PRECLINICAL CUSHINGS-SYNDROME - AN UNEXPECTED FREQUENT CAUSE OF POOR GLYCEMIC CONTROL IN OBESE-DIABETIC PATIENTS

OBJECTIVE Autonomous cortisol secretion without clinical stigmata of G ushing's syndrome (CS) has been recently recognized and termed pre-cli nical or subclinical GS. The common assumption is that GS is an extrem ely rare cause of uncontrolled diabetes; however, the prevalence of th is entity has not been studied. We assessed the prevalence of pre-clin ical GS among obese patients with uncontrolled diabetes. PATIENTS AND DESIGN (1) In a retrospective analysis, the medical records of 63 pati ents with endogenous GS were reviewed. (2) In a cross-sectional study, 90 obese patients (BMI >25 kg/m(2)) followed in a University Hospital and the local Health Fund endocrine and diabetes clinics, with poorly controlled diabetes (glycosylated haemoglobin >9%), underwent an over night 1 mg dexamethasone suppression. In patients with non-suppressibl e cortisol levels (>140 nmol/l), Liddle's 2 and 8 mg dexamethasone sup pression tests and imaging studies were performed. MEASUREMENTS The pr evalence of poorly controlled diabetes, the major presenting symptom o f CS, was assessed in the retrospective analysis. The prevalence of 't rue' GS and the false positive rate in the overnight dexamethasone sup pression test were calculated. The endocrine evaluation of the patient s with pre-clinical GS and the effects of surgical cure on glycaemic c ontrol are described.RESULTS In the retrospective analysis, 11 (17.5%) had diabetes and 2 (3.2%) lacked the classic physical characteristics of the syndrome. In the cross-sectional study, 4 patients failed to s uppress plasma cortisol (<140 nmol/l). In one patient the diagnosis of GS was not confirmed by a standard Liddle's test and was therefore co nsidered false positive. In the other 3, the diagnosis of GS was confi rmed (prevalence of 3.3%, 95% confidence interval 1-9%). In all other patients the overnight cortisol suppression test was normal (cortisol level 47.3 +/- 2.5 nmol/l (mean +/- SEM)). After surgical treatment of GS, glycaemic control was markedly improved in all 5 patients (2 from retrospective and 3 from cross-sectional studies). CONCLUSIONS The pr evalence of pre-clinical Gushing's syndrome in obese patients with poo rly controlled diabetes appears to be considerably higher than previou sly believed. The overnight dexamethasone suppression test proved to b e a simple, sensitive and highly specific screening test for Gushing's syndrome despite the presence of obesity and hyperglycaemia.