Functional Hypercorticism Relations to the Metabolic Syndrome

Functional hypercorticism (FH) is characterized with visceral body fat distribution (VFD), hypersensitive hypothalamicpituitary-adrenal (HPA) axis with increased sensitivity to stimuli and decreased sensitivity to inhibition, reduced cortisol suppression during OGTT, hyperplasia of the adrenal glands and indicates positive dependence on the age. The aim of this study was to determine the relationship of the FH, expressed as a percentage of reduction of basal cortisol levels (CS%) during OGTT, with the parameters of the metabolic syndrome (MS): homeostatic assessment model (HOMA) as an index of insulin resistance (IR), basal insulin levels, lipid profile, blood pressure, BFD as well as adrenal glands magnitude. The examinees were 127 healthy women, divided in 3 groups according to CS%: 1 gr. with CS%>60% (good suppression), 2 gr. with CS% 40-60 % (moderate suppression) and 3 gr. with FH and CS%<40% (very bad suppression). Anthropometric measurements included body mass index (BMI, kg/m), as well as waist/hip ratio (WHR) and waist/thigh ratio (WTR) as indexes of VFD. IR was assessed by HOMA. Lipid profile was determined also. Adrenal glands surfaces and volumes were determined by echotomography. HOMA values were 3.94±2.56 in the 1 gr., (5.77±2.96) in the 2 gr. and (8.55±7.22) in the 3 gr. HOMA values were significantly (p<0.0001) highest in the 3 group. Insulin levels in the 1 gr were 17±11μU/ml, in the 2 gr were 23.6±11μU/ml and in the 3gr were 30.96±33μU/ml. The 3 group with functional hypercorticism was hyperinsulinemic and insulin resistant with significantly highest HOMA and insulin values (p<0,0001). WHR was 0.89±0.009 in the 1 gr, (0.98±0.009) in the 2 gr., and (1.03±0.1) in the 3 group. WTR in the 1 group was 1.49±0.14, in the 2 gr was 1.66±0.14 and in the 3 gr was 1.79±0.19. The 3 group with functional hypercorticism was characterized with increased values of anthropometric indexes of VFD. WHR and WTR were significantly highest in the 3 group (p<0.0001). BMI was 30±8kg/m, 39±9kg/m, and 40±9kg/m in the correspondent groups. Sistolic blood pressure was 120±16 mmHg, in the 1 gr, (135±19 mmHg) in the 2gr, and (139±19 mmHg) in the 3 gr. It was significantly highest in the 3 group (p<0.001). Right adrenal gland volume was 3±2 cm in the 1gr., (5.1±3 cm ) in the 2gr. and (6.64±3.74 cm) in the 3gr. Left adrenal volume was 3±2.9cm in the 1 gr., (5.1±2 cm) in the 2 gr. and significantly highest in the 3 group (6,43±3.74cm). TG levels were significantly different between the groups (1.25±0,56; 1.57±0.68 and 1.78±0.82 mmol/l) (p<0,008), as well as HDL ch (1.13±0.46; 1.08±0.26; and 0.9±0.2 mmol/l) (p<0,05). The 3 group with functional hypercorticism was characterized with dyslipidemic profile. Conclusion: functional hypercorticism is characterized with hyperinsulinemia and insulin resistance (increased HOMA values), obesity, visceral body fat distribution, increased adrenal glands magnitude, increased blood pressure and dyslipidemic profile. This indicates that the functional hypercorticism which is characterized with the disturbance of the adrenal glands function, namely reduced CS% during OGTT and increased adrenal glands magnitude is positively related to the parameters of the metabolic syndrome and it could be considered as an important etiologic factor of the metabolic syndrome. Introduction Obesity, particularly central obesity, insulin resistance, hyperinsulinemia, glucose intolerance, hypertension and dyslipidemia, has been categorized as a single syndrome termed "metabolic syndrome". Each component of the MS is an established cardiovascular risk factor in individuals with and without diabetes. When combined in MS, these risk factors become much more powerful. Many studies have documented the superior role of abdominal adiposity as a risk factor for cardiovascular morbidity/mortality compared with overall obesity estimated by BMI. Even lean individuals with central weight gain can have the MS. Cushing's syndrome and the MS share clinical similarities. These similarities led to the hypothesis that a dysregulation of the HPA axis in the form of "functional hypercortisolism" (FH) could be a cause for abdominal obesity and its different metabolic consequences (1). The previous study discovered that reduced CS% during OGTT was associated with exaggerated visceral obesity and increased AGM, it enabled estimate of the adrenal glands function, and could be used as a clinical diagnostic criterion for discovery of the HPA axis disturbance in FH. In this study, the relationship between CS% as a diagnostic parameter of FH and features of the MS was investigated, and it was correlated with the overall phenotype of the MS in a cohort of healthy women, in order to discover it as an etiologic factor of the MS. Materials and methods The examinees were 127 healthy women. Endocrine, cardiovascular, hepatal, renal and other diseases were excluded and use of any medication. BMI was determined as weight to height ratio (kg/m). Central obesity was quantified clinically with a measuring tape: waist circumference was measured in standing subjects midway between the lowest rib and the iliac crest. Hip cicrcumference was measured over the trochanter major and WHR was calculated as a measure of central obesity, as well as WTR, which was calculated as a ratio of waist to thigh circumference measured at its highest level. Each ______________________ Cor espondence to: S. Subeska Stratrov , Clinic of Endocrinology, Diabetes and Metabolic Disorders, Medical Faculty, Skopje, R. Macedonia BANTAO Journal 3 (2): p 150; 2005 _______________________________ Correspondence to: Goce B Spasovski, MD, PhD, Department of Nephrology, Clinical Center Skopje, Vodnjanska 17, 1000 Skopje, Macedonia, Fax: +389 2 3220 935 or +389 2 3231 501, E-mail: [email protected] individual underwent 75-g oral glucose tolerance test (OGTT). Cortisol levels (C), glucose and insulin levels were determined in 127 healthy women in 0, 30, 60, 90, 120 and 180 min of the test. CS% as a determinant of adrenal gland function was calculated as a percentage of reduction of the basal to the lowest C during the test, which was corrected in cases with C increase in the 30 and 60 min. The examinees were divided in 3 groups according to CS%: 1 gr. with CS%>60% (good suppression), 2 gr. with CS% 40-60 % (moderate suppression) and 3 gr. with FH and CS%<40% (very bad suppression). Adrenal glands surfaces and volumes were determined by echotomography in 56 women. HOMA [fasting insulin (mU/ml) x fasting plasma glucose (mmol/l)/22,5] was applied to obtain an estimate of IR. Following lipid parameters were determined: triglyceride levels (TG), total cholesterol (TH), HDL chol., LDL chol, TH/HDL, LDL/HDL. Statistical analysis was performed by SPSS 8,0. Results CS% correlated significantly negatively with WHR, WTR,BMI, AGV (p<0,0001), also with AGSright (p<0,011) and AGSleft (p<0,006). Their increase was associated with reduction of CS%. The 3 gr. with FH and reduced CS% was characterized with increased age and extreme visceral obesity, as well as increased adrenal glands magnitude, insulin and HOMA levels, blood pressure, lipid fractions and reduced HDL. Graph 1. Anthropometric, hormonal, metabolic and ultrasound results in dependence on CS%