Adrenal Disorders — Causes, Symptoms, Diagnosis & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

The adrenal glands are paired endocrine glands situated above each kidney, consisting of an outer cortex (producing glucocorticoids — mainly cortisol; mineralocorticoids — mainly aldosterone; and adrenal androgens — DHEA, androstenedione) and an inner medulla (producing catecholamines — adrenaline/epinephrine and noradrenaline/norepinephrine). Adrenal disorders arise from either excess or deficiency of these hormones. Major adrenal conditions include: Addison's disease (primary adrenal insufficiency — cortisol and aldosterone deficiency), Cushing's syndrome (cortisol excess), primary hyperaldosteronism (Conn's syndrome — aldosterone excess), phaeochromocytoma/paraganglioma (catecholamine-secreting tumours), and congenital adrenal hyperplasia (CAH). Adrenal incidentalomas (adrenal masses found incidentally on imaging) are increasingly common (found in 4-7% of abdominal CT scans) and require systematic evaluation. Combined, adrenal disorders — though individually rare — represent a clinically important group requiring specialist endocrinology evaluation, as delayed diagnosis carries significant morbidity, particularly from adrenal crisis in untreated adrenal insufficiency.

Addison's disease (primary adrenal insufficiency): autoimmune adrenalitis accounts for 70-80% of cases in developed countries (autoantibodies against 21-hydroxylase); tuberculosis (most common cause globally); adrenal metastases (lung, breast, melanoma); haemorrhage (Waterhouse-Friderichsen syndrome in meningococcal sepsis). Secondary adrenal insufficiency: ACTH deficiency from pituitary disease or — most commonly — prolonged supraphysiological corticosteroid use. Cushing's syndrome: ACTH-dependent (80%) — pituitary adenoma (Cushing's disease, 70%), ectopic ACTH (small cell lung cancer, carcinoid), vs. ACTH-independent (20%) — adrenal adenoma, carcinoma. Primary hyperaldosteronism (Conn's): bilateral adrenal hyperplasia (60-70%) or aldosterone-producing adenoma (30-40%) — causes secondary hypertension in approximately 5-10% of all hypertensive patients and 20% of resistant hypertension. Phaeochromocytoma: typically adrenal medullary tumour — 10% rule (10% bilateral, 10% extra-adrenal, 10% malignant, 10% hereditary — now revised upward: 20-25% have germline mutations including SDHx, VHL, NF1, RET, MAX).

Addison's disease: insidious onset of fatigue, weight loss, anorexia, nausea, postural hypotension (orthostatic dizziness on standing), muscle weakness, salt craving, hyponatraemia, hyperkalaemia, and hypoglycaemia. Pathognomonic feature: hyperpigmentation (tan skin, accentuated in palmar creases, buccal mucosa, skin folds, and scars — from elevated ACTH stimulating melanocortin receptors). Adrenal crisis: acute circulatory collapse (hypotension, tachycardia, impaired consciousness) precipitated by illness, surgery, or stress in undiagnosed or under-replaced patients — a life-threatening emergency. Cushing's syndrome: central obesity (buffalo hump, supraclavicular fat pads), moon face, thin skin with easy bruising and purple striae (more than 1 cm wide over abdomen), proximal myopathy, hypertension, diabetes mellitus, osteoporosis, hirsutism, menstrual irregularity, and psychiatric disturbance (depression, psychosis). Conn's syndrome: hypertension (often drug-resistant), hypokalaemia (muscle weakness, polyuria, cramps). Phaeochromocytoma: classic triad of episodic headache, sweating, and palpitations with hypertension (sustained or paroxysmal — the 'hypertensive crises').

Addison's disease: 9am cortisol — if below 100 nmol/L, Addison's is likely; if above 500 nmol/L, normal. Synacthen (short ACTH stimulation) test: IV/IM 250mcg synthetic ACTH; cortisol measured at 0 and 30 minutes — peak below 500 nmol/L is diagnostic of adrenal insufficiency. Plasma ACTH (elevated in primary, suppressed in secondary adrenal insufficiency). Anti-21-hydroxylase antibodies (positive in autoimmune Addison's). Cushing's syndrome: 24-hour urinary free cortisol (UFC); late-night salivary cortisol (elevated — loss of diurnal variation); 1 mg overnight dexamethasone suppression test (cortisol fails to suppress below 50 nmol/L in Cushing's); CRH stimulation test and high-dose dexamethasone test distinguish pituitary from ectopic ACTH source. Pituitary MRI for Cushing's disease; adrenal CT/MRI for adrenal causes; IPSS (inferior petrosal sinus sampling) is the gold standard for distinguishing pituitary from ectopic ACTH. Conn's syndrome: aldosterone-to-renin ratio (ARR) — elevated is the best screening test; adrenal CT; adrenal vein sampling (gold standard to lateralise to unilateral or bilateral disease). Phaeochromocytoma: plasma free metanephrines or 24-hour urinary fractionated metanephrines — high sensitivity (95-99%); adrenal CT or MRI for localisation.

