How is a diagnosis of pediatric adrenal insufficiency (Addison disease) confirmed by serum control testing, and does salivary cortisol testing also have value?

Updated: Mar 10, 2020
  • Author: Kimberly Tafuri, DO; Chief Editor: Sasigarn A Bowden, MD  more...
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Answer

A diagnosis of adrenal insufficiency is confirmed if the serum cortisol level is less than 18 mcg/dL in the presence of a markedly elevated serum adrenocorticotropic hormone (ACTH) concentration and plasma renin activity. Based on normative data of children of various ages, adrenal insufficiency is likely if the serum cortisol concentration is less than 18 mcg/dL 30-60 minutes after intravenous (IV) administration of 250 mcg of cosyntropin (synthetic ACTH 1-24) in children over age 2 years. The cosyntropin test dose may be decreased to 15 mcg/kg for infants and 125 mcg for children under age 2 years. [2, 3, 46]

These criteria may not apply to premature or low-birth-weight infants, who have low cortisol secretion and, most likely, decreased cortisol binding to carrier proteins. [4] Therefore, the diagnosis of adrenal insufficiency in premature infants remains problematic.

If the serum cortisol level is low and the ACTH value is elevated, measurement of antiadrenal antibodies may be informative. Antibodies to one or more steroidogenic enzymes, particularly 21-hydroxylase, are often found in patients with autoimmune adrenal disease.

When a patient's serum cortisol response to cosyntropin is subnormal but his or her serum ACTH level is not elevated, the possibility of central adrenal insufficiency should be considered. Other indications of pituitary dysfunction, such as previous glucocorticoid exposure (suggesting a suppressed hypothalamic-pituitary-adrenal axis) or evidence of other pituitary dysfunction (suggesting hypopituitarism) are helpful.

In central adrenal insufficiency, a 3-day stimulation with ACTH produces a normal cortisol response, indicating intact adrenal glands and implying that the initial low cortisol response to cosyntropin was related to chronic ACTH deficiency. ACTH gel (ACTHar Gel) is administered at 25 U/m2 every 12 hours for 3 days. Plasma cortisol levels should increase to more than 40 mcg/dL in response. This procedure is now seldom performed since plasma ACTH concentrations can be measured.

Salivary cortisol testing

A study by Chao et al indicated that salivary cortisol can be used to confirm or replace serum cortisol testing in the diagnosis of adrenal insufficiency in children. The investigators measured salivary cortisol via liquid chromatography–tandem mass spectrometry, employing a cutoff value of 500 ng/dL for salivary cortisol and 18 μg/dL for serum cortisol. They found that during high-dose adrenocorticotropic hormone (ACTH) stimulation testing, salivary and serum cortisol each had 100% specificity and sensitivity in the detection of adrenal insufficiency in pediatric patients. [47]


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