The document discusses the anatomy and functions of the pituitary gland and hypothalamus. It describes the hormones produced and regulated by the anterior and posterior pituitary. It then covers common lesions of the hypothalamic-pituitary axis including tumors, trauma, and genetic defects. The clinical manifestations of various pituitary hormone deficiencies and excesses are summarized.
13. Clinical Manifestations of Lesions of
Hypothalamic Pituitary Axis
➢ Mass effects: Headaches, Visual Field and CN
III-VI Defects, Obstructive Hydrocephalus, CSF
Rhinorrhea, Hypothalamic Syndromes (DI, SIADH,
thirst/ appetite/ satiety/ sleep/ temperature regulation),
Frontal/ Temporal Lobe Dysfunction
➢ Endocrine Effects:
▪ Hypopituitarism: TSH/ ACTH/ GH/ LH-FSH/ Prolactin
▪ Hyperpituitarism: TSH/ ACTH/ GH/ LH-FSH/ Prolactin
14. Syndrome of Panhypopituitarism
➢ Progressive loss of Anterior Pituitary function:
FSH/LH and GH; TSH; ACTH.
➢ Hypopituitarism with DI is suggestive of
Hypothalamic etiology.
17. Syndrome of Panhypopituitarism
➢ FSH / LH deficiency:
▪ In women: Oligo-amenorrhea, Infertility, “Post-menopausal”
symptomatology, Bone loss.
▪ In Men: Decreased Libido, ED, Gynecomastia with loss of
secondary sexual characteristics, Bone loss.
▪ Labs: Gonadotropins inappropriately low for E2 in women
and T in men.
18. Syndrome of Panhypopituitarism
➢ GH deficiency in Adults:
▪ Symptoms: Reduced muscle mass and
decreased exercise performance, Increased
abdominal adiposity, Decreased psychosocial
well being.
▪ Signs: Central adiposity, thin dry skin,
Decreased muscle strength.
▪ Labs: Hyperinsulinemia, Dyslipidemia,
“Low-normal” IGF-1 with inadequate response
on Insulin tolerance test/ L-Dopa test/ L-Arginine
test.
19. Syndrome of Panhypopituitarism
➢ GH deficiency in Children:
▪ GH deficiency (especially prior to onset of puberty)
leads to growth retardation/ short stature.
▪ Thyroid and Corticosteroid replacement are
necessary for GH action in patients with
panhypopituitarism.
20. Syndrome of Panhypopituitarism
➢ TSH deficiency:
▪ Symptoms: Fatigue, Cold intolerance, Lethargy,
Constipation, Diminished appetite, Weight gain,
Hoarseness of voice, Menorrhagia.
▪ Signs: Bradycardia, Hypothermia, Pale/ cool/ dry skin,
dry hair, “hung up” DTRs, stupor/ coma in severe cases.
▪ Labs: “Low-normal” TSH with low Free T4, Abnormal
TRH Stimulation test, Hyponatremia in severe cases.
21. Syndrome of Panhypopituitarism
➢ ACTH deficiency:
▪ Symptoms: Weakness, Fatigue, Nausea/ Vomiting,
Weight loss
▪ Signs: Pale skin with inability to tan, Postural
Hypotension.
▪ Labs: Mineralocorticoid function is preserved, Low AM
cortisol, +/- ACTH Stimulation test, Poor pituitary ACTH
reserve on Insulin tolerance test/ CRH stimulation test/
Metyrapone test.
23. Empty Sella Syndrome
➢ Defects in diaphragma sella allowing herniation of
arachnoid membrane into the hypophyseal fossa
thereby leading to transmission of ICP and
compressing the pituitary against the walls of the
sella.
➢ Primary vs. Acquired (Surgery, Radiation therapy,
Infarction)
➢ Pituitary function is usually normal +/- mild
elevations of Prolactin.
25. Clinical Manifestations of Lesions of
Hypothalamic Pituitary Axis
➢ Mass effects: Headaches, Visual Field and CN III-VI Defects,
Obstructive Hydrocephalus, CSF Rhinorrhea, Hypothalamic
Syndromes (DI, SIADH, thirst/ appetite/ satiety/ sleep/
temperature regulation), Frontal/ Temporal Lobe Dysfunction
➢ Endocrine Effects:
▪ Hypopituitarism: TSH/ ACTH/ GH/ LH-FSH/ Prolactin
▪ Hyperpituitarism: TSH/ ACTH/ GH/ LH-FSH/ Prolactin
26. Pituitary Adenoma
➢ Microadenomas are < 10mm.
➢ Macroadenomas are ≥ 10mm.
