Adrenal, Pituitary & Endocrine Emergencies — Adrenal Insufficiency/Crisis, Pituitary Disorders, and Other Acute Endocrine Presentations - USMLE Step 2

SECTION 1

Historical Context & Motivation

The adrenal glands and pituitary have fascinated physicians since the earliest anatomists dissected the human body, yet the clinical significance of their dysfunction remained enigmatic for centuries. In 1855, Thomas Addison published his landmark monograph linking progressive adrenal destruction to a fatal syndrome of hypotension, weight loss, and skin hyperpigmentation—what we now call Addison disease. This work laid the foundation for understanding that certain glands produce substances essential for life, even though the term "hormone" would not be coined for another fifty years. The recognition that abrupt withdrawal or failure of these hormonal systems could precipitate hemodynamic collapse and death drove decades of research into replacement therapy and acute management protocols.

1855 • Addison's Monograph

Thomas Addison describes the clinical features of chronic adrenal insufficiency and links them to tuberculous destruction of the adrenal glands.

1914 • Harvey Cushing & the Pituitary

Harvey Cushing publishes The Pituitary Body and Its Disorders, establishing the pituitary as the "master gland" and describing syndromes of pituitary excess and insufficiency.

1949 • Cortisone Synthesis

Hench and Kendall demonstrate the therapeutic power of cortisone, earning the Nobel Prize and enabling lifesaving glucocorticoid replacement for adrenal insufficiency.

1970s • HPA Axis Suppression Recognized

Widespread use of exogenous glucocorticoids reveals that iatrogenic adrenal suppression—not autoimmune destruction—is the most common cause of adrenal crisis in the modern era.

2003 • Endocrine Society Guidelines

Evidence-based guidelines formalize stress-dose steroid protocols, cosyntropin stimulation testing, and management algorithms for acute endocrine emergencies.

Despite these advances, endocrine emergencies remain a major source of morbidity and mortality in clinical practice. Adrenal crisis alone carries a mortality rate exceeding 6% per episode in hospitalized patients, often because the diagnosis is delayed in the setting of nonspecific symptoms such as fatigue, nausea, and hypotension. The central question for the clinician is: How do you rapidly identify and treat hormonal failures that mimic sepsis, surgical emergencies, and other acute presentations?

SECTION 2

Core Principles & Definitions

Endocrine emergencies arise when hormonal excess or deficiency becomes acutely life-threatening. The most frequently tested scenarios on USMLE Step 2 involve the hypothalamic-pituitary-adrenal (HPA) axis, the hypothalamic-pituitary-thyroid (HPT) axis, and the regulation of calcium, glucose, and catecholamines. Understanding these emergencies requires a firm grasp of feedback loops, the distinction between primary (end-organ), secondary (pituitary), and tertiary (hypothalamic) dysfunction, and the concept of hormonal reserve that is unmasked only during physiological stress.

Adrenal Crisis

An acute, life-threatening state of cortisol deficiency presenting with refractory hypotension, hyponatremia, hyperkalemia (primary), hypoglycemia, and often precipitated by physiological stress in a patient with inadequate adrenal reserve.

Pituitary Apoplexy

Sudden hemorrhage or infarction of the pituitary gland—usually within a pre-existing adenoma—causing acute headache, visual field defects, ophthalmoplegia, and potentially fatal secondary adrenal insufficiency.

Myxedema Coma

The extreme, decompensated form of hypothyroidism characterized by hypothermia, altered mental status, hypoventilation, and bradycardia. Despite its name, frank coma is not always present.

Thyroid Storm

Acute, severe thyrotoxicosis with hyperthermia (>40°C), tachyarrhythmias, delirium, and multi-organ dysfunction. Often triggered by infection, surgery, or iodine load in uncontrolled Graves disease.

Pheochromocytoma Crisis

Paroxysmal or sustained catecholamine excess producing hypertensive emergency, tachycardia, diaphoresis, headache, and risk of stroke, MI, or aortic dissection. Alpha-blockade must precede beta-blockade.

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KEY TAKEAWAY

Think of the HPA axis like a thermostat-furnace system: the hypothalamus is the thermostat, the pituitary is the control wiring, and the adrenal glands are the furnace. If you cut the power supply (abrupt glucocorticoid withdrawal), the furnace is intact but cannot fire—and the house freezes. Whether the failure is at the thermostat, the wiring, or the furnace itself determines the laboratory pattern and the urgency of your intervention.

