Clinical Features Of Cushing’s Syndrome And Immunohistochemical Study Of Adrenal Glucocorticoid Receptor

ObjectiveTo analyze the clinical characteristics of different types of Cushing’s syndrome(CS),and study expression of adrenal glucocorticoid receptor(GR)in different types of Cushing’s syndrome by immunohistochemistry.MethodsA total of 68 patients of Cushing’s syndrome first diagnosed by surgical pathology in the Department of Endocrinology and Metabolism,Tianjin Medical University General Hospital from Jan.2009 to Jun.2018 were collected and analyzed retrospectively.And we performed GR immunohistochemical analysis of adrenal pathology sections from different types of Cushing’s syndrome.ResultsA total of 68 patients with Cushing’s syndrome were included in this study,including 11 males and 57 females.Their age at diagnosis was 39.5±13.8 years.The patients were divided into 4 groups according to different causes.These included 42 patients with Cushing disease(CD),20 patients with adrenal adenoma,5 with ACTH-independent macronodular adrenal hyperplasia(AIMAH)and 1 with Primary pigmented nodular adrenocortical disease(PPNAD).There were no significant differences in age,body mass index(BMI),systolic and diastolic blood pressure between the groups.The median duration of each group was 12 months.Among the 5patients in AIMAH group,4 patients had bilateral adrenal lesions,and only one case was found on the left side.All the 20 patients with Cushing’s syndrome caused by adrenal adenoma were unilateral adrenal lesions.The main complaints of the patients were varied.The most common complaints were full-moon face,centripetal obesity,hirsute and weight gain.There are 72.1% of Cushing’s syndrome patients with hypertension,64.9% with different degrees of abnormal glucose metabolism,52.9%with abnormal bone metabolism,61.8% and 35.3% with hyperlipidemia and fatty liver respectively,33.8% with hypothyroidism,and 7.3% and 10.3% withhyperparathyroidism and kidney stones,and 11.8% of patients had hyperuricemia.About 32% of patients with CS have hypokalemia.And the potassium levels is 3.70± 0.55mmol/L.24 h Urinary free cortisol(UFC)(575.88±374.41ug/24h)was significantly negatively correlated with serum potassium levels.In all types of CS,patients with elevated LDH can reach more than 76%.LDH activity was significantly related to plasma free cortisol and 24 h UFC(r=0.349,r=0.393;p<0.01).LDH activity was significantly negative related to serum potassium and chloride(r=-0.359,r=-0.319;p<0.01).With the reduction of 50% from the baseline value of 24 hUFC.The sensitivity of LDDST to the adrenal adenoma group,AIMAH group and Cushing’s disease group was 100%,80%,and 80%,The diagnostic sensitivity of HDDST to adrenal adenoma group,AIMAH group and Cushing’s disease group was100%,80%,67%.In the imaging examination,there were 8 patients with Cushing’s syndrome complicated with pituitary and adrenal lesions at the same time.Two patients were caused by adrenal adenoma.The ACTH value was less than 5 pg/ml(0-46 pg/ml).24 h UFC was not suppressed after high dose dexamethasone suppression test(HDDST).Six CS patients was caused by Cushing disease.Average values of ACTH was 78.2 pg/ml.After HDDST,the 24 hUFC level of 4 patients was more than 50% lower than the base value.Glucocorticoid receptor(GR)immunohistochemical staining shows that the receptor specific distribution in the cytoplasm of hyperplastic nodulesa of PPNAD,which can be used to identify nodule of lesion in adrenal tissue.In the adenoma and AIMAH adrenal tissue,no obvious GR staining was observed.In the normal adrenal tissue,no GR staining was observed in the cortex,and only slight staining was observed in the medulla.ConclusionCushing’s syndrome is more common in women of reproductive stage,and the complaints are complex and diverse,combined with varying degrees of hypertension,abnormal glucose and bone metabolism,and hypokalemia and so on.Most Cushing’s syndrome is associated with elevated LDH.For patients with Cushing’s syndrome who have both pituitary and adrenal imaging abnormalities,we should pay close attention to the ACTH levels and HDDST.GR staining should be added in thepathological analysis of adrenal glands in suspected PPNAD,which is significance for the localization of nodules in the diagnosis of this disease.