Pituitary Disease

Question 1

Reivew: hormones of anterior v. posterior pituitary

Answer 1

Anterior: FSH, LH, ACTH, GH, prolactin, TSH

Posterior: ADH, oxytocin

Question 2

What are the possible pituitary diseases?

Answer 2

• *Pituitary tumors** - can be hormone secreting or non-hormone secreting
• note that this is distinct from pituitary hyperplasia i.e. lactotroph hyperplasia during pregnancy

Non-pituitary lesions: benign tumors (craniopharyngioma, meningioma)

Cysts

Malignant tumors (chordoma, metastatic tumors-breast, lung)

Lymphoma

Granulomatous i.e. sarcoidosis, TB

Lesions of hypothalamus i.e. craniopharyngiomas, germ cell tumors, infiltrative lesions i.e. sarcoid, langerhans cell, TB

Vasculary lesions - aneurysm

Pituitary apoplexy: hemorrhage/infarction

Sheehan syndrome: pituitary infarction

Head trauma

Genetic dz: PROP1, PROU1F1 mutations

Empty sella syndrome: CSF into pituitary area

Question 3

Genetic mutations that can cause pituitary disease?

Answer 3

• *PROP1 mutation**: most common familial/sporatic congenital combined pituitary hormone deficiencies
• autosomal recessive
• it’s mutation encoding TF’s necessary for differentiation of the diff cell types –> deficiency of almost all the hormones

PROU1F1 mutation: autosomal recessive/dominant
- mutaiton of TF necessary for differentiation of somatotroph, lactotroph, thyrotroph cells –> deficiency of these hormones

Question 4

Craniopharyngioma

Answer 4

Benign cell rest tumors (displaced cells)

Arise from remnants of Rathke’s pouch anywhere from hypothalmus to stalk to pituitary gland

Colid or mixed solid/cystic

Bimodal distribution of occurrence: half kids, half adults

Typically present with vision loss, signs/sx of pituitary hormone insufficiency

Treat with surger/radiotherapy

* You’re often deciding between pituitary tumors and craniopharyngioma

Question 5

Signs and sx of pituitary mass lesions/disease

Answer 5

Visual & neuro abnormalities

Signs and sx of hypopituitarism

Signs & sx of hormone hypersecretion syndrome from a hormone-secreting pituitary tumor

Can be incidentally noted on head imaging study done for another reason
- MRI = gold standar

Question 6

Visual & neuro abnormalities in pituitary dz

Answer 6

Headache: common but not specific

• *Visual field deficit**: bc lesion compresses optic chiasm
• bitemporal hemianopsia (blindness on lateral halves of vision)

Cranial nerve dysfunction: CN III, IV, VI; more likely with sudden expansion

Question 7

Secondary adrenal insufficiency

Answer 7

Pituitary ACTH deficiency –> decreased adrenal cortisol production

Lethargy, weakness, anorexia, nausea, weight loss, postural dizziness, hypotension, hyponatremia

Tx: oral hydrocortisone

Question 8

Secondary hypothyroidism

Answer 8

Abnormal pituitary TSH secretion –> TH deficiency

Fatigue, dry skin, constipation, bradycardia, cold intolerance, delayed relaxation of deep tendon reflexes, puffiness

Tx: oral thyroid hormone

Question 9

Secondary hypogonadism

Answer 9

Women: oligo-amenorrhea, infertility, estrogen deficiency, osteopenia

Men: decreased libido, erectile dysfunction, gynecomastia, infertility, osteopenia

Tx: women: estrogen/progesterone replacement if premenopasual

• *men**: testosterone
• *both**: gonadotropin or HCG therapy to restore fertility

Question 10

Growth hormone deficiency (in adults)

Answer 10

Mild: increased fat mass, decreased lean body mass, increased cholesterol, increased CV risk markers i.e. CRP, decreased bone density

Tx: controversial; daily injections of rhGH to normalize serum IGF-I level

Question 11

Vasopressin deficiency

Answer 11

Reduced ability to concentrate urine –> huge volume of dilute urine, thirst

Check urine volume, osmolarity, specific gravity, serum sodium (hypernatremia), dehydration test (for dilute urine despite dehydration)

Tx: DDAVP nasal spray or pills

Question 12

Benign neoplasms that are monoclonal in origin- options?

