Screening Cushing’s Syndrome in Obesity Tiryakioglu O et al. CS screening in simple obesity is usually not performed unless the patient has other clinical features of CS, such as poorly controlled hypertension, diabetes, osteoporosis with rapid progression, or hypokalemia that is unresponsive to the therapy. Delayed identification of SCS in obese patients results in the progression of CS, with the risk of irreversible complications. We therefore initiated a screening program for CS in our simple obese outpatients. The use of sensitive assays resulted in a significant improvement in the identification of CS. We documented 14 cases of CS in a sample of 150 simple obese patients. The high proportion of patients with Cushing’s syndrome that we identified despite the rareness of CS could be because we screened for CS in an obese population. These findings argue that every patient with simple obesity should be investigated for CS. Some patients with type 2 diabetes and poor glycemic control may also have subclinical CS (SCS), and these patients should be screened for CS. Recent studies have provided a rationale for the systemic screening of CS in patients with type 2 diabetes.16,17 Hypercortisolism can result in insulin resistance; glucose intolerance (or type 2 diabetes) secondary to insulin resistance occurs in approximately 75% of patients with CS. In this subgroup, 50% of the subjects had overt type 2 diabetes (20-25% of all CS patients). It has been well documented since the 1960s that patients with CS typically suffer from hyperinsulinemia, insulin resistance, and type 2 diabetes.19,20 Catargi et al. screened 200 overweight inpatients with type 2 diabetes and poor glycemic control (HbA1c >8%).15 None displayed the specific clinical features of CS in addition to their poorly-controlled type 2 diabetes. A total of 52 (26%) patients had impaired 1-mg DMS (failure to suppress cortisol <2.1 µg/dL). Of these, 17 (8.5%) displayed at least one additional biological abnormality of the hypothalamic-pituitary-adrenal axis. Imaging studies showed abnormalities in 11 of these 17 patients (5.5% of the whole series). Definitive occult CS was identified in 4 patients (2%), with 3 (1.5%) having Cushing’s disease and 1 (0.5%) with surgically proven adrenal adenoma. However, definitive diagnosis of CS in the remaining seven patients (3.5%) required further investigation. A unilateral adrenal tumor of 10-29 mm was subsequently revealed by REFERENCES CLINICS 2010;65(1):9-13 abdominal CT and iodocholesterol scintigraphy. These seven patients, therefore, had probable adrenal-dependent CS but did not undergo surgery. Six months after treatment for CS, a mean 5.5% reduction in body weight and a mean 2.5% reduction in HbA1c were reported in four patients. Oral antidiabetic medications were resumed in one patient, and the daily insulin dose was dramatically reduced in another. This study highlights the need to perform prospective CS screening on overweight, poorly controlled type 2 diabetic patients. 15 Assessment of 24-h UFC is a convenient screening test for CS in outpatient clinics. The false-negative rate for UFC is extremely low, though false-positive rates tend to be high. CS can, therefore, be excluded if 24-h UFC is normal. In patients with elevated 24-h UFC levels, a diagnosis of CS should be confirmed by a 1-mg overnight dexamethasone suppression test. In our study group, only 14 of 30 patients having elevated UFC were confirmed as having CS by the 1-mg DMS test. The remaining 16 obese patients were considered to be false-positives. Wood et al. established that suppression of plasma cortisol to less than 1.8 µg/dL excluded CS without an increase in the false-positive rate. 21 A study by Baid SK et al. demonstrated that the results of screening tests specific to CS may be falsely abnormal in overweight and obese populations.22 In our study, definitive CS was identified in 13 of 14 patients with unsuppressed serum cortisol after the results of the 1-mg DMS test were considered. One patient declined further investigation. The remaining 13 patients underwent further biochemical and imaging studies. Definitive diagnoses of CS were proven by histological analysis of surgically-removed material. Among 30 patients with elevated 24-h UFC, levels were significantly more elevated in the group of patients with unsuppressed cortisol after administration of 1 mg DMS (p=0.002) than in simple obese patients with suppressed cortisol levels. Distinguishing simple obese patients from CS presents a challenge for the physician. Future studies on larger patient populations will be required to address the true prevalence of CS. Appropriate study groups will include patients with relevant clinical features, including simple obesity, poorly controlled diabetes, osteoporosis, and PCOS. 1. Kuczmarski RJ, Flegal KM, Campbell SM, Johnson CL. Increasing prevalance of overweight among US adults: The National Health and Nutrition Examination Surveys, 1960 to 1991. JAMA. 1994;272:205-11. 3. Huang Z, Hankinson SE, Colditz GA, Stampfer MJ, Hunter DJ, Manson JE, et al. Dual effects of weight and weight gain on breast cancer risk. JAMA. 1997;278:1407-11. 2. Manson JE, Colditz GA, Stampfer MJ, Willet WJ, Rosner B, Manson RR, et al. A prospective study of obesity and risk of coronary heart disease in women. N Engl J Med. 1990;322:882-9. 4. Colditz GA, Willet WC, Stampfer MJ, Manson JE, Hennekenz CE, Arky RA, et al. Weight as a risk factor for clinical diabetes in women. Am J Epidemiol. 1990;132:501-13. 12