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BACKGROUND Patients with normoalbuminuria and a reduced estimated glomerular filtration rate (eGFR) account for a considerable proportion of type 2 diabetes patients. The aim of this research was to investigate the epidemiological and clinical characteristics of normoalbuminuric kidney disease in a Chinese population. METHODS We included 8131 diabetic patients from a multicenter prospective study in China. Based on eGFR and urinary albumin-to-creatinine ratio (UACR), participants were stratified into four groups-normal albuminuria, albuminuria, normoalbuminuria with eGFR

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension.Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017.Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged

Background To evaluate the efficacy of pulsatile gonadotropin-releasing hormone (GnRH) therapy in patients with hypogonadism caused by hypopituitarism so as to guide clinical treatment. Methods Clinical manifestations, laboratory examinations, and imaging features were collected from 22 patients with hypopituitarism that led to hypogonadism who were treated with pulsatile GnRH. Data were analyzed and the patients were followed up. Results The average age at which patients began to use pulsatile GnRH was 22.8±3.7 years old. The duration of pulsatile GnRH administration ranged from 3 to 60 months, with an average of 20.5±12.1 months. The dosage of GnRH administered was 10-12 µg/90 minutes. Patients were followed up for 26-81 months, with an average of 50.5±17.3 months. After pulsatile GnRH treatment, the clinical manifestations and hormone levels of these patients improved to varying degrees. The luteinizing hormone (LH) and testosterone (T) levels of 7 patients increased to the normal range, sperm could be detected in seminal fluid samples of 5 patients, and 2 patients successfully reproduced. Within the good-response group, 71.4% of patients achieved spermatogenesis within an average of 13 months of treatment. In patients who had poor response to gonadotropin therapy prior to pulsatile GnRH therapy, 25% achieved spermatogenesis, and 37.5% reached the normal range of LH and T. The levels of LH after pulsatile GnRH treatment was positively correlated with the peak levels of LH and testicular volume prior to treatment (P Conclusions Pulsatile GnRH therapy can improve gonadal function in most patients with hypogonadism caused by hypopituitarism. Patients were able to achieve spermatogenesis, especially in patients who were poor-responders to gonadotropin treatment. Patients with greater basal testicular volume may respond better to pulsatile GnRH treatment. The GnRH stimulation test not only helps to evaluate the reserve function of pituitary GnRH cells at a certain time but may also serve as a prognostic factor. The results of this study form a basis for guiding clinical therapeutic choices.

Background: Subclinical hypothyroidism is diagnosed based on serum thyrotropin (TSH) reference intervals, which in turn are affected by many factors. Methods: Data were acquired from a Chinese nati...

Purpose: To investigate the clinical characteristics, endocrinological function, and etiologies of patients with bilateral adrenal lesions.Methods: A retrospective study of 777 patients with bilateral adrenal lesions was conducted at the Chinese General Hospital of the People’s Liberation Army between January 2013 and January 2018. Patient demographic features, hormonal profiles, imaging findings, and histopathological findings were reviewed from the database records. Results: Of the 777 patients with bilateral adrenal lesions, 495 were men, and the mean age at diagnosis was 52.0±13.0 years. A total of 511 (65.8%) cases were benign, followed by adrenal metastases (n=224, 28.8%), pheochromocytoma (n=26, 3.3%), adrenal lymphoma (n=9, 1.2%), and adrenal corticocarcinoma (ACC) (n=7, 0.9%). Hormonal evaluation revealed that 34.3% of bilateral adrenal lesions were functional. The primary etiologies of functional lesions were primary aldosteronism (16.6%, 129/777) , and PBMAH (8.8%, 68/777). Patients with lymphoma and metastases were significantly older than those with benign nonfunctional lesions (60.4±11.0 years vs. 54.5±10.4 years and 57.9±10.8 years vs. 54.5±10.4 years, respectively; PConclusion: Benign adrenal lesions and metastases to the lungs are the most common causes of bilateral adrenal lesions, and primary aldosteronism and BMAH are the most prevalent functional lesions. In addition, our findings suggest that patients with lymphoma or metastases are older and possess larger masses.

BackgroundOverweight and obesity are well-known risk factors for type 2 diabetes mellitus (T2DM). The effect of the maximum body mass index (BMImax), which indicates the highest body weight before the diagnosis of T2DM, is not fully understood. This study aimed to explore the predictive value of BMImax in the progression of diabetes.MethodsThis prospective study recruited 2018 subjects with normal glucose tolerance in Beijing, China. The subjects were followed up for eight years, and the association between BMImax and glucose outcomes was evaluated.ResultsNinety-seven of the 2,018 participants developed diabetes by the end of the study. Compared to individuals with normal glucose tolerance, those who developed diabetes were characterized by higher levels of fasting plasma glucose (FPG), 2 h postload glucose (PBG), glycosylated hemoglobin (HbA1c), systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-c), a higher prevalence of a familial history of diabetes and a lower level of high‐density lipoprotein cholesterol (HDL-c). Multivariate regression analysis of sex-stratified groups suggested that FPG, HbA1c, SBP and familial history of diabetes were independent risk factors for diabetes, but that BMImax was a unique indicator for female patients.ConclusionsBMImax might be an independent predictor of T2DM in females, but it does not seem to be associated with the risk of diabetes in males. BMImax could be regarded as an indicator in the prevention and management of diabetes.

