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

The adrenal glands are paired triangular organs sitting atop each kidney that produce vital hormones governing survival, stress response, fluid balance, and metabolism. The adrenal cortex produces cortisol (stress response, immune modulation, glucose regulation), aldosterone (sodium and potassium balance, blood pressure regulation), and androgens (sex hormone precursors). The adrenal medulla produces catecholamines — adrenaline (epinephrine) and noradrenaline (norepinephrine) — governing the fight-or-flight response. Adrenal disorders arise from either deficient or excessive hormone secretion, or from tumours of the gland. The most clinically important conditions include Addison's disease (primary adrenal insufficiency — cortisol and aldosterone deficiency); Cushing's syndrome (pathological hypercortisolism from any cause); pheochromocytoma and paraganglioma (catecholamine-secreting tumours causing hypertensive crises); and primary hyperaldosteronism (Conn's syndrome — excess aldosterone causing hypertension and hypokalaemia). Adrenal incidentalomas — adrenal masses discovered incidentally on imaging — are found in 4-5% of CT scans and require functional evaluation. Although individually rare, adrenal disorders cause significant morbidity and mortality if unrecognised.

Causes differ by condition. Addison's disease (primary adrenal insufficiency): autoimmune adrenalitis — destruction of adrenal cortex by T-cell-mediated autoimmunity — accounts for 80-90% of cases in high-income countries; other causes include bilateral adrenal tuberculosis or histoplasmosis (most common cause globally), bilateral adrenal metastases (lung, breast, kidney, melanoma), haemorrhage into the adrenals (Waterhouse-Friderichsen syndrome from meningococcal septicaemia), and adrenoleukodystrophy. Cushing's syndrome: most commonly iatrogenic from long-term exogenous corticosteroid use; endogenous Cushing's syndrome is caused by pituitary adenoma secreting ACTH (Cushing's disease — 70% of endogenous cases), ectopic ACTH secretion (small cell lung carcinoma, carcinoid tumours — 10%), or cortisol-secreting adrenal adenoma or carcinoma. Pheochromocytoma and paraganglioma: ~30-40% are hereditary — genetic syndromes include MEN2 (RET mutation), VHL syndrome, neurofibromatosis type 1 (NF1), and succinate dehydrogenase (SDH) gene mutations. Primary hyperaldosteronism: bilateral adrenal hyperplasia (most common, 60%) or unilateral aldosterone-producing adenoma (Conn's adenoma — 35%).

Symptoms vary dramatically between conditions. Addison's disease (adrenal insufficiency) presents insidiously with profound fatigue, general weakness, unintentional weight loss, nausea, vomiting, abdominal pain, anorexia, postural hypotension (dizziness on standing), and salt craving. The hallmark physical sign is hyperpigmentation — darkening of the skin in sun-exposed areas, skin creases, buccal mucosa, gums, and surgical scars — caused by excess ACTH stimulation of melanocortin receptors (not present in secondary adrenal insufficiency). Adrenal crisis (acute adrenal failure) presents as a medical emergency with severe hypotension, shock, confusion, and vomiting, often triggered by illness, surgery, or missed steroid doses. Cushing's syndrome: central (truncal) obesity with thin limbs, moon face (facial rounding), cervicobrachial fat pad (buffalo hump), abdominal purple striae wider than 1 cm, easy bruising, skin thinning, hypertension, hyperglycaemia, proximal myopathy (difficulty rising from a chair), and osteoporosis. Pheochromocytoma: the classic triad of episodic severe pounding headache, profuse sweating, and palpitations — often precipitated by exercise, emotional stress, or certain medications — with associated hypertension (may be paroxysmal or sustained). Primary hyperaldosteronism: typically presents as resistant hypertension, hypokalaemia (muscle weakness, cramping, polyuria), and metabolic alkalosis.

Diagnosis requires condition-specific biochemical testing. Adrenal insufficiency: morning serum cortisol below 100 nmol/L is strongly suggestive; 100-500 nmol/L is indeterminate and requires Synacthen testing (short ACTH stimulation test — cortisol below 550 nmol/L at 30 or 60 minutes confirms adrenal insufficiency). Plasma ACTH distinguishes primary (high ACTH) from secondary/central (low ACTH) adrenal insufficiency. Anti-21-hydroxylase antibodies confirm autoimmune aetiology. Cushing's syndrome: three first-line screening tests — 24-hour urinary free cortisol (elevated on two separate collections), late-night salivary cortisol (elevated on two occasions, using cortisol circadian rhythm loss), and 1 mg overnight dexamethasone suppression test (failure to suppress morning cortisol below 50 nmol/L). Once confirmed, ACTH level and 8 mg dexamethasone suppression test (high-dose) localise the source; pituitary MRI for ACTH-dependent Cushing's; bilateral inferior petrosal sinus sampling (BIPSS) distinguishes pituitary from ectopic ACTH source. Pheochromocytoma: plasma metanephrines (sensitivity 97%) and 24-hour urine metanephrines are the primary tests; CT/MRI adrenals for localisation; MIBG scintigraphy or PET for paraganglioma. Primary hyperaldosteronism: elevated aldosterone-to-renin ratio (ARR) is the screening test; CT adrenals followed by adrenal vein sampling to lateralise before surgery.

