Inherited Adrenal Hypoplasia: Not Just for Kids!

Lin Lin; John C. Achermann


Clin Endocrinol. 2004;60(5) 

In This Article

What Is Adrenal Hypoplasia?

Adrenal hypoplasia is underdevelopment or atrophy of the adrenal glands, and can occur in secondary or primary forms. Secondary adrenal hypoplasia results from impaired secretion of ACTH from pituitary corticotropes or due to ACTH resistance, and is caused by a lack of tropic stimulation of the adrenal gland. Glucocorticoid synthesis and release are primarily affected in these cases. In contrast, primary adrenal hypoplasia results from abnormal adrenal development and function, usually due to abnormalities in transcription factors expressed within the adrenal gland itself. Primary adrenal hypoplasia often affects the zona glomerulosa, causing mineralocorticoid insufficiency and salt loss, as well as impaired glucocorticoid synthesis and release.

Diagnostic clues to the specific cause of adrenal hypoplasia can often be obtained from the patient's biochemical profile at presentation, family history and from any associated clinical features found. Obtaining a reliable measurement of serum ACTH (especially prior to steroid treatment) can be extremely useful in differentiating ACTH insufficiency (inappropriately low ACTH) from ACTH resistance or primary hypoplasia (elevated ACTH). Similarly, evidence of hyponatraemia or hyperkalaemia, low aldosterone, or elevated plasma renin activity would reflect impaired mineralocorticoid secretion. Whilst potentially life-saving steroid treatment should not be delayed, obtaining samples for these tests at the time of presentation can often make the diagnosis easier, and readdressing this once steroid treatment has been started can be challenging.

An overview of inherited forms of adrenal hypoplasia and their associated features is shown in Fig. 1 and Table 1 . The differential diagnosis of inherited adrenal hypoplasia includes other causes of panhypopituitarism or ACTH deficiency; ACTH resistance of unknown origin [familial glucocorticoid deficiency 2 (FGD2)]; and other causes of Addison's disease or adrenal destruction. Patients with congenital adrenal hyperplasia (e.g. 21-hydroxylase deficiency) or lipoid adrenal hyperplasia [due to defects in steroidogenic acute regulatory protein (StAR), or CYP11A] often have a diagnostic biochemical profile, abnormalities in gonadal steroid production and enlarged adrenals on imaging. However, adrenal imaging is not always reliable, especially early in life, and relatively small adrenals have been reported occasionally in patients with mutations in StAR.

Overview of the hypothalamic-pituitary(corticotrope)-adrenal axis. Mutations in the genes listed have been shown to cause adrenal hypoplasia in humans (reprinted with permission from Achermann et al., 2001). ATII, angiotensin II; LCH, Langerhans' cell histiocytosis; FGD2, familial glucocorticoid deficiency type 2; ALD, adrenoleukodystrophy.


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