Answer 12

Lactotroph = prolactin secreting

Somatotroph = GH secreting

Corticotroph = ACTH secreting

Thyrotroph = TSH secreting

Gonadotroph = usually clinically nonfunctioning; may secrete FSH/LH/alpha-subunit

Rarely lacto/somatotroph: GH/prolactin

Rarely pluri-hormone secreting

Question 13

What are most clinically non-functioning pituitary tumors derived from?

Answer 13

Gonadotroph cells

Usually don’t produce a clinical hypersecretion syndrome

Usually large at presentation –> signs of mass lesion/ s&sx of hypopituitarism

Tx: transphenoidal surgery + radiotherapy if recurrence

RARELY: LH –> increased testosterone, early puberty in males
FSH –> ovarian hyperstim in females

Question 14

Acromegaly: etiology

Answer 14

Lots of GHRH –> stimulates GH secretion from pituitary in pulsatile fasion –> produciton of IGF-1 which goes into circulation

In acromegaly, GH comes out in pulsatile fashion but bsln is high –> high GH, high IGF-1

Question 15

Cushing’s disease

Answer 15

Corticotroph pituitary adenoma

ACTH from pituitary –> cortisol production in adrenal gland –> neg feedback to stop ACTH release from pituitary (normally)

In tumor, ACTH is high, cortisol is high, neg feedback is turned off

Clinical: central obesity, facial fullness, thin skin, bruising, proximal muscle weakness, diabetes, htn

Mostly females, 20-40 years old

Check for high urine free cortisol, normal/high ACTH, localization to confirm pituitary source

Treat with transsphenoidal surgery & radiation if recurrence

Question 16

TSH producing pituitary tumor: signs, testing, tx

Answer 16

Signs of hyperthyroidism: tremor, sweating, smooth skin, stare, palpitations, weight loss, goiter

Elevated free thryoxine (T4) levels

TSH normal or elevated

Tx: transphenoidal surgery, radiation, somatostatin analog therapy (inhibits TSH release)

Question 17

Hyperprolactinemia: what can cause it?

Answer 17

Prolactin secreting tumor = prolactinoma

Also: anything that interrupts the tract between pituitary/hypothalamus & disrupts dopamine going to pituitary to suppress prolactin

• Acromegaly
• Other sellar masses
• Infiltrative disorders
• Hypothalmic & pituitary stalk dz or damage

Other: primary hypothyroidism, seizures, PCOS, neurogenic causes (chest wall trauma, surgery, herpes zoster), renal insufficiency, cirrhosis, meds

Question 18

Which meds can cause hyperprolactinemia?

Answer 18

Most commonly:

Antipsychotics: phenothiazines, butyrophenones, atypicals

Antidepressants: tricyclics, MAO inhibitors, SSRIs

Also:

Antihypertensives: verapamil, methyldopa, reserpine

GI meds: chloropromazine, metoclopramide, doperidone, H2 blockers

Question 19

Clinical manifestations of hyperprolactinemia?

Answer 19

Prolactin suppresses gonadotropins –> low LH/FSH –> gonadal dysfunction

Women: oligo-amenorrhea, infertility, galactorrhea, estrogen deficiency, acne hirsuitism (excess hair growth), osteopenia

Men: decreased libido, erectile dysfunction, gynecomastia, galactorrhea, infertility, osteopenia

Question 20

Treatment of hyperprolactinemia?

Answer 20

• *Dopamine agonist therapy**: it suppresses prolactin levels, shrinks tumor
• Bromocriptine, cabergoline
• for small tumors, you can taper the meds off

Surgery & radiation thrapy occasionally used

Careful follow up w/out treatment is an option for patients if they don’t have macroadenoma, are asymptomatic, normal gonadal function, not seeking fertility

Treatment goals: restore gonadal function, resolve galactorrhea, reduce/stabilize tumor, normalize prolactin level