Pituitary Pituitary DisordersDisorders

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

The Pituitary GlandThe Pituitary Gland

Located at Located at the base of the base of the skullthe skull

Anterior and Anterior and Posterior Posterior lobeslobes

Portal Portal connection connection from the from the hypothalamuhypothalamuss

Anterior Lobe Posterior Anterior Lobe Posterior LobeLobe

Growth hormone Growth hormone (GH)(GH)

Gondadotrophs Gondadotrophs (LH/FSH)(LH/FSH)

TSHTSH ProlactinProlactin Corticotropin Corticotropin

(ACTH)(ACTH)

OxytocinOxytocin VasopressinVasopressin

Normal Changes in Normal Changes in PregnancyPregnancy

Anterior lobe size doubles-triples due to Anterior lobe size doubles-triples due to lactotrophs.lactotrophs.

Placental estrogens stimulate lactotroph Placental estrogens stimulate lactotroph proliferationproliferation

Decreased response to GnRH, dec. LH/FSHDecreased response to GnRH, dec. LH/FSH Decrease pituitary GH, inc. placental GHDecrease pituitary GH, inc. placental GH Increase CRH (prob. Placental origin) Increase CRH (prob. Placental origin)

during 2 & 3 trimestersduring 2 & 3 trimesters 2-4 X increase in ACTH, despite inc. in 2-4 X increase in ACTH, despite inc. in

bound and free cortisol.bound and free cortisol.

HyperprolactinemiaHyperprolactinemia

CausesCauses: : 1. disruption of dopamine (tumor, trauma, 1. disruption of dopamine (tumor, trauma,

infiltrative lesions)infiltrative lesions) 2. hypothyroid (increases TRH)2. hypothyroid (increases TRH) 3. estrogen increase (pregnancy)3. estrogen increase (pregnancy) 4. chest wall burns – nueronal effect like 4. chest wall burns – nueronal effect like

sucklingsuckling 5. chronic renal failure, returns to nml after 5. chronic renal failure, returns to nml after

transplanttransplant 6. drugs (verapamil, H2 blockers, estrogens, 6. drugs (verapamil, H2 blockers, estrogens,

opiates, dopamine receptor antagonists, opiates, dopamine receptor antagonists, reserpine, a-methyldopa)reserpine, a-methyldopa)

ProlactinomasProlactinomas

Most common functional pituitary tumorMost common functional pituitary tumor 10% are lactotroph and somatotroph 10% are lactotroph and somatotroph

such as GH producingsuch as GH producing Presents with amenorrhea and infertilityPresents with amenorrhea and infertility Prolactinomas lose TRH responseProlactinomas lose TRH response Microadenomas <10mm on MRIMicroadenomas <10mm on MRI Macroadenomas >10mmMacroadenomas >10mm

Treatment Pregnancy Not Treatment Pregnancy Not DesiredDesired

Treat only if symptomatic Treat only if symptomatic (HA, vision changes)(HA, vision changes)

Dopamine agonist (Bromocriptine) Dopamine agonist (Bromocriptine) 1.25mg qhs 1 wk, then BID1.25mg qhs 1 wk, then BID If intolerant with nausea, may give vaginallyIf intolerant with nausea, may give vaginally Not recommended for breastfeedingNot recommended for breastfeeding

Transspenoidal surgery if unsuccessfulTransspenoidal surgery if unsuccessful

Risks of surgery:

*4.6% post-op neurologiccomplication: 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

Treatment Pregnancy DesiredTreatment Pregnancy Desired

If macroIf macro, shrink size b/f preg with , shrink size b/f preg with bromocriptine (36% will develop bromocriptine (36% will develop neurologic symptoms)neurologic symptoms)

If causing major visual defect and If causing major visual defect and unresponsive, consider unresponsive, consider transspenoidal surgery b/f preg. transspenoidal surgery b/f preg.

