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

2. 2 Abbreviations ACTH- adrenocorticotropic hormone ACTH- adrenocorticotropic hormone TSH- thyroid stimulating hormone TSH- thyroid stimulating hormone LH- leutinizing hormone LH- leutinizing hormone FSH- follicle stimulating hormone FSH- follicle stimulating hormone hCG-human chorionic gonodatropin hCG-human chorionic gonodatropin ADH- antidiuretic hormone ADH- antidiuretic hormone 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 re- uptake inhibitor

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

4. 4 Hypopituitarism Hormone deficiencies may be single or multiple. Hormone deficiencies may be single or multiple. 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) 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)

5. 5 Hypopituitarism 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. 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. TSH-  Thyroid Hormone- Hypothyroidism: weakness, cold intolerance, constipation, skin/hair changes, hyperlipidemia, wt. gain.

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

7. 7 Lab, Diagnostics and Treatment Possibilities:  ACTH  Cortisol  hyponatremia, hypoglycemia;  TSH  free T4;  LH, FSH  Testosterone, Estradiol. Possibilities:  ACTH  Cortisol  hyponatremia, hypoglycemia;  TSH  free T4;  LH, FSH  Testosterone, Estradiol. MRI- Visualization of Pituitary neoplasms and other CNS pathology. MRI- Visualization of Pituitary neoplasms and other CNS pathology. Transphenoidal pituitary surgery (if tumor) followed by endocrine replacement therapy: L- Thyroxin, Testosterone or Estrogen, Cortisol, hGH. Transphenoidal pituitary surgery (if tumor) followed by endocrine replacement therapy: L- Thyroxin, Testosterone or Estrogen, Cortisol, hGH.

8. 8 Diabetes Insipidus Central: Deficiency of AVP/ADH Primary: Pituitary intact; familial forms (rare). Secondary: Damage to pituitary or pituitary stalk by tumor, surgery, anoxia. 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.). 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.).

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

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

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

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

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

14. Pituitary Gigantism/Acromegaly Images.google.com

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

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

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

18. 18 Pituitary Tumor Images.google.com

19. 19 Treatment of Acromegaly Transphenoidal microsurgery, which may result in transient or permanent hypopituitarism. Transphenoidal microsurgery, which may result in transient or permanent hypopituitarism. Octreotide-a somatostatin (somatotropin release- inhibiting factor) analog. Suppresses GH secretion; used in patients who continue to have excessive GH release post-op; very expensive; injected  shrinks some tumors Octreotide-a somatostatin (somatotropin release- inhibiting 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.

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

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

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

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

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