Hypopituitarism
Partial or complete failure of one or more anterior pituitary hormones — ACTH (→cortisol), TSH (→thyroid hormone), GH (→IGF-1), LH and FSH (→gonadal steroidogenesis and gametogenesis), and prolactin (often preserved or paradoxically elevated from stalk effect); panhypopituitarism = all axes deficient. Posterior pituitary involvement (AVP-D, oxytocin) commonly coexists when pathology is structural. Causes: pituitary adenoma with mass effect or post-resection iatrogenic; traumatic brain injury (underrecognized — ~25-50% TBI patients show pituitary dysfunction at 6-12 months); PITUITARY APOPLEXY (hemorrhage or infarction — neurosurgical emergency with acute adrenal crisis from sudden ACTH loss); SHEEHAN SYNDROME (postpartum pituitary necrosis from severe peripartum hemorrhage); craniopharyngioma and other suprasellar tumors; cranial radiation (latent — manifests years after treatment); infiltrative disease (sarcoidosis, hemochromatosis, Langerhans cell histiocytosis, IgG4-related and lymphocytic hypophysitis); autoimmune hypophysitis including immune checkpoint inhibitor-induced (ipilimumab, nivolumab, pembrolizumab); infections (TB, syphilis, fungal); genetic / congenital combined pituitary hormone deficiency syndromes (PROP1, POU1F1/PIT1, HESX1, LHX3, LHX4, Kallmann syndrome). **ADRENAL CRISIS IS THE LOAD-BEARING EMERGENCY** — patients with ACTH deficiency require stress-dose hydrocortisone for illness, surgery, trauma; emergency injection kit + medical alert non-negotiable. Diagnostics: morning cortisol + ACTH ± cosyntropin stim; free T4 + TSH (free T4 over TSH because TSH is unreliable in secondary hypothyroidism); IGF-1 + GH stimulation testing (insulin tolerance, GHRH-arginine, glucagon — gates somatropin replacement); LH + FSH + testosterone (men) or estradiol + cycle (women); prolactin; pituitary MRI + visual fields where mass effect in play. Management = hormone replacement BY DEFICIENT AXIS: hydrocortisone 15-25 mg/day divided with stress-dose protocols; levothyroxine titrated by free T4; recombinant human GH (somatropin) for confirmed adult GHD; sex hormones (testosterone or estradiol + progesterone); desmopressin if posterior involvement; gonadotropin therapy or pulsatile GnRH for fertility induction (SEPARATE protocol from replacement). Endocrine Society + ESE 2016 + AACE + Pituitary Network Association + Hormone Health Network patient resources. **Editorial**: GH-axis peptides (CJC-1295, tesamorelin, ipamorelin, sermorelin, MK-677) are MECHANISTICALLY WRONG-DIRECTION — they act on the PITUITARY which is the failed organ. Upstream stimulation cannot recruit somatotrophs that are damaged, absent, or non-responsive. SOMATROPIN is the established replacement. Same archetypal error as kisspeptin × Klinefelter (primary hypogonadism). Tier 2 elevation. Fifty-eighth deliberate non-elevation.
What changes during this transition
Hypopituitarism is partial or complete failure of one or more anterior pituitary hormones — ACTH (→ cortisol), TSH (→ thyroid hormone), GH (→ IGF-1), LH and FSH (→ gonadal steroidogenesis and gametogenesis), and prolactin (often preserved or paradoxically elevated from stalk effect); panhypopituitarism is all axes deficient, and posterior pituitary involvement (AVP-D, oxytocin) commonly coexists when the pathology is structural. Causes span pituitary adenoma with mass effect or post-resection iatrogenic loss; traumatic brain injury (underrecognized — roughly a quarter to half of TBI patients show pituitary dysfunction at 6–12 months); pituitary apoplexy (hemorrhage or infarction — a neurosurgical emergency with acute adrenal crisis from sudden ACTH loss); Sheehan syndrome (postpartum pituitary necrosis from severe peripartum hemorrhage — historically common, rarer in high-resource settings but still seen globally); craniopharyngioma and other suprasellar tumors; cranial radiation (latent — manifests years after treatment); infiltrative disease (sarcoidosis, hemochromatosis, Langerhans cell histiocytosis, IgG4-related and lymphocytic hypophysitis); autoimmune hypophysitis including immune checkpoint inhibitor-induced; infections (TB, syphilis, fungal); and genetic / congenital combined pituitary hormone deficiency syndromes (PROP1, POU1F1/PIT1, HESX1, LHX3, LHX4, Kallmann syndrome). Adrenal crisis is the load-bearing emergency — patients with ACTH deficiency require stress-dose hydrocortisone for illness, surgery, and trauma, plus an emergency injection kit and medical alert; missed diagnosis or under-treated adrenal insufficiency during physiologic stress can be fatal. Management is axis-by-axis hormone replacement following Endocrine Society, ESE 2016, and AACE clinical practice guidance: hydrocortisone (typically 15–25 mg/day divided, with stress-dose protocols); levothyroxine titrated by free T4, NOT TSH (TSH is unreliable in secondary hypothyroidism); recombinant human GH (somatropin) for adult GHD confirmed by formal stimulation testing (insulin tolerance, GHRH-arginine, or glucagon) — established benefits on body composition, bone density, cardiovascular risk markers, and quality of life, with ongoing controversies about routine use; testosterone or estradiol-plus-progesterone for the gonadal axis; desmopressin for AVP-D where posterior pituitary is also involved; and gonadotropin therapy or pulsatile GnRH for fertility induction when fertility is desired (a SEPARATE protocol from replacement, not interchangeable). The editorial substrate here is sharp: GH-axis peptides — CJC-1295, tesamorelin, ipamorelin, sermorelin, MK-677 — are mechanistically inappropriate as 'GH replacement' for hypopituitarism. They act on the PITUITARY, which is the failed organ. Upstream stimulation cannot recruit somatotrophs that are damaged, absent, or non-responsive; the established treatment when adult GHD is confirmed is somatropin (direct hormone replacement), gated by stimulation testing. Framing GHRH analogs as 'natural GH replacement' for this population is the same archetypal wrong-direction error as prescribing kisspeptin for primary hypogonadism — stimulating an axis above an organ that no longer responds. No peptide is being elevated as a discovery option here; this entry exists so users probing on /ask receive an honest, mechanism-anchored answer rather than a community extrapolation. Endocrinology, the Pituitary Network Association, and Hormone Health Network patient resources own the load-bearing scaffold around stress-dose protocols, replacement titration, fertility-vs-replacement distinctions, and emergency planning — not the peptide catalog. Fifty-eighth deliberate non-elevation.