Bromocriptine until Bromocriptine until preg occurs, then stop.preg occurs, then stop.

During PregnancyDuring Pregnancy Visual field check q2-3 mos. Visual field check q2-3 mos.

and MRI prnand MRI prn If neurologic symptoms occur If neurologic symptoms occur

during preg, usually about during preg, usually about 14wga, restart treatment.14wga, restart treatment. Class BClass B

If severe and unresponsive:If severe and unresponsive: 22ndnd trimester: consider surgery trimester: consider surgery

PTL riskPTL risk 33rdrd trimester: wait until PP trimester: wait until PP

AcromegalyAcromegaly

98% GH pituitary adenoma98% GH pituitary adenoma 1/3 of all functional 1/3 of all functional

pituitary adenomaspituitary adenomas Stimulates growth of skin, Stimulates growth of skin,

connective tissue, connective tissue, cartilage, bone, and visceracartilage, bone, and viscera

Nitrogen retention, insulin Nitrogen retention, insulin antagonism, and antagonism, and lipogenesislipogenesis

Risks of Long Term Excess Risks of Long Term Excess GHGH

ArthropathyArthropathy NeuropathyNeuropathy CardiomyopathyCardiomyopathy Respiratory Respiratory

obstruction obstruction Diabetes MellitusDiabetes Mellitus

Hypertension: Hypertension: exaterbates exaterbates cardiomyopathycardiomyopathy NOT ReversibleNOT Reversible

increased risk of increased risk of tumors:tumors: leiomyomataleiomyomata colon polypscolon polyps

Reduced overall survival by an average of 10 years

DiagnosisDiagnosis

•Somatomedian-C levels and IGF-1 levelsSomatomedian-C levels and IGF-1 levels•If pregnant: special assay to distinguish If pregnant: special assay to distinguish placental GHplacental GH•70% pitutary GH responds to TRH, placental 70% pitutary GH responds to TRH, placental variant variant does not.does not.

TreatmentTreatment Goal: lower the serum insulin-like growth Goal: lower the serum insulin-like growth

factor to normal for age/genderfactor to normal for age/gender Surgically accessible micro- or Surgically accessible micro- or

Macroadenomas:Macroadenomas: Transspenoidal surgeryTransspenoidal surgery

22ndnd Line therapy: Somatostatin analogs or Line therapy: Somatostatin analogs or Dopamine agonistsDopamine agonists

33rdrd Line therapy: Somatostatin receptor Line therapy: Somatostatin receptor antagonistantagonist

Last resort: Radiation Last resort: Radiation

Pregnancy and AcromegalyPregnancy and Acromegaly

D/C tx with confirmation D/C tx with confirmation GH Maternal to Fetal transfer negligible, GH Maternal to Fetal transfer negligible,

except for glu intolerance.except for glu intolerance. If severe neurologic sympts, try If severe neurologic sympts, try

BromocriptineBromocriptine May not dec. GH, shrink lactotrophsMay not dec. GH, shrink lactotrophs

Somatostatin analogs have been used in 3 Somatostatin analogs have been used in 3 pts with no ill effects to fetus, despite pts with no ill effects to fetus, despite transplacental passage.transplacental passage.

Cushing’s DiseaseCushing’s Disease

High ACTH leads to High ACTH leads to excess excess glucocorticoidglucocorticoid

Incidence may be Incidence may be 5-25 per million5-25 per million

Women are 3-8X Women are 3-8X more likely than more likely than menmen

Cushing’s diseaseCushing’s disease Centripetal obesityCentripetal obesity Moon face; buffalo humpMoon face; buffalo hump Skin atrophySkin atrophy Easily bruisedEasily bruised StriaeStriae Cutaneous fungal infectionsCutaneous fungal infections HyperpigmentationHyperpigmentation Oligo or amenorrheaOligo or amenorrhea Hirsutism and Virilization Hirsutism and Virilization

with adrenal tumorswith adrenal tumors

Cushing’s DiseaseCushing’s Disease

Proximal muscle Proximal muscle wasting & weaknesswasting & weakness

OsteoporosisOsteoporosis Glucose intoleranceGlucose intolerance HTN, hypokalemiaHTN, hypokalemia ThromboembolismThromboembolism Depression, PsycDepression, Psyc InfectionInfection GlaucomaGlaucoma

