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Pathophysiology
Clinical meaning
Panhypopituitarism is deficiency of all anterior pituitary hormones (ACTH, TSH, LH/FSH, GH, prolactin) ± posterior pituitary (ADH — central diabetes insipidus). The anterior pituitary has a characteristic vulnerability pattern based on cell location and vascular supply: gonadotrophs (LH/FSH) are most vulnerable and lost first, followed by somatotrophs (GH), thyrotrophs (TSH), and corticotrophs (ACTH) — thus the mnemonic 'Go Look For The Adenoma' reflects the order of hormone loss. Causes include pituitary tumors (most common — non-functioning adenoma), surgical resection, radiation therapy, Sheehan syndrome (postpartum pituitary necrosis from hemorrhagic shock), pituitary apoplexy (hemorrhage into adenoma), autoimmune hypophysitis (including checkpoint inhibitor-induced), infiltrative disease (sarcoidosis, hemochromatosis, histiocytosis), and traumatic brain injury (TBI — 12-15% develop hypopituitarism). The clinical presentation depends on the number and severity of hormone deficits: ACTH deficiency is the most acutely dangerous (adrenal crisis), TSH deficiency causes secondary hypothyroidism, and gonadotropin deficiency causes hypogonadism.
Diagnostics & workup:
- Complete pituitary panel: morning cortisol (8 AM), ACTH, TSH, free T4, LH, FSH, testosterone (males) or estradiol (females), IGF-1, prolactin
- ACTH stimulation test: if morning cortisol 3-15 mcg/dL (indeterminate); peak cortisol < 18 = adrenal insufficiency
- TFTs: secondary hypothyroidism — low free T4 with low/inappropriately normal TSH (TSH is unreliable for monitoring secondary hypothyroidism — must follow free T4)
- IGF-1: screening for GH deficiency; if low, confirm with insulin tolerance test (ITT — gold standard) or glucagon stimulation test
- Serum sodium and osmolality: central DI causes hypernatremia, dilute urine (urine osmolality < 300), polyuria (> 3 L/day); water deprivation test with DDAVP if diagnosis uncertain
- Pituitary MRI with gadolinium: identify sellar/suprasellar mass, empty sella, stalk thickening (infiltrative disease), hemorrhage (apoplexy)
- Visual field testing: for any sellar mass approaching optic chiasm
- Baseline DEXA: GH and sex hormone deficiency both cause osteoporosis
Risk factors:
- Pituitary adenoma (most common cause — non-functioning macroadenoma causing mass effect on normal pituitary tissue)
- Pituitary surgery (transsphenoidal) — variable rates of new hormone deficits depending on tumor size and surgical extent
- Cranial radiation (dose-dependent — GH most sensitive, ACTH most resistant; effects may develop years after radiation)
- Sheehan syndrome (postpartum hemorrhage with hypotension — pituitary gland enlarges during pregnancy and is vulnerable to ischemia)
- Pituitary apoplexy (hemorrhage into pituitary adenoma — sudden headache, visual loss, hormonal crisis)
- Immune checkpoint inhibitors (ipilimumab, nivolumab, pembrolizumab — hypophysitis in 5-17%)
- Traumatic brain injury (hypopituitarism in 12-15% — screening recommended at 3 and 12 months post-TBI)
- Infiltrative diseases: sarcoidosis (neurosarcoidosis), hemochromatosis (iron deposition in gonadotrophs), Langerhans cell histiocytosis
Management
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Prescribing & monitoring
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Takeaways
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