Background To determine the efficacy and safety of umbilical cord-derived mesenchymal stem cells (UC-MSCs) in Chinese adults with type 2 diabetes mellitus (T2DM). Methods In this single-center, double-blinded, randomized, placebo-controlled phase II trial, 91 patients were randomly assigned to receive intravenous infusion of UC-MSCs (n = 45) or placebo (n = 46) three times with 4-week intervals and followed up for 48 weeks from October 2015 to December 2018. The primary endpoint was the percentage of patients with glycated hemoglobin (HbA1c) levels of Results At 48 weeks, 20% of the patients in the UC-MSCs group and 4.55% in the placebo group reached the primary endpoint (p p p p˃0.05; p = 0.0081 between both groups). The glucose infusion rate (GIR) increased significantly in the UC-MSCs group (from 3.12 to 4.76 mg/min/kg, p p ˃ 0.05; p Conclusions UC-MSCs transplantation could be a potential therapeutic approach for Chinese adults with T2DM. Trial registration This study was registered on ClinicalTrials.gov (identifier: NCT02302599).

Ectopic ACTH syndrome (EAS) accounts for 10–20% of endogenous Cushing’s syndrome (CS). Hardly any cases of adrenal medullary hyperplasia have been reported to ectopically secrete adrenocorticotropic hormone (ACTH). Here we describe a series of three patients with hypercortisolism secondary to ectopic production of ACTH from adrenal medulla. Cushingoid features were absent in case 1 but evident in the other two cases. Marked hypokalemia was found in all three patients, but hyperglycemia and osteoporosis were present only in case 2. All three patients showed significantly elevated serum cortisol and 24-h urinary cortisol levels. The ACTH levels ranged from 19.8 to 103.0pmol/L, favoring ACTH-dependent Cushing’s syndrome. Results of bilateral inferior petrosal sinus sampling (BIPSS) for case 1 and case 3 confirmed ectopic origin of ACTH. The extremely high level of ACTH and failure to suppress cortisol with high dose dexamethasone suppression test (HDDST) suggested EAS for patient 2. However, image studies failed to identify the source of ACTH secretion. Bilateral adrenalectomy was performed for rapid control of hypercortisolism. After surgery, cushingoid features gradually disappeared for case 2 and case 3. Blood pressure, blood glucose and potassium levels returned to normal ranges without medication for case 2. The level of serum potassium also normalized without any supplementation for case 1 and case 3. The ACTH levels of all three patients significantly decreased 3-6 months after surgery. Histopathology revealed bilateral adrenal medullary hyperplasia and immunostaining showed positive ACTH staining located in adrenal medulla cells. In summary, our case series reveals the adrenal medulla to be a site of ectopic ACTH secretion. Adrenal medulla-originated EAS makes the differential diagnosis of ACTH-dependent Cushing’s syndrome much more difficult. Control of the hypercortisolism is mandatory for such patients.

BACKGROUND Adrenocorticotropic hormone (ACTH)-independent Cushing’s syndrome (CS) is mostly due to unilateral tumors, with bilateral tumors rarely reported. Its common causes include primary pigmented nodular adrenocortical disease, ACTH-independent macronodular adrenal hyperplasia, and bilateral adrenocortical adenomas (BAAs) or carcinomas. BAAs causing ACTH-independent CS are rare; up to now, fewer than 40 BAA cases have been reported. The accurate diagnosis and evaluation of BAAs are critical for determining optimal treatment options. Adrenal vein sampling (AVS) is a good way to diagnose ACTH-independent CS. CASE SUMMARY A 31-year-old woman had a typical appearance of CS. The oral glucose tolerance test showed impaired glucose tolerance and obviously increased insulin and C-peptide levels. Her baseline serum cortisol and urine free cortisol were elevated and did not show either a circadian rhythm or suppression with dexamethasone administration. The peripheral 1-deamino-8-D-arginine-vasopressin (DDVAP) stimulation test showed a delay of the peak level, which was 1.05 times as high as the baseline level. Bilateral AVS results suggested the possibility of BAAs. Abdominal computed tomography showed bilateral adrenal adenomas with atrophic adrenal glands (right: 3.1 cm × 2.0 cm × 1.9 cm; left: 2.2 cm × 1.9 cm × 2.1 cm). Magnetic resonance imaging of the pituitary gland demonstrated normal findings. A left adenomectomy by retroperitoneoscopy was performed first, followed by resection of the right-side adrenal mass 3 mo later. Biopsy results of both adenomas showed cortical tumors. Evaluations of ACTH and cortisol showed a significant decrease after left adenomectomy but could still not be suppressed, and the circadian rhythm was absent. Following bilateral adenomectomy, this patient has been administered with prednisone until now, all of her symptoms were alleviated, and she had normal blood pressure without edema in either of her lower extremities. CONCLUSION BAAs causing ACTH-independent CS are rare. AVS is of great significance for obtaining information on the functional state of BAAs before surgery.

