Familial Glucocorticoid Deficiency Workup

Updated: Feb 16, 2019
  • Author: Andrea M Haqq, MD, MHS, FRCPC, FAAP; Chief Editor: Sasigarn A Bowden, MD, FAAP  more...
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Laboratory Studies

Patients should receive a baseline 9 am serum cortisol and adrenocorticotropic hormone (ACTH) stimulation test.

Familial glucocorticoid deficiency (FGD) is characterized in laboratory testing by a low or low-normal first morning serum cortisol and markedly elevated ACTH levels in contrast to a normal renin-aldosterone axis. Cortisol levels are typically in the range of less than 10-75 ng/mL (reference range is 50-150 ng/mL), whereas ACTH values are typically in the range of greater than 300-7000 ng/L (reference range is 10-80 ng/L).

The cortisol levels are unresponsive to exogenous ACTH stimulation (Cortrosyn stimulation test).

Plasma results reveal normal very long chain fatty acid (VLCFA) levels, thus ruling out adrenoleukodystrophy.

Serum tests include the following:

  • Test sodium, potassium, aldosterone, and renin levels.

  • Supine and standing renin and aldosterone concentrations are within the reference range in FGD, revealing normal variability in response to salt restriction. Note that although renin and aldosterone levels are typically normal in FGD, rare cases of minor impairment in the renin-aldosterone axis have been reported .

  • The electrolyte abnormalities, including hyponatremia and hyperkalemia, are not usually present. These abnormalities typically characterize other adrenal diseases.

  • FGD is often characterized by low levels of serum dihydroxyepiandrosterone sulphate (DHEAS).

  • Consider a diagnosis of congenital adrenal hyperplasia in any infant with signs of glucocorticoid deficiency. The most common form, 21-hydroxylase deficiency, can be ruled out by reference range 17-hydroxyprogesterone levels. Virilized genitalia may be present in some female infants with congenital adrenal hyperplasia, although this does not occur in FGD.

Patients with adrenoleukodystrophy also present with multiple adrenal hormone deficiencies. VLCFA levels are elevated in adrenoleukodystrophy.

Antiadrenal antibodies can usually be detected in patients with Addison disease (AD), an autoimmune form of adrenal insufficiency, and may be useful in ruling out AD as a diagnostic possibility.

Ophthalmologic examination is indicated when the diagnosis of Allgrove syndrome (AS) is under consideration. AS is characterized by glucocorticoid deficiency, alacrima (absence of tears), achalasia of the cardia, and a wide spectrum of neurologic abnormalities.

Alacrima is determined by a Schirmer test that provides a semiquantitative measure of tearing. In this test, a standardized test strip is placed in the conjunctival sac and wetting of the strip over a 5-minutes interval is determined. Alacrima is defined as less than 10 mm of wetting.

Slit lamp examination and fluorescein staining may be helpful in illustrating corneal pathology secondary to decreased tear production. Should these tests indicate a diagnostic possibility of AS, other investigations are warranted and include barium esophagraphy, esophageal manometry, endoscopy, neurologic evaluation, brainstem auditory evoked response (BAER), and autonomic testing.

For hypoglycemia testing, obtain a CBC count, serum glucose level, and a comprehensive metabolic panel with and without cerebrospinal fluid (CSF) studies for protein, glucose, cell count, and culture. In any patient presenting with seizures, ruling out hypoglycemia as the inciting cause is imperative. In some cases, a lumbar puncture may also be indicated. These investigations are not specific in making a diagnosis of FGD, but they can provide important clues to the etiology of the seizure.

Hypopituitarism can also lead to adrenal insufficiency. If ACTH levels are low in the setting of adrenal insufficiency, clinically evaluate other pituitary hormones with specific laboratory testing.