Pituitary Disorders

Pituitary DisordersJo Choudhry, M.D. PGY-1The Pituitary GlandLocated at the base of the skullAnterior and Posterior lobesPortal connection from the hypothalamus

Anterior Lobe Posterior LobeGrowth hormone (GH)Gondadotrophs (LH/FSH)TSHProlactinCorticotropin (ACTH)OxytocinVasopressinNormal Changes in PregnancyAnterior lobe size doubles-triples due to lactotrophs.Placental estrogens stimulate lactotroph proliferationDecreased response to GnRH, dec. LH/FSHDecrease pituitary GH, inc. placental GHIncrease CRH (prob. Placental origin) during 2 & 3 trimesters2-4 X increase in ACTH, despite inc. in bound and free cortisol.

HyperprolactinemiaCauses: 1. disruption of dopamine (tumor, trauma, infiltrative lesions)2. hypothyroid (increases TRH)3. estrogen increase (pregnancy)4. chest wall burns nueronal effect like suckling5. chronic renal failure, returns to nml after transplant6. drugs (verapamil, H2 blockers, estrogens, opiates, dopamine receptor antagonists, reserpine, a-methyldopa)

ProlactinomasMost common functional pituitary tumor10% are lactotroph and somatotroph such as GH producingPresents with amenorrhea and infertilityProlactinomas lose TRH responseMicroadenomas 10mm

Treatment Pregnancy Not DesiredTreat only if symptomatic (HA, vision changes)Dopamine agonist (Bromocriptine) 1.25mg qhs 1 wk, then BIDIf intolerant with nausea, may give vaginallyNot recommended for breastfeedingTransspenoidal 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 palsiesTreatment Pregnancy DesiredIf macro, shrink size b/f preg with bromocriptine (36% will develop neurologic symptoms)If causing major visual defect and unresponsive, consider transspenoidal surgery b/f preg. Bromocriptine until preg occurs, then stop.

During PregnancyVisual field check q2-3 mos. and MRI prnIf neurologic symptoms occur during preg, usually about 14wga, restart treatment.Class BIf severe and unresponsive:2nd trimester: consider surgeryPTL risk3rd trimester: wait until PP

Acromegaly98% GH pituitary adenoma1/3 of all functional pituitary adenomasStimulates growth of skin, connective tissue, cartilage, bone, and visceraNitrogen retention, insulin antagonism, and lipogenesis

Risks of Long Term Excess GHArthropathyNeuropathyCardiomyopathyRespiratory obstruction Diabetes MellitusHypertension: exaterbates cardiomyopathyNOT Reversibleincreased risk of tumors:leiomyomatacolon polypsReduced overall survival by an average of 10 yearsDiagnosis

Somatomedian-C levels and IGF-1 levelsIf pregnant: special assay to distinguish placental GH70% pitutary GH responds to TRH, placental variant does not.TreatmentGoal: lower the serum insulin-like growth factor to normal for age/genderSurgically accessible micro- or Macroadenomas:Transspenoidal surgery2nd Line therapy: Somatostatin analogs or Dopamine agonists3rd Line therapy: Somatostatin receptor antagonistLast resort: Radiation

Pregnancy and AcromegalyD/C tx with confirmation GH Maternal to Fetal transfer negligible, except for glu intolerance.If severe neurologic sympts, try BromocriptineMay not dec. GH, shrink lactotrophsSomatostatin analogs have been used in 3 pts with no ill effects to fetus, despite transplacental passage.

Cushings DiseaseHigh ACTH leads to excess glucocorticoidIncidence may be 5-25 per millionWomen are 3-8X more likely than men

Cushings diseaseCentripetal obesityMoon face; buffalo humpSkin atrophyEasily bruisedStriaeCutaneous fungal infectionsHyperpigmentationOligo or amenorrheaHirsutism and Virilization with adrenal tumors

Cushings DiseaseProximal muscle wasting & weaknessOsteoporosisGlucose intoleranceHTN, hypokalemiaThromboembolismDepression, PsycInfectionGlaucoma

Complications if PregnantRare due to decreased fertility

Premature birthSAB, StillbirthsIUGRNeonatal adrenal insufficiencyMaternal: HTN, DM, CHF, Death

DiagnosisCushings Syndrome:24 hr urine cortisol excretionIf not 3x nml, measure pm salivary cortisol

Cushings Disease vs. Syndrome:HIGH dose Dexamethasone suppression test (8mg overnight)Successful if Pituitary originTreatmentTranssphenoidal surgeryPituitary irradiationAdrenalectomy (Surgical, Mitotane)Nelsons Syndrome: expanding intrasellar tumor and hyperpigmentationPregnancy: 1st Trimester: Surgery2nd Trimester: Adrenal Enzyme Inhibitors vs. surgery3rd Trimester: Early delivery, enzyme inhibitors until lung maturity

Thyrotropin-secreting Adenoma