Exploring the temporal relation between body mass index and corticosteroid metabolite excretion in childhood

Britt J. Van Keulen*, Conor V. Dolan, Ruth Andrew, Brian R. Walker, Hilleke E.Hulshoff Pol, Dorret I. Boomsma, Joost Rotteveel, Martijn J.J. Finken

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


Childhood obesity is associated with alterations in hypothalamus–pituitary–adrenal (HPA) axis activity. However, it is unknown whether these alterations are a cause or a consequence of obesity. This study aimed to explore the temporal relationship between cortisol production and metabolism, and body mass index (BMI). This prospective follow-up study included 218 children (of whom 50% were male), born between 1995 and 1996, who were assessed at the ages of 9, 12 and 17 years. Morning urine samples were collected for assessment of cortisol metabolites by gas chromatography-tandem mass spectrometry, enabling the calculation of cortisol metabolite excretion rate and cortisol metabolic pathways. A cross-lagged regression model was used to determine whether BMI at various ages during childhood predicted later cortisol production and metabolism parameters, or vice versa. The cross-lagged regression coefficients showed that BMI positively predicted cortisol metabolite excretion (p = 0.03), and not vice versa (p = 0.33). In addition, BMI predicted the later balance of 11β-hydroxysteroid dehydrogenase (HSD) activities (p = 0.07), and not vice versa (p = 0.55). Finally, cytochrome P450 3A4 activity positively predicted later BMI (p = 0.01). Our study suggests that changes in BMI across the normal range predict alterations in HPA axis activity. Therefore, the alterations in HPA axis activity as observed in earlier studies among children with obesity may be a consequence rather than a cause of increased BMI.

Original languageEnglish
Article number1525
Pages (from-to)1-9
Number of pages9
Issue number5
Early online date23 May 2020
Publication statusPublished - May 2020


Funding: B.R.W. is a Wellcome Trust Investigator. R.A. and B.R.W. were supported by a British Heart Foundation Programme Grant, and by a Wellcome Trust equipment grant. This work was supported by the Netherlands Organization for Scientific Research (NWO, 51.02.060 (HHP, DB), 668.772 (HHP); NWO-MagW 480-04-004; NWO/SPI 56-464-14192). D.I.B. acknowledges the KNAW Academy Professor Award (PAH/6635).

FundersFunder number
Netherlands Organization for Scientific ResearchNWO-MagW 480-04-004, 51.02.060, 668.772, NWO/SPI 56-464-14192
Wellcome Trust
British Heart Foundation
Koninklijke Nederlandse Akademie van WetenschappenPAH/6635


    • BMI
    • Glucocorticoids
    • HPA axis
    • Obesity

    Cohort Studies

    • Netherlands Twin Register (NTR)


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