Abstract
Metabolic syndrome (MetS) is characterized by central obesity, hypertension, insulin
resistance, and hypercholesterolemia. Hypothalamic-pituitary-adrenal (HPA) axis activity
is frequently abnormal in MetS, and excessive cortisol exposure may be implicated
in metabolic derangements. We investigated the hypothesis that cortisol and adrenocorticotropic
hormone (ACTH) responses to a standardized neuroendocrine challenge test would be
associated with indices of MetS in a community sample of healthy adults. Healthy adults,
125 men and 170 women, without significant medical problems or chronic medications
were recruited from the community. Participants completed the dexamethasone/corticotropin-releasing
hormone (Dex/CRH) test, and anthropometric measurements, blood pressure, glycosylated
hemoglobin (HbA1c), and cholesterol were measured. Participants reported on their
history of early life stress and recent stress, as well as mood and anxiety symptoms.
Cortisol and ACTH responses to the Dex/CRH test were negatively associated with measures
of central adiposity (p<0.001) and blood pressure (p<0.01), and positively associated
with HDL cholesterol (p<0.01). These findings remained significant after controlling
for body mass index (BMI). Measures of stress and anxiety and depressive symptoms
were negatively correlated with cortisol and ACTH responses in the Dex/CRH test but
were not related to MetS indices. That altered HPA axis function is linked to MetS
components even in a healthy community sample suggests that these processes may be
involved in the pathogenesis of MetS. Identification of premorbid risk processes might
allow for detection and intervention prior to the development of disease.
Key words
metabolic syndrome - HPA axis - cortisol - ACTH - corticotrophin-releasing hormone
