What is the role of adrenocorticotropic hormone (ACTH) testing in the workup of pediatric adrenal insufficiency (Addison disease)?

Updated: Mar 10, 2020
  • Author: Kimberly Tafuri, DO; Chief Editor: Sasigarn A Bowden, MD  more...
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The standard ovine corticotropin-releasing hormone (CRH) stimulation test (1 mcg/kg over 1 min) may be helpful in the differential diagnosis of adrenal insufficiency. A lack of a 2-fold increase in serum adrenocorticotropic hormone (ACTH) concentration indicates pituitary dysfunction. A 2-fold or greater rise in ACTH without a concomitant rise in serum cortisol to more than 18-20 mcg/dL implies primary adrenal insufficiency. [48] Ovine CRH is difficult to obtain, and this test is mainly performed for research purposes.

A study by Iwanaga et al indicated that CRH stimulation tests can be effectively used in the diagnosis of relative adrenal insufficiency in preterm infants. Administering CRH stimulation tests to preterm infants with relative adrenal insufficiency and to those without it, the investigators found that neither base nor peak serum cortisol levels differed between the two groups. However, in the group with relative adrenal insufficiency, significant reductions were seen in delta cortisol levels and in the responsive ratio (peak-to-base ratio). [49]

The best dose of cosyntropin to administer for a cosyntropin stimulation test remains controversial, [50, 51, 52, 53] and this issue remains unresolved in the pediatric age group.

The standard dose is 250 mcg intravenously; some pediatric endocrinologists reduce the cosyntropin dose to 50-125 mcg for infants. Very low cosyntropin doses (1 mcg or 0.5 mcg/m2) have been used in the belief that the low-dose test is more sensitive for central adrenal insufficiency. [54] Meta-analysis suggested that the low-dose cosyntropin stimulation test may be superior, but the difference was small. [50] There actually may be a higher rate of false-positive test results with the low-dose ACTH stimulation test. [55]

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