➢ Majority are monoclonal and not malignant.
➢ May or may not be functional.
➢ Mass effects and hypopituitarism may be present
irrespective of functional status.
➢ Functioning (secretes hormones) vs. non-functioning
29. TSH secreting Pituitary Adenoma
➢ TSH molecule may be biologically inactive or may cause
clinical hyperthyroidism resembling Graves’ disease.
➢ TSH levels are variable, from normal to as high as 500s.
➢ Diagnosis: Inappropriately elevated TSH in presence of
high T3/T4 is highly suggestive. Alpha Subunit levels
may be significantly elevated.
➢ Treatment: Pituitary Surgery, Radiation therapy,
Octreotide.
30. FSH/LH secreting Pituitary Adenoma
➢ No characteristic syndrome of hormone excess is seen.
➢ Occasionally-
▪ In Men: +/- testicular enlargement, hypogonadal
symptoms.
▪ In Women: +/- hypogonadal signs and symptoms.
➢ Treatment: Pituitary surgery, Radiation therapy.
32. ACTH secreting Pituitary Adenoma
(Cushing’s Disease)
➢ Accounts for about 60-70% of cases of Cushing’s
syndrome.
➢ Symptoms: Fatigue, Weight gain, Easy bruising,
Headaches, Irregular menses, Psychiatric symptoms from
depression to frank psychosis.
➢ Signs: Plethoric “Moon facies”, ”Buffalo hump”, Central
adiposity with thin extremities, Hyperpigmentation,
Hypertension, Hirsuitism, Acne, Purple striae, Proximal
myopathy.
33. ACTH secreting Pituitary Adenoma
(Cushing’s Disease)
➢ Labs: IFG/IGT, Hypokalemia and Alkalosis, Leukocytosis,
Lymphopenia, Bone loss on DXA.
➢ Diagnosis : Elevated 24 hour urinary free cortisol and/or
lack of suppression by low dose dexamethasone, Elevated
ACTH levels, Ectopic ACTH syndrome ruled out.
➢ Treatment: Pituitary surgery, Medical therapy as
temporizing measure, Radiation therapy
34. GH secreting Pituitary Adenoma
(Acromegaly)
➢ “Acral” and “facial” growth in Adults (once the
epiphyses of long bones are fused).
➢ 40% may co-secrete Prolactin.
➢ Symptoms: Headaches, Arthralgias, Fatigue,
Hyperhidrosis, entrapment neuropathies, Sleep
Apnea, Deepening of voice, Impotence in men,
irregular menses in women.
35. GH secreting Pituitary Adenoma
(Acromegaly and Gigantism)
➢ Signs: “Coarsening” of facial features, enlarged hands
and feet secondary to soft tissue hypertrophy, oral
malocclusion and increased spacing between teeth,
Moist “doughy” skin, increased heel pad thickness,
Hypertension, Goiter.
➢ Labs: IFG/IGT, +/- elevated Prolactin, Hypogonadism.
➢ Diagnosis: Elevated IGF-1, Abnormal GTT.
➢ In children, gigantism occurs because of accelerated
linear growth (growth plates haven’t fused yet)
36. Diseases associated with
Acromegaly
■ DM
■ Arthritis and carpal tunnel syndrome
secondary to hypertrophy of joint cartilage
■ Hypogonadism
■ Sleep Apnea
■ HTN, LVH
■ Colon Polyps
42. Prolactin secreting Pituitary Adenoma
➢ Most common Pituitary lesion.
➢ Majority are microprolactinomas, few are
macroprolactinomas.
➢ E2 stimulates lactotroph proliferation.
➢ Note: Physiologic elevation of Prolactin is seen in
pregnancy.
➢ Idiopathic Prolactinoma: When the etiology is
unclear. A subset of these patients may have
macroprolactinemia.
43. Prolactin secreting Pituitary Adenoma
➢ Prolactin >200ng/ml is consistent with
Prolactinoma
➢ Prolactin <50ng/ml is often secondary to
physiologic causes.
➢ Prolactin 20-100ng/ml may be secondary to
pituitary stalk compression by tumors not actively
secreting Prolactin.
44. Prolactin secreting Pituitary Adenoma
➢ Clinical Presentation: Signs and Symptoms of
hypogonadism (especially amenorrhea and infertility in
pre-menopausal women) +/- galactorrhea (especially in
women) and gynecomastia (in men) +/- tumor mass
effects.
➢ Diagnosis: Elevated Prolactin levels in the presence of
Pituitary lesion on imaging and other causes of
Hyperprolactinemia ruled out.
