The Hypothalamic‐Pituitary‐Adrenal Axis Activity in Obesity and the Metabolic Syndrome

<jats:p><jats:bold><jats:sc>Abstract: </jats:sc></jats:bold> <jats:bold>A hypothetical role of glucocorticoids in human obesity has been suggested since the abdominal obesity phenotype and syndromes of endogenous or exogenous hypercortisolism share several clinical, metabolic, and cardiovascular similarities. An emerging body of evidence indicates that both neuroendocrine dysregulation of the hypothalamic‐pituitary‐adrenal (HPA) axis as well as peripheral alterations of cortisol metabolism may play a role in the pathophysiology of abdominal obesity. Major alterations of the HPA axis <jats:italic>in vivo</jats:italic> may be identified in different ways. They include evaluation of hormone concentrations: (<jats:italic>a</jats:italic>) in basal conditions, in blood, urine, or saliva samples; (<jats:italic>b</jats:italic>) during dynamic studies following stimulation with different neuropeptides or psychological stress challenges, or suppression with inhibiting agents of the HPA axis at different levels; and (<jats:italic>c</jats:italic>) after mixed meals or meals containing different nutrient compositions. In addition, alteration of peripheral cortisol metabolism can be detected by direct measurement of cortisol metabolites in urine, although this is a matter of more complex investigation. Alterations of the HPA axis in abdominal obesity are associated with insulin resistance, which suggests a direct responsibility of these hormonal alterations in the susceptibility of affected patients to develop both metabolic and cardiovascular diseases. According to available data, no single marker probably has the power to detect subtle alterations of the HPA axis in conditions, such as the abdominal obesity and the metabolic syndrome. On the contrary, they indicate the need for multiple parameters. At present, evaluation of urinary free cortisol, particularly during the night‐time, and salivary‐free cortisol appear to be promising for these purposes, whereas dynamic tests should be reserved for specific clinical settings, involving well‐characterized patients.</jats:bold> </jats:p>