11.1 Pituitary Apoplexy, DI, and Panhypopituitarism (01.R.1–4)

A thunderclap headache in a patient with a known pituitary macroadenoma is not a migraine workup. The same is true of a postpartum patient who cannot lactate after a massive hemorrhage, or of a fresh transsphenoidal patient whose urine output is 400 mL per hour of water-colored urine. This section covers pituitary apoplexy, Sheehan syndrome, central diabetes insipidus (DI), and panhypopituitarism. Independent OpenExamPrep material here follows topics listed under endocrine and salt-water disorders in the ABPN Content Specifications (01.R.1–4). It is not an ABIM or ABPN product.

Why these items show up on this examination

The vignette is almost never "name the releasing hormone." It is a 54-year-old with a nonfunctioning macroadenoma who develops sudden headache, a drooping eyelid, and a systolic pressure of 82 mm Hg; a resident who starts levothyroxine before hydrocortisone; or a brain-dead donor whose sodium is 162 mEq/L while urine pours into the bag. Those items test recognition, the order of hormone replacement, and which analog of antidiuretic hormone to reach for.

Pituitary apoplexy: the clinical picture

Pituitary apoplexy is acute hemorrhage or ischemic infarction of the pituitary, most often inside a macroadenoma (commonly a previously silent nonfunctioning adenoma). The gland sits in the sella, the optic chiasm sits above it, and the cavernous sinuses sit on either side. Sudden expansion therefore produces three clusters of findings at once: meningeal irritation, chiasmal visual loss, and ocular motor nerve palsies.

Classic presentation:

• Sudden severe headache, often retro-orbital, with nausea and vomiting. The story overlaps subarachnoid hemorrhage. Blood can spill into the suprasellar cistern and the spinal fluid can be xanthochromic. If you only think "SAH," you will send the patient to angiography and miss the endocrine emergency.
• Visual-field loss, classically bitemporal hemianopsia from chiasmal compression, or a dense unilateral deficit if one optic nerve is flattened.
• Ophthalmoplegia. Cranial nerve III is the most common extraocular palsy because it sits medially in the cavernous sinus: ptosis, a dilated pupil, and a globe that sits down and out. CN IV and VI palsies occur. Facial pain or a V1 sensory change can accompany cavernous sinus involvement.
• Altered consciousness when the hematoma is large, hydrocephalus develops, or acute cortisol deficiency produces shock.
• Acute hypopituitarism, especially ACTH/cortisol deficiency. Hyponatremia, hypoglycemia, and refractory hypotension are cortisol failure until you have given steroid.

Precipitants worth naming: anticoagulation or thrombolysis, dopamine-agonist start or withdrawal, pituitary dynamic testing, pregnancy and the early puerperium, major surgery or hypotension, hypertension, and head trauma. Many patients have no identified trigger. A known adenoma is a gift; a first presentation of an occult macroadenoma is the trap.

Sheehan syndrome is ischemic, not a hemorrhagic adenoma story

Sheehan syndrome is ischemic necrosis of a pituitary that enlarged during pregnancy and then suffered hypotension from postpartum hemorrhage. The gland's portal blood supply does not tolerate that insult. Acute Sheehan physiology in the ICU is failure to lactate, persistent hyponatremia, hypoglycemia, and hypotension that looks like "just blood loss" until you give hydrocortisone. Later it is amenorrhea, fatigue, and secondary hypothyroidism. Visual and cranial-nerve findings are less dramatic than in hemorrhagic apoplexy of a macroadenoma, because there is no sudden extrasellar mass. Treat the acute endocrine failure the same way: steroid first.

Imaging and the SAH look-alike

MRI is the preferred study: T1/T2 sellar hematoma or infarction, extrasellar extension, and chiasmal compression. CT is what you will get first in a crashing patient and can show a hyperdense sellar mass, but it misses some infarctive apoplexy. If the story is thunderclap headache, you will also be ruling out aneurysmal SAH. That is appropriate. Do not let a negative vascular study stop you from looking at the sella and drawing a cortisol. Give steroid on clinical suspicion; do not wait for the 8 a.m. endocrine panel if the patient is hypotensive or has a severe visual deficit.