BackgroundUniversal salt iodization (USI) was implemented in mainland China in 1996. The prevalence of hyperthyroidism and its risk factors now require examination.MethodsData were acquired from a nationwide Thyroid, Iodine, and Diabetes Epidemiological survey (TIDE 2015–2017) of 78,470 subjects from 31 provinces. Iodine status, and thyroid hormones and antibodies were measured. ResultsAfter two decades of USI, the prevalence of overt hyperthyroidism (OH), Graves’ disease (GD), severe subclinical hyperthyroidism (severe SCH), and mild subclinical hyperthyroidism (mild SCH) in mainland China was 0.78%, 0.53%, 0.22%, and 0.22%, respectively. OH and GD prevalence were higher in women than in men (OH: 1.16% vs. 0.64%, Pvs. 0.37%, Pvs. 0.81%, Pvs. 0.57%, PConclusionOH and GD prevalences in mainland China are stable after two decades of USI. Iodine deficiency, elevated thyroid antibody levels, and middle age are the main risk factors for OH and GD. The severe SCH population, rather than the mild SCH population, shows similar characteristics to the OH population.

The anti-thyroglobulin antibody (TgAb) has been suggested to be more common in patients with papillary thyroid cancer (PTC). Here, we performed a retrospective study investigated the correlation between TgAb level and PTC in Chinese patients between 2011 and 2015. Patients with goiter who underwent thyroidectomy and received a confirmed pathological diagnosis were enrolled into the study. Clinical characteristics and preoperative thyroglobulin antibody (TgAb) level data were collected from all enrolled patients. Based on the preoperative TgAb test results, patients were divided into a TgAb negative (TgAb–) group (

Background Obesity is an increasing problem worldwide and is one of the underlying risk factors for prediabetes. Although WHtR, BMI, WC and WHR were found to be associated with dysglycemia, in view of significant differences in basic characteristics, glycemic metabolism, and ethnicity, it is of practical value to investigate which indicators are the most useful measures to predict the incidence of prediabetes in Chinese population. The aim of this study was to compare the value of different anthropometric measures of obesity in the detection of prediabetes in a cohort study in China and to identify the best cut-off point of predicting prediabetes in this population. Methods The present study was a part of the ongoing Risk Evaluation of cAncers in Chinese diabetic Individuals: an IONgitudinal (REACTION) study. After 7 years of follow-up, a total of 2568 individuals in Beijing were analyzed. Waist-to-height ratio (WHtR), body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) were measured at baseline and during follow-up. These four values were divided into tertiles. Fast blood glucose and postprandial blood glucose were tested. The association of these four anthropometric values with blood glucose were tested using multiple logistic analysis. Results A total of 2568 normoglycemic participants (810 males and 1758 females) were recruited, with an average age of 62.68 ± 6.97 years. After 7 years of follow-up, 52 subjects had developed newly diagnosed diabetes, and 423 individuals had developed prediabetes. Among those with prediabetes, 278 had IGT, 105 had IFG, and 40 had IGT + IFG. The incidences of prediabetes and diabetes were calculated to be 115.3 per 1000 person-years and 14.2 per 1000 person-years, respectively. Multivariable regression analysis revealed that there was no significant difference in the WHtR, BMI, WC, WHR among those with diabetes and nondiabets. In the general population and the group of females with prediabetes, we found that WHtR was the best value to predict prediabetes, and with an increase in the WHtR, the possibility of prediabetes increased by 90% or 102%, respectively. In the group of males, WHR was the most associated with prediabetes, and people in Tertile 2 was 2.62 times more likely to suffer from prediabetes than those in Tertile 1. For females, the optimal cut-off points of WHtR, BMI, WC and WHR were 0.48, 23.5 kg/m2, 75.6 cm and 0.84, respectively. For males, the optimal cut-off points of the WHtR, BMI, WC and WHR were 0.50, 25.5 kg/m2, 88.9 cm and 0.93, respectively. Conclusion In a Chinese study population, WHtR was the best predictor of the development of prediabetes in the general population and in females 7 years in advance, while WHR could predict the development of prediabetes in males. Early identification of prediabetes can better prevent diabetes.