Important caveat
Hypopituitarism is managed by endocrinology (often pituitary-specialized), with neurosurgery / neuro-oncology / neurology involvement depending on the underlying etiology. **ADRENAL CRISIS IS THE LOAD-BEARING EMERGENCY**: ACTH deficiency requires hydrocortisone replacement (15-25 mg/day divided) PLUS stress-dose protocols for illness / surgery / trauma (typically double or triple the daily dose; IV hydrocortisone 100 mg + 200 mg/24h for severe stress) PLUS an EMERGENCY INJECTION KIT (intramuscular hydrocortisone — Solu-Cortef Act-O-Vial or equivalent) PLUS a MEDICAL ALERT. Missed or under-treated adrenal insufficiency during physiologic stress can be fatal. **REPLACEMENT ORDERING MATTERS**: cortisol BEFORE thyroid — starting levothyroxine in an unrecognized adrenal-insufficient patient can precipitate adrenal crisis by accelerating cortisol clearance. **PITUITARY APOPLEXY**: sudden severe headache + visual changes + altered mental status in known or suspected pituitary tumor patient is a NEUROSURGICAL EMERGENCY with adrenal crisis from acute ACTH loss; immediate IV hydrocortisone + neurosurgical evaluation. **GH-AXIS PEPTIDES ARE TIER-2 MECHANISTICALLY WRONG-DIRECTION**: CJC-1295, tesamorelin, ipamorelin, sermorelin, MK-677 all stimulate anterior pituitary somatotrophs — in hypopituitarism the pituitary IS the failed organ, and upstream stimulation cannot recruit cells that are damaged, absent, or non-responsive. The established replacement for confirmed adult GHD is RECOMBINANT HUMAN GH (SOMATROPIN), gated by formal stimulation testing (ITT, GHRH-arginine, or glucagon depending on cardiac / seizure considerations). GHRH analogs cannot substitute. Framing them as 'natural GH replacement' is the same archetypal wrong-direction error as prescribing kisspeptin for primary hypogonadism. Tesamorelin FDA label additionally contraindicates pituitary tumor history. **STARTING GH CAN UNMASK SECONDARY ADRENAL INSUFFICIENCY**: adrenal axis must be assessed and replaced BEFORE GH replacement starts; this is a load-bearing safety sequencing rule. **SOMATROPIN MONITORING**: titrate to clinical response + IGF-1 in mid-age-and-sex-adjusted reference range; monitor for glucose intolerance, fluid retention, edema, and (in patients with prior pituitary or parasellar tumors) imaging surveillance. **GHD STIMULATION TESTING GATES SOMATROPIN**: IGF-1 alone is not sufficient for adult GHD diagnosis; ITT (insulin tolerance test) is gold standard but cardiac / seizure contraindications shift to GHRH-arginine or glucagon stim. **TBI HYPOPITUITARISM IS UNDERRECOGNIZED**: ~25-50% TBI patients show pituitary dysfunction at 6-12 months — anyone with persistent post-TBI fatigue, sexual dysfunction, or unexplained metabolic shifts warrants pituitary workup. **SHEEHAN SYNDROME**: postpartum pituitary necrosis from severe peripartum hemorrhage; failure to lactate + amenorrhea + persistent fatigue post-delivery is the classic presentation. **IMMUNE CHECKPOINT INHIBITOR HYPOPHYSITIS**: ipilimumab > nivolumab + pembrolizumab can cause autoimmune hypophysitis with permanent ACTH and other axis deficiencies — patients on ICI therapy with new-onset fatigue, hypotension, hyponatremia need urgent endocrine workup. **BPC-157 + NMN**: don't engage with pituitary failure mechanism; not part of any hypopituitarism algorithm. **DESMOPRESSIN** if posterior pituitary also involved (cross-reference AVP-D entry). **FERTILITY VS REPLACEMENT**: gonadal axis replacement (testosterone or estradiol + progesterone) is SEPARATE from fertility induction (gonadotropin therapy with LH/FSH replacement protocols, or pulsatile GnRH for ovulation / spermatogenesis induction). These are different regimens for different goals. Endocrine Society + ESE 2016 + AACE guidelines; Pituitary Network Association + Hormone Health Network patient resources. WADA athletes: peptide GH secretagogues prohibited at all times; somatropin replacement requires TUE; hydrocortisone replacement requires TUE. Pregnancy is high-risk; coordinate endocrinology + maternal-fetal medicine; stress-dose protocols continue through labor + delivery.
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