Glucocorticoid before thyroid hormone

Nearly every adult with apoplexy has at least one anterior-pituitary deficit. Central adrenal insufficiency is reported in a large majority in many series (commonly more than 70%). It is the deficit that kills in the first hours. UK Society for Endocrinology pituitary-apoplexy guidance (2010/2011) and subsequent endocrine-emergency practice put hydrocortisone in the resuscitation bay:

• Draw electrolytes, cortisol, free T4, TSH, and a co-oximetry set if you can do it without delaying treatment.
• Give hydrocortisone 100–200 mg IV as a bolus, then either 50–100 mg every 6 hours or a continuous infusion of about 2–4 mg/h (about 200 mg/24 h). High-dose hydrocortisone has enough mineralocorticoid activity that you do not add fludrocortisone in the acute window.
• Indications to start empirically, even before the cortisol result: hemodynamic instability, reduced consciousness, reduced visual acuity, or a severe field cut.

Levothyroxine comes after glucocorticoid is on board. Central hypothyroidism is common, and a low free T4 looks like a reason to push thyroid hormone first. That sequence is the classic error. Thyroid hormone increases cortisol clearance and metabolic demand. Starting T4 in a patient who cannot make ACTH is a way to unmask or worsen adrenal crisis. If free T4 is low, replace thyroid hormone after or with hydrocortisone, never instead of it. Sex-steroid and growth-hormone replacement are outpatient and convalescent problems.

Dexamethasone is sometimes used for vasogenic edema around the chiasm, but it is a poor sole glucocorticoid in crisis if you still need mineralocorticoid coverage and a cortisol assay you can interpret. Hydrocortisone is the workhorse.

Surgery versus conservative care

Not every apoplexy goes to the operating room at 2 a.m. Urgent transsphenoidal decompression is for declining consciousness, severe or worsening visual acuity, or a severe persistent field defect. Isolated stable ophthalmoplegia, including an isolated CN III palsy, often improves with steroids and time; many teams observe that group. A hemodynamically unstable patient still gets steroid and resuscitation before the trip down the hall. Once stable, care belongs in a center that can provide transsphenoidal surgery plus endocrine and ophthalmologic follow-up. Visual recovery is better when severe visual loss is decompressed early, but "early" does not mean skipping the hydrocortisone.

Panhypopituitarism: ICU order of operations

Panhypopituitarism is deficiency of multiple anterior-pituitary axes (and sometimes ADH). Causes in this unit: apoplexy, Sheehan syndrome, surgery, radiation, tumors, infiltrative disease, and traumatic stalk injury. The examination cares about priority, not a complete outpatient replacement list.

Stalk disconnection can raise prolactin (loss of dopamine inhibition) while the other anterior hormones fall. Complete gland necrosis drops prolactin. Neither result changes the first syringe: hydrocortisone.

Patients with known hypopituitarism who then have infection, surgery, or trauma need a stress dose, not their 15 mg oral morning tablet. Use the same hydrocortisone regimen as crisis. If the patient cannot take oral steroid, they are in crisis until the IV dose is running.

Worked picture: a 38-year-old day-3 after postpartum hemorrhage is hypotensive on modest norepinephrine, sodium 126 mEq/L, glucose 54 mg/dL, and she has not lactated. Free T4 is low. The correct first syringe is hydrocortisone, then glucose, then volume. Levothyroxine is not the opener. Testosterone or estrogen is irrelevant today.

Central diabetes insipidus

Central DI is ADH (vasopressin) deficiency. Without ADH, collecting-duct aquaporin channels stay closed, and the kidney writes a large volume of dilute urine even while plasma is concentrating. In the neuro ICU the usual settings are pituitary surgery, brain death, severe TBI, anterior communicating aneurysm rupture or surgery, and herniation that wrecks the hypothalamus.

