Definition and epidemiology
Primary adrenal insufficiency (PAI, Addison disease when autoimmune) is failure of the adrenal cortex to produce sufficient glucocorticoid and/or mineralocorticoid, with loss of negative feedback driving a compensatory rise in ACTH. That high ACTH distinguishes primary from central (secondary) insufficiency and explains the hyperpigmentation of mucosa, palmar creases and scars.
Etiology in children differs sharply from adults. Congenital adrenal hyperplasia (CAH) — most often 21-hydroxylase deficiency — accounts for the majority of pediatric PAI; autoimmune adrenalitis (isolated or as part of autoimmune polyglandular syndromes), adrenoleukodystrophy, congenital adrenal hypoplasia, ACTH resistance syndromes, infection (tuberculosis), infiltration, and bilateral adrenal haemorrhage make up the remainder. PAI is rare but dangerous: presentation is frequently as an undiagnosed crisis precipitated by intercurrent illness.
Clinical features
Chronic PAI is insidious — fatigue, anorexia, weight loss or poor growth, nausea, abdominal pain, salt craving, postural dizziness and hyperpigmentation. In neonates and infants, suspect it with poor feeding, vomiting, failure to thrive, hypoglycaemic seizures, or ambiguous genitalia/salt-wasting (CAH). Because symptoms are non-specific, the diagnosis is often made only when the child decompensates.
Adrenal crisis — the emergency
Adrenal crisis is a life-threatening, can’t-miss emergency. It is precipitated by infection, trauma, surgery, fasting, or abrupt withdrawal of steroids. The hallmark is hypotension/shock disproportionate to the apparent illness, with the characteristic biochemistry of glucocorticoid and mineralocorticoid deficiency:
- Hyponatraemia and hyperkalaemia (mineralocorticoid loss)
- Hypoglycaemia (glucocorticoid loss — especially in infants/young children)
- Metabolic acidosis, dehydration, and circulatory collapse
Treatment is empirical and must not wait for confirmatory results: parenteral glucocorticoid (hydrocortisone) plus aggressive isotonic fluid resuscitation and glucose correction, alongside treatment of the precipitant. Draw a cortisol/ACTH sample first if it does not delay therapy, but giving steroid takes priority over diagnostic purity.
Diagnosis
Outside a crisis, the biochemical pillars are a low morning serum cortisol with an inappropriately elevated ACTH; a subnormal cortisol response to a standard-dose ACTH (Synacthen) stimulation test confirms it. Elevated plasma renin with low/inappropriate aldosterone confirms mineralocorticoid deficiency. Once PAI is established, define the cause: 17-hydroxyprogesterone (CAH), 21-hydroxylase and adrenal-cortex autoantibodies, very-long-chain fatty acids (adrenoleukodystrophy in boys), and imaging where infiltration/haemorrhage is suspected.
See the full criteria: Primary Adrenal Insufficiency
Red flags
- Shock or hypotension not explained by the presenting illness
- Hyponatraemia with hyperkalaemia and/or hypoglycaemia
- Hyperpigmentation with weight loss and salt craving
- Hypoglycaemic seizure in an infant; vomiting neonate with salt-wasting
- A known PAI patient who is vomiting, febrile or post-operative — treat as impending crisis
Management overview
Maintenance therapy replaces what the gland cannot make: a glucocorticoid (hydrocortisone is preferred in growing children) and, in primary disease, a mineralocorticoid (fludrocortisone); infants additionally need salt supplementation. The single most important safety concept is stress dosing — glucocorticoid requirements must be increased (typically doubled or tripled) during febrile illness, vomiting, trauma or surgery, with a switch to parenteral hydrocortisone if oral intake fails. Every family must carry an emergency hydrocortisone injection, a medical-alert identifier, and written sick-day rules, and should be drilled on recognising early crisis. Lifelong pediatric endocrinology follow-up monitors growth, pubertal progression and over/under-replacement.
References
- Bornstein SR, et al. Endocrine Society Guideline. J Clin Endocrinol Metab. 2016;101:364–389.
- Rushworth RL, et al. Adrenal Crisis. N Engl J Med. 2019;381:852–861.
- Ergun-Longmire B, et al. PAI in the pediatric population. Pediatr Med. 2023.
Decision support for qualified clinicians only — verify against current primary guidelines and your clinical judgement.