50. Diabetes Insipidus
➢ Excretion of a “large” volume (usually >4 L/d) of
hypotonic urine in absence of glycosuria.
➢ Differential Diagnosis:
▪ Hypothalamic/ Central DI
▪ Nephrogenic DI
▪ Primary Polydipsia
➢ Serum Sodium is usually maintained in the
normal range. Diagnosis is suggested by
inappropriately low Urine Osmolality in relation to
the Serum Osmolality.
52. Diabetes Insipidus
Clinical Features:
➢ Central DI: Relatively abrupt onset of symptoms,
Preference for cold liquids, Polyuria and Thirst
persisting through the night.
➢ Nephrogenic DI: Lithium, Demeclocycline use,
Hypokalemia, Hypercalcemia.
➢ “Psychogenic” Polydipsia: Erratic course,
Symptoms exacerbated during stress, Minimal
disruption of sleep (lack of nocturia), Underlying
psychiatric disease.
53. Treatment of DI
➢ Adequate water replacement is essential to avoid
metabolic complications.
➢ Central DI: DDAVP (Selective action on
antidiuretic V2 receptors, minimal on pressor V1
receptors)
➢ Nephrogenic DI: Thiazide leading to greater
proximal tubular reabsorption of glomerular filtrate.
54. SIADH
➢ Hyponatremia with low plasma osm
➢ Urine less than maximally dilute
➢ Increased urine sodium
➢ Euvolemia
➢ Normal thyroid and adrenal fxn
➢ No drugs that increase ADH
57. Thyroid Physiology
■ Under regulation of the hypothalamus (TRH) and
pituitary (TSH)
■ Thyroid gland synthesizes and releases thyroid
hormone
■ Thyroid consists of thyroid follicles containing
colloid material that contains thyroglobulin
■ Thyroglobulin is a glycoprotein involved in thyroid
hormone synthesis
58. Thyroid Hormone
■ T4 and to lesser extent T3 is released from thyroid gland
■ Majority T3 is produced peripherally by deiodination of T4
■ Majority T4 and T3 is bound to thyroid binding globulin
(TBG) and albumin
■ T4 is bound more tightly than T3 to TBG
■ Only the free hormone is active
■ T3 has higher affinity for thyroid receptor
■ T3 is the more active thyroid hormone
61. Thyroid
■ T3 uptake
■ Indirect measurement of free T4
■ Constant x T3 resin Uptake x Total T4
■ Inverse relationship with TBG (in situations whn TBG is
high (pregnancy, OCP use), then T3U will be low.
■ T3U is inversely proportional to the percentage of total
T4 that is protein-bound
67. Primary Hypothyroidism
■ Hashimoto’s
■ Most common cause hypothyroidism
■ Women>men
■ Incidence increases with age
■ Autoimmune destruction of thyroid gland
■ Associated with positive anti-TPO and/or
anti-thyroglobulin antibody
■ Slowly progressive
■ May coexist with other autoimmune diseases
68. Hashimoto’s
■ Labs
■ High TSH, low Total T4, total T3, T3 resin Uptake, and
free T4; positive thyroid peroxidase and/or anti
thyroglobulin antibodies
■ We don’t usually measure free T3
■ Treatment
■ Thyroxine replacement
■ T4 vs T3
■ Subclinical hypothyroidism
■ Modestly elevated TSH with normal T4/T3
■ Indications for treatment
■ Hypercholesterolemia
■ Symptoms consistent with hypothyroidism
70. Post Partum Hypothyroidism
■ Recovery phase
■ Self limiting
■ Can reoccur with future pregnancies
■ Positive Thyroid Peroxidase antibodies associated
with increase risk of later developing permanent
hypothyroidism
71. Primary Hypothyroidism (other)
■ Iatrogenic/Drugs
■ Thyroidectomy
■ Radioablation
■ Anti-thyroid medications
■ Lithium, Amiodarone, Interferon
■ Frequently underlying autoimmune process
■ Iodine deficiency
■ Rare in well-developed countries
■ Dyshormonogenesis
■ Rare
■ Enzymatic defect in biosynthesis
■ Leads to hypothyroidism and goiter
72. Myxedema Coma
■ End stage severe longstanding
hypothyroidism
■ Endocrinology emergency
■ Elderly
■ Hypothermia, bradycardia, hypotension
■ Predisposing condition
■ Cold, infection, trauma, CNS depressants
73. Myxedema Coma
■ Treatment
■ Supportive care
■ correction hypothermia, treat underlying illness, IV
