TABLE 1

Congenital and inborn causes of primary adrenal insufficiency

Category and cause		Key features^{^a}
Congenital adrenal hyperplasia¹	21-Hydroxylase deficiency	Most common subtype Classic variant causes deficiency of both cortisol and aldosterone Can also cause virilization in females due to accumulation of dehydroepiandrosterone metabolites
	11-Beta-hydroxylase deficiency	Accumulation of aldosterone precursor 11-deoxycorticosterone results in hypertension and hypokalemia
	3-Beta-hydroxylase deficiency	Lack of dehydroepiandrosterone conversion to testosterone causes ambiguous genitalia in boys
Other enzymatic abnormality¹⁷	Aldosterone synthase deficiency	Isolated mineralocorticoid deficiency
Other enzymatic abnormality¹⁷	Deficiency of P450 side-chain cleavage enzyme	Slows the rate-limiting step in cortisol synthesis
ACTH resistance²³	Familial glucocorticoid deficiency type 1	Tall stature, isolated deficiency of glucocorticoids, and generally normal aldosterone production
ACTH resistance²³	3A (Allgrove, AAA) syndrome	Achalasia, Addison disease, alacrimia, AAAS gene mutation
Adrenoleuko dystrophy²³	Accumulation of very long chain fatty acid in adrenal cortex	Inhibited response to ACTH; X-linked recessive disorder associated with neurologic deficits that predominantly affects males and typically presents in adolescence
Congenital adrenal dysgenesis¹	Congenital but can also be secondary to ACTH deficiency	Hypotrophy of adrenal cortex, adrenal insufficiency, hypogonadism, especially in males due to reduction in adrenal androgens
Others (rare)^1,17,23	Wolman disease	Lysosomal acid lipase deficiency that results in accumulation of fat and diffuse punctate adrenal calcification causing adrenal insufficiency Very poor prognosis
	Abetalipoproteinemia	Fat malabsorption results in lack of cholesterol to make steroids
	Mitochondrial disorders	External ophthalmoplegia, retinal degeneration, cardiac conduction defects

↵^aNot all listed primary adrenal conditions necessarily present with both glucocorticoid and mineralocorticoid deficiency.
AAA = achalasia, Addison disease, alacrimia; ACTH = adrenocorticotropic hormone