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Endocrine DiseasesEndocrine Diseases

Pituitary GlandPituitary Gland

University of New EnglandUniversity of New England

Physician Assistant ProgramPhysician Assistant Program

J.B. Handler, M.D. J.B. Handler, M.D.

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AbbreviationsAbbreviations

ACTH- ACTH- adrenocorticotropic adrenocorticotropic hormonehormone

TSH- thyroid stimulating TSH- thyroid stimulating hormonehormone

LH- leutinizing hormoneLH- leutinizing hormone FSH- follicle stimulating FSH- follicle stimulating

hormonehormone hCG-human chorionic hCG-human chorionic

gonodatropingonodatropin ADH- antidiuretic ADH- antidiuretic

hormonehormone

GH- growth hormoneGH- growth hormone CO- cardiac outputCO- cardiac output DI- diabetes insipidusDI- diabetes insipidus IGF- insulin growth factorIGF- insulin growth factor OCP- oral contraceptive pillOCP- oral contraceptive pill LFT- liver function testLFT- liver function test AVP- arginine vasopressinAVP- arginine vasopressin DJD- degenerative joint diseaseDJD- degenerative joint disease SSRI- selective serotonin re-SSRI- selective serotonin re-

uptake inhibitoruptake inhibitor

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Pituitary HormonesPituitary Hormones

Anterior PituitaryAnterior Pituitary: Growth Hormone, Prolactin, : Growth Hormone, Prolactin, ACTH, TSH, LH, FSH.ACTH, TSH, LH, FSH.

Posterior PituitaryPosterior Pituitary: Arginine Vasopressin (ADH, : Arginine Vasopressin (ADH, AVP), Oxytocin.AVP), Oxytocin.

Hypothalamus: Release of regulatory hormones, Hypothalamus: Release of regulatory hormones, most of which stimulate release of pituitary most of which stimulate release of pituitary hormones. Exception: Prolactin-release is hormones. Exception: Prolactin-release is inhibited by dopamine.inhibited by dopamine.

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HypopituitarismHypopituitarism

Hormone deficiencies may be single or Hormone deficiencies may be single or multiple.multiple.

Etiologies: Genetic defects, tumors Etiologies: Genetic defects, tumors (pituitary adenoma), autoimmune, trauma, (pituitary adenoma), autoimmune, trauma, irradiation, stroke/intracerebral hemorrhage, irradiation, stroke/intracerebral hemorrhage, peri-partum (Sheehan’s syndrome- pituitary peri-partum (Sheehan’s syndrome- pituitary infarction following post partum shock or infarction following post partum shock or hemorrhage)hemorrhage)

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HypopituitarismHypopituitarism

LH/FSHLH/FSH- - Sex Hormones- If congenital: Sex Hormones- If congenital: hypogonadismhypogonadism- delayed adolescence. If acquired - delayed adolescence. If acquired as an adult: loss of secondary sex characteristics as an adult: loss of secondary sex characteristics (beard, axillary and pubic hair, etc) libido, (beard, axillary and pubic hair, etc) libido, amenorrhea, infertility; low testosterone/estrogen.amenorrhea, infertility; low testosterone/estrogen.

TSHTSH- - Thyroid Hormone- Thyroid Hormone- HypothyroidismHypothyroidism: : weakness, cold intolerance, constipation, skin/hair weakness, cold intolerance, constipation, skin/hair changes, hyperlipidemia, wt. gain.changes, hyperlipidemia, wt. gain.

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ACTHACTH- - Cortisol-Cortisol-Adrenal insufficiencyAdrenal insufficiency: : Weakness, fatigue, weight loss, hypotension.Weakness, fatigue, weight loss, hypotension.

Growth Hormone-In adults: obesity, asthenia, Growth Hormone-In adults: obesity, asthenia, decreased CO. In children-serious growth decreased CO. In children-serious growth disturbance.disturbance.

Panhypopituitarism-lack all of the anterior Panhypopituitarism-lack all of the anterior pituitary hormones.pituitary hormones.

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Lab, Diagnostics and TreatmentLab, Diagnostics and Treatment

Possibilities: Possibilities: ACTHACTHCortisol Cortisol hyponatremia, hyponatremia, hypoglycemia; hypoglycemia; TSH TSH free T4; free T4; LH, FSH LH, FSH Testosterone, Estradiol.Testosterone, Estradiol.

MRI- Visualization of Pituitary neoplasms and MRI- Visualization of Pituitary neoplasms and other CNS pathology.other CNS pathology.