Addison's disease: lifelong glucocorticoid replacement (hydrocortisone 15-20 mg/day in 2-3 divided doses, largest dose on waking) and mineralocorticoid replacement (fludrocortisone 50-200 mcg once daily). Sick day rules: double the hydrocortisone dose during fever, illness, or minor procedures; parenteral hydrocortisone (IM/IV 100 mg) for vomiting, severe illness, or adrenal crisis — patients carry an emergency hydrocortisone injection kit. Adrenal crisis: immediate IV hydrocortisone 100 mg bolus + IV fluid resuscitation — medical emergency. Cushing's syndrome: surgical excision — transsphenoidal pituitary adenomectomy for Cushing's disease (remission in 70-85%); adrenalectomy for adrenal tumours; medical therapy (ketoconazole, metyrapone, osilodrostat, pasireotide) for unresectable or persistent disease. Conn's syndrome: unilateral adenoma — laparoscopic adrenalectomy (cures hypertension in 30-50%, reduces BP further in most). Bilateral hyperplasia — mineralocorticoid receptor antagonist (spironolactone 100-400 mg or eplerenone 100-200 mg). Phaeochromocytoma: alpha-blockade first (phenoxybenzamine or doxazosin) for minimum 10-14 days, then add beta-blockade if needed, followed by laparoscopic adrenalectomy — adequate pre-operative preparation is essential to prevent hypertensive crisis during surgery.

Adrenal crisis (acute adrenal insufficiency) is the most life-threatening complication of Addison's disease and of iatrogenic adrenal suppression from chronic glucocorticoid therapy — precipitated by intercurrent illness, surgery, vomiting, or missed steroid doses. It presents with profound hypotension, severe hyponatraemia, hyperkalaemia, and hypoglycaemia, progressing to shock and death without immediate IV hydrocortisone 100 mg bolus plus 200 mg over 24 hours and saline resuscitation. Unrecognised or undertreated adrenal insufficiency has a mortality rate approaching 6% per crisis episode. Cushing's syndrome complications: severe osteoporosis with vertebral and hip fragility fractures (30–50% of patients develop fracture), hypertension and accelerated cardiovascular disease (3–5-fold increased cardiovascular mortality), diabetes mellitus (type 2 diabetes in 60–80% with florid Cushing's), susceptibility to opportunistic infections (Pneumocystis jirovecii pneumonia, cryptococcal meningitis — from severe immunosuppression), muscle wasting and myopathy, avascular necrosis of the femoral head, and psychiatric disorders (depression, psychosis). Phaeochromocytoma crisis — paroxysmal hypertension exceeding 300/150 mmHg from catecholamine surge — can cause hypertensive encephalopathy, MI, stroke, aortic dissection, or pulmonary oedema; mortality risk is high if the tumour is manipulated without adequate alpha-blockade. Conn's syndrome causes hypertension-related target organ damage (stroke, MI, cardiac hypertrophy), hypokalaemia-induced cardiac arrhythmias, and rhabdomyolysis from severe potassium depletion.

Adrenal insufficiency prevention: avoid prolonged high-dose corticosteroid use and taper slowly after prolonged courses to prevent secondary adrenal suppression. All patients on long-term steroids must have sick day rules and carry a steroid card. Patients with confirmed adrenal insufficiency must carry an emergency hydrocortisone injection kit and medical alert bracelet/card indicating 'adrenal insufficiency'. Family screening for hereditary adrenal conditions: MEN2 (RET gene — phaeochromocytoma + medullary thyroid cancer), VHL syndrome, SDHx mutations — genetic counselling and periodic biochemical and imaging surveillance. Adrenal incidentalomas: functional assessment (exclude subclinical Cushing's, phaeochromocytoma, and hyperaldosteronism) and size-based imaging follow-up protocol. Tumours above 4 cm or showing growth on follow-up imaging are referred for surgical consideration to exclude adrenocortical carcinoma.

Adrenal crisis is a life-threatening emergency: seek immediate emergency care (999/911) for collapse, severe hypotension, confusion, or loss of consciousness in a patient with known adrenal insufficiency — or if you suspect undiagnosed adrenal insufficiency in someone with unexplained shock, hypoglycaemia, hyponatraemia, and hyperpigmentation. Patients with known Addison's who are vomiting and unable to take oral steroids must receive emergency IM/IV hydrocortisone without delay. See an endocrinologist urgently for: new-onset hypertension with hypokalaemia (possible Conn's syndrome); episodic headache, sweating, and palpitations with hypertension (possible phaeochromocytoma — never attempt adrenal biopsy before biochemically excluding phaeochromocytoma). Refer to endocrinology for any adrenal incidentaloma found on imaging.