SECTION 3

Visual Explanation — The HPA Axis & Points of Failure

The HPA axis diagram illustrates the stimulatory pathway (green arrows: CRH → ACTH → Cortisol) and the negative feedback loop (red dashed line). Three callout boxes on the right show where primary, secondary, and tertiary failure occurs, with the corresponding laboratory patterns summarized at the bottom.

The critical clinical distinction lies in whether aldosterone is affected. In primary adrenal insufficiency the entire adrenal cortex is destroyed, so both cortisol and aldosterone are lost, producing hyperkalemia and salt-wasting. In secondary and tertiary forms, aldosterone secretion is preserved because it is primarily regulated by the renin-angiotensin-aldosterone system (RAAS) rather than ACTH. This is why secondary adrenal insufficiency typically presents with hyponatremia (from impaired free water excretion due to cortisol deficiency) but without the life-threatening hyperkalemia seen in Addison disease. Hyperpigmentation, driven by elevated ACTH and its co-secreted melanocyte-stimulating hormone (MSH), is also exclusive to primary disease.

SECTION 4

Pathophysiology & Diagnostic Framework

Adrenal Insufficiency — Acute Pathophysiology

Cortisol is essential for maintaining vascular tone, hepatic gluconeogenesis, and immunomodulation. During physiological stress—infection, surgery, trauma—cortisol demand rises five- to tenfold. When the adrenal cortex cannot mount an appropriate response, the resulting relative cortisol deficiency leads to vasodilatory shock that is refractory to fluids and vasopressors, mimicking septic shock. Simultaneously, loss of cortisol's permissive effect on catecholamine action compounds the hemodynamic instability. Hyponatremia develops through impaired free water excretion (cortisol normally suppresses ADH), while hyperkalemia in primary disease results from concurrent aldosterone deficiency causing impaired renal potassium secretion.

The Cosyntropin (ACTH) Stimulation Test

COSYNTROPIN STIMULATION TEST INTERPRETATION

Baseline cortisol drawn \to 250 μg cosyntropin IV \to cortisol at 30 & 60 min

Normal response: peak cortisol ≥ 18–20 μg/dL (500–550 nmol/L). A blunted response (<18 μg/dL) confirms adrenal insufficiency. In secondary AI, the test may be normal if the pituitary lesion is recent (adrenals have not yet atrophied), so clinical suspicion must remain high.

Pituitary Apoplexy — Mechanism

Pituitary adenomas outgrow their blood supply and are susceptible to hemorrhagic infarction. Precipitants include anticoagulation, post-cardiac surgery hypotension, and dynamic pituitary testing with GnRH or CRH. The sudden gland expansion causes compression of the optic chiasm (producing a bitemporal hemianopsia), cranial nerves III, IV, and VI within the cavernous sinus (causing ophthalmoplegia), and destruction of functioning pituitary tissue. The most immediate threat to life is acute secondary adrenal insufficiency; therefore, empiric IV hydrocortisone must be given before any imaging or surgical planning.

Thyroid Storm vs. Myxedema Coma — Opposing Extremes

These represent the two poles of thyroid dysfunction pushed to their lethal extremes. Thyroid storm is diagnosed clinically—no single lab value distinguishes it from uncomplicated thyrotoxicosis—using the Burch-Wartofsky Point Scale (BWPS), which assigns points for temperature, heart rate, CNS effects, GI-hepatic dysfunction, and the presence of a precipitant. A score ≥ 45 is highly suggestive. Treatment follows the mnemonic PTU-Block-Iodine-Steroids: propylthiouracil (blocks synthesis and T₄→T₃ conversion), beta-blocker (controls adrenergic symptoms), iodine given at least one hour after PTU (Wolff-Chaikoff effect), and glucocorticoids (block peripheral conversion and treat potential relative adrenal insufficiency).

In contrast, myxedema coma presents with profound hypothermia, hypoventilation with CO₂ retention, bradycardia, and altered sensorium. It typically occurs in elderly patients with undiagnosed or undertreated hypothyroidism exposed to a cold environment or sedating medications. Treatment centers on IV levothyroxine (loading dose 200–400 μg), with empiric IV hydrocortisone given concurrently because unmasking occult adrenal insufficiency with thyroid hormone replacement can precipitate adrenal crisis.

SECTION 5

Detailed Classification of Endocrine Emergencies

This classification diagram summarizes six major endocrine emergencies with their cardinal clinical features and first-line treatment. The bottom panel highlights the distinguishing features most commonly tested on Step 2.