Purpose: The expressions of antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) are very common in the sera of patients with autoimmune thyroid diseases (AITD). The relationship between thyroid autoantibodies and the occurrence of glucose and lipid metabolic disorders remains unclear. This study was performed to investigate the correlation between the presence of serum TPOAb/TgAb and those metabolic disorders in euthyroid general population. Methods: The data of this study were derived from the Thyroid Disease, Iodine status, and Diabetes National epidemiological (TIDE) survey from all 31 provinces of mainland China. A total of 17,964 euthyroid subjects including 5,802 males (4,000 with TPOAb−TgAb− and 1,802 with TPOAb+/TgAb+) and 12,162 females (8,000 with TPOAb−TgAb− and 4,162 with TPOAb+/TgAb+) were enrolled in this study. The blood glucose and lipid levels were compared between individuals with TPOAb−TgAb− and those with TPOAb+TgAb−, TPOAb−TgAb+, TPOAb+TgAb+. Results: Both fasting blood glucose (FBG) concentration and the proportion of individuals with impaired FBG (IFG) showed the decreased trends in TPOAb−TgAb+ males as compared with TPOAb−TgAb− men. There were significantly lower FBG and higher HDL-C levels as well as tendencies toward decreased incidences of IGT and hypertriglyceridemia in TPOAb−TgAb+ females when compared with TPOAb−TgAb− women. Binary logistic regression analysis further showed that serum TgAb single positivity in males was an independent protective factor for IFG with an OR of 0.691 (95% CI, 0.503–0.949). For females, serum TgAb single positivity was an independent protective factor for hypertriglyceridemia with an OR of 0.859 (95% CI, 0.748–0.987). Trend test showed that with the increase of serum TgAb level, there were significant decreases in the prevalence of IFG among the men with TSH ≤ 2.5 mIU/L and that of hypertriglyceridemia in the women, especially among non-obese females. Conclusion: Serum TgAb single positivity may imply a reduced risk of IFG in euthyroid men and that of hypertriglyceridemia in euthyroid women. The mechanisms for the independent protective roles of TgAb await further investigation.

Background. Functional pancreatic neuroendocrine neoplasms (PanNENs) are very rare disorders but have complex spectrum, including insulinoma, gastrinoma, glucagonoma, somatostatinoma, and VIPoma. Patients with PanNENs usually present with characteristic symptoms caused by corresponding hormone hypersecretion. It has always been challenging in dealing with such rare but complicated disorders. In this report, we analyzed the clinical characteristics of functional PanNENs in a large cohort of Chinese patients and summarized our clinical experience in diagnosis and treatment. Methods. The retrospective analysis was performed in patients with a definite diagnosis of functional PanNENs hospitalized in Chinese PLA General Hospital between 2000 and 2020. The clinical characteristics, surgical information, and pathological findings were extracted from their medical records and were analyzed. Results. Totally, 286 patients (gender: male 103 and female 183; age: 45.55 ± 15.23 years old) were diagnosed with definite functional PanNENs. The most frequent functional PanNENs were insulinoma (266/286) followed by glucagonoma (10/286), somatostatinoma (3/286), adrenocorticotropic hormone- (ACTH-) producing tumor (3/286), gastrinoma (2/286), and VIPoma (2/286). Nine patients were diagnosed with multiple endocrine neoplasia type 1 (MEN1) in which all the associated functional PanNENs were insulinomas. The duration from symptoms’ onset to confirmed diagnosis was 3.67 ± 4.28 years. Two hundred and eighty patients with tumor localized in pancreatic or with limited metastasis underwent surgery. The symptoms associated with hormonal oversecretion were improved significantly after surgery. Five patients with unresectable metastases or tumor recurrence after surgery were administrated with systemic chemotherapy or other targeted therapies. With these various therapies, the symptoms were also partially relieved. According to findings in pathological and immunochemical examination, all the functional PanNENs were categorized into NEN-G1 (41.95%), NEN-G2 (54.90%), NEN-G3 (3.15%), and NEC-G3 (0%). Conclusion. Patients with suspected functional PanNENs should have a systematic endocrine examination at diagnosis. Multidisciplinary collaborations are essential for precise diagnosis and tumor localization. A successful surgery or other targeted therapies can improve the prognosis of patients with such rare but complex disorders.

Objective To analyze the pathology of the patients with nonfunctional adrenal tumor (NFA), and explore the optimal diameter cut-off value. Methods The clinical data of 243 patients with NFA, evaluated in the Department of Endocrinology and operated in the Department of Urology of General Hospital of Chinese PLA from Feb. 1996 to Jan. 2016, were collected. The patients were divided into two groups according to pathology: those in real demand of surgery were classified to the surgery-need group (n=57), while the others were categorized as the surgery-unwanted group (n=186). The general situation, pathological type and tumor diameter of the two groups and the factors affecting the surgery were analyzed, and the ROC curve was used to explore the optimal surgery cut-off value, which represents the maximum value of the sum of sensitivity and specificity. Results Of the 57 patients in surgery-need group (27 males and 30 females), the lesions were on the right in 31 cases, on the left in 25 cases, and on bilateral sides in 1 case; the median of lesion diameter was 4.5cm, and the average age was 41.5±12.1 years old. Of the 186 patients in surgery-unwanted group (87 males and 99 females), the lesions were on the right in 99 cases, on the left in 86 cases, and on bilateral sides in 1 case; the median of lesion diameter was 3.0cm, and the average age was 50.6±10.9 years old. Logistic regression revealed that lesion diameter might be a risk factor (OR=1.340, 95%CI 1.266-1.418, P=0.000) and age be a protective factor (OR=0.942, 95%CI 0.929-0.955, P=0.000) for real demand of surgery. The area under the ROC curve (AUC) of lesion diameter was 0.757(95%CI 0.681-0.833). The optimal cut-off value was 4.1cm (sensitivity 60.7% and specificity 83.0%). Conclusions Younger patients with bigger lesion diameter may have greater possibility for surgery. The optimal surgery cut-off value of the lesion diameter is 4.1cm. DOI: 10.11855/j.issn.0577-7402.2016.11.11

