Panhypopituitarism (Hypopituitarism)

Etiology and pathophysiology: 1) Pituitary tumors and treatment effects - macroadenomas (>1 cm) compress normal pituitary; surgery and radiation cause additional damage; gradual hormone loss often follows GH > LH/FSH > TSH > ACTH order; 2) Sheehan syndrome - postpartum hemorrhage causes pituitary necrosis; classic presentation with failure to lactate, amenorrhea, secondary adrenal insufficiency; rare in developed countries; 3) Pituitary apoplexy - acute hemorrhage/infarction of pituitary, often into preexisting adenoma; severe headache, ophthalmoplegia, visual loss, acute hormone deficiency requiring emergency stress-dose steroids; 4) Traumatic brain injury - 25-50% of moderate-severe TBI develop hypopituitarism, often missed; screen at 3-6 months and 12 months post-injury; 5) Cranial irradiation - dose-dependent damage; GH most sensitive, then gonadotropins, ACTH, TSH; lifelong follow-up needed; 6) Infiltrative - sarcoidosis (often with DI), hemochromatosis (with bronze diabetes, cardiomyopathy), lymphocytic hypophysitis (autoimmune, postpartum or IgG4-related), tuberculosis; 7) Congenital - combined pituitary hormone deficiency due to transcription factor mutations (PROP1, POU1F1, LHX3, HESX1).

Clinical manifestations by deficiency: 1) ACTH deficiency (secondary adrenal insufficiency) - fatigue, weakness, weight loss, hypotension, hypoglycemia, hyponatremia (no hyperkalemia unlike primary), pale skin (no hyperpigmentation); life-threatening if unrecognized in stress; 2) TSH deficiency (central hypothyroidism) - fatigue, cold intolerance, weight gain, constipation; low TSH and low free T4 (TSH not elevated as in primary); 3) Gonadotropin deficiency - women: oligomenorrhea/amenorrhea, infertility, hot flashes; men: decreased libido, erectile dysfunction, decreased muscle mass, loss of body hair, infertility; 4) GH deficiency - in adults: decreased lean body mass, central obesity, decreased exercise capacity, dyslipidemia, decreased quality of life, increased cardiovascular risk; in children: growth failure; 5) Prolactin deficiency - inability to lactate (Sheehan); 6) Posterior pituitary - central diabetes insipidus with polyuria, polydipsia (rare with isolated anterior involvement; common with infiltrative disease and trauma).

Diagnosis and management: 1) Hormone testing - 8 AM cortisol (<3 μg/dL diagnostic, >18 excludes; intermediate needs ACTH stimulation), free T4 with TSH (low both = central hypothyroidism), morning testosterone (men) or estradiol with FSH/LH (women), IGF-1 for GH axis, prolactin (high suggests stalk effect, low suggests deficiency); 2) Stimulation tests - insulin tolerance test (gold standard for GH and ACTH but high risk), glucagon stimulation, ACTH stimulation test (after 4-6 weeks of chronic deficiency), GHRH-arginine for GH; 3) MRI pituitary with contrast - identify tumor, empty sella, infiltrative changes; 4) Treatment - hydrocortisone 15-25 mg/day in 2-3 divided doses, double or triple during illness/stress, IV stress doses for surgery/severe illness; levothyroxine 1.5-1.7 mcg/kg/day after cortisol replacement (treating hypothyroidism first can precipitate adrenal crisis); testosterone replacement for men, estrogen-progestin for premenopausal women; GH replacement for confirmed deficiency in symptomatic adults (titrated to IGF-1 mid-normal range); desmopressin for DI; 5) Patient education - medical alert bracelet, emergency injection kit, sick day rules, stress dosing during illness; lifelong endocrine follow-up.