Investigation In Clinical Features,Serum Parameters And Complications Of Cushing’s Syndrome

Part I Investigation of clinical features and complications in 105 patients with Cushing’s syndromeObjective:To retrospectively investigate the occurrence of complications in Cushing’s syndrome, while comparing the characteristics of clinical, biochemical parameters and complications among different etiologies, and analyze the risk factors for the complications.Patients and methods:Patients with Cushing’s syndrome who were admitted to Endocrinology Department of Huashan Hospital from 2011 to 2013 were enrolled in the study. Data of clinical features, serum and urinary biochemical parameters including cortisol levels and hormones of other pituitary axes, pituitary MRI, adrenal CT scan, electrocardiogram and echocardiography were collected to evaluate the changes in metabolic parameters, cardiovascular system, liver, kidney, skeletal system as well as other pituitary axes. Univariate analysis was done by comparison between patients who had complications or not, and the degree of correlation between different parameters was examined by linear correlation analysis. Multiple logistic regression model was used for multivariate analysis.Results:1) Patients characteristics:A total of 105 patients were enrolled in the study, among whom 17 were male and 88 were female. The mean age of all patients was 34.49+1.25 (range:14-68). As for the etiology diagnosis,84 were Cushing’s disease,4 were ectopic adrenocorticotropic hormone syndrome (EAS),14 were adrenal adenoma and1 was adrenal cancer. For two patients the causes were not clear.2) Comparison between different etiologies:Changes in appearance such as central obesity were similar between patients with Cushing’s disease and adrenal adenoma, but not those with EAS, among whom fatigue was the most common clinical feature. Cortisol levels and the severity of hypokalemia, hypercoagulable state and impaired thyroid function were highest in EAS, while disease duration was shortest among all the etiologies.24hUFC levels were higher in adrenal adenoma than in Cushing’s disease, while disease duration was shorter in adrenal adenoma than in Cushing’s disease. No significant difference in other complications was found among different etiologies.3) Cardiovascular risk factors:56.2% of the patients were overweight or obese. Hypertension was present in 69.2% of the patients, while impaired glucose metabolism in 56.2%, dyslipidemia in 73.8% and hypercoagulable state in 65.7%. Linear correlation analysis showed that the highest systolic and diastolic blood pressure levels before treatment,2-h plasma glucose values in OGTT, BMI adjusted HOMA-IR were all positively correlated with 24hUFC, while APTT values were negatively correlated with 24hUFC. No significant correlation was found between serum lipid parameters and serum or urine cortisol levels. Hypertension was the only risk factor which coexisted with other risk factors.4) Cardiovascular complications:ST-T abnormalities on electrocardiogram were observed in 26.4% of the patients; 52.8% of the patients exhibited structural and functional abnormalities of left ventricular. Univariate analysis showed that the occurrence of ST-T abnormalities was related to 24hUFC, hypertension and HbAlc levels. Logistic regression analysis showed that hypertension was an independent risk factor of structural and functional abnormalities of left ventricular.5) Hepatic complications:37.6% of the patients exhibited fat liver, the occurrence of which was related to BMI and HOMA-IR analyzed by logistic regression model. Impaired liver function was observed in 24% of the patients, mainly with the manifestation of elevated aminotransferase. ALT was positively correlated with 24hUFC. Logistic regression analysis showed that after adjusting sex, the occurrence of impaired liver function was related to the existence of fat liver and cortisol levels.6) Renal complications:Urine dipstick protein tests were positive in 16.2% of the patients, while no significant correlated factors were found. The median eGFR value calculated by CG equation was 128.45ml/min (108.3,147.52), with eGFR<60ml/min observed in one patient. The median eGFR value calculated by modified MDRD equation was 147.75ml/min/1.73m2 (131.05,171.16).Although not statistically significant, the decrease in GFR was supposed to be related to the existence of hypertension. Nephrolithiasis occurred in 31.3% of the patients. Univariate analysis showed that the occurrence of nephrolithiasis was related to the existence of hypertension.7) Osteoporosis and bone turnover markers:Osteoporosis occurred in 32.3% of the patients according to lumbar-spine bone mineral density. The correlation between bone formation marker N-Mid and bone resorption marker CTX-1 was lost, and N-Mid levels were negatively correlated to cortisol levels while CTX-1 were positively correlated to cortisol levels. Regardless of the existence of osteoporosis, serum 25-Hydroxyvitamin D levels were severely decreased, and vitamin D deficiency was found in 89.5% of the patients. No significant association was found between the occurrence of osteoporosis and sexual hormones and cortisol.8) Thyroid axis:52.9% of the patients exhibited impaired thyroid function, the main manifestation of which was decrease in TSH and FT3 accompanied by FT4 decrease in a few patients. Impaired thyroid function was independent of tumor size and previous surgery in Cushing’s disease. TSH, FT3, FT4 were all negatively correlated with 24hUFC.9) Gonad axis:Menstrual abnormality occurred in 63.6% of the female patients. Loss of libido occurred in only one male patients while 93.3% of the patients exhibited low testosterone levels. In female patients, LH and E2 were negatively correlated with 24hUFC, while no significant correlation was found in male patients.Conclusion:Patients with Cushing’s syndrome could develop systemic complications which seriously affect mortality rate and life quality. Hypercortisolism degree could directly affect blood pressure, glucose metabolism, degree of insulin resistance, coagulation parameters, liver function, bone turnover markers, thyroid function and female gonadotropin levels. Hypertension, impaired glucose metabolism, fat liver, impaired bone turnover are associated with increased risk for complications. It is necessary to control the primary disease as soon as possible with active supportive therapy.Part Ⅱ Serum irisin levels in Cushing’s syndromeObjective:To investigate serum irisin levels in Cushing’s syndrome and possible correlated parameters.Methods:39 Patients with Cushing’s syndrome admitted to Endocrinology Department of Huashan Hospital were compared with controls matched for age and BMI. Serum irisin, glucose and lipid metabolic parameters, serum and urine cortisol levels were measured. Linear correlation analysis was performed to assess the degree of correlation between irisin, metabolic parameters and cortisol levels.Results:Serum irisin levels were significantly increased in Cushing’s syndrome compared with control group. Sex stratified analysis showed that in female patients, serum irisin levels were significantly increased compared with control group and the difference was greater than the overall patients. No significant difference was found in male patients. Serum irisin levels were positively correlated with TC levels in patients with Cushing’s syndrome.Conclusion:Irisin may not be associated with the occurrence of metabolism dysfunction in Cushing’s syndrome and may exert a protective effect. The elevation of irisin levels may be a compensatory response to hyperlipidaemia and elevated body fat percentage.