title: Adrenal function in adult long-term survivors of nephroblastoma and neuroblastoma.
abstract: 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 1μg 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.
authors.affiliation: Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital Rotterdam, Dr. Molewaterplein 60, Rotterdam, The Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: van Waas
authors.forename: Sebastian J C M M
authors.initials: SJ
authors.lastname: Neggers
authors.forename: Judith P
authors.initials: JP
authors.lastname: van Eck
authors.forename: Max M
authors.initials: MM
authors.lastname: van Noesel
authors.forename: Aart-Jan
authors.initials: AJ
authors.lastname: van der Lely
authors.forename: Frank H
authors.initials: FH
authors.lastname: de Jong
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.forename: Marry M
authors.initials: MM
authors.lastname: van den Heuvel-Eibrink
mesh_terms: D000293:Adolescent; D000311:Adrenal Glands / Q000503:physiopathology*; D000309:Adrenal Insufficiency / Q000209:etiology; D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D002648:Child; D002675:Child, Preschool; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D007680:Kidney Neoplasms / Q000401:mortality / Q000503:physiopathology*; D008297:Male; D009447:Neuroblastoma / Q000401:mortality / Q000503:physiopathology*; D017741:Survivors; D009396:Wilms Tumor / Q000401:mortality / Q000503:physiopathology*
chemical_list: D008078:Cholesterol, LDL; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone