Pituitary Disorders Jo Choudhry, M.D. PGY-1

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Pituitary Disorders Jo Choudhry, M.D. PGY-1

  1. 1. Pituitary Disorders Jo Choudhry, M.D. PGY-1
  2. 2. The Pituitary Gland <ul><li>Located at the base of the skull </li></ul><ul><li>Anterior and Posterior lobes </li></ul><ul><li>Portal connection from the hypothalamus </li></ul>
  3. 3. Anterior Lobe Posterior Lobe <ul><li>Growth hormone (GH) </li></ul><ul><li>Gondadotrophs (LH/FSH) </li></ul><ul><li>TSH </li></ul><ul><li>Prolactin </li></ul><ul><li>Corticotropin (ACTH) </li></ul><ul><li>Oxytocin </li></ul><ul><li>Vasopressin </li></ul>
  4. 4. Normal Changes in Pregnancy <ul><li>Anterior lobe size doubles-triples due to lactotrophs. </li></ul><ul><li>Placental estrogens stimulate lactotroph proliferation </li></ul><ul><li>Decreased response to GnRH, dec. LH/FSH </li></ul><ul><li>Decrease pituitary GH, inc. placental GH </li></ul><ul><li>Increase CRH (prob. Placental origin) during 2 & 3 trimesters </li></ul><ul><li>2-4 X increase in ACTH, despite inc. in bound and free cortisol. </li></ul>
  5. 5. Hyperprolactinemia <ul><li>Causes : </li></ul><ul><ul><li>1. disruption of dopamine (tumor, trauma, infiltrative lesions) </li></ul></ul><ul><ul><li>2. hypothyroid (increases TRH) </li></ul></ul><ul><ul><li>3. estrogen increase (pregnancy) </li></ul></ul><ul><ul><li>4. chest wall burns – nueronal effect like suckling </li></ul></ul><ul><ul><li>5. chronic renal failure, returns to nml after transplant </li></ul></ul><ul><ul><li>6. drugs (verapamil, H2 blockers, estrogens, opiates, dopamine receptor antagonists, reserpine, a-methyldopa) </li></ul></ul>
  6. 6. Prolactinomas <ul><li>Most common functional pituitary tumor </li></ul><ul><li>10% are lactotroph and somatotroph such as GH producing </li></ul><ul><li>Presents with amenorrhea and infertility </li></ul><ul><li>Prolactinomas lose TRH response </li></ul><ul><li>Microadenomas <10mm on MRI </li></ul><ul><li>Macroadenomas >10mm </li></ul>
  7. 7. Treatment Pregnancy Not Desired <ul><li>Treat only if symptomatic </li></ul><ul><ul><li>(HA, vision changes) </li></ul></ul><ul><li>Dopamine agonist (Bromocriptine) </li></ul><ul><ul><li>1.25mg qhs 1 wk, then BID </li></ul></ul><ul><ul><li>If intolerant with nausea, may give vaginally </li></ul></ul><ul><ul><li>Not recommended for breastfeeding </li></ul></ul><ul><li>Transspenoidal surgery if unsuccessful </li></ul>
  8. 8. Risks of surgery : *4.6% post-op neurologic complication: infarction/hemorrhage *2-10.5% Diabetes Insipidous *8.8% fluid and electrolyte *2% Cerebrospinal fluid rhinorrhea *2% Meningitis *3.2% cranial nerve 3,4,or 6 palsies
  9. 9. Treatment Pregnancy Desired <ul><li>If macro , shrink size b/f preg with bromocriptine (36% will develop neurologic symptoms) </li></ul><ul><li>If causing major visual defect and unresponsive, consider transspenoidal surgery b/f preg. </li></ul><ul><li>Bromocriptine until </li></ul><ul><li>preg occurs, then stop. </li></ul>
  10. 10. During Pregnancy <ul><li>Visual field check q2-3 mos. and MRI prn </li></ul><ul><li>If neurologic symptoms occur during preg, usually about 14wga, restart treatment. </li></ul><ul><ul><li>Class B </li></ul></ul><ul><li>If severe and unresponsive: </li></ul><ul><ul><li>2 nd trimester: consider surgery </li></ul></ul><ul><ul><ul><li>PTL risk </li></ul></ul></ul><ul><ul><li>3 rd trimester: wait until PP </li></ul></ul>
  11. 11. Acromegaly <ul><li>98% GH pituitary adenoma </li></ul><ul><li>1/3 of all functional pituitary adenomas </li></ul><ul><li>Stimulates growth of skin, connective tissue, cartilage, bone, and viscera </li></ul><ul><li>Nitrogen retention, insulin antagonism, and lipogenesis </li></ul>
  12. 12. Risks of Long Term Excess GH <ul><li>Arthropathy </li></ul><ul><li>Neuropathy </li></ul><ul><li>Cardiomyopathy </li></ul><ul><li>Respiratory obstruction </li></ul><ul><li>Diabetes Mellitus </li></ul><ul><li>Hypertension: exaterbates cardiomyopathy </li></ul><ul><ul><li>NOT Reversible </li></ul></ul><ul><li>increased risk of tumors: </li></ul><ul><ul><li>leiomyomata </li></ul></ul><ul><ul><li>colon polyps </li></ul></ul>Reduced overall survival by an average of 10 years
  13. 13. Diagnosis <ul><li>Somatomedian-C levels and IGF-1 levels </li></ul><ul><li>If pregnant: special assay to distinguish placental GH </li></ul><ul><li>70% pitutary GH responds to TRH, placental variant does not. </li></ul>
  14. 14. Treatment <ul><li>Goal: lower the serum insulin-like growth factor to normal for age/gender </li></ul><ul><li>Surgically accessible micro- or Macroadenomas: </li></ul><ul><ul><li>Transspenoidal surgery </li></ul></ul><ul><li>2 nd Line therapy: Somatostatin analogs or Dopamine agonists </li></ul><ul><li>3 rd Line therapy: Somatostatin receptor antagonist </li></ul><ul><li>Last resort: Radiation </li></ul>
  15. 15. Pregnancy and Acromegaly <ul><li>D/C tx with confirmation </li></ul><ul><li>GH Maternal to Fetal transfer negligible, except for glu intolerance. </li></ul><ul><li>If severe neurologic sympts, try Bromocriptine </li></ul><ul><ul><li>May not dec. GH, shrink lactotrophs </li></ul></ul><ul><li>Somatostatin analogs have been used in 3 pts with no ill effects to fetus, despite transplacental passage. </li></ul>
  16. 16. Cushing’s Disease <ul><li>High ACTH leads to excess glucocorticoid </li></ul><ul><li>Incidence may be 5-25 per million </li></ul><ul><li>Women are 3-8X more likely than men </li></ul>
  17. 17. Cushing’s disease <ul><li>Centripetal obesity </li></ul><ul><li>Moon face; buffalo hump </li></ul><ul><li>Skin atrophy </li></ul><ul><li>Easily bruised </li></ul><ul><li>Striae </li></ul><ul><li>Cutaneous fungal infections </li></ul><ul><li>Hyperpigmentation </li></ul><ul><li>Oligo or amenorrhea </li></ul><ul><li>Hirsutism and Virilization with adrenal tumors </li></ul>
  18. 18. Cushing’s Disease <ul><li>Proximal muscle wasting & weakness </li></ul><ul><li>Osteoporosis </li></ul><ul><li>Glucose intolerance </li></ul><ul><li>HTN, hypokalemia </li></ul><ul><li>Thromboembolism </li></ul><ul><li>Depression, Psyc </li></ul><ul><li>Infection </li></ul><ul><li>Glaucoma </li></ul>
  19. 19. Complications if Pregnant <ul><li>Rare due to decreased fertility </li></ul><ul><li>Premature birth </li></ul><ul><li>SAB, Stillbirths </li></ul><ul><li>IUGR </li></ul><ul><li>Neonatal adrenal insufficiency </li></ul><ul><li>Maternal: HTN, DM, CHF, Death </li></ul>
  20. 20. Diagnosis <ul><li>Cushing’s Syndrome : </li></ul><ul><li>24 hr urine cortisol excretion </li></ul><ul><li>If not 3x nml, measure pm salivary cortisol </li></ul><ul><li>Cushing’s Disease vs. Syndrome : </li></ul><ul><li>HIGH dose Dexamethasone suppression test (8mg overnight) </li></ul><ul><ul><li>Successful if Pituitary origin </li></ul></ul>
  21. 21. Treatment <ul><li>Transsphenoidal surgery </li></ul><ul><li>Pituitary irradiation </li></ul><ul><li>Adrenalectomy (Surgical, Mitotane) </li></ul><ul><ul><li>Nelson’s Syndrome : expanding intrasellar tumor and hyperpigmentation </li></ul></ul><ul><li>Pregnancy: </li></ul><ul><ul><li>1 st Trimester: Surgery </li></ul></ul><ul><ul><li>2 nd Trimester: Adrenal Enzyme Inhibitors vs. surgery </li></ul></ul><ul><ul><li>3 rd Trimester: Early delivery, enzyme inhibitors until lung maturity </li></ul></ul>
  22. 22. Thyrotropin-secreting Adenoma <ul><li><1% of all hyperthyroidism cases </li></ul><ul><li>25% of adenomas secrete other hormones </li></ul><ul><li>Goiter, visual defects, menstral irreg, galatorrhea </li></ul><ul><li>Lab: </li></ul><ul><li>Normal or High TSH </li></ul><ul><li>High total and free T4 and High T3 </li></ul><ul><li>MRI </li></ul>
  23. 23. Treatment <ul><li>Transsphenoidal surgery </li></ul><ul><ul><li>1/3 Cure </li></ul></ul><ul><ul><li>1/3 improvement </li></ul></ul><ul><ul><li>1/3 no change </li></ul></ul><ul><li>Dopamine Agonist </li></ul><ul><li>Somatostatin Analogue (Octreotide) </li></ul><ul><ul><li>Works so well, may give before surgery </li></ul></ul><ul><ul><li>Nausea, diarrhea, bloating, glu intolerance, cholelithiasis </li></ul></ul><ul><li>Do NOT use antithyroid therapy </li></ul>
  24. 24. Gonadotroph adenoma <ul><li>Usually considered non-functioning </li></ul><ul><ul><li>Secrete inefficiently, variably </li></ul></ul><ul><li>Presents with nuerologic symptoms </li></ul><ul><li>Difficult to Diagnose </li></ul><ul><ul><li>Rule out other adenomas </li></ul></ul><ul><ul><li>Prepubertal girls= breast devel, vag. Bleeding </li></ul></ul><ul><ul><li>Premenopausal= amenorrhea, oligo </li></ul></ul>
  25. 25. Gonadotroph adenoma vs. menopause and ovarian failure <ul><li>High FSH with low LH </li></ul><ul><li>High serum free alpha subunit </li></ul><ul><li>High estridiol, FSH, thickened endometrium and polycystic ovaries </li></ul>
  26. 26. Treatment of non-functioning and gonadotrophin macroadenomas <ul><li>Transsphenoidal surgery </li></ul><ul><li>+/- Radiation </li></ul>
  27. 27. Hypopituitarism <ul><li>76% tumor or treatment of tumor </li></ul><ul><ul><li>Mass effect of adenoma on other hormones </li></ul></ul><ul><ul><li>Surgical resection of non-adenomatous tissue </li></ul></ul><ul><ul><li>Radiation of pituitary </li></ul></ul><ul><ul><ul><li>Check hormones 6 mos after and then yearly </li></ul></ul></ul><ul><li>13% extrapituitary tumor </li></ul><ul><ul><li>Craniopharyngioma </li></ul></ul><ul><li>8% unknown </li></ul><ul><li>1% sarcoidosis </li></ul><ul><li>0.5% Sheehan’s syndrome </li></ul>