Feature	Primary AI	Secondary AI	Tertiary AI
Most common cause	Autoimmune adrenalitis (developed world); TB (developing world)	Pituitary adenoma, surgery, Sheehan syndrome, apoplexy	Abrupt withdrawal of exogenous glucocorticoids
ACTH level	↑↑ Elevated	↓ Low / inappropriately normal	↓ Low
Cortisol	↓ Low	↓ Low	↓ Low
Aldosterone	↓ Deficient (→ ↑K⁺, salt wasting)	Normal (RAAS intact)	Normal (RAAS intact)
Hyperpigmentation	Present (↑ACTH = ↑MSH)	Absent	Absent
Cosyntropin test	Blunted (adrenals destroyed)	Blunted if chronic; may be normal if acute onset	Blunted if chronic suppression; may be normal if recent

Comparison of primary, secondary, and tertiary adrenal insufficiency

SECTION 6

Worked Example — Acute Adrenal Crisis Management

A 42-year-old woman with known systemic lupus erythematosus on chronic prednisone 15 mg daily presents to the emergency department with a three-day history of nausea, vomiting, and diarrhea due to viral gastroenteritis. She ran out of her prednisone two days ago and was unable to refill the prescription. Vitals: BP 78/42 mmHg, HR 118 bpm, T 37.1°C. Labs: Na⁺ 128 mEq/L, K⁺ 4.1 mEq/L, glucose 58 mg/dL, random cortisol 2.1 μg/dL. How do you manage this patient?

Managing Acute Adrenal Crisis in a Patient on Chronic Glucocorticoids

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Step 1 — Recognize the Clinical Syndrome

This patient has refractory hypotension, hyponatremia, and hypoglycemia in the setting of abrupt glucocorticoid withdrawal. The random cortisol of 2.1 μg/dL during physiological stress (normal stress response should produce cortisol > 18–20 μg/dL) confirms adrenal crisis. The normal potassium (K⁺ 4.1) and absence of hyperpigmentation indicate this is tertiary (iatrogenic) adrenal insufficiency, not primary—her adrenals are intact but atrophied from chronic exogenous steroid use.

Diagnosis: Adrenal crisis due to abrupt corticosteroid withdrawal
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Step 2 — Administer Stress-Dose Steroids Immediately

Do not wait for confirmatory testing. Give hydrocortisone 100 mg IV bolus immediately, followed by 50 mg IV every 8 hours. Hydrocortisone is preferred over dexamethasone because it has both glucocorticoid and mineralocorticoid activity. However, if you plan to perform a cosyntropin stimulation test, dexamethasone (4 mg IV) may be used instead because it does not cross-react with the cortisol assay.

Hydrocortisone 100 mg IV bolus stat
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Step 3 — Aggressive Volume Resuscitation

Administer isotonic (0.9%) normal saline with 5% dextrose (D5NS) to address both dehydration and hypoglycemia simultaneously. The hypotension in adrenal crisis is multifactorial—volume depletion plus loss of cortisol's permissive effect on vascular catecholamine sensitivity. Most patients require 2–3 liters in the first few hours. Blood pressure often responds dramatically once cortisol is replaced.

D5NS infusion; target MAP > 65 mmHg
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Step 4 — Address the Precipitant

Treat the underlying stressor—in this case, manage the gastroenteritis with antiemetics and supportive care. Endocrine emergencies often present during intercurrent illness because the physiological stress demand exceeds the patient's diminished cortisol reserve. Once stable, identify and address the reason the patient could not obtain her medications.

Antiemetics, supportive care for gastroenteritis; social work consult for medication access
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Step 5 — Taper & Educate

Once the acute crisis resolves (usually 24–48 hours), taper stress-dose steroids back to the patient's baseline replacement dose. Critically, educate the patient on sick-day rules: double or triple oral glucocorticoid dose during febrile illness, provide an emergency IM hydrocortisone injection kit, and ensure she wears a medical alert bracelet. These preventive measures are as important as the acute treatment and are frequently tested on board examinations.

Taper to home dose; educate on sick-day rules, emergency injection kit, and medical alert identification

SECTION 7

Strengths, Pitfalls & Diagnostic Comparisons

Endocrine emergencies are notoriously difficult to diagnose because they frequently mimic more common conditions. Adrenal crisis mimics septic shock; pituitary apoplexy mimics subarachnoid hemorrhage or meningitis; thyroid storm can be confused with sympathomimetic intoxication or malignant hyperthermia; and myxedema coma may be attributed to hypothermia, drug overdose, or simply "failure to thrive" in an elderly patient. The key to avoiding missed diagnoses is maintaining a high index of suspicion and understanding the specific clinical contexts in which these emergencies arise.

