Paediatrics: Adrenal insufficiency

Adrenal insufficiency

·  1^o adrenal failure: results in both reduced glucocorticoid (cortisol) and mineralocorticoid (aldosterone) production. Adrenocorticotrophin (ACTH) levels are elevated due to reduced cortisol negative feedback drive.

·  2^o adrenal failure: is due to either reduced corticotrophin-releasing factor (CoRF) or reduced ACTH production (or both) and results in reduced cortisol production only. Mineralocorticoid activity remains normal as this is mainly regulated by the angiotensin–renin system.

Causes of adrenal insufficiency

Primary

Acquired

·  Autoimmune adrenalitis (Addison’s disease).

·  Adrenal infection, e.g. tuberculosis.

·  Adrenal haemorrhage/infarction.

·  Latrogenic: adrenolectomy; drugs (e.g. ketoconazole).

Congenital

·  Congenital adrenal hyperplasia.

·  Congenital adrenal hypoplasia.

·  Adrenoleucodystrophy.

·  Familial glucocorticoid deficiency.

Secondary

·  Defects of hypothalamus/pituitary structures:

·  congenital—pituitary hypoplasia;

·  intracranial masses: tumours (e.g. glioma, germinoma); craniopharyngioma;

·  intracranial inflammation: Langerhan’s histiocytosis;

·  intracranial infections;

·  cranial radiotherapy/irradiation;

·  neurosurgery;

·  traumatic brain injury.

·  Suppression of hypothalamic–pituitary–adrenal axis:

·  glucocorticoid therapy;

Cushing’s disease (after pituitary tumour removal).

Clinical features

The age of onset and manifestations will depend on the underlying cause. Clinical features may be subtle and a high index of suspicion is often re-quired. Typically, clinical features are gradual in onset with partial insuf-ficiency leading to complete adrenal insufficiency with impaired cortisol responses to stress and illness (adrenal crises):

·anorexia and weight loss;

·fatigue and generalized weakness;

·dizziness (hypotension);

·salt craving (primary adrenal insufficiency);

·hyperpigmentation (primary adrenal insufficiency);

·reduced pubic/axillary hair (primary adrenal insufficiency);

·hypoglycaemia (neonates/infants).

Diagnosis

Basal serum cortisol and ACTH

Note: Random basal cortisol levels are often within the normal range and cannot be relied on. Inappropriately low basal cortisol during ‘stress’ sug-gests adrenal insufficiency. A basal cortisol level of >550nmol/L usually excludes this diagnosis. An elevated early morning (09.00 hours) ACTH level for the level of cortisol is suggestive of primary adrenal insufficiency.

Adrenal stimulation tests

Usually required to establish a diagnosis of adrenal insufficiency and are used to demonstrate inappropriately low serum cortisol responses to physiological or pharmacological stimulation of the adrenal glands.

·Insulin tolerance test: considered the gold standard test. Insulin-induced mild hypoglycaemia is used to assess the integrity of the entire hypothalamic–pituitary–adrenal axis. Serum cortisol response to hypoglycaemia (>550nmol/L) is normal.

·ACTH stimulation (synacthen) test: serum cortisol is measured at baseline and at +30 and +60min after IV/IM of synthetic ACTH (short synacthen test). Serum cortisol response >550nmol/L at 60min is considered normal. Recent onset secondary adrenal insufficiency may produce a normal response to a short synacthen test.

Other investigations

·Serum electrolytes: serum sodium (low); serum potassium (high).

·Adrenal antibody titres (Addison’s disease).

·Adrenal imaging: US; CT scan.

·Adrenal androgen profile: serum/urine.

·Molecular genetic studies.

Pituitary imaging: CT or MRI scan