Bedside diagnosis is a pattern, not a single number:

• High urine output, commonly >250–300 mL/h for consecutive hours, or more than about 3 L/day in a patient who is not getting a matching water load.
• Urine specific gravity <1.005 (often 1.001–1.003). Specific gravity is the 2 a.m. test. Urine osmolality is the cleaner number: typically <200–300 mOsm/kg and inappropriately low for a high plasma osmolality.
• Rising plasma sodium and plasma osmolality. If sodium is falling while urine output is high, think natriuresis, mannitol, or a large hypotonic infusion — not uncomplicated DI.

Confirm that the urine is dilute. Osmotic diuresis from mannitol, hyperglycemia, or high-protein feeds produces high output with a higher urine specific gravity and urine osmolality. Post-obstructive diuresis and the recovery phase of ATN also polyurese, but the urine is not water. A patient on 200 mL/h of 0.45% saline will make urine; that is iatrogenic water, not DI.

Desmopressin (DDAVP) is a synthetic V2-selective analog. It is the drug for isolated central DI once you have confirmed dilute polyuria and a climbing sodium (or a sodium already high). Typical ICU doses are 1–2 mcg IV or subcutaneous, with an effect lasting about 8–12 hours; some patients need 0.5 mcg to start so you do not overshoot. Oral tablets (often 0.05–0.2 mg) work when the gut works. Intranasal DDAVP is a poor ICU choice after transsphenoidal surgery: packs, blood, and CSF make absorption a lottery. Watch for the other side of the knife — if DDAVP is on board and hypotonic fluid continues, sodium can crash.

Vasopressin (aqueous arginine vasopressin) hits V1 and V2. The V1 effect vasoconstricts. That is why a low-dose infusion (commonly about 0.01–0.04 units/min in adult donor and shock protocols) is the right tool when DI and vasodilatory hypotension travel together. Brain-dead donors are the prototype: polyuria, rising sodium, and a falling SVR. Titrate vasopressin to urine output and MAP. Adding a huge DDAVP dose without a pressor plan treats only the kidney.

After pituitary surgery: the triphasic response

Stalk trauma produces a three-act play that the examination loves:

1. Early DI (hours to about day 1–3): axonal shock, no ADH release, dilute polyuria, rising sodium. Treat with cautious DDAVP and matching free-water replacement (enteral water or D5W), not with an automatic standing DDAVP every 8 hours that you forget to cancel.
2. Antidiuretic / SIADH-like phase (often days 4–10): dying posterior-pituitary terminals dump stored ADH. Urine output falls, urine concentrates, sodium falls. A standing DDAVP order from day 1 plus free water is how patients arrive at Na 118 mEq/L.
3. Lasting DI if enough magnocellular neurons are gone.

Not every patient completes all three acts. Many have only transient DI. The operational rule is reassess urine specific gravity and sodium every few hours in the first postoperative week, and treat the phase in front of you.

After brain death

Central DI is common once the hypothalamus and posterior pituitary infarct. Unreplaced water losses wreck donor organs through hypernatremia and hypovolemia. Vasopressin infusion is first-line in most donor-care bundles because it treats both DI and the vasodilated circulation. DDAVP is added or used alone when blood pressure is already solid and polyuria is the remaining problem. Follow sodium; a donor sodium in the high 150s is a procurement problem, not a trivia point.

Exam traps

Starting levothyroxine before hydrocortisone in apoplexy or Sheehan syndrome. Calling every postoperative polyuria DI without a specific gravity. Treating osmotic diuresis with DDAVP. Leaving a standing DDAVP order through the SIADH phase of the triphasic response. Using only nasal DDAVP after transsphenoidal packing. Treating brain-death DI with fluid restriction. Replacing testosterone in the resuscitation bay while cortisol is still missing.