Endocrine Emergency	Key Mimics	Distinguishing Clue
Adrenal crisis	Septic shock, acute abdomen, DKA	Hypotension refractory to fluids/pressors; hyponatremia + hypoglycemia; eosinophilia; history of steroid use or autoimmune disease
Pituitary apoplexy	Subarachnoid hemorrhage, meningitis, cavernous sinus thrombosis	Known pituitary adenoma; ophthalmoplegia + visual field cut (not typical of SAH); MRI shows sellar hemorrhage
Thyroid storm	Sepsis, sympathomimetic toxicity, malignant hyperthermia, NMS	History of Graves disease or goiter; exophthalmos; BWPS ≥ 45; precipitant (surgery, iodine contrast, infection)
Myxedema coma	Hypothermia, drug overdose, CVA, sepsis in elderly	Delayed relaxation phase of reflexes; non-pitting edema (myxedema); thyroidectomy scar; markedly elevated TSH
Pheochromocytoma crisis	Essential hypertensive crisis, cocaine/amphetamine intoxication, panic attack	Paroxysmal episodes; triad of headache + palpitations + diaphoresis; family history of MEN2; provoked by anesthesia induction or tumor palpation

Differential diagnosis and distinguishing clues for endocrine emergencies

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CLINICAL PEARL

When you encounter refractory hypotension in the ICU that does not respond to fluids and vasopressors, always consider adrenal insufficiency as a treatable cause. A single dose of IV hydrocortisone is low-risk and potentially lifesaving. Similarly, in any patient with altered mental status plus hypothermia, check a TSH—myxedema coma is rare but has a 30–60% mortality if untreated.

SECTION 8

Connection to Advanced Clinical Concepts

The management of endocrine emergencies intersects with several advanced clinical domains that are increasingly represented on Step 2 CK and in clinical practice. Critical illness-related corticosteroid insufficiency (CIRCI) is a nuanced concept in which ICU patients with septic shock may have relative adrenal insufficiency despite cortisol levels that would be considered "normal" in a non-stressed state. The CORTICUS trial and subsequent Surviving Sepsis Campaign guidelines suggest that low-dose hydrocortisone (200 mg/day continuous infusion) should be considered for patients with septic shock refractory to fluids and vasopressors, a recommendation that blurs the line between endocrinology and critical care medicine.

Concept	Basic Level (Step 2)	Advanced Level (Clinical Practice)
Adrenal insufficiency	Diagnose with cosyntropin test; treat with hydrocortisone; distinguish primary vs. secondary	CIRCI in sepsis; dual-energy CT for adrenal hemorrhage; immunotherapy-related adrenalitis (checkpoint inhibitors)
Pituitary disease	Recognize apoplexy; test all anterior pituitary axes; order MRI sella	Hypophysitis from anti-PD-1/PD-L1 therapy; transsphenoidal surgery complications; GH replacement controversies
Thyroid emergencies	Recognize thyroid storm vs. myxedema coma; follow treatment algorithms	Amiodarone-induced thyrotoxicosis (Type 1 vs. 2); gestational thyrotoxicosis; post-checkpoint inhibitor thyroiditis
Catecholamine excess	Suspect pheochromocytoma; order plasma metanephrines; α-block before β-block	Paraganglioma syndromes (SDH mutations); MIBG therapy; intraoperative hemodynamic management

Step 2 foundations versus advanced clinical applications

An increasingly tested topic is immune checkpoint inhibitor-induced endocrinopathies. Anti-CTLA-4 agents (ipilimumab) frequently cause hypophysitis, while anti-PD-1/PD-L1 agents more commonly cause thyroiditis and, less frequently, primary adrenal insufficiency or type 1 diabetes. These iatrogenic endocrinopathies can present acutely and may be the first sign of immune-related adverse events, making it essential for all clinicians—not just oncologists—to recognize and manage them.

SECTION 9

Practice Problems

Question 1: CONCEPTUAL

A patient with primary adrenal insufficiency presents with skin hyperpigmentation, hyperkalemia, and hyponatremia. Explain the pathophysiological mechanism that accounts for each of these three findings. Why would a patient with secondary adrenal insufficiency NOT have hyperpigmentation or hyperkalemia?