Transphenoidal pituitary surgery (if tumor) Transphenoidal pituitary surgery (if tumor) followed by followed by endocrine replacement therapyendocrine replacement therapy: L-: L-Thyroxin, Testosterone or Estrogen, Cortisol, Thyroxin, Testosterone or Estrogen, Cortisol, hGH.hGH.

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Diabetes InsipidusDiabetes Insipidus

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

Nephrogenic: Inability of the kidneys to respond Nephrogenic: Inability of the kidneys to respond to ADH; congenital (lack ADH receptors) and to ADH; congenital (lack ADH receptors) and acquired forms (pyelonephritis, post-obstructive, acquired forms (pyelonephritis, post-obstructive, tubular interstitial disease, drug induced tubular interstitial disease, drug induced (demeclocycline, lithium), hypercalcemia, etc.).(demeclocycline, lithium), hypercalcemia, etc.).

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Signs, Symptoms & DiagnosticsSigns, Symptoms & Diagnostics

Intense thirst, polyuria (2-20 L/d).Intense thirst, polyuria (2-20 L/d). Lab: Serum- hypernatremia; urine- low Lab: Serum- hypernatremia; urine- low

specific gravity.specific gravity. Other pituitary deficiencies may be present.Other pituitary deficiencies may be present.

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DiagnosticsDiagnostics

Vasospressin challengeVasospressin challenge: Desmopressin : Desmopressin administered SC or intranasal results in administered SC or intranasal results in dramatic decrease in urine volume in central dramatic decrease in urine volume in central DI; no response with nephrogenic DI.DI; no response with nephrogenic DI.

Differential Dx of polyuria/polydipsea: DI, Differential Dx of polyuria/polydipsea: DI, Diabetes Mellitus, psychogenic polydypsia.Diabetes Mellitus, psychogenic polydypsia.

Complications: Severe dehydration, Complications: Severe dehydration, hypernatremia.hypernatremia.

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TreatmentTreatment

Central DI: Partial deficiency may require Central DI: Partial deficiency may require no treatment other than fluids. Complete no treatment other than fluids. Complete deficiency: Desmopressin (SC, IM, oral, deficiency: Desmopressin (SC, IM, oral, intranasal); lowest effective dose to avoid intranasal); lowest effective dose to avoid hyponatremia.hyponatremia.

Nephrogenic DI: May respond to Nephrogenic DI: May respond to Indomethacin which increases renal Indomethacin which increases renal sensitivity to AVP by blocking the action of sensitivity to AVP by blocking the action of prostaglandin E.prostaglandin E.

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Acromegaly and GigantismAcromegaly and Gigantism

Excessive GH release, almost always from Excessive GH release, almost always from a pituitary adenoma.a pituitary adenoma.

GH effects mediated by increased GH effects mediated by increased production of IGF-I in liver.production of IGF-I in liver.

These tumors often produce prolactin in These tumors often produce prolactin in addition to GHaddition to GH additional Sx (see additional Sx (see below).below).

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Signs and SymptomsSigns and Symptoms

Dependent on when the tumor develops.Dependent on when the tumor develops. If before closure of epiphyses: GigantismIf before closure of epiphyses: Gigantism After epiphyseal closure: Acromegaly. After epiphyseal closure: Acromegaly.

Characterized by enlargement of the hands, Characterized by enlargement of the hands, jaw, feet; coarse facial features; bones of jaw, feet; coarse facial features; bones of the skull enlarge; deep voice.the skull enlarge; deep voice.

Pituitary Gigantism/AcromegalyPituitary Gigantism/Acromegaly

Images.google.com

AcromegalyAcromegaly

Images.google.com

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

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Signs and SymptomsSigns and Symptoms

Associated findings: Associated findings: Hypertension, Hypertension, cardiomegaly cardiomegaly (dilated cardiomyopathy)(dilated cardiomyopathy), , insulin resistance/diabetes, insulin resistance/diabetes, DJDDJD. If . If untreated, progressive cardiovascular untreated, progressive cardiovascular morbidity and premature death.morbidity and premature death.

HypogonadismHypogonadism reflects co-secretion of reflects co-secretion of prolactin (see below) or pituitary prolactin (see below) or pituitary compression with decreased LH/FSH.compression with decreased LH/FSH.

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Lab and Diagnostic FindingsLab and Diagnostic Findings

Bloodwork (Following an overnight fast): serum Bloodwork (Following an overnight fast): serum IGF-I (IGF-I (5x nl with Acromegaly), prolactin, 5x nl with Acromegaly), prolactin, glucose; all may be elevated. TSH/Thyroxin if glucose; all may be elevated. TSH/Thyroxin if low, suggests additional pituitary pathology. low, suggests additional pituitary pathology.

