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Standard and Low-Dose Short Adrenocorticotropin Test Compared with Insulin-Induced Hypoglycemia for Assessment of the Hypothalamic-Pituitary-Adrenal Axis in Children with Idiopathic Multiple Pituitary Hormone Deficiencies

Institute for Endocrinology and Diabetes, Schneider Children’s Medical Center of Israel, Petah Tiqva 49292 Israel; and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

Address all correspondence and requests for reprints to: Naomi Weintrob, Institute of Pediatric and Adolescent Endocrinology, Schneider Children’s Medical Center of Israel, 14 Kaplan Street, Petah Tiqva 49292, Israel.

Insulin-induced hypoglycemia (IIH) is the gold standard test for assessment of the integrity of the hypothalamic-pituitary-adrenal (HPA) axis, but it may be hazardous. We sought to determine whether the standard (250 µg) or low-dose (1 µg/1.73 m²) short ACTH test can replace IIH in patients with idiopathic multiple pituitary hormone deficiencies (MPHD). Three groups of subjects were studied: 1) control group, children with early or accelerated puberty and no other evidence of adrenal or pituitary pathology (n = 13, age 10.1 ± 2.2 yr, 3 males); 2) patients with idiopathic hypothalamic pituitary insufficiency and either isolated GH deficiency or MPHD and preserved HPA function (n = 20, age 13.7 ± 4.4 yr, 13 males); and 3) MPHD patients with impaired HPA axis function (n = 10, age 16.8 ± 4.8 yr, 9 males).

IIH and the 250 µg and 1 µg/1.73 m² ACTH tests were performed in groups 2 and 3; group 1 underwent only the ACTH tests. Pass peak cortisol level was defined as 520 nmol/L. No significant difference was noted between the standard and low-dose tests in the 30-min cortisol response to ACTH. Basal and peak cortisol levels attained on both ACTH tests were similar in groups 1 and 2 and significantly lower in group 3 (P < 0.0001). Both the 250 and 1 µg ACTH tests were highly correlated with IIH (r = 0.71, P < 0.0001 for the 250 µg, r = 0.7, P < 0.0001 for the 1 µg, n = 30), and both demonstrated high sensitivity (90% each) and specificity (100% and 90%, respectively) compared with IIH. We conclude that in idiopathic MPHD patients, both the standard and low-dose ACTH tests are equivalent to IIH in detecting HPA insufficiency. We suggest that they can replace IIH as a screening test for the integrity of the HPA axis in children with suspected MPHD.

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