Each adrenal gland has two parts:

• Adrenal cortex — makes cortisol (glucocorticoid: raises glucose, maintains blood pressure and stress response, suppresses inflammation), aldosterone (mineralocorticoid: retains sodium and water, excretes potassium), and adrenal androgens
• Adrenal medulla — makes catecholamines (epinephrine, norepinephrine)

Cortisol is controlled by the hypothalamic-pituitary-adrenal axis: CRH → pituitary ACTH → cortisol, which feeds back to suppress CRH and ACTH. Aldosterone is controlled mainly by the renin-angiotensin system and potassium.

Primary aldosteronism (hyperaldosteronism) — autonomous aldosterone production (adenoma or bilateral hyperplasia) → hypertension, often resistant, with hypokalemia (in a minority), low renin. It is a common, under-diagnosed cause of hypertension.

Pheochromocytoma — catecholamine-secreting tumor of the adrenal medulla (paraganglioma if outside the adrenal) → episodic or sustained hypertension.

Cushing syndrome — see table; also emotional lability, depression, insomnia, acne, facial plethora, kidney stones, and infection with masked signs (cortisol hides fever and inflammation).

Adrenal insufficiency — gradual fatigue, weakness, anorexia, weight loss, orthostatic dizziness, salt craving, bronze skin and dark mucous membranes (primary).

Adrenal crisis — severe hypotension or shock, dehydration, vomiting, abdominal pain, fever, confusion, hypoglycemia, hyperkalemia; triggered by infection, surgery, trauma, vomiting and diarrhea, or missed doses.

Pheochromocytoma — classic triad of episodic headache, sweating (diaphoresis), and palpitations/tachycardia, with paroxysmal severe hypertension, pallor, tremor, anxiety, hyperglycemia; attacks may follow exertion, abdominal pressure, certain drugs, or anesthesia.

Primary aldosteronism — hypertension, muscle weakness, cramps, polyuria (from hypokalemia).

Cushing syndrome

• Screening (at least two of): overnight 1-mg dexamethasone suppression test (cortisol fails to suppress), late-night salivary cortisol, 24-hour urine free cortisol
• Plasma ACTH locates the cause: adrenal tumor → high cortisol, low ACTH (negative feedback); pituitary or ectopic source → high cortisol, high or normal ACTH
• Then pituitary MRI or adrenal CT as indicated
• Labs: glucose, potassium

Adrenal insufficiency

• Early-morning serum cortisol (low)
• ACTH stimulation test (cosyntropin) — confirms the adrenal cannot respond
• Plasma ACTH — distinguishes primary (high ACTH) from secondary (low or normal ACTH)
• Sodium, potassium, glucose, renin (high in primary)
• Do not delay treatment of suspected crisis to complete testing — draw cortisol and ACTH, then treat

Primary aldosteronism

• Screening test: plasma aldosterone concentration and renin (aldosterone-to-renin ratio), with potassium. The 2025 Endocrine Society guideline recommends screening all adults with hypertension, not only high-risk groups
• Confirmatory testing (e.g., saline infusion or oral sodium loading suppression test) when needed, then adrenal CT and adrenal venous sampling to separate one-sided from bilateral disease
• Measure potassium with the test; low potassium can falsely lower aldosterone — if screening is negative with hypokalemia, correct potassium and repeat. Most antihypertensives can be continued, with interfering drugs managed case by case

Pheochromocytoma

• Plasma free metanephrines or 24-hour urine fractionated metanephrines; then CT or MRI
• Some drugs (e.g., tricyclic antidepressants) can cause false positives

Cushing syndrome

• Taper or reduce exogenous glucocorticoids where possible (never stop abruptly)
• Surgery: transsphenoidal pituitary adenoma removal (Cushing disease) or adrenalectomy (adrenal tumor); glucocorticoid replacement is needed afterward until the axis recovers
• Drugs that block cortisol production: ketoconazole (hepatotoxicity, QT prolongation, many interactions), metyrapone (hypertension, hypokalemia, hirsutism), osilodrostat (adrenal insufficiency, QT prolongation, hypokalemia); mitotane — adrenolytic (destroys adrenal cortex tissue; used for adrenal carcinoma): GI upset, CNS effects, adrenal insufficiency — needs glucocorticoid replacement; teratogenic
• Treat hypertension, hyperglycemia, bone loss

Adrenal insufficiency

• Hydrocortisone (or prednisone) daily, split doses with the larger dose in the morning to mimic normal rhythm
• Fludrocortisone for primary disease (replaces aldosterone) — monitor BP, edema, potassium; liberal salt intake
• Stress dosing ("sick-day rules") — double or triple the oral glucocorticoid dose during fever or significant illness as instructed; injectable hydrocortisone if vomiting or unable to take pills; higher IV doses for surgery

Adrenal crisis (emergency)

• Immediate hydrocortisone 100 mg IV (or IM), then continued IV hydrocortisone (e.g., 200 mg/24 h) — do not wait for test results
• Rapid IV 0.9% sodium chloride (about 1 L in the first hour), then as needed; dextrose for hypoglycemia
• Treat the trigger; cardiac monitoring for hyperkalemia

Primary aldosteronism

• Unilateral adenoma: laparoscopic adrenalectomy
• Bilateral disease: mineralocorticoid receptor antagonist — spironolactone (hyperkalemia, gynecomastia, menstrual changes; antiandrogenic — generally avoided in pregnancy) or eplerenone (hyperkalemia); avoid potassium supplements and salt substitutes once on them; monitor potassium and creatinine

Pheochromocytoma

• Preoperative alpha blockade first (phenoxybenzamine or doxazosin) for about 7–14 days, with liberal salt and fluid intake to restore volume
• Beta blocker is added only after adequate alpha blockade, to control tachycardia — starting a beta blocker first can cause unopposed alpha stimulation and a hypertensive crisis
• Laparoscopic adrenalectomy
• Hypertensive crisis: IV phentolamine, nitroprusside, or nicardipine

Listed in priority order.

