Discuss the causes, clinical features, investigations and management of adrenal insufficiency, including adrenal crisis.

Definition & Classification

Adrenal insufficiency is deficient production of adrenocortical hormones — glucocorticoid (cortisol), and in primary disease also mineralocorticoid (aldosterone) and adrenal androgens.

Pathophysiology of the Clinical Signs

• Cortisol deficiency → fatigue, weight loss, hypoglycaemia, hypotension, inability to withstand stress.
• Aldosterone deficiency (primary only) → sodium loss and potassium retention: hyponatraemia, hyperkalaemia, hypovolaemia, postural hypotension, salt craving.
• Loss of negative feedback (primary only) → high ACTH from the POMC precursor, which also generates melanocyte-stimulating hormone → hyperpigmentation.
• Adrenal androgen deficiency → loss of axillary and pubic hair and reduced libido in women.

Clinical Features

Chronic (insidious, and frequently missed for months):

• Profound fatigue, weakness, anorexia, weight loss, nausea, vomiting, abdominal pain, diarrhoea.
• Postural dizziness and hypotension.
• Hyperpigmentation — the hallmark of primary disease: most marked in palmar creases, knuckles, scars, buccal mucosa, gums, areolae and pressure points.
• Salt craving; myalgia and arthralgia; depression and irritability.
• Vitiligo may coexist in autoimmune disease.
• In women, loss of axillary and pubic hair.

Associated autoimmune disease: thyroid disease, type 1 diabetes, pernicious anaemia — the autoimmune polyglandular syndromes.

Adrenal (addisonian) Crisis

A life-threatening emergency precipitated by infection, trauma, surgery, vomiting, or abrupt withdrawal of steroids, in a patient with undiagnosed or inadequately replaced insufficiency.

Features: profound hypotension and shock refractory to fluids and vasopressors, severe vomiting and abdominal pain (may mimic an acute abdomen), fever, confusion progressing to coma, hypoglycaemia, hyponatraemia with hyperkalaemia, and hypovolaemia.

Investigations

• Serum electrolytes: hyponatraemia with hyperkalaemia (primary), hypoglycaemia, sometimes hypercalcaemia and a mild metabolic acidosis.
• 8–9 a.m. serum cortisol: a clearly low value supports the diagnosis; a clearly normal value largely excludes it; intermediate values require dynamic testing.
• Short Synacthen (ACTH stimulation) test — the confirmatory investigation. Measure cortisol before and after synthetic ACTH; failure of cortisol to rise adequately confirms adrenal insufficiency.
• Plasma ACTH — distinguishes the level of the lesion: markedly raised in primary, low or inappropriately normal in secondary and tertiary disease.
• Plasma renin and aldosterone: high renin with low aldosterone in primary disease.
• Adrenal autoantibodies (21-hydroxylase); if negative, investigate for other causes.
• Imaging: CT adrenals — small atrophic glands in autoimmune disease; enlarged glands with calcification in tuberculosis; masses in metastases or haemorrhage. MRI pituitary in secondary disease.
• Screen for tuberculosis in the Indian setting — chest X-ray, Mantoux, sputum studies.

Management

Adrenal crisis:

1. Intravenous hydrocortisone immediately, then repeated doses or a continuous infusion.

2. Aggressive fluid resuscitation with isotonic saline; add dextrose for hypoglycaemia.

3. Correct hypoglycaemia and electrolyte disturbance — hyperkalaemia usually resolves with fluids and steroid.

4. Identify and treat the precipitant — infection is the commonest.

5. Monitor closely; taper to oral maintenance as the patient recovers. Mineralocorticoid is not needed at high hydrocortisone doses, which have intrinsic mineralocorticoid activity.

Long-term replacement:

• Glucocorticoid: hydrocortisone in divided doses mimicking the diurnal rhythm — the largest dose on waking. Prednisolone is an alternative.
• Mineralocorticoid: fludrocortisone in primary disease only; titrate against postural blood pressure, potassium and renin.
• Androgen replacement (DHEA) may be considered in women with persistent low libido and energy.
• Treat the underlying cause — antitubercular therapy where tuberculosis is responsible.

Patient education — the most important long-term intervention:

• Never stop steroids abruptly.
• "Sick day rules": double the glucocorticoid dose during fever or intercurrent illness, and seek urgent care if vomiting prevents oral intake.
• Carry a steroid emergency card and medical alert bracelet; keep an emergency hydrocortisone injection kit at home, with the patient and family trained to use it.
• Inform every treating doctor and dentist; additional cover is required for surgery and procedures.