Screening Cushing’s Syndrome in Obesity Tiryakioglu O et al. symptoms of the disorder. Nevertheless, a significant number of CS patients present only with simple obesity13-14 or with type 2 diabetes mellitus and poor glycemic control.15-17 Metabolic syndrome may also indicate the presence of CS. Patients without specific clinical features of CS have been referred to as sub-clinical Cushing’s syndrome (SCS)15 patients, and the diagnosis of SCS affords a considerable challenge to the physician. We accordingly set out to determine the frequency of CS in patients presenting with simple obesity in the absence of other specific signs or symptoms indicative of CS. PATIENTS AND METHODS This study included 150 consecutive simple obese patients (129 female, 21 male, mean age: 44.41 ± 13.34 yr, body mass index (BMI) > 25 kg/m2) who were followed and treated at the Endocrinology Metabolism outpatient clinic at Cerrahpasa Medical Faculty between June 2003 and June 2004. Written informed consent was obtained from all patients before commencement of the study. Review of patient medical history was used to exclude subjects in which the dexamethasone suppression test could be biased either by medication (including exogenous glucocorticoid intake) or by other factors known to influence the test (including drug use, alcoholism, obvious depression, or pregnancy). None of the patients had nephropathy (creatinine clearance <30 ml/min), acute illness, or sleep disorders. All patients in our study had simple obesity; none of them had diabetes mellitus. Since the patients had simple obesity, careful examinations did not reveal hirsutism, buffalo hump, easy bruising, or any other manifestations suggestive of CS suggestive manifestations. Clinical characteristics recorded included BMI and anthropometric measurements. Morning blood samples following fasting (12 h) were drawn from an antecubital vein for determination of the concentrations of adrenocorticorticotropic hormone (ACTH) (N: 0-46 pg/ml), cortisol (N: 5-28 µg/dL), glucose, insulin (N: 0-20 µ IU/L), serum lipids (total cholesterol, LDL, HDL, VLDL-cholesterol, and triglyceride), free thyroxin (fT4) (N: 0.93-1.77 ng/dL), and thyrotropin (TSH) (N: 0.15-3.7 IU/ml). Urine (24 h) was collected from each subject in order to perform urinary free cortisol (UFC) measurements. Patients whose 24-h UFC excretion exceeded 100µg/ dL were defined as abnormal. All patients subsequently underwent a 1-mg overnight dexamethasone suppression test (DMS). Suppression of serum cortisol to <1.8 µg/dL after dexamethasone administration was the cut-off point for normal suppression without consideration of 24-h UFC. Measurement of serum ACTH levels and an 8-mg DMS 10 CLINICS 2010;65(1):9-13 were performed as second-step investigations in all patients who failed to achieve serum cortisol suppression <1.8 µg/ dL after administration of 1 mg DMS. Complementary imaging studies, magnetic resonance imaging (MRI) of the sella, cavernous sinus sampling, and abdominal computed tomography (CT) were performed when the results of the second-step evaluations were consistent with ACTH- dependent or ACT-independent CS. Insulin, cortisol, fT4, TSH, and ACTH were assessed by radioimmunoassay (RIA) using a Packard Riastar gamma counter (Perkin-Elmer, Waltham, MA, USA) and commercial assay kits. Other biochemical laboratory tests were measured with an Olympus AU 600 autoanalyser (Olympus, Tokyo, Japan). Insulin resistance was assessed using the homeostasis model assessment ratio (HOMA-R) formula (18). Calculations were done with SPSS software (version 10; SPSS Inc, Chicago, IL, USA), and differences in the values of the variables between the groups were evaluated by the Mann-Whitney U test. The degree of the correlation between parameters was evaluated by regression analysis. A value of p<0.05 was considered to be statistically significant. RESULTS We analyzed a series of patients presenting with simple obesity for the presence of sub-clinical CS. The clinical characteristics and laboratory findings for these patients are summarized in Tables 1 and 2. Table 1 - Summary of physical examination findings in the patient group BMI (kg/m2) Waist (cm) Waist-to-hip ratio Systolic blood pressure (mm/Hg) Diastolic blood pressure (mm/Hg) (Mean ± SD) (n=150) 35.76 ± 7.13 104.07 ± 15.77 0.98 ± 0.92 135.13 ± 20.49 87.23 ± 13.03 In 37 patients (24%), 24-h UFC excretion exceeded the cut-off point (median, 30; interquartile range (IQR), 16-103 gµ/24 h). Fourteen patients had unsuppressed cortisol levels as indicated by the 1-mg dexamethasone suppression test. Complementary imaging studies were performed on these 14 CS patients, which revealed pituitary microadenoma in 9 patients, adrenal adenoma in 3 patients, and adrenal carcinoma in 1 patient. Histological diagnosis was obtained in 13 patients; one patient declined to undergo surgical intervention for definitive diagnosis (Table 3).