Objective: To investigate the role of PSMA in the differential diagnosis of adrenocortical carcinoma samples (ACCs) and adrenocortical adenoma samples (ACAs), to validate the prognostic role of PSMA in patients with ACCs, and to explore the possibility that this marker can differentiate localized ACCs from adrenal metastases from other sites.Methods: PSMA protein expression in tissue samples from 50 ACCs, 90 ACAs (including 20 from patients who presented with Cushing's syndrome, 20 aldosterone-producing adenomas and 50 non-functional tumors) and 10 tissues that were metastases from other primary sites was assessed by immunohistochemistry. The clinical and pathological characteristics were compared, the intensity and density were analyzed, and the prognostic role was evaluated.Results: The analysis of clinical and pathological features revealed that the size of ACCs was greater than that of benign tissues and the ACC patients were older than the ACA patients (p < 0.01). The percentage of PSMA-positive vessels, the mean intensity and the degree of staining density were found to be significantly lower in ACAs than in ACCs (p < 0.01). In these 140 samples, 60% of the ACCs were grouped in the positive category. The samples were negative for metastases that were from other primary sites. The ENSAT stage and Ki-67 were correlated with PSMA expression. The survival distribution revealed that high PSMA expression did not show any prognostic relevance in the current ACCs series. Those samples with a score of > 3.5 were 75 times more likely to be malignant (OR = 75). We established a cut-off score of 3.5 (p < 0.05), which had 46% sensitivity and 99% specificity. Paralleling PSMA and Ki-67 maximized the area under the curve, with 72% sensitivity and 100% specificity.Conclusions: Our results strongly confirm that PSMA is helpful for distinguishing benign from malignant tumors and that its high expression levels correlate with a high ENSAT stage and high proliferation. The combination of PSMA and Ki-67 can be particularly useful. Furthermore, PSMA might be a useful tool for the identification of localized adrenal carcinoma and metastatic carcinoma.

Background Type 2 diabetes mellitus (T2DM) is a significant burden in China, where approximately 114 million patients have been diagnosed with diabetes. Chinese patients present with prominent β-cell failure, with resulting deficiency in insulin secretion, particularly early phase insulin secretion leading to postprandial hyperglycemia. Sitagliptin, a selective once-daily oral dipeptidyl peptidase-4 inhibitor, has been shown to improve glycemic control as monotherapy and in combination with other antihyperglycemic agents, including sulfonylureas and metformin. Methods This was a multicenter randomized double-blind placebo-controlled study conducted in China. The study assessed the safety and efficacy of the addition of sitagliptin 100 mg once daily versus placebo on changes from baseline at Week 24 in HbA1c, fasting plasma glucose (FPG) and 2-h post-meal glucose (PMG). Patients were aged 18–79 years, had T2DM with inadequate glycemic control, and were taking a sulfonylurea, with or without metformin. Results After 24 weeks, sitagliptin reduced HbA1c, FPG, and 2-h PMG significantly more than placebo (between-treatment differences: −0.61 %, −16.8 mg/dL, and −32.9 mg/dL, respectively; P

Background Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a rare condition with untypical subclinical symptoms of Cushing's syndrome (CS). This study aimed to compare the clinical and pathological features of PBMAH with unilateral cortisol-secreting adrenal adenoma (UAA). Methods We prospectively included 46 PBMAH patients and 205 UAA patients from January 2000 to February 2014. Cortisol levels and 24 hours urine free cortisol (UFC) were determined at baseline and during dexamethasone suppression test (DST) using the chemiluminescence method. Computed tomography (CT) examination of the adrenal glands was performed in all patients. For patients treated with adrenalectomy, hematoxylin, and eosin, staining was performed for pathological examination. Results The proportion of patients with autonomous cortisol secretion was significantly higher in PBMAH patients (39.1%) than UAA patients (6.8%). The PBMAH patients showed significantly lower levels of basal cortisol, low dose dexamethasone suppressed cortisol, and high dose dexamethasone suppressed cortisol than the UAA patients (452.6±183.3 vs. 578.7±166.4 nmol/L, P=0.003; 394.5±298.9 vs. 549.2±217.7 nmol/L, P=0.002; 397.3±282.3 vs. 544.3±187.6 nmol/L, P=0.003). Similarly, the PBMAH patients had significantly lower levels of basal 24 hours UFC, low dose dexamethasone suppressed 24 hours UFC, and high dose dexamethasone suppressed 24 hours UFC than the UAA patients (1,144.4±1,048.1 vs. 1,674.9±1,520.4 nmol/24 h, P=0.032; 1,157.3±1,483.5 vs. 1,940.1±1,360.9 nmol/24 h, P=0.003; 1,256.4±1,767.0 vs. 1,969.9±1,361.7 nmol/24 h, P=0.011). Conclusions PBMAH is often associated with atypical CS symptoms. The clinical and imaging features of PBMAH are useful for the differential diagnosis of this disease.