Complications if PregnantComplications if Pregnant

Rare due to decreased fertilityRare due to decreased fertility

Premature birthPremature birth SAB, StillbirthsSAB, Stillbirths IUGRIUGR Neonatal adrenal insufficiencyNeonatal adrenal insufficiency Maternal: HTN, DM, CHF, DeathMaternal: HTN, DM, CHF, Death

DiagnosisDiagnosis

Cushing’s SyndromeCushing’s Syndrome:: 24 hr urine cortisol excretion24 hr urine cortisol excretion If not 3x nml, measure pm salivary If not 3x nml, measure pm salivary

cortisolcortisol

Cushing’s Disease vs. SyndromeCushing’s Disease vs. Syndrome:: HIGH dose Dexamethasone suppression HIGH dose Dexamethasone suppression

test (8mg overnight)test (8mg overnight) Successful if Pituitary originSuccessful if Pituitary origin

TreatmentTreatment Transsphenoidal surgeryTranssphenoidal surgery Pituitary irradiationPituitary irradiation Adrenalectomy (Surgical, Mitotane)Adrenalectomy (Surgical, Mitotane)

Nelson’s SyndromeNelson’s Syndrome: expanding intrasellar : expanding intrasellar tumor and hyperpigmentationtumor and hyperpigmentation

Pregnancy: Pregnancy: 11stst Trimester: Surgery Trimester: Surgery 22ndnd Trimester: Adrenal Enzyme Inhibitors vs. Trimester: Adrenal Enzyme Inhibitors vs.

surgerysurgery 33rdrd Trimester: Early delivery, enzyme inhibitors Trimester: Early delivery, enzyme inhibitors

until lung maturityuntil lung maturity

Thyrotropin-secreting Thyrotropin-secreting AdenomaAdenoma

<1% of all hyperthyroidism cases<1% of all hyperthyroidism cases 25% of adenomas secrete other hormones25% of adenomas secrete other hormones Goiter, visual defects, menstral irreg, Goiter, visual defects, menstral irreg,

galatorrheagalatorrhea

Lab:Lab:Normal or High TSHNormal or High TSHHigh total and free T4 and High T3High total and free T4 and High T3

MRI MRI

TreatmentTreatment Transsphenoidal surgeryTranssphenoidal surgery

1/3 Cure1/3 Cure 1/3 improvement1/3 improvement 1/3 no change1/3 no change

Dopamine AgonistDopamine Agonist Somatostatin Analogue (Octreotide)Somatostatin Analogue (Octreotide)

Works so well, may give before surgeryWorks so well, may give before surgery Nausea, diarrhea, bloating, glu intolerance, Nausea, diarrhea, bloating, glu intolerance,

cholelithiasischolelithiasis Do NOT use antithyroid therapyDo NOT use antithyroid therapy

Gonadotroph adenomaGonadotroph adenoma Usually considered non-functioningUsually considered non-functioning

Secrete inefficiently, variablySecrete inefficiently, variably Presents with nuerologic symptomsPresents with nuerologic symptoms Difficult to DiagnoseDifficult to Diagnose

Rule out other adenomasRule out other adenomas Prepubertal girls= breast devel, vag. Prepubertal girls= breast devel, vag.

