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BACKGROUND: Children undergoing hematopoietic cell transplantation (HCT) are at high-risk of developing adrenocortical insufficiency (AI).

OBJECTIVES: Primary objective of this study was to determine prevalence of AI in pediatric HCT recipients.

DESIGN/METHODS: Under an IRB approved study, we identified HCT recipients who were tested for AI at our institution. Adrenocortical function was evaluated by ACTH stimulation tests (stim test). A low-dose stim test was performed by giving 1 mcg cosyntropin intravenously and measuring serum cortisol levels at 0, 10, 20 and 30 minutes. A high-dose stim test was performed by giving 15 mcg per kg (max 250 mcg) cosyntropin and measuring serum cortisol levels at 0, 30 and 60 minutes. AI was diagnosed if peak serum cortisol level was below 18 mcg/dL. AI was classified as (1) adrenal suppression from the effects of exogenous glucocorticoids or other medications on hypothalamic-pituitary (HP) axis, (2) central AI due to direct effect on HP region by tumor, surgery, or cranial radiation therapy; or (3) primary AI due to adrenal gland pathology.

RESULTS: Between years 2006 -2017, 269 patients, median age 10.2 years (range 0.1 – 22.4) underwent 349 transplants (59% allogeneic, 41% autologous). Of these, 66 patients who had 87 transplants underwent adrenocortical function testing. In those tested, a majority of the transplants were allogeneic (73.6%) and were performed for malignant diseases (66.7%); and 38 patients had prior glucocorticoid exposure (57.6%). A total of 83 stim tests were performed, and no adverse effects were noted. Of these, 63 were high-dose, 6 were low-dose, and 14 were low-dose followed by high-dose. AI was observed in 14/66 patients (21%). The most common cause of AI was adrenal suppression (12/14 cases, 86%); 10 had exposure to glucocorticoids and 2 to megestrol. One patient had primary AI related to MIRAGE syndrome, and another from adrenal gland resection. There was a higher rate of AI in patients with acute GVHD (29%) compared to those without acute GVHD (12%). Of the 31 children with acute GVHD, 23 (74%) were found to have normal adrenal gland function despite prior glucocorticoid exposure.

CONCLUSIONS: We observed a high prevalence of AI in pediatric HCT recipients. The stim tests demonstrated recovery of HPA axis in a majority of patients with acute GVHD and prior glucocorticoid exposure. ACTH stimulation testing is a useful, objective measure of HPA axis function; it should be used to guide replacement and stress dosing of glucocorticoids in high risk HCT recipients.

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Use of ACTH Stimulation Test to Diagnose Adrenocortical Insufficiency in Pediatric HCT Recipients