Adrenal function in adult long-term survivors of nephroblastoma and neuroblastoma

Background: Adrenal insufficiency, or relative insufficiency, might partly explain increased mortality rates in nephroblastoma and neuroblastoma survivors after unilateral adrenalectomy. Objective: To assess adrenal function and its metabolic effects in survivors after adrenalectomy. Methods: In this cross-sectional study, 67 adult long-term survivors of nephroblastoma, 36 survivors of neuroblastoma and 49 control subjects participated. Adrenal function was assessed by a 1 μg short Synacthen-test. Levels of cortisol, adrenocorticotrophic hormone (ACTH), low (LDL-C) and high-density lipoprotein-cholesterol (HDL-C), triglycerides, apolipoprotein-B, glucose and insulin were assessed in blood samples taken at baseline. In addition, cortisol levels were assessed after 30 (t = 30) and 60 min. Homoeostatic Model Assessment (HOMA) was calculated. Results: Adrenal insufficiency was not present in survivors. Interestingly, baseline serum cortisol levels were higher in survivors after unilateral adrenalectomy (mean 503 nmol/l) (N = 46) than in survivors with both adrenals intact (mean 393 nmol/l, P = 0.002) (N = 52), and than in controls (mean 399 nmol/l, P = 0.013) (N = 49). After correcting for age, sex and use of oral oestrogens, unilateral adrenalectomy was independently associated with elevated baseline cortisol and ACTH levels. Baseline cortisol levels were positively associated with triglycerides (P < 0.001), LDL-C (P = 0.004), apolipoprotein-B (P < 0.001) and HOMA (P = 0.008). Conclusions: No adrenal insufficiency was observed in survivors of nephroblastoma and neuroblastoma. Survivors treated with unilateral adrenalectomy had relatively high basal cortisol and ACTH levels, indicating a higher central setpoint of the hypothalamic-pituitary-adrenal axis. This higher setpoint was associated with lipid concentrations and insulin resistance and can therefore influence the cardiovascular risk profile in long-term survivors of nephroblastoma and neuroblastoma.

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