Endocrine Diseases Pituitary Gland University of New England

Endocrine Diseases Pituitary Gland University of New England Physician Assistant Program J. B. Handler, M. D. 1

Abbreviations n n n ACTHadrenocorticotropic hormone TSH- thyroid stimulating hormone LH- leutinizing hormone FSH- follicle stimulating hormone h. CG-human chorionic gonodatropin ADH- antidiuretic hormone n n n n n GH- growth hormone CO- cardiac output DI- diabetes insipidus IGF- insulin growth factor OCP- oral contraceptive pill LFT- liver function test AVP- arginine vasopressin DJD- degenerative joint disease SSRI- selective serotonin reuptake inhibitor 2

Pituitary Hormones n n n Anterior Pituitary: Growth Hormone, Prolactin, ACTH, TSH, LH, FSH. Posterior Pituitary: Arginine Vasopressin (ADH, AVP), Oxytocin. Hypothalamus: Release of regulatory hormones, most of which stimulate release of pituitary hormones. Exception: Prolactin-release is inhibited by dopamine. 3

Hypopituitarism Hormone deficiencies may be single or multiple. n Etiologies: Genetic defects, tumors (pituitary adenoma), autoimmune, trauma, irradiation, stroke/intracerebral hemorrhage, peri-partum (Sheehan’s syndrome- pituitary infarction following post partum shock or hemorrhage) n 4

Hypopituitarism n n LH/FSH- Sex Hormones- If congenital: hypogonadism- delayed adolescence. If acquired as an adult: loss of secondary sex characteristics (beard, axillary and pubic hair, etc) libido, amenorrhea, infertility; low testosterone/estrogen. TSH- Thyroid Hormone- Hypothyroidism: weakness, cold intolerance, constipation, skin/hair changes, hyperlipidemia, wt. gain. 5

n n n ACTH- Cortisol-Adrenal insufficiency: Weakness, fatigue, weight loss, hypotension. Growth Hormone-In adults: obesity, asthenia, decreased CO. In children-serious growth disturbance. Panhypopituitarism-lack all of the anterior pituitary hormones. 6

Lab, Diagnostics and Treatment n n n Possibilities: ACTH Cortisol hyponatremia, hypoglycemia; TSH free T 4; LH, FSH Testosterone, Estradiol. MRI- Visualization of Pituitary neoplasms and other CNS pathology. Transphenoidal pituitary surgery (if tumor) followed by endocrine replacement therapy: LThyroxin, Testosterone or Estrogen, Cortisol, h. GH. 7

Diabetes Insipidus n n Central: Deficiency of AVP/ADH Primary: Pituitary intact; familial forms (rare). Secondary: Damage to pituitary or pituitary stalk by tumor, surgery, anoxia. Nephrogenic: Inability of the kidneys to respond to ADH; congenital (lack ADH receptors) and acquired forms (pyelonephritis, post-obstructive, tubular interstitial disease, drug induced (demeclocycline, lithium), hypercalcemia, etc. ). 8

Signs, Symptoms & Diagnostics Intense thirst, polyuria (2 -20 L/d). n Lab: Serum- hypernatremia; urine- low specific gravity. n Other pituitary deficiencies may be present. n 9

Diagnostics Vasospressin challenge: Desmopressin administered SC or intranasal results in dramatic decrease in urine volume in central DI; no response with nephrogenic DI. n Differential Dx of polyuria/polydipsea: DI, Diabetes Mellitus, psychogenic polydypsia. n Complications: Severe dehydration, hypernatremia. n 10

Treatment Central DI: Partial deficiency may require no treatment other than fluids. Complete deficiency: Desmopressin (SC, IM, oral, intranasal); lowest effective dose to avoid hyponatremia. n Nephrogenic DI: May respond to Indomethacin which increases renal sensitivity to AVP by blocking the action of prostaglandin E. n 11

Acromegaly and Gigantism Excessive GH release, almost always from a pituitary adenoma. n GH effects mediated by increased production of IGF-I in liver. n These tumors often produce prolactin in addition to GH additional Sx (see below). n 12

Signs and Symptoms Dependent on when the tumor develops. n If before closure of epiphyses: Gigantism n After epiphyseal closure: Acromegaly. Characterized by enlargement of the hands, jaw, feet; coarse facial features; bones of the skull enlarge; deep voice. n 13

Pituitary Gigantism/Acromegaly Images. google. com

Acromegaly “She has Man Hands”: J. Seinfeld, late 1990’s Images. google. com

Signs and Symptoms Associated findings: Hypertension, cardiomegaly (dilated cardiomyopathy), insulin resistance/diabetes, DJD. If untreated, progressive cardiovascular morbidity and premature death. n Hypogonadism reflects co-secretion of prolactin (see below) or pituitary compression with decreased LH/FSH. n 16

Lab and Diagnostic Findings n n n Bloodwork (Following an overnight fast): serum IGF-I ( 5 x nl with Acromegaly), prolactin, glucose; all may be elevated. TSH/Thyroxin if low, suggests additional pituitary pathology. Glucose challenge post fast- Elevated GH levels help confirm the diagnosis (should normally be < 1 ng/m. L). MRI- Usually identifies a pituitary adenoma. 17

Pituitary Tumor Images. google. com 18

Treatment of Acromegaly n n Transphenoidal microsurgery, which may result in transient or permanent hypopituitarism. Octreotide-a somatostatin (somatotropin releaseinhibiting factor) analog. Suppresses GH secretion; used in patients who continue to have excessive GH release post-op; very expensive; injected shrinks some tumors – Dopaminergic agents (cabergoline, oral) useful especially if tumor co-secretes prolactin shrinks some tumors. – Pegvisomant- GH receptor antagonist, new. 19

Hyperprolactinemia Prolactin induces lactation during pregnancy (along with estrogen and progesterone). n Control of prolactin production is inhibitory, mediated by dopamine. n Etiologies: Pituitary microadenoma (may also produce GH), drugs (SSRI’s, thiazides, Cimetidine, Tricyclics, OCP, others); hypothyroidism, renal failure and cirrhosis. n 20

Signs and Symptoms n n n High prolactin levels suppress Gn. RH LH/FSH, resulting in hypogonatropic hypogonadism. Females: Pre-menopausal woman develop galactorrhea, oligo/amenorrhea and infertility, decreased libido, vaginal dryness. Males: Decreased libido, erectile dysfunction, gynecomastia, but no galactorrhea. 21

Lab and Diagnostic Findings Baseline labs should include h. CG, TSH, Free Thyroxine, Creatinine and BUN, LFT’s and Prolactin levels. n In the absence of pregnancy and renal failure, a Prolactin level >250 ng/m. L is highly suspicious/diagnostic of Prolactinoma. n Imaging- MRI n 22

Treatment DC offending drug if present. n Correct other possible etiologies. n Microprolactinomas grow very slowly and patients with mild symptoms can be followed without intervention. n 23

Treatment With symptoms of hypogonadism/infertility or larger tumors: Dopamine agonists (Cabergoline, Bromocriptine) can successfully treat symptoms, correct amenorrhea and galactorrhea, and shrink the tumor. n Transphenoidal pituitary surgery reserved for individuals with large macroadenomas that abut/compress the optic chiasm. n 24