Treatment is specific to the underlying condition. Addison's disease (primary adrenal insufficiency): lifelong glucocorticoid replacement with hydrocortisone 15-25 mg/day in two or three divided doses (morning dose larger to mimic the physiological cortisol circadian rhythm) plus mineralocorticoid replacement with fludrocortisone 100-200 mcg/day for aldosterone deficiency. Sick-day rules: dose must be doubled or tripled during illness, fever, vomiting, or physical stress, and IV hydrocortisone 100 mg is required for surgery or serious illness. All patients carry an emergency IM hydrocortisone injection kit. DHEA replacement may benefit women with fatigue and low libido. Cushing's syndrome: pituitary Cushing's disease — transsphenoidal adenomectomy by an experienced pituitary neurosurgeon is the first-line treatment, with remission in 70-80% of microadenomas. Adrenal adenoma — laparoscopic adrenalectomy. Medical therapy (ketoconazole, metyrapone, osilodrostat, or pasireotide) for cases not amenable to surgery. Iatrogenic Cushing's — gradual steroid tapering under endocrinology guidance. Pheochromocytoma: pre-operatively alpha-blockade (phenoxybenzamine or doxazosin) for at least 10-14 days before laparoscopic adrenalectomy — failure to alpha-block pre-operatively risks fatal intraoperative hypertensive crisis. Primary hyperaldosteronism: unilateral aldosterone-producing adenoma — laparoscopic adrenalectomy cures hypertension in 40-60%; bilateral hyperplasia — spironolactone 12.5-200 mg/day or eplerenone.

Unrecognised Addison's disease can precipitate a life-threatening adrenal crisis — severe hypotension, refractory shock, hyponatraemia (serum sodium below 120 mmol/L), hyperkalaemia, hypoglycaemia, and altered consciousness — triggered by intercurrent illness, surgery, gastrointestinal fluid loss, or missed doses; adrenal crisis carries a mortality of up to 6% per episode. Untreated Cushing's syndrome causes progressive osteoporosis with vertebral and hip fractures, poorly controlled type 2 diabetes, severe hypertension, thromboembolic disease (DVT and pulmonary embolism — risk elevated 4-fold), opportunistic infections from immune suppression, and a 4-fold increased cardiovascular mortality. Cushing's syndrome with hypertension uncontrolled has a significantly elevated risk of haemorrhagic stroke. Untreated pheochromocytoma carries high risk of sudden-onset hypertensive crisis triggering hypertensive encephalopathy, haemorrhagic stroke, acute myocardial infarction, or sudden cardiac death — lethal without emergency alpha-blockade. Untreated primary hyperaldosteronism causes resistant hypertension with markedly elevated cardiovascular risk (stroke, heart failure, atrial fibrillation) disproportionate to the level of blood pressure elevation, and hypokalaemia causing severe muscle weakness, paralysis, and arrhythmias.

Addison's disease patients must strictly follow sick-day rules — doubling hydrocortisone for mild illness, tripling for fever above 38.5°C or significant illness, and administering emergency IM hydrocortisone 100 mg for vomiting or surgery — and wear a steroid emergency medical alert bracelet at all times. Always carry an emergency IM hydrocortisone injection kit (Solu-Cortef Act-O-Vial) and train family members to administer it. Patients on long-term corticosteroids for any condition must never stop abruptly — iatrogenic adrenal insufficiency requires gradual weaning over weeks to months under medical supervision. Bone density (DEXA) scanning is recommended for all patients with Cushing's syndrome or on long-term corticosteroids; prescribe calcium, vitamin D, and bisphosphonates as indicated. Cardiovascular risk factor screening and management (hypertension, dyslipidaemia, glucose) is essential in Cushing's syndrome, as cardiovascular risk may persist even after remission. Genetic testing and counselling is recommended for all pheochromocytoma and paraganglioma patients regardless of family history — 40% have an identifiable germline mutation. Regular endocrinology follow-up with annual biochemical monitoring is lifelong for patients with adrenal insufficiency and post-surgical adrenal conditions.

Seek emergency care for acute adrenal crisis: sudden severe weakness, low blood pressure, vomiting, abdominal pain, confusion, or collapse — particularly in a patient on long-term steroids or with known Addison's disease. This is a life-threatening medical emergency requiring immediate IV hydrocortisone 100mg. See an endocrinologist promptly for: unexplained persistent fatigue with weight loss, darkened skin (especially in skin creases, gums, and scars), persistent low blood pressure, salt craving, or low sodium on blood tests — these suggest adrenal insufficiency. See a doctor for unexplained weight gain concentrated in the face, neck, and trunk with stretch marks, high blood pressure, and glucose intolerance — suggesting Cushing's syndrome. Carry a steroid emergency card and emergency hydrocortisone injection kit if you have known adrenal insufficiency.