10.3 Pituitary Emergencies, Adrenal Excess & Critical Illness-Related Corticosteroid Insufficiency

Pituitary Apoplexy

Pituitary apoplexy is hemorrhage or infarction of the pituitary gland, almost always within an undiagnosed adenoma.

• Triggers: anticoagulation, cardiac surgery with bypass, major hemodynamic swings, dynamic pituitary testing, dopamine agonists, pregnancy, and head trauma. Many cases are spontaneous.
• Presentation:
  • Sudden severe headache (often retro-orbital or thunderclap).
  • Visual loss or bitemporal hemianopsia from chiasmal compression.
  • Ophthalmoplegia from cavernous sinus involvement, most often cranial nerve III (ptosis, a dilated pupil, and diplopia).
  • Nausea and vomiting, meningismus, and altered consciousness.
  • Hypotension, hyponatremia, and hypoglycemia from acute corticotropin deficiency.
• Mimics: subarachnoid hemorrhage (CT may show only a sellar lesion, so look specifically at the sella), bacterial meningitis, and cavernous sinus thrombosis.
• Imaging: pituitary MRI is the test of choice; CT often misses the hemorrhage.
• Management:
  1. Give hydrocortisone immediately (100 mg IV, then 50 mg every 6 hours or an infusion) before any confirmatory testing. Draw a cortisol first only if it does not cause delay.
  2. Resuscitate with isotonic fluid and correct glucose and sodium.
  3. Obtain urgent neurosurgical and ophthalmologic evaluation. Transsphenoidal decompression is indicated for severe or progressive visual loss or reduced consciousness; stable patients without visual compromise are often managed conservatively.
  4. Replace other hormones later: thyroid hormone only after glucocorticoid replacement, because levothyroxine first can precipitate adrenal crisis.

Sheehan syndrome is postpartum pituitary infarction after obstetric hemorrhage. The acute form presents with hypotension, hypoglycemia, and hyponatremia; the chronic form presents with failure of lactation, amenorrhea, and fatigue. Unlike primary adrenal failure, potassium is normal or low because aldosterone, which is regulated by renin and potassium, is preserved, and hyperpigmentation is absent.

Central Diabetes Insipidus (Arginine Vasopressin Deficiency)

• ICU settings: transsphenoidal surgery, traumatic brain injury, subarachnoid hemorrhage, hypoxic injury, and progression to brain death, where loss of posterior pituitary function causes massive polyuria.
• Diagnosis: urine output above about 3 mL/kg/h with urine osmolality below about 300 mOsm/kg (specific gravity below 1.005) and a rising serum sodium and osmolality. Exclude osmotic diuresis from mannitol, hyperglycemia, contrast, and resolving acute kidney injury, and exclude excessive free water administration.
• Confirm the type: desmopressin concentrates the urine in central diabetes insipidus and has little effect in the nephrogenic form (lithium, hypercalcemia, hypokalemia, tubular disease).
• Management:
  • Desmopressin 1 to 2 micrograms IV or SC, repeated by response, or an infusion of arginine vasopressin in unstable patients and organ donors.
  • Replace the free water deficit and ongoing losses with hypotonic fluid (dextrose 5% or 0.45% saline), correcting chronic hypernatremia by no more than about 10 to 12 mEq/L in 24 hours.
  • Track hourly urine output, sodium every 2 to 4 hours during active treatment, and watch for the triphasic response after pituitary surgery: early diabetes insipidus, then a SIADH phase around days 5 to 10 (where continued desmopressin causes dangerous hyponatremia), then permanent diabetes insipidus.
• In the organ donor, desmopressin or vasopressin plus careful sodium control protects kidney and liver grafts.

Adrenal Excess in the ICU

Severe endogenous hypercortisolism, usually from ectopic ACTH (small cell lung cancer, bronchial or thymic carcinoid, medullary thyroid cancer) or adrenocortical carcinoma, is a critical care problem in its own right:

• Metabolic signature: hypokalemic metabolic alkalosis (cortisol saturates 11-beta-hydroxysteroid dehydrogenase type 2 and acts on mineralocorticoid receptors), severe hyperglycemia, hypertension, and proximal myopathy.
• Complications: opportunistic infection (Pneumocystis, invasive fungal disease), venous thromboembolism, psychosis, fractures, and poor wound healing.
• Clues to ectopic ACTH over Cushing disease: rapid onset with little typical body habitus change, marked hypokalemia, very high ACTH and cortisol, and hyperpigmentation.
• Management:
  • Block steroidogenesis: metyrapone, ketoconazole, osilodrostat, or etomidate by infusion in the ICU when oral therapy is not possible (etomidate inhibits 11-beta-hydroxylase at sub-hypnotic doses, with intensive monitoring).
  • Mifepristone blocks the receptor but cannot be monitored with cortisol levels.
  • Replace potassium and add spironolactone or eplerenone.
  • Give Pneumocystis prophylaxis and thromboprophylaxis.
  • Treat the tumor; bilateral adrenalectomy is a rescue for uncontrollable hypercortisolism.
  • Anticipate relative adrenal insufficiency after cortisol is suddenly normalized ("steroid withdrawal") and replace hydrocortisone.

Exogenous steroid excess matters too: patients on long-term glucocorticoids (prednisone above about 5 mg daily for more than 3 weeks) have suppressed adrenal axes and need stress dosing. Note that hydrocortisone and prednisolone cross-react with cortisol immunoassays, whereas dexamethasone does not, which is why dexamethasone is used when testing is planned.

Critical Illness-Related Corticosteroid Insufficiency (CIRCI)

CIRCI is inadequate glucocorticoid activity for the severity of illness, caused by impaired cortisol production, reduced cortisol metabolism, tissue resistance, and low cortisol-binding proteins. It is suspected in:

• Vasopressor-dependent shock.
• Persistent hypoglycemia, hyponatremia, or eosinophilia.
• Unexplained fever and ongoing inflammation.

Testing limitations: total cortisol is misleading when albumin is low, because most cortisol is protein-bound; a delta cortisol after 250 micrograms of cosyntropin below 9 micrograms/dL and a random cortisol below 10 micrograms/dL were proposed criteria, but neither reliably predicts who benefits from steroids. Consensus guidelines and the Surviving Sepsis Campaign therefore treat clinically, without routine ACTH stimulation testing.

Where steroids have evidence in critical illness:

• Septic shock: hydrocortisone 200 mg/day (50 mg every 6 hours or an infusion), suggested by the 2026 Surviving Sepsis Campaign. APROCCHSS added fludrocortisone and showed a mortality benefit; ADRENAL showed faster shock reversal without a mortality difference.
• Severe community-acquired pneumonia without shock or influenza: hydrocortisone reduced mortality in CAPE COD.
• Moderate-to-severe ARDS: dexamethasone reduced ventilator days and mortality in the DEXA-ARDS trial; corticosteroids are suggested with caution.
• COVID-19 requiring oxygen: dexamethasone 6 mg daily (RECOVERY).
• Acute adrenal crisis: hydrocortisone 100 mg IV then 200 mg/day, with isotonic fluid and dextrose.

Do not give steroids reflexively for undifferentiated hypotension without a plausible indication: hyperglycemia, ICU-acquired weakness, delirium, and immune suppression are real costs.