fluids with glucose
■ IV thyroid replacement
■ Corticosteroids
75. Hypothyroidism
■ Miscellaneous
■ Dosing T4
■ Elderly vs young
■ Start at 25ug and titrate up
■ 1.5ug/kg body weight
■ Treat TSH within normal range
■ Exception secondary/tertiary hypothyroidism-free T4 upper end
of normal
■ Consider R/O adrenal insufficiency
■ Primary vs secondary hypothyroidism
76. Hypothyroidism in Pregnancy
■ Thyroid Binding Globulin (TBG) increases with
pregnancy
■ Pregnant women with underlying thyroid disease
often unable to increase thyroid hormone
production
■ Patient given instruction as soon as pregnancy
confirmed increase dose by 30%
■ Some evidence hypothyroidism in 1st
trimester
associated with mental disability in offspring
■ Goal TSH in pregnancy is less than in
non-pregnant patients (< 2)
77. Differential for thyroiditis: low
uptake on scan
■ Infectious
■ Acute
(suppurative)-fungal,
parasite, bacterial,
PCP, rare
■ Subacute: usually viral
in origin
(granulomatous: de
Quervain’s)--tender
gland
■ Painless (non
post-partum)
■ Amiodarone-Induced
■ Radiation Induced
■ Traumatic
■ Autoimmune: painless
■ Chronic Lymphocytic
(Hashimotos)
■ Postpartum
78. Subacute Thyroiditis
■ Often history viral illness
■ Neck tenderness
■ During recovery phase transient period hypothyroidism
lasting weeks to several months
■ Usually transient
■ Positive antibodies associated with increased risk of
developing primary hypothyroidism
79. Stages of subacute and
postpartum thyroiditis
■ Hyperthyroid phase occurs first, usually in first 3
months after the viral illness or pregnancy and
thyroid pain
■ Followed by several weeks of a transitory phase
when euthyroidism occurs
■ Followed by a hypothyroid phase for several
months
■ Followed by a Recovery phase when the patient
returns to euthyroidism
81. Subacute Thyroiditis
■ Labs
■ TSH, Total T4 and T3 resin Uptake or free T4,
total T3, and thyroid antibodies
■ ESR: high
■ Serum thyroglobulin: high in all forms thyroiditis
■ Imaging
■ Uptake and Scan: low uptake
82. Subacute Thyroiditis
■ Treatment
■ Depending on stage
■ Beta blockers
■ Anti inflammatory
■ High dose PTU (decrease peripheral conversion
T4→ T3)
■ Steroids
■ Thyroid hormone
83. Hyperthyroidism
■ Thyrotoxicosis
■ Excess thyroid hormone from any cause
■ Low TSH +/- elevated T4/T3
■ Radioactive Iodine uptake and scan helps to
differentiate various forms
86. RAIU: most useful test in the
differentiatal dx of thyrotoxicosis
■ High uptake
■ Graves: diffuse pattern
■ Toxic Multinodular
Goiter: irregular patern
■ Solitary Toxic
Adenoma: increased in
one area of thyroid
■ Low Uptake
■ Factitious: low
thyroglobulin levels
■ Iodine-Induced
■ Thyroiditis: have high
thyroglobulin levels;
may have high ESR or
antibodies, depending
on cause
87. Grave’s Disease
■ Most common cause hyperthyroidism (60-70%)
■ Autoimmune activation TSH receptor
■ Thyroid Stimulating Immunoglobulin
■ Familial
■ Women > Men
■ Associated with other autoimmune diseases
■ Vitiligo, Pernicious Anemia, Myasthenia Gravis, Addison’s disease,
TIDM
■ Anti-TPO and Anti-Thyroglobulin antibodies may also be
present
■ May have positive Thyroid stimulating immunoglobulins
and/or positive Thyroid receptor antibodies
88. Grave’s Disease
■ Triad
■ Thyroid bruit, dermopathy, proptosis are all
pathognomonic
■ Labs
■ Suppressed TSH, elevated T4 and/or T3, increased T3
uptake
■ Imaging
■ Uptake and scan
■ Increased, diffuse uptake
93. Grave’s Disease: Treatment
■ Anti-thyroid medications
■ PTU
■ Inhibits synthesis thyroid hormone
■ Decreases peripheral conversion T4 → T3
■ Does not block release preformed thyroid hormone
■ Side effects
■ Agranulocytosis, hepatitis, urticaria
■ 18-24 months treatment to decrease chance of relapse
■ Preferred pretreatment in surgery
94. Grave’s Disease: Treatment
