High-end normal adrenocorticotropic hormone and cortisol levels are associated with specific cardiovascular risk factors in pediatric obesity: a cross-sectional study

Flavia Prodam, Roberta Ricotti, Valentina Agarla, Silvia Parlamento, Giulia Genoni, Caterina Balossini, Gillian Elisabeth Walker, Gianluca Aimaretti, Gianni Bona, Simonetta Bellone, Flavia Prodam, Roberta Ricotti, Valentina Agarla, Silvia Parlamento, Giulia Genoni, Caterina Balossini, Gillian Elisabeth Walker, Gianluca Aimaretti, Gianni Bona, Simonetta Bellone

Abstract

Background: The hypothalamic-pituitary-adrenal (HPA) axis, and in particular cortisol, has been reported to be involved in obesity-associated metabolic disturbances in adults and in selected populations of adolescents. The aim of this study was to investigate the association between morning adrenocorticotropic hormone (ACTH) and cortisol levels and cardiovascular risk factors in overweight or obese Caucasian children and adolescents.

Methods: This cross-sectional study of 450 obese children and adolescents (aged 4 to 18 years) was performed in a tertiary referral center. ACTH, cortisol, cardiovascular risk factors (fasting and post-challenge glucose, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, and hypertension) and insulin resistance were evaluated. All analyses were corrected for confounding factors (sex, age, puberty, body mass index), and odds ratios were determined.

Results: ACTH and cortisol levels were positively associated with systolic and diastolic blood pressure, triglycerides, fasting glucose and insulin resistance. Cortisol, but not ACTH, was also positively associated with LDL-cholesterol. When adjusted for confounding factors, an association between ACTH and 2 h post-oral glucose tolerance test glucose was revealed. After stratification according to cardiovascular risk factors and adjustment for possible confounding factors, ACTH levels were significantly higher in subjects with triglycerides ≥90th percentile (P <0.02) and impaired fasting glucose or glucose tolerance (P <0.001). Higher cortisol levels were found in subjects with blood pressure ≥95th percentile and LDL-cholesterol ≥90th percentile. Overall, the highest tertiles of ACTH (>5.92 pmol/l) and cortisol (>383.5 nmol/l) although within the normal range were associated with increases in cardiovascular risk factors in this population.

Conclusions: In obese children and adolescents, high morning ACTH and cortisol levels are associated with cardiovascular risk factors. High ACTH levels are associated with high triglyceride levels and hyperglycemia, while high cortisol is associated with hypertension and high LDL-cholesterol. These specific relationships suggest complex mechanisms through which the HPA axis may contribute to metabolic impairments in obesity, and merit further investigations.

Figures

Figure 1
Figure 1
Tanner-dependent (A) and age-dependent (B) adrenocorticotropic hormone (ACTH) (pmol/l) and cortisol (nmol/l) levels in 406 overweight and obese children and adolescents (filled circles, males, left panel; open circles, females, right panel). Cortisol levels were higher in the Tanner 4 to 5 stages than the Tanner 1 stage in the whole group (P <0.02*) and in females (P <0.02*). ACTH levels were higher in Tanner 4 to 5 stages (P <0.001*) and in 14.0 to 15.9 years (P <0.01*) in males than in females. Significance was maintained when the model included body mass index (BMI) (or BMI standard deviation score (BMISDS)) and homoeostasis model assessment of insulin resistance (HOMA-IR) as covariates. *Indicates significance of analysis of covariance (ANCOVA) analysis.

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