We aimed to investigate the association between excess body mass index (BMI) and papillary thyroid cancer (PTC) in an operative population, and the impact of higher BMI on clinicopathological aggressiveness of PTC.Charts of 10,844 consecutive patients with thyroid nodules undergoing partial or total thyroidectomy between 1993 and 2015 were reviewed. Patients diagnosed with PTC were stratified in 4 groups: BMI < 18.5 (underweight), 18.5 ≤ BMI < 24 (normal-weight), 24 ≤ BMI < 28 (overweight) and BMI ≥ 28(obese). The impacts of high BMI on prevalence and clinicopathological parameters of PTC were retrospectively analyzed in both univariate and multivariate binary logistic regression analysis.For every 5-unit increase in body mass, the odds of risk-adjusted malignance increased by 36.6%. The individuals who were obese and overweight were associated with high risk of thyroid cancer [odds ratio (OR)= 1.982, P < .001; OR= 1.377, P < .001; respectively] compared to normal weight patients, and this positive association was found in both genders. Obesity was independent predictors for tumors larger than 1 cm (OR = 1.562, P < .001) and multifocality (OR = 1.616, P < .001). However, there was no difference in cervical lymph node (LN) metastasis among BMI groups. Crude analysis showed BMI was associated with advanced tumor-node-metastasis (TNM) stage (relative risk, approximately 1.23 per 5 BMI units, P < .001), but this association disappeared after adjusting for confounding factors.Obesity was significantly associated with the risk of PTC in a large, operative population. Higher BMI was significantly associated with larger tumor size and multifocal tumor.

Pituitary stalk interruption syndrome (PSIS) is associated with simultaneous or subsequent pituitary hormone deficiencies (PHDs). Although the clinical features of multiple PHDs are well known, the status of the thyrotrophic axis in PSIS has not been thoroughly investigated. The clinical data of 89 PSIS patients and 34 Sheehan syndrome (SS) patients were retrospectively analyzed. The prevalence of central hypothyroidism in the PSIS patients and the SS patients was 79.8% and 70.6%, respectively. The thyroid-stimulating hormone (TSH) levels in the PSIS patients were significantly higher in comparison with the SS patients (5.13 ± 3.40 vs 1.67 ± 1.20 mU/L, P

Primary macronodular adrenal hyperplasia (PMAH), also known in the past as bilateral macronodular adrenalhyperplasia or adrenocorticotropin (ACTH)-independent macronodular adrenal hyperplasia, is a rare type of Cushing's syndrome (CS) and is associated with bilateralenlargement of the adrenal glands. It accounts for

The study aimed to investigate the gender-related differences of disease onset, age distribution, blood type, clinical characteristics, and malignant behaviors of differentiated thyroid carcinoma (DTC) in Chinese patients. A total of 7385 consecutive thyroid cancer patients who underwent thyroidectomy were retrospectively reviewed. 4087 (55.3%) were diagnosed as benign and the other (3298, 44.7%) were as malignant. DTC accounted for 97.6% in the malignant tumor. More single nodules turned out to be DTC in male compared to multiple nodules (46.9% vs. 40.4%, P = 0.004). The proportion increased along with the increase of year during 2000–2013, which was from 7.5% to 68.1% in males and from 16.2% to 66.7% in females. The level of preoperative TSH was significantly higher in patients with DTC compared to the patients with benign (1.97 vs. 1.57 mIU/L, P

Aims Analyze the clinical applicability of glucose metabolism indexes and continuous glucose monitoring data on the qualitative diagnosis of insulinoma. Methods Involve 22 patients with insulinoma (insulinoma group), 11 patients with hypoglycemia (hypoglycemia group) and 31 people with normal glucose tolerance (control group). HbA1c, fasting blood glucose (FBG), insulin (FINS) and C-peptide (FCP) was tested. Using CGMS to monitor the blood glucose for three consecutive days and selecting the monitoring data of 24 h thereof, figuring out, with the aid of EasyGV Version 9.0, the mean glucose (MG), the standard deviation (SD) of blood glucose, CONGA (continuous overall net glycemic action), J-Index, LI (Lability Index), LBGI (Low Blood Glucose Index), HBGI (High Blood Glucose Index), GRADE (glycaemic risk assessment diabetes equation), MAGE (mean aplitude of glycaemic excursions), M value, MAG (mean absolute glucose). Results (1) FBG and LBG of insulinoma group are lower than those of control group and those of hypoglycemia group while FINS and FCP of insulinoma group are markedly higher than those of the other two groups; (2) the MG and CONGA of insulinoma group are lower than those of control group and its indexes like ST, LI, LBGI, GRADE, MAGE, M value and MAG are higher than those of control group; there are differences between the indexes of insulinoma group and those of hypoglycemia group in CONGA (lower than that of hypoglycemia group), LBGI (higher than that of hypoglycemia group), and M value (higher than that of hypoglycemia group). By drawing the ROC curve and calculating Youden index, the cut-off values of LBGI, M value, CONGA are respectively as 4.06, 7.79, 4.38, and the best index of differential diagnosis is LBGI. Conclusion Continuous glucose monitoring data can be used to diagnose insulinoma and blood glucose fluctuation indicators such as LBGI, M value, CONGA might be useful to identify insulinoma.