BleedingBleeding Premenopausal= amenorrhea, oligoPremenopausal= amenorrhea, oligo

Gonadotroph adenoma vs. Gonadotroph adenoma vs. menopause and ovarian failuremenopause and ovarian failure

High FSH with low LHHigh FSH with low LH High serum free alpha subunitHigh serum free alpha subunit High estridiol, FSH, thickened High estridiol, FSH, thickened

endometrium and polycystic ovariesendometrium and polycystic ovaries

Treatment of non-functioning Treatment of non-functioning and gonadotrophin and gonadotrophin macroadenomasmacroadenomas

Transsphenoidal surgeryTranssphenoidal surgery +/- Radiation+/- Radiation

HypopituitarismHypopituitarism 76% tumor or treatment of tumor76% tumor or treatment of tumor

Mass effect of adenoma on other hormonesMass effect of adenoma on other hormones Surgical resection of non-adenomatous Surgical resection of non-adenomatous

tissuetissue Radiation of pituitaryRadiation of pituitary

Check hormones 6 mos after and then yearlyCheck hormones 6 mos after and then yearly 13% extrapituitary tumor13% extrapituitary tumor

CraniopharyngiomaCraniopharyngioma 8% unknown8% unknown 1% sarcoidosis1% sarcoidosis 0.5% Sheehan’s syndrome0.5% Sheehan’s syndrome

Infiltrative LesionsInfiltrative Lesions

Hereditary HemochromatosisHereditary Hemochromatosis Fe deposition in pituitaryFe deposition in pituitary Gonadotropin deficiency most commonGonadotropin deficiency most common Tx repeat phlebotomyTx repeat phlebotomy

Pituitary ApoplexyPituitary Apoplexy Sudden hemorrhage into pituitary Sudden hemorrhage into pituitary Severe, sudden HA; diplopia; hypopituitarismSevere, sudden HA; diplopia; hypopituitarism Sudden ACTH def. is life-threatening hypotensionSudden ACTH def. is life-threatening hypotension Tx: surgical decompressionTx: surgical decompression

Sheehan SyndromeSheehan Syndrome

Infarction of Pituitary after substantial Infarction of Pituitary after substantial blood loss during childbirthblood loss during childbirth

Incidence: 3.6%Incidence: 3.6% No correlation between severity of No correlation between severity of

hemorrage and symptomshemorrage and symptoms Severe: recognized days to weeks PPSevere: recognized days to weeks PP

Lethargy, anorexia, weight loss, unable to Lethargy, anorexia, weight loss, unable to BFBF

Sheehan’s SyndromeSheehan’s Syndrome Typically long interval between Typically long interval between

obstetric event and diagnosisobstetric event and diagnosis Of 25 cases studied:Of 25 cases studied:

50% permanent amenorrhea50% permanent amenorrhea The rest had scanty-rare mensesThe rest had scanty-rare menses Most lactation was poor to absentMost lactation was poor to absent

Dx: MRI empty sella turcicaDx: MRI empty sella turcica

Sheehan’s and PregnancySheehan’s and Pregnancy

TX with hormonesTX with hormones 87% live births87% live births 13% SAB13% SAB 0 Stillbirths0 Stillbirths 0 Maternal deaths0 Maternal deaths

Don’t TXDon’t TX 58% live births58% live births 42% SAB42% SAB 1 Stillbirth1 Stillbirth 3 Maternal deaths3 Maternal deaths

Labor: HYDRATION!!

IV Cortisol: adjusted for pt’s state 25-75mg q6 hr

Lymphocytic HypophysitisLymphocytic Hypophysitis

22 y/o female died of circulatory 22 y/o female died of circulatory collapse 8 hours after appy. She was collapse 8 hours after appy. She was 14 mos. PP and had developed 214 mos. PP and had developed 2ndnd amenorrhea.amenorrhea.Autopsy: lymphocytic infiltration of Autopsy: lymphocytic infiltration of pituitary and thyroidpituitary and thyroid

Symptoms: HA, lethargy, weight loss, Symptoms: HA, lethargy, weight loss, hyperprolactinemiahyperprolactinemia

Lymphocytic HypophysisLymphocytic Hypophysis

Scheithauer et al, ’90Scheithauer et al, ’90 69 women that died during preg or PP69 women that died during preg or PP 5 had the disease, 4/5 died at 38-41 wga5 had the disease, 4/5 died at 38-41 wga

Consider especially if no hemorrhageConsider especially if no hemorrhage

TX: HRT (thyroid, cortisol)TX: HRT (thyroid, cortisol)

Pituitary NecrosisPituitary Necrosis

Pregnant Diabetic Patients Pregnant Diabetic Patients Due to vascular changesDue to vascular changes

DX: severe, midline HA and vomitting DX: severe, midline HA and vomitting in 3in 3rdrd trimester followed by decrease trimester followed by decrease of insulin requirementsof insulin requirements

3/8 cases reported: assoc. with fetal 3/8 cases reported: assoc. with fetal and then maternal deathand then maternal death

Central Diabetes InsipidusCentral Diabetes Insipidus Polydipsia and Polyuria (2-15 Polydipsia and Polyuria (2-15

Liters/day)Liters/day) Abrupt onsetAbrupt onset 30-50% are idiopathic30-50% are idiopathic

Dec. production by Dec. production by hypothalamushypothalamus

Surgery or TraumaSurgery or Trauma Rare with Sheehan’sRare with Sheehan’s

Mild, undetectable degreeMild, undetectable degree

Hypothalamus

Pituitary

Kidney

Dx of Central DIDx of Central DI Water Deprivation test:Water Deprivation test:

Restrict p.o. fluids or administer Restrict p.o. fluids or administer hypertonic saline to increase serum hypertonic saline to increase serum osmolality to 295-300 mosmol/kg (nml: osmolality to 295-300 mosmol/kg (nml: 275-290)275-290)

Central DI: urine osmolality still low and Central DI: urine osmolality still low and returns to normal after administer returns to normal after administer vasopressinvasopressin

Nephrogenic DI: exogenous vasopressin Nephrogenic DI: exogenous vasopressin does not alter urine osmolality muchdoes not alter urine osmolality much

Pregnancy and Central D.I.Pregnancy and Central D.I. Transient D.I. during pregnancy due to Transient D.I. during pregnancy due to

acquired or hereditary D.I.acquired or hereditary D.I. Latent: Unable to sustain during pregnancyLatent: Unable to sustain during pregnancy

Transient Arginine Vasopressin resistant, Transient Arginine Vasopressin resistant, but L-Deamino, 8-D-arginine vasopressin but L-Deamino, 8-D-arginine vasopressin (DDAVP=Desmopressin) responsive(DDAVP=Desmopressin) responsive High amounts of placental vasopressinaseHigh amounts of placental vasopressinase

D.I. antedates pregnancy. Most D.I. antedates pregnancy. Most deteriorate due to vasopressinasedeteriorate due to vasopressinase

Treatment of Treatment of Central D.I.Central D.I.

DDAVP (Desmopressin Acetate)DDAVP (Desmopressin Acetate) Synthetic analogSynthetic analog Not catabolized by Not catabolized by

vasopressinasevasopressinase No vasopressor actionNo vasopressor action Administered intranasally (rec.) or Administered intranasally (rec.) or

p.o.p.o. Titrate 10-20ug qd or bidTitrate 10-20ug qd or bid Safe in pregnancy and Safe in pregnancy and

breastfeedingbreastfeeding

ReferencesReferences Saunders; Maternal-Fetal Medicine 5Saunders; Maternal-Fetal Medicine 5thth Edition; Chapter 51 ppg. 1083-1094. Edition; Chapter 51 ppg. 1083-1094. Weiss, R; Refetoff, S; Weiss, R; Refetoff, S; Thyrotropin Secreting Pituitary AdenomasThyrotropin Secreting Pituitary Adenomas; Up To Date online Jan. 2005; ; Up To Date online Jan. 2005;

