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Recovery of the hypothalamic-pituitary-adrenal axis in children and adolescents after surgical cure of Cushing's disease

Recovery of the hypothalamic-pituitary-adrenal axis in children and adolescents after surgical cure of Cushing's disease

Journal of Clinical Endocrinology and Metabolism 97(5): 1483-1491

Recovery of the hypothalamic-pituitary-adrenal axis (HPAA) after transsphenoidal surgery (TSS) for Cushing's disease (CD) in children has not been adequately studied. Our objective was to assess time to recovery of the HPAA after TSS in children with CD. This was a case series at the National Institutes of Health Clinical Center. Fifty-seven patients with CD (6-18 yr, mean 13.0 ± 3.1 yr) given a standard regimen of glucocorticoid tapering after TSS were studied out of a total of 73 recruited. ACTH (250 μg) stimulation tests were administered at approximately 6-month intervals for up to 36 months. Age, sex, pubertal status, body mass index, length of disease, midnight cortisol, and urinary free cortisol at diagnosis were analyzed for effects on recovery. The main outcome measure was complete recovery of the HPAA as defined by a cortisol level of at least 18 μg/dl in response to 250 μg ACTH. Full recovery was reached by 43 (75.4%) of 57 patients, with 29 of the 43 (67.4%) and 41 of the 43 (95.3%) recovering by 12 and 18 months, respectively. The overall mean time to recovery was 12.6 ± 3.3 months. Kaplan-Meier survivor function estimated a 50% chance of recovering by 12 months after TSS and 75% chance of recovering within 14 months. By receiver operating characteristic curve assessment, the cutoff of at least 10-11 μg/dl of cortisol as the peak of ACTH stimulation testing at 6 months after TSS yielded the highest sensitivity (70-80%) and specificity (64-73%) to predict full recovery of the HPAA at 12 months. Two of the four patients that recovered fully within 6 months had recurrent CD. Although this is not a randomized study, we present our standardized tapering regimen for glucocorticoid replacement after TSS that led to recovery of the HPAA in most patients within the first postoperative year. Multiple factors may affect this process, but an early recovery may indicate disease recurrence.

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Accession: 036394942

Download citation: RISBibTeXText

PMID: 22399509

DOI: 10.1210/jc.2011-2325

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