Background The aim of the present study was to assess the relationship between night sleep duration and glycemic and triglyceride (TG) levels among people with different glycemic status. Methods In all, 18 121 subjects aged ≥40 years were enrolled in this cross-sectional study, including 4318 with impaired glucose regulation (IGR), 4225 with diabetes, and 9578 with normal glucose regulation (NGR). The IGR + diabetes and NGR groups were divided into three subgroups according to self-reported night sleep duration as follows: (i) 9 h. The associations of sleep duration with HbA1c, fasting plasma glucose (FPG), 2-h post-load plasma glucose (PPG), and TG levels were examined. Results Long night sleep duration (>9 h) was associated with higher HbA1c, FPG, PPG, and TG levels compared with sleep duration of 6–9 h (P 9小时）的患者具有较高的HbA1c、FPG、PPG和TG水平（P值均

In the present study, the case of a female patient with pseudo-hermaphrodism caused by an androgen-producing adrenocortical tumor is presented, and the possible mechanism is investigated. The expression of the luteinizing hormone/human chorionic gonadotrophin (LH/hCG) receptor in tumor tissues and normal adrenal tissues was analyzed using immunohistochemistry. Furthermore, the activities of 3β-hydroxysteroid dehydrogenase 2 (HSD2), cytochrome P450 17α-hydroxylase (CYP17) and 17β-hydroxysteroid dehydrogenase 3 (HSD3) enzymes were measured using enzyme-linked immunosorbent assay, and the expression levels of 3β-HSD2, 17β-HSD3, CYP17 and LH/hCG receptor mRNA were determined by quantitative polymerase chain reaction (qPCR). Immunohistochemical staining for the LH/hCG receptor was negative in the tumor tissue and positive in the normal adrenal tissue. The activities of 3β-HSD2 and CYP17 in the tumor tissue were higher than those in the normal tissue (P

Type 2 diabetes mellitus (T2DM) is a significant burden in China, where approximately 114 million patients have been diagnosed with diabetes. Chinese patients present with prominent β-cell failure, with resulting deficiency in insulin secretion, particularly early phase insulin secretion leading to postprandial hyperglycemia. Sitagliptin, a selective once-daily oral dipeptidyl peptidase-4 inhibitor, has been shown to improve glycemic control as monotherapy and in combination with other antihyperglycemic agents, including sulfonylureas and metformin.This was a multicenter randomized double-blind placebo-controlled study conducted in China. The study assessed the safety and efficacy of the addition of sitagliptin 100 mg once daily versus placebo on changes from baseline at Week 24 in HbA1c, fasting plasma glucose (FPG) and 2-h post-meal glucose (PMG). Patients were aged 18-79 years, had T2DM with inadequate glycemic control, and were taking a sulfonylurea, with or without metformin.After 24 weeks, sitagliptin reduced HbA1c, FPG, and 2-h PMG significantly more than placebo (between-treatment differences: -0.61 %, -16.8 mg/dL, and -32.9 mg/dL, respectively; P 0.001 for all). The addition of sitagliptin was generally well tolerated, with a comparable incidence of adverse events and drug-related adverse events in both treatment groups. The sitagliptin group had a higher incidence of symptomatic hypoglycemia than the placebo group (25/248 [10.1 %] vs 13/249 [5.2 %], respectively; P = 0.042).Sitagliptin 100 mg once daily significantly improved glycemic control in Chinese patients with T2DM who had inadequate glycemic control with sulfonylurea, with or without metformin therapy. The addition of sitagliptin was generally well tolerated. (clinicaltrials.gov: NCT01590771).