■ Anti-thyroid medication
■ Methimazole
■ Inhibits synthesis only
■ Preferred treatment prior to RAI
■ Same side effects as PTU
■ Cross reactivity
■ Beta Blocker
■ Symptomatic relief
■ Decrease peripheral conversion T4→T3
95. Grave’s Disease
■ Treatment
■ Radioactive iodine
■ Exacerbation of hyperthyroidism and eye disease
■ Pretreatment drug of choice is methimazole (hold 5-7 days prior to
RAI)
■ Hypothyroidism wanted/potential side effect
■ Iodine: used in severe thyrotoxicosis or storm
■ Blocks release thyroid hormone
■ Wolf Chaikoff Effect (Escape)
■ Surgery
■ Rarely used
■ Pretreatment indicated with PTU/Iodine
■ Major complications are hypothyroidism, hypoparathyroidism, damage
to recurrent laryngeal nerve
97. Toxic Multinodular Goiter
■ Accounts for 20-30% cases hyperthyroidism
■ Nodular goiter on exam
■ Milder increase in T4/T3
■ RAI uptake and Scan
■ Normal to high patchy uptake
■ RAI treatment of choice
■ Large doses of iodine may precipitate
thyrotoxicosis in Non-Toxic MNG
98. Toxic Adenoma
■ AKA Plummer’s Disease
■ 3-5% toxic adenoma
■ Caused by solitary hyperfunctioning nodule
■ Nodule may be palpable on exam
■ Low TSH with elevated T4 and/or T3
■ RAI uptake and scan
■ Normal to high uptake
■ Solitary hot nodule
■ Remainder glands suppressed
■ RAI treatment of choice
99. Hyperthyroidism due to Iodine
■ Iodine Induced
■ Jod Basedow
■ Underlying thyroid pathology
■ Self limiting
■ History IV contrast obtained within several weeks of
onset or pt is on Amiodarone
■ Low TSH, elevated T4, typically normal T3
■ Low RAI uptake
■ Pretreatment
■ Symptomatic relief
100. Hyperthyroidism due to Meds
■ Medications
■ Lithium
■ Amiodarone
■ Type I vs Type II
■ Increased thyroid hormone production vs destructive
thyroiditis
■ Often difficult to differentiate
■ Treatment (depending on Type I vs II)
■ Discontinue amiodarone
■ Anti-thyroid medications (Type 1), steroids (type II),
beta-blocker, surgery
101. Hyperthyroidism: other causes
■ Factitious
■ Low TSH
■ Low RAI uptake
■ Decreased thyroglobulin
■ Elevated in thyroiditis
■ Molar Pregnancy and Choriocarcinoma
■ Stimulatory effect of hCG, which structurally resembles TSH
■ Struma Ovarii
■ Ectopic thyroid tissue
■ RAI uptake and scan
■ Uptake in pelvis and no uptake in neck
■ TSH producing pituitary adenomas
■ Extremely rare
■ Suspect with elevated T4/T3 and normal/high TSH
102. Apathetic Hyperthyroidism
■ Seen in the elderly
■ Thyrotoxicosis without the adrenergic
manifestations
■ Appear depressed, often diagnosed with
mxyedema
■ Weight loss, atrial fibrillation, CHF, muscle
weakness
■ Often Toxic MNG underlying disorder
104. Hyperthyroidism Emergency
■ Thyroid Storm
■ Decompensated form of severe thyrotoxicosis
■ Uncommon, life threatening condition
■ Precipitating event
■ ex. Infection, trauma, surgery, DKA
■ Fever, tachycardia, neurological abnormalities,
hypertension followed by cardiovascular collapse
■ Treatment
■ Anti-thyroid medications, iodine, steroids, B-blockers, control
hyperthermia
106. Sick Euthyroid Syndrome
■ Seen in critically ill patients
■ Low TSH, free T4, and T3
■ Elevated Reverse T3*
■ No treatment
108. Thyroid Nodule
■ Extremely common
■ Approximately 50% patients over 65 will
have at least 1 thyroid nodule on US
■ Incidentaloma
110. Thyroid Nodules
■ Benign
■ Non toxic Goiter
■ Not associated with inflammation or neoplastic process
■ Causes
■ Majority unknown
■ Iodine deficiency
■ Iodine excess
■ Dyshormonogenesis
■ Radiation
■ Cyst
■ Adenoma
■ Thyroiditis
113. Thyroid Cancer
■ Treatment
■ Surgery
■ Radioactive iodine to ablate any remnant thyroid tissue
■ Thyroid replacement after surgery and RAI
■ Suppression of TSH without overt hyperthyroidism
■ Follow Up
■ Physical Exam
■ TFTs including Thyroglobulin
■ Thyrogen whole body scan
■ Ultrasound