Show answer

In primary adrenal insufficiency, destruction of the adrenal cortex eliminates both cortisol and aldosterone production. Low cortisol removes negative feedback on the hypothalamus and pituitary, causing marked elevation of ACTH. Because ACTH is cleaved from the same precursor molecule (proopiomelanocortin, or POMC) as melanocyte-stimulating hormone (MSH), elevated ACTH is accompanied by elevated MSH, which stimulates melanocytes and produces hyperpigmentation. Aldosterone deficiency impairs renal sodium reabsorption and potassium secretion in the distal nephron, producing hyponatremia and hyperkalemia. In secondary adrenal insufficiency, the pituitary fails to produce ACTH, so there is no elevated MSH and thus no hyperpigmentation. Furthermore, aldosterone secretion is largely regulated by the renin-angiotensin system (which remains intact), so potassium handling is preserved.

Question 2: BASIC CALCULATION

A 55-year-old man on chronic prednisone 20 mg daily undergoes elective surgery. His surgical team plans to administer stress-dose steroids. The standard stress-dose protocol calls for hydrocortisone 100 mg IV every 8 hours on the day of surgery. Given that 20 mg of prednisone is equivalent to approximately 80 mg of hydrocortisone (using a 4:1 conversion factor), how much additional glucocorticoid activity (in hydrocortisone equivalents) is the patient receiving per day compared to his baseline?

Show answer

The patient's baseline prednisone 20 mg daily is equivalent to 80 mg of hydrocortisone per day (20 × 4 = 80 mg). The stress-dose protocol provides 100 mg × 3 = 300 mg of hydrocortisone per day. Therefore, the additional glucocorticoid activity is 300 − 80 = 220 mg of hydrocortisone equivalents per day above baseline. This roughly four-fold increase over the patient's chronic replacement dose approximates the physiological cortisol surge expected during major surgical stress, which can reach 150–300 mg per day of cortisol equivalent.

Question 3: INTERMEDIATE

A 28-year-old woman presents 5 days postpartum with inability to breastfeed, fatigue, and lightheadedness. She had a complicated delivery with massive postpartum hemorrhage requiring transfusion of 6 units of packed red blood cells. Vital signs show BP 90/58 mmHg, HR 102 bpm. Labs: Na⁺ 130 mEq/L, K⁺ 4.0 mEq/L, glucose 65 mg/dL, TSH 0.8 mIU/L (low-normal), free T₄ 0.4 ng/dL (low). What is the most likely diagnosis, and what is the first medication you should administer?

Show answer

This presentation is classic for Sheehan syndrome (postpartum pituitary necrosis) resulting from ischemic infarction of the pituitary gland following massive obstetric hemorrhage. The pituitary enlarges during pregnancy (due to lactotroph hyperplasia) and is vulnerable to hypotension-related ischemia. The inability to lactate reflects prolactin deficiency. The low free T₄ with an inappropriately low-normal TSH confirms central (secondary) hypothyroidism. The hypotension and hypoglycemia suggest concomitant ACTH deficiency causing secondary adrenal insufficiency. Critically, the first medication to administer is IV hydrocortisone (not levothyroxine), because initiating thyroid hormone replacement before cortisol replacement can accelerate cortisol metabolism and precipitate an acute adrenal crisis. Once cortisol is replaced, levothyroxine can be safely started. Additional testing should evaluate all anterior pituitary axes (FSH, LH, GH, prolactin) and an MRI of the sella should be obtained.

Question 4: APPLIED

A 62-year-old man with known Graves disease, poorly compliant with methimazole, presents to the ED two days after undergoing coronary artery bypass grafting. He is febrile to 40.3°C, has atrial fibrillation with a ventricular rate of 162 bpm, is delirious, and has profuse diarrhea. Bilirubin is 3.2 mg/dL. The surgical team suspects postoperative sepsis. Using the Burch-Wartofsky Point Scale, explain why thyroid storm should be strongly considered, and outline the correct order of pharmacologic interventions.

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The Burch-Wartofsky Point Scale assigns points as follows: temperature 40.3°C (30 points), heart rate >140 with atrial fibrillation (25 + 10 = 35 points), CNS dysfunction with delirium (20 points), GI-hepatic dysfunction with diarrhea and elevated bilirubin (20 points), and a clear precipitant (surgery) (10 points), totaling approximately 115 points—far exceeding the 45-point threshold suggestive of thyroid storm. The correct pharmacologic order is: (1) Propylthiouracil (PTU) 500–1000 mg loading dose, which blocks new thyroid hormone synthesis and inhibits peripheral T₄ to T₃ conversion; (2) beta-blocker (propranolol preferred, as it also inhibits T₄→T₃ conversion) to control heart rate, with rate-controlling doses titrated carefully given the hemodynamic instability; (3) iodine (Lugol's solution or SSKI) given at least one hour after PTU to exploit the Wolff-Chaikoff effect and block release of preformed hormone—giving iodine before PTU would provide substrate for additional hormone synthesis; (4) hydrocortisone 100 mg IV every 8 hours to block peripheral conversion and address potential relative adrenal insufficiency. Supportive measures include aggressive cooling, IV fluids, and ICU monitoring.

Question 5: CRITICAL THINKING

A 70-year-old man with metastatic melanoma is being treated with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1). On cycle 3, he develops fatigue, weight loss, and postural dizziness. Labs show Na⁺ 126 mEq/L, K⁺ 5.8 mEq/L, cortisol 1.8 μg/dL (AM), ACTH 340 pg/mL (markedly elevated), and TSH 78 mIU/L with free T₄ 0.2 ng/dL. Synthesize these findings: How many distinct endocrinopathies does this patient have? Which is most immediately life-threatening? How does the pattern of ACTH and cortisol help you determine the level of the lesion for each axis, and how does this inform your understanding of checkpoint inhibitor-induced endocrine toxicity?

Show answer

This patient has at least two distinct checkpoint inhibitor-induced endocrinopathies. First, the markedly elevated ACTH (340 pg/mL) with profoundly low cortisol (1.8 μg/dL) combined with hyperkalemia (K⁺ 5.8) constitutes primary adrenal insufficiency—the adrenal gland itself is failing, as demonstrated by the intact pituitary drive (high ACTH) attempting to compensate. This pattern is more consistent with adrenalitis (direct immune-mediated destruction of the adrenal cortex), which is more commonly associated with anti-PD-1 therapy. The hyperkalemia confirms aldosterone is also deficient, consistent with primary disease. Second, the markedly elevated TSH (78 mIU/L) with low free T₄ (0.2 ng/dL) indicates primary hypothyroidism—likely immune-mediated thyroiditis causing thyroid destruction. The elevated TSH demonstrates intact pituitary function, ruling out hypophysitis as the cause. The most immediately life-threatening condition is the primary adrenal insufficiency with hyperkalemia, which places the patient at risk for cardiac arrhythmia and adrenal crisis. Treatment priority is IV hydrocortisone and management of hyperkalemia (cardiac monitoring, calcium gluconate, insulin/glucose, kayexalate). Levothyroxine should be started only after cortisol replacement is established. This case illustrates that checkpoint inhibitors can simultaneously attack multiple endocrine organs through distinct mechanisms, and the ACTH-cortisol and TSH-T₄ patterns precisely localize each lesion to the end-organ (primary) level rather than the pituitary (secondary) level, which has different therapeutic and prognostic implications.

SUMMARY

Summary — Endocrine Emergencies

Summary

Endocrine emergencies demand rapid recognition and treatment because hormonal failures can mimic more common conditions and escalate to cardiovascular collapse. Adrenal crisis presents with refractory hypotension, hyponatremia, and hypoglycemia and is treated with IV hydrocortisone 100 mg bolus plus normal saline—do not delay treatment to await confirmatory testing. Distinguish primary AI (↑ACTH, ↓aldosterone, hyperpigmentation, hyperkalemia) from secondary/tertiary AI (↓ACTH, preserved aldosterone, no hyperpigmentation). The cosyntropin stimulation test confirms the diagnosis, with a peak cortisol < 18 μg/dL indicating adrenal insufficiency.

Pituitary apoplexy is characterized by sudden headache, visual field defects, and ophthalmoplegia—give steroids before imaging. Thyroid storm (BWPS ≥ 45) requires sequential therapy: PTU → beta-blocker → iodine (1 hour after PTU) → glucocorticoids. In myxedema coma, always give hydrocortisone before levothyroxine to prevent precipitating adrenal crisis. For pheochromocytoma crisis, alpha-blockade must always precede beta-blockade to avoid unopposed alpha-stimulation and worsening hypertension. Finally, remember that checkpoint inhibitor-induced endocrinopathies are increasingly common and can cause simultaneous multi-organ endocrine failure—always localize the lesion using the ACTH-cortisol and TSH-T₄ axes before initiating treatment.