The PTH receptor (PTH1R) activates multiple signaling pathways, including extracellular signal-regulated kinases 1 and 2 (ERK1/2). The role of epidermal growth factor receptor (EGFR) transactivation in ERK1/2 activation by PTH in distal kidney cells, a primary site of PTH action, was characterized. ERK1/2 phosphorylation was stimulated by PTH and blocked by the EGFR inhibitor, AG1478. Upon PTH stimulation, metalloprotease cleavage of membrane-bound heparin-binding fragment (HB-EGF) induced EGFR transactivation of ERK. Conditioned media from PTH-treated distal kidney cells activated ERK in HEK-293 cells. AG1478 added to HEK-293 cells ablated transactivation by conditioned media. HB-EGF directly activated ERK1/2 in HEK-293 cells. Pretreatment of distal kidney cells with the metalloprotease inhibitor GM-6001 abolished transactivation of ERK1/2 by PTH. The role of the PTH1R COOH terminus in PTX-sensitive ERK1/2 activation was characterized in HEK-293 cells transfected with wild-type PTH1R, with a PTH1R mutated at its COOH terminus, or with PTH1R truncated at position 480. PTH stimulated ERK by wild-type, mutated and truncated PTH1Rs 21-, 27- and 57-fold, respectively. Thus, the PTH1R COOH terminus exerts an inhibitory effect on ERK activation. EBP50, a scaffolding protein that binds to the PDZ recognition domain of the PTH1R, impaired PTH but not isoproterenol or calcitonin-induced ERK activation. Pertussis toxin inhibited PTH-stimulated ERK1/2 by mutated and truncated PTH1Rs and abolished ERK1/2 activation by wild-type PTH1R. We conclude that ERK phosphorylation in distal kidney cells by PTH requires PTH1R activation of Gi, which leads to stimulation of metalloprotease-mediated cleavage of HB-EGF and transactivation of the EGFR and is regulated by EBP50.

To evaluate the outcomes of intravenous glucocorticoid therapy with or without orbital radiotherapy for moderate-to-severe Graves' ophthalmopathy.A total of 83 patients with moderate-to-severe Graves' ophthalmopathy were retrospectively analyzed. Intravenous glucocorticoid was given to patients for 3 consecutive days every four weeks in 1-3 circles. The regimens included intravenous glucocorticoid alone (n = 36) and intravenous glucocorticoid plus orbital radiotherapy (n = 47). Photophobia, lacrimation, eye pain, soft tissue congestion, edema, exophthalmos and diplopia were compared before and after treatment. The symptoms and efficacies were compared between two groups.During a 12-week follow-up, clinical activity score (CAS), exophthalmos and diplopia all improved after treatment (P0.05). However, the changes of CAS, exophthalmos or diplopia showed no inter-group differences (P0.05). The overall clinical response was 50% in glucocorticoid group and 63.8% in glucocorticoid plus orbital radiotherapy group. And there was no statistical difference (P0.05).Moderate-to-severe Graves' ophthalmopathy may be relieved by pulsed intravenous glucocorticoid with or without orbital radiotherapy. There is no inter-group difference in short-term efficacies.

The diagnosis of malignant thyroid nodules is still a clinical challenge. This study aimed to determine the ultrasonographic characteristics of papillary thyroid carcinoma. The ultrasonographic and pathological data of 2453 thyroid nodules in a cohort of 1895 Chinese patients who underwent thyroidectomy from January 2010 to December 2012 were retrospectively reviewed. Anteroposterior and transversal (AP/TR) diameters ≥1, solid structure, infiltrative margins, hypoechoic appearance, and microcalcifications were more common in malignant nodules than in benign nodules (P 10 mm). However, in small nodules (diameter ≤10 mm), only AP/TR ≥1 and infiltrative margins were independent risk factors of malignancy (P

To summarize the disease distribution characteristics of adrenal lesions and analyze the changes of disease spectrum so as to further guide clinical practices.All clinical data of adrenal lesion patients hospitalized between 1993 and 2013 were collected. Their profiles of gender ratio, visiting age, final diagnosis and year of hospitalization were retrospectively analyzed.A total of 4 049 patients with adrenal lesions were admitted. There were 2 004 males and 2 045 females with a mean age of 46.82 ± 13.36 years. The number of cases gradually increased year-on-year. And the visiting age was 30-60 years. The annual proportion of adrenal incidentaloma out of total adrenal lesions gradually increased with advancing age. Among them, 3 014 received endocrine function assessments. And there were non-functional lesions (n = 1 503, 49.88%) , adrenal Cushing's syndrome (n = 259, 8.60%), primary aldosteronism (n = 665, 22.04%) and pheochromocytoma (n = 235, 7.80%) . The proportion of non-functional lesions rose from 20.97% to 54.11% (P0.05). The proportion of primary aldsteronism declined from 29.84% to 20.43% (P0.05). And the proportion of adrenal Cushing syndrome changed slightly (P0.05). The proportion of pheochromocytoma declined from 18.55% to 6.99% (P0.05).The number of patients gradually increased over the last two decades.So did the proportion of adrenal incidentaloma. The disease spectrum of adrenal lesions has changed. And the proportion of non-functional lesions increased while that of functional lesions declined.

Kallmann syndrome, a form of idiopathic hypogonadotropic hypogonadism, is characterized by developmental abnormalities of the reproductive system and abnormal olfaction. Despite association of certain genes with idiopathic hypogonadotropic hypogonadism, the genetic inheritance and expression are complex and incompletely known. In the present study, seven Kallmann syndrome pedigrees in an ethnic Han Chinese population were screened for genetic mutations. The exons and intron–exon boundaries of 19 idiopathic hypogonadotropic hypogonadism (idiopathic hypogonadotropic hypogonadism)-related genes in seven Chinese Kallmann syndrome pedigrees were sequenced. Detected mutations were also