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BACKGROUND: Childhood cancer survivors with brain tumors are at high risk of developing adrenocortical insufficiency (AI).

OBJECTIVES: Primary objective of this study was to determine prevalence of AI in children with brain tumors.

DESIGN/METHODS: Under an IRB approved study, we performed retrospective chart review to identify children treated for brain tumors. Adrenocortical function was evaluated by ACTH stimulation test (“stim test”). 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 levels were below 18 mcg/dL. AI was classified as (1) central AI due to direct effect on hypothalamicpituitary (HP) region by tumor, surgery, or cranial radiation therapy; (2) adrenal suppression from the effects of exogenous glucocorticoids or other medications on hypothalamic-pituitary (HP) axis; and (3) primary AI due to adrenal gland pathology.

RESULTS: Four-hundred-one children, median age 8 years (range: 0.1 – 19) were diagnosed with brain tumors between 2006-2017 at our institution. Adrenocortical function testing was performed on 56 patients. A total of 72 stim tests were performed, and no adverse effects were noted. Of these 52 were high-dose, 13 were low-dose, and 7 were low-dose followed by highdose. AI was observed in 16/56 (29%) cases. All cases (16/16, 100%) were considered to be central, related to direct tumor effects on HP region, cranioradiation therapy and / or surgery. Exogenous glucocorticoids or megestrol causing adrenal suppression contributed in 4 (25%) cases. Amongst those undergoing stim testing, other endocrinopathies were common (43/56, 77%). We observed a higher rate of AI in patients with direct involvement of HPA by tumor (41% vs. 21%), and those undergoing surgery in HPA region (63% vs. 21%), and those with other endocrinopathies (33% vs. 18%).

CONCLUSIONS: We observed a high prevalence of AI in pediatric patients with brain tumors. Children with tumors involving the HP region are at high-risk and should have adrenal function evaluated early especially prior to intracranial surgery. Children with medulloblastomas who received cranial radiotherapy, and those with multiple endocrinopathies should be screened for late onset central AI. ACTH stim test is a useful and objective measure of hypothalamicpituitary- adrenal axis function and should be considered in routine practice in management of this high-risk population.

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Use of ACTH Stimulation Test to Diagnose Adrenocortical Insufficiency in Children with Brain Tumors