www.uptodate.com www.uptodate.com Synder,P.; Synder,P.; Clinical Manifestations and diagnosis of gonadotroph and other clinically nonfunctioning Clinical Manifestations and diagnosis of gonadotroph and other clinically nonfunctioning

adenomasadenomas; Up To Date online; Jan. 2005; www.uptodate.com ; Up To Date online; Jan. 2005; www.uptodate.com Barker,F; Klibanski,A; Swearingin,B; Barker,F; Klibanski,A; Swearingin,B; Transsphenoidal Surgery for Pituitary Tumors in the United Transsphenoidal Surgery for Pituitary Tumors in the United

States, 1996-2000: Mortality, Morbidity, and the Effects of Hospital and Surgeon Volume;States, 1996-2000: Mortality, Morbidity, and the Effects of Hospital and Surgeon Volume; Journal of Journal of Clinical Endocrinology and Metabolism Vol. 88, No. 10, ppg. 4709-4719.Clinical Endocrinology and Metabolism Vol. 88, No. 10, ppg. 4709-4719.

Nieman, L; Orth, D; Nieman, L; Orth, D; Clinical manifestations of Cushing’s Syndrome;Clinical manifestations of Cushing’s Syndrome; Up To Date online; Jan. 2005; Up To Date online; Jan. 2005; www.uptodate.com www.uptodate.com

Nieman, L; Orth, D; Nieman, L; Orth, D; Treatment of Cushing’s Syndrome: Diminishing adrenal cortisol synthesis.Treatment of Cushing’s Syndrome: Diminishing adrenal cortisol synthesis. Up To Up To Date online; Jan. 2005; www.uptodate.com Date online; Jan. 2005; www.uptodate.com

Synder, P; Abrahamson, M; Synder, P; Abrahamson, M; Management of lactotroph adenoma (prolactinoma) during pregnancy;Management of lactotroph adenoma (prolactinoma) during pregnancy; Up To Date online; Jan. 2005; www.uptodate.com Up To Date online; Jan. 2005; www.uptodate.com

Melmed, S; Melmed, S; Treatment of Acromegaly;Treatment of Acromegaly; Up To Date online; Jan. 2005; www.uptodate.com Up To Date online; Jan. 2005; www.uptodate.com Melmed, S; Melmed, S; Clinical manifestations of acromegaly; Clinical manifestations of acromegaly; Up To Date online; Jan. 2005; www.uptodate.com Up To Date online; Jan. 2005; www.uptodate.com Synder, P; Synder, P; Treatment of Hypopituitarism; Treatment of Hypopituitarism; Up To Date online; Jan. 2005; www.uptodate.com Up To Date online; Jan. 2005; www.uptodate.com Abrahamson, M; Synder, P; Abrahamson, M; Synder, P; Causes of hypopituitarism;Causes of hypopituitarism; Up To Date online; Jan. 2005; Up To Date online; Jan. 2005;

www.uptodate.com www.uptodate.com Garner, P. Garner, P. Pituitary Disorders of Pregnancy;Pituitary Disorders of Pregnancy; Endotext.com; Chapter 2A; March 2002. Endotext.com; Chapter 2A; March 2002. Rose, B.; Rose, B.; Causes of Central Diabetes Insipidous; Causes of Central Diabetes Insipidous; Up To Date online; Jan. 2005; www.uptodate.com Up To Date online; Jan. 2005; www.uptodate.com Rose, B.; Rose, B.; Treatment of Central Diabetes Insipidous;Treatment of Central Diabetes Insipidous; Up To Date online; Jan. 2005; Up To Date online; Jan. 2005;

www.uptodate.com www.uptodate.com Rose, B; Rose, B; Diagnosis of polyuria and Diabetes insipidus;Diagnosis of polyuria and Diabetes insipidus; Up To Date online; Jan. 2005; Up To Date online; Jan. 2005;

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