum
o Blood samples should be drawn in the  9:1
morning before the patient has gotten
out of bed Norepinephrine
o To avoid markedly increased results
o Furosemide stimulation test or upright  Produced by the sympathetic ganglia
posture (+) result  Highest concentration is found in the brain
 Low aldosterone level (CNS)
(confirmation for  Act as a neurotransmitter in both CNS and SNS
hypoaldosteronism)  Major metabolites:
 40g intake of Furosemide the o MHPG (3-methoxy-4-
night before as well as the hydroxyphenylglycol) which can be
morning of the test found in CSF and urine
 In the morning after the intake of o VMA (Vanillylmandelic acid) which is
40 mg Furosemide the patient found in urine
remain in upright position for 2-3
hours and the serum Epinephrine
aldosterone and furosemide
levels are assayed  Most abundant medullary hormone
 Normally it should be increased  Produced from norepinephrine and comes only
(50% above the baseline) in from the adrenal
healthy persons
 Called the “flight or fight hormone” because it is
 Even in patients with
released in response to physiologic (injuries) or
hypertension it increases
psychological (stress anxiety) threats
o Saline suppression test (+) result
 Any form or stress that increases cortisol levels
 High aldosterone levels stimulates its production
 It increases glucose concentration through
Weak Androgens
glycogenolysis
 Best collected from: indwelling catheter
 Serve as precursors for the production of more
 Major metabolites:
potent androgens and estrogens in tissues
o VMA
 Produce as by-products of cortisol synthesis that
o Metanephrine
are regulated by ACTH
o Normetanephrine
 Precursors: pregnenolone and 17-OH
pregnenolone o HVA (homovanillic acid)
 Examples: DHEA (dehydroepiandrosterone) and
androstenedione Dopamine
 DHEA, the principal adrenal androgen, is
converted to estrone  The major intact catecholamine present in the
urine (not metabolized in the presence of urine)
 Clinical Chemistry 2
Week 11- Parathyroid Gland Part 2 and 3
 A catecholamine produced in the body by the  May be congenital (cryptorchidism, klinefelter’s
decarboxylation of 3,4-dihydroxyphenylalanine syndrome, and 5-alpha-reductase deficiency) or
(DOPA) acquired (varicocele, tumor, orchitis)
 Major metabolites: HVA  Decreased testosterone levels and increased
FSH and LH levels
Clinical Disorder Post-Testicular Infertility
 Due to disorders of sperm transport and function
Pheochromocytoma  Testosterone, FSH, and LH levels- normal
 Tumors of the adrenal medulla or sympathetic
ganglia Estrogens
 Commonly seen in 3rd to 5th decades of life
 Due to overproduction of catecholamine  They are important for the promotion of breast
 Classic symptoms: tachycardia, tightness of development, maturation of the external
chest, sweating and pallor genitalia, deposition of body fat and termination
 (+) high urinary excretion of metanephrine and of linear growth- secondary sexual characteristic
normetanephrine in the female
o Most sensitive screening test (Pisano  In conjunction with progesterone, they function
method) in uterine growth and regulation of menstrual
 >2000pg/mL of plasma catecholamine- cycle, and maintenance of pregnancy
diagnostic for pheochromocytoma  Deficiency results in irregular and incomplete
 Clonidine test differentiates borderline results development of the endometrium
(1000-2000pg/mL) of plasma catecholamines  It is not produced by the ovaries after
o Pheochromocytoma (no response) menopause
 Precursors: acetate, cholesterol, progesterone,
Neuroblastoma and testosterone
 A fatal malignant condition in children resulting  Estrone and estriol are metabolites of
to excessive production of norepinephrine intraovarian and extraglandular conversion
 (+) high urinary excretion of HVA or VMA or
both, and dopamine Estrone (EI)
 Most abundant estrogen in post-menopausal
Reproductive Hormones women
Testosterone
Estradiol (E2)
 Most potent male androgen  Most potent estrogen secreted by the ovary
 Synthesis by the Leydig cells of the testis of the  Most abundant estrogenin pre-menopausal
male women
 It causes growth and development of the  Serve as negative feednack for FSH
reproductive system, prostate and external  It is used in assessing ovarian function
genitalia  60%  bound to albumin; 38%  SHBG; 2%
 60%  bound to Sex hormone binding globulin free
(SHBG)
 40%  bound to albumin Estriol (E3)
 Levels demonstrate a circadian pattern and peak  Estrogen is abundant during pregnancy
at the time of awakening (7am); fall to their  Metabolite of estradiol
lowest levels at 8PM  The estrogen found in maternal urine
 Infertility may be pretesticular, testicular and  The major estrogen secreted by the placenta
posttesticular  Used to assess the fetoplacental unit
(fetoplacental viability), post date gestations and
Pretesticular infertility intrauterine retardation
 Due to hypothalamic or pituitary lesions  Used as a marker for Down Syndrome (together
 Testosterone, FSH, and LH levels- normal or with AFP and HCG)
decrease  Plasma is preferred over urine for diagnostic
testing
Testicular Infertility
Progesterone
 Clinical Chemistry 2
Week 11- Parathyroid Gland Part 2 and 3
 Produced by the granulosa (lutein) cells of the
corpus luteum in the female; prime secretory Serotonin (5-hydroxytryptamine)
product of the ovary
 Serves to prepare the uterus for pregnancy and  Is an amine derived from hydroxylation and
the lobules of the breast for lactation decarboxylation of tryptophan
 Used primarily for the evaluation of fertility in  It is synthesized by argentaffin cells, primarily in
females GI tract
 Deficiency results in failure of implantation of  Also found in high concentrations in pineal gland
embryo and CNS
 Intermediate in the synthesis of adrenal steroids  It binds to platelets and released during
and androstenedione coagulation
 The single best hormone to determine whether  Urinary metabolite:
ovulation occurred o 5-HIAA (hydroxy indole acetic acid)
 Metabolites: prenanediones, pregnanalones,  A diagnostic marker for
pregnanediols carcinoid syndrome
 Test for 5-HIAA: Ehrlich’s aldehyde test: (+)
Dehydroepiandrosterone (DHEA) purple color

 Weak androgen Somatostatin

 Androgen primarily derived from the adrenal
gland  Also called growth inhibiting hormone
 Valuable in the assessment of adrenal cortical  It is found in the GIT, hypothalamus and the data
function cells of the pancreatic islets
 Is an inhibitor of growth hormone, glucagon and
Miscellaneous Hormones insulin
Human Chorionic Gonadotropin (HCG)

 Produced by the placenta during pregnancy

 Serves to maintain progesterone production by
the corpus luteum in the early pregnancy
 It can be detected 1-2 days after fertilization
 Used for pregnancy testing

Human Placental Lactogen (HPL)

 It is functionally, structurally and immunologically

similar to GH and PRL (Prolactin)
 It is produced by the placenta and can be
measured in urine, serum and amniotic fluid
 It stimulates development of mammary gland
 It increases maternal plasma glucose levels and
promotes positive nitrogen balance

Gastrin

 Is a peptide secreted by the G cells of the

antrum of the stomach
 Major stimulus: presence of peptide
 It is released in response to vagal stimulation
and food in the stomach
 It causes secretion of the HCI by parietal cells in
the body of the stomach
 Is the diagnostic marker for Zollinger-Ellison
Syndrome (ZES) or the islet cell tumor
 Increased levels: ZES, achlorhydria, chronic
renal failure