Glucose challenge post fast- Elevated GH levels Glucose challenge post fast- Elevated GH levels help confirm the diagnosis (should normally be < help confirm the diagnosis (should normally be < 1ng/mL).1ng/mL).

MRI- Usually identifies a pituitary adenoma.MRI- Usually identifies a pituitary adenoma.

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Pituitary TumorPituitary Tumor

Images.google.com

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Treatment of AcromegalyTreatment of Acromegaly

Transphenoidal microsurgeryTransphenoidal microsurgery, which may result , which may result in transient or permanent hypopituitarism.in transient or permanent hypopituitarism.

Octreotide-a somatostatin (somatotropin release-Octreotide-a somatostatin (somatotropin release-inhibiting factor) analog. Suppresses GH inhibiting factor) analog. Suppresses GH secretion; used in patients who continue to have secretion; used in patients who continue to have excessive GH release post-op; very expensive; excessive GH release post-op; very expensive; injectedinjectedshrinks some tumorsshrinks some tumors– Dopaminergic agents (cabergoline, oral) useful Dopaminergic agents (cabergoline, oral) useful

especially especially if tumor co-secretes prolactinif tumor co-secretes prolactin shrinks shrinks some tumors.some tumors.

– Pegvisomant- GH receptor antagonist, new.Pegvisomant- GH receptor antagonist, new.

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HyperprolactinemiaHyperprolactinemia

Prolactin induces lactation during Prolactin induces lactation during pregnancy (along with estrogen and pregnancy (along with estrogen and progesterone).progesterone).

Control of prolactin production is Control of prolactin production is inhibitoryinhibitory, mediated by dopamine., mediated by dopamine.

Etiologies: Etiologies: Pituitary microadenomaPituitary microadenoma (may (may also produce GH), drugs (SSRI’s, thiazides, also produce GH), drugs (SSRI’s, thiazides, Cimetidine, Tricyclics, OCP, others); Cimetidine, Tricyclics, OCP, others); hypothyroidism, renal failure and cirrhosis.hypothyroidism, renal failure and cirrhosis.

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Signs and SymptomsSigns and Symptoms

High prolactin levels suppress GnRHHigh prolactin levels suppress GnRHLH/FSH, LH/FSH, resulting in hypogonatropic hypogonadism.resulting in hypogonatropic hypogonadism.

Females: Pre-menopausal woman develop Females: Pre-menopausal woman develop galactorrhea, galactorrhea, oligo/amenorrhea and infertilityoligo/amenorrhea and infertility, , decreased libido, vaginal dryness. decreased libido, vaginal dryness.

Males: Decreased libido, erectile dysfunction, Males: Decreased libido, erectile dysfunction, gynecomastia, but no galactorrhea. gynecomastia, but no galactorrhea.

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Lab and Diagnostic FindingsLab and Diagnostic Findings

Baseline labs should include hCG, TSH, Baseline labs should include hCG, TSH, Free Thyroxine, Creatinine and BUN, Free Thyroxine, Creatinine and BUN, LFT’s and Prolactin levels.LFT’s and Prolactin levels.

In the absence of pregnancy and renal In the absence of pregnancy and renal failure, a Prolactin level >250ng/mL is failure, a Prolactin level >250ng/mL is highly suspicious/diagnostic of highly suspicious/diagnostic of Prolactinoma.Prolactinoma.

Imaging- MRIImaging- MRI

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TreatmentTreatment

DC offending drug if present.DC offending drug if present. Correct other possible etiologies.Correct other possible etiologies. Microprolactinomas grow very slowly and Microprolactinomas grow very slowly and

patients with mild symptoms can be patients with mild symptoms can be followed without intervention.followed without intervention.

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TreatmentTreatment

With symptoms of hypogonadism/infertility With symptoms of hypogonadism/infertility or larger tumors: or larger tumors: Dopamine agonistsDopamine agonists ((CabergolineCabergoline, Bromocriptine) can , Bromocriptine) can successfully treat symptoms, correct successfully treat symptoms, correct amenorrhea and galactorrhea, and shrink amenorrhea and galactorrhea, and shrink the tumor.the tumor.

Transphenoidal pituitary surgery Transphenoidal pituitary surgery reservedreserved for individuals with large macroadenomas for individuals with large macroadenomas that abut/compress the optic chiasm.that abut/compress the optic chiasm.