ACTH and cortisol response to combined corticotropin releasing hormone-arginine vasopressin stimulation in obese males and its relationship to body weight, fat distribution and parameters of the metabolic syndrome

Abstract

OBJECTIVES: To investigate the activity of the hypothalamic ± pituitary ± adrenal (HPA) axis in male obesity and its relationship with several prominent parameters of the metabolic syndrome. DESIGN: A cross-sectional clinical study of the activity of the HPA axis in groups of obese males and normal-weight controls. SUBJECTS: Seventeen obese non-diabetic males with a body mass index (BMI) b 28 and eight normal-weight controls were examined. MEASUREMENTS: Fat free mass (FFM) and fat mass (FM) were measured by bioelectrical impedance, and the waistto-hip circumference ratio (WHR) was calculated in all subjects. Baseline samples were taken for sex hormone and lipid determination, and an oral glucose tolerance test (OGTT) was performed for glucose and insulin determination. The activity of the HPA axis was determined by the combined administration of human corticotropin releasing hormone (CRH) (100 m mg) and arginine vasopressin (AVP) (0.3 IU). RESULTS: As expected, FFM and FM and the WHR were higher in obese men than in controls, as were fasting insulin and stimulated (as area under the curve (AUC)) glucose and insulin concentrations. Baseline adrenocorticotropin (ACTH) and cortisol concentrations were similar in both groups, but stimulated (as AUC), ACTH was higher (P`0.05) in obese subjects than in controls, whereas no signi®cant difference in cortisol AUC was present. Since the main differences between obese subjects and controls were present during the early 30 min of the test, the correlation coef®cients between total and incremental ACTH AUC 0 ± 30 min and cortisol AUC 0 ± 30 min and all other variables were analyzed. A signi®cant correlation coef®cient was present between them and all anthropometric parameters, fasting insulin and insulin AUC , but not with androgens and gonadotrophins. In addition, a signi®cant correlation was present between total and incremental ACTH AUC 0 ± 30 min and triglyceride concentrations. However, after adjusting for BMI or FM values, all correlation coef®cients became non-signi®cant, except the one between incremental ACTH AUC 0 ± 30 min and insulin AUC (P`0.05). CONCLUSION: These ®ndings indicate that obese men may also have an altered pituitary response to combined CRHaAVP stimulation, which appears to be predominantly related to body size and total body fat. ACTH hyperresponsiveness after CRHaAVP stimulation also appears to be related to hyperinsulinaemia, but underlying mechanisms of this relationship remain to be elucidated.

Glucocorticoids and 11beta-Hydroxysteroid Dehydrogenase in Adipose Tissue

“…More convincingly, recent large studies confirm that total cortisol production rate is somewhat enhanced in obesity in men as well as women Fraser et al, 1999;Stewart et al, 1999). This is further supported by evidence that HPA axis responsiveness to stimuli such as acute stress, CRH/AVP (Pasquali et al, 1999), adrenergic manipulations (Pasquali et al, 2000), hypoglycaemia, or a standard meal (Marin et al, 1992;Hautanen and Adlercreutz, 1993) is enhanced in idiopathic obesity, particularly visceral obesity (Pasquali et al, 2000). Moreover, the cortisol response to particular types of food may differ with the locus of adiposity, as viscerally obese women show lower HPA axis responses to high-fat and protein but greater responses to high-carbohydrate meals, compared to peripherally obese and lean subjects (Vicennati et al, 2002).…”

Senior Author Correspondence Information

“…More convincingly, recent large studies confirm that total cortisol production rate is somewhat enhanced in obesity in men as well as women Fraser et al, 1999;. This is further supported by evidence that HPA axis responsiveness to stimuli such as acute stress, CRH/AVP (Pasquali et al, 1999), adrenergic manipulations (Pasquali et al, 2000), hypoglycaemia, or a standard meal (Marin et al, 1992;Hautanen and Adlercreutz, 1993) is enhanced in idiopathic obesity, particularly visceral obesity (Pasquali et al, 2000). Moreover, the cortisol response to particular types of food may differ with the locus of adiposity, as viscerally obese women show lower HPA axis responses to high-fat and protein but greater responses to high-carbohydrate meals, compared to peripherally obese and lean subjects (Vicennati et al, 2002).…”

Obesity and corticosteroids: 11β-Hydroxysteroid type 1 as a cause and therapeutic target in metabolic disease

“…Although plasma cortisol levels appear normal in the metabolic syndrome or obesity, there are exaggerated dynamic cortisol responses (Pasquali et al, 1999) In particular, abdominal obesity associates with increased urinary free cortisol excretion and increased total cortisol production rates (Marin et al, 1992, Stewart et al, 1999.…”