1. Adrenal crisis — airway and circulation: establish IV access immediately; give IV fluids and IV hydrocortisone together, without delay; check glucose and potassium; cardiac monitoring; monitor BP, output, and mental status
2. Pheochromocytoma
   • Monitor BP frequently; report severe spikes with headache, palpitations, sweating
   • Avoid palpating the abdomen over the tumor and avoid triggers (stress, straining, certain drugs such as metoclopramide and some anesthetic agents)
   • After adrenalectomy: watch for hypotension (catecholamine drop) and hypoglycemia (rebound insulin); give fluids as ordered; check glucose frequently for 24–48 hours
3. Cushing syndrome — safety
   • Infection prevention (hand hygiene, avoid sick contacts); look for subtle signs because fever may be blunted
   • Fall and fracture precautions (osteoporosis, muscle weakness)
   • Skin protection — gentle handling, pad bony areas, avoid tape
   • Monitor glucose, BP, weight, potassium, edema
4. After adrenalectomy (any cause) — monitor for adrenal insufficiency and give prescribed glucocorticoid replacement; watch fluid and electrolyte shifts
5. Adrenal insufficiency — monitor orthostatic BP, weight, sodium, potassium, glucose; give glucocorticoids on schedule; never omit doses for NPO status without an order
6. Diet
   • Cushing: low sodium, low calorie/carbohydrate, high protein, potassium-rich, calcium and vitamin D
   • Addison: adequate sodium (salt), adequate carbohydrate and protein; avoid potassium excess
7. Emotional support — body image changes and mood swings in Cushing syndrome

Long-term glucocorticoid therapy

• Never stop suddenly — the body's own adrenal glands are suppressed; abrupt withdrawal can cause adrenal crisis; the dose is tapered
• Take with food in the morning; monitor glucose and BP; report infection signs early; bone health (calcium, vitamin D, weight-bearing exercise)

Adrenal insufficiency

• Lifelong replacement; take doses on time
• Sick-day rules: double (or triple) the glucocorticoid dose during fever, infection, or other illness as instructed by the provider, and seek care if vomiting or unable to keep pills down
• Carry an emergency hydrocortisone injection kit; teach family to use it
• Wear medical alert identification and carry a steroid emergency card
• Tell all providers (surgery, dental work) about the condition — stress-dose cover is needed
• Report dizziness, weight loss, nausea, or darkening skin (under-replacement) and swelling or weight gain (over-replacement)

Primary aldosteronism

• Spironolactone/eplerenone: avoid potassium supplements and potassium-based salt substitutes; report breast tenderness (spironolactone), muscle weakness, or palpitations

Pheochromocytoma

• Rise slowly during alpha blockade (orthostatic hypotension, nasal congestion); increase salt and fluids as directed
• Long-term follow-up with yearly metanephrines (recurrence); genetic counseling may be offered

• Adrenal crisis — shock, hypoglycemia, hyperkalemia; fatal if untreated
• Hypertensive crisis in pheochromocytoma — stroke, MI, arrhythmia, pulmonary edema
• Post-adrenalectomy hypotension and hypoglycemia
• Cushing: serious infection, fractures, diabetes, heart disease, thromboembolism, psychosis
• Primary aldosteronism: hypokalemic arrhythmias, stroke, atrial fibrillation, kidney damage
• Abrupt steroid withdrawal after long-term therapy

• Cushing: central obesity, moon face, buffalo hump, purple striae, easy bruising, thin skin, muscle wasting, osteoporosis, hyperglycemia, hypertension, hypokalemia — weight gain, not loss
• Adrenal tumor → high cortisol, low ACTH; pituitary source → high cortisol, high ACTH
• Addison (primary): hypotension, hyponatremia, hyperkalemia, hypoglycemia, hyperpigmentation
• Plasma ACTH distinguishes primary (high) from secondary (low/normal) adrenal insufficiency
• Adrenal crisis: IV access, rapid IV 0.9% saline and IV hydrocortisone 100 mg immediately — do not delay steroid
• Sick-day rules: double or triple glucocorticoid dose during illness; injection kit; medical ID
• Never stop long-term steroids abruptly → adrenal crisis
• Primary aldosteronism: hypertension ± hypokalemia; aldosterone-renin screening — 2025 guideline: screen all adults with hypertension; treat with adrenalectomy or spironolactone/eplerenone
• Pheochromocytoma: episodic headache, sweating, palpitations with severe hypertension; plasma free metanephrines
• Pheo pre-op: alpha blocker first, then beta blocker; do not palpate abdomen; post-op hypotension and hypoglycemia
• Mitotane destroys adrenal cortex (adrenolytic); ketoconazole and metyrapone block cortisol synthesis