  28. 28. Infiltrative Lesions <ul><li>Hereditary Hemochromatosis </li></ul><ul><ul><li>Fe deposition in pituitary </li></ul></ul><ul><ul><li>Gonadotropin deficiency most common </li></ul></ul><ul><ul><li>Tx repeat phlebotomy </li></ul></ul><ul><li>Pituitary Apoplexy </li></ul><ul><ul><li>Sudden hemorrhage into pituitary </li></ul></ul><ul><ul><li>Severe, sudden HA; diplopia; hypopituitarism </li></ul></ul><ul><ul><li>Sudden ACTH def. is life-threatening hypotension </li></ul></ul><ul><ul><li>Tx: surgical decompression </li></ul></ul>
  29. 29. Sheehan Syndrome <ul><li>Infarction of Pituitary after substantial blood loss during childbirth </li></ul><ul><li>Incidence: 3.6% </li></ul><ul><li>No correlation between severity of hemorrage and symptoms </li></ul><ul><li>Severe: recognized days to weeks PP </li></ul><ul><ul><li>Lethargy, anorexia, weight loss, unable to BF </li></ul></ul>
  30. 30. Sheehan’s Syndrome <ul><li>Typically long interval between obstetric event and diagnosis </li></ul><ul><li>Of 25 cases studied: </li></ul><ul><ul><li>50% permanent amenorrhea </li></ul></ul><ul><ul><li>The rest had scanty-rare menses </li></ul></ul><ul><ul><li>Most lactation was poor to absent </li></ul></ul><ul><li>Dx: MRI empty sella turcica </li></ul>
  31. 31. Sheehan’s and Pregnancy <ul><li>TX with hormones </li></ul><ul><li>87% live births </li></ul><ul><li>13% SAB </li></ul><ul><li>0 Stillbirths </li></ul><ul><li>0 Maternal deaths </li></ul><ul><li>Don’t TX </li></ul><ul><li>58% live births </li></ul><ul><li>42% SAB </li></ul><ul><li>1 Stillbirth </li></ul><ul><li>3 Maternal deaths </li></ul>Labor : HYDRATION!! IV Cortisol: adjusted for pt’s state 25-75mg q6 hr
  32. 32. Lymphocytic Hypophysitis <ul><li>22 y/o female died of circulatory collapse 8 hours after appy. She was 14 mos. PP and had developed 2 nd amenorrhea. </li></ul><ul><li>Autopsy: lymphocytic infiltration of pituitary and thyroid </li></ul><ul><li>Symptoms: HA, lethargy, weight loss, hyperprolactinemia </li></ul>
  33. 33. Lymphocytic Hypophysis <ul><li>Scheithauer et al, ’90 </li></ul><ul><ul><li>69 women that died during preg or PP </li></ul></ul><ul><ul><li>5 had the disease, 4/5 died at 38-41 wga </li></ul></ul><ul><li>Consider especially if no hemorrhage </li></ul><ul><li>TX: HRT (thyroid, cortisol) </li></ul>
  34. 34. Pituitary Necrosis <ul><li>Pregnant Diabetic Patients </li></ul><ul><ul><li>Due to vascular changes </li></ul></ul><ul><li>DX: severe, midline HA and vomitting in 3 rd trimester followed by decrease of insulin requirements </li></ul><ul><li>3/8 cases reported: assoc. with fetal and then maternal death </li></ul>
  35. 35. Central Diabetes Insipidus <ul><li>Polydipsia and Polyuria (2-15 Liters/day) </li></ul><ul><li>Abrupt onset </li></ul><ul><li>30-50% are idiopathic </li></ul><ul><ul><li>Dec. production by </li></ul></ul><ul><ul><li>hypothalamus </li></ul></ul><ul><li>Surgery or Trauma </li></ul><ul><li>Rare with Sheehan’s </li></ul><ul><ul><li>Mild, undetectable degree </li></ul></ul>Hypothalamus Pituitary Kidney
  36. 36. Dx of Central DI <ul><li>Water Deprivation test: </li></ul><ul><ul><li>Restrict p.o. fluids or administer hypertonic saline to increase serum osmolality to 295-300 mosmol/kg (nml: 275-290) </li></ul></ul><ul><ul><li>Central DI: urine osmolality still low and returns to normal after administer vasopressin </li></ul></ul><ul><ul><li>Nephrogenic DI: exogenous vasopressin does not alter urine osmolality much </li></ul></ul>
  37. 37. Pregnancy and Central D.I. <ul><li>Transient D.I. during pregnancy due to acquired or hereditary D.I. </li></ul><ul><ul><li>Latent: Unable to sustain during pregnancy </li></ul></ul><ul><li>Transient Arginine Vasopressin resistant, but L-Deamino, 8-D-arginine vasopressin (DDAVP=Desmopressin) responsive </li></ul><ul><ul><li>High amounts of placental vasopressinase </li></ul></ul><ul><li>D.I. antedates pregnancy. Most deteriorate due to vasopressinase </li></ul>
  38. 38. Treatment of Central D.I. <ul><li>DDAVP (Desmopressin Acetate) </li></ul><ul><ul><li>Synthetic analog </li></ul></ul><ul><ul><li>Not catabolized by vasopressinase </li></ul></ul><ul><ul><li>No vasopressor action </li></ul></ul><ul><ul><li>Administered intranasally (rec.) or p.o. </li></ul></ul><ul><ul><li>Titrate 10-20ug qd or bid </li></ul></ul><ul><ul><li>Safe in pregnancy and breastfeeding </li></ul></ul>
  39. 39. References <ul><li>Saunders; Maternal-Fetal Medicine 5 th Edition; Chapter 51 ppg. 1083-1094. </li></ul><ul><li>Weiss, R; Refetoff, S; Thyrotropin Secreting Pituitary Adenomas ; Up To Date online Jan. 2005; www.uptodate.com </li></ul><ul><li>Synder,P.; Clinical Manifestations and diagnosis of gonadotroph and other clinically nonfunctioning adenomas ; Up To Date online; Jan. 2005; www.uptodate.com </li></ul><ul><li>Barker,F; Klibanski,A; Swearingin,B; Transsphenoidal Surgery for Pituitary Tumors in the United States, 1996-2000: Mortality, Morbidity, and the Effects of Hospital and Surgeon Volume; Journal of Clinical Endocrinology and Metabolism Vol. 88, No. 10, ppg. 4709-4719. </li></ul><ul><li>Nieman, L; Orth, D; Clinical manifestations of Cushing’s Syndrome; Up To Date online; Jan. 2005; www.uptodate.com </li></ul><ul><li>Nieman, L; Orth, D; Treatment of Cushing’s Syndrome: Diminishing adrenal cortisol synthesis. Up To Date online; Jan. 2005; www.uptodate.com </li></ul><ul><li>Synder, P; Abrahamson, M; Management of lactotroph adenoma (prolactinoma) during pregnancy; Up To Date online; Jan. 2005; www.uptodate.com </li></ul><ul><li>Melmed, S; Treatment of Acromegaly; Up To Date online; Jan. 2005; www.uptodate.com </li></ul><ul><li>Melmed, S; Clinical manifestations of acromegaly; Up To Date online; Jan. 2005; www.uptodate.com </li></ul><ul><li>Synder, P; Treatment of Hypopituitarism; Up To Date online; Jan. 2005; www.uptodate.com </li></ul><ul><li>Abrahamson, M; Synder, P; Causes of hypopituitarism; Up To Date online; Jan. 2005; www.uptodate.com </li></ul><ul><li>Garner, P. Pituitary Disorders of Pregnancy; Endotext.com; Chapter 2A; March 2002. </li></ul><ul><li>Rose, B.; Causes of Central Diabetes Insipidous; Up To Date online; Jan. 2005; www.uptodate.com </li></ul><ul><li>Rose, B.; Treatment of Central Diabetes Insipidous; Up To Date online; Jan. 2005; www.uptodate.com </li></ul><ul><li>Rose, B; Diagnosis of polyuria and Diabetes insipidus; Up To Date online; Jan. 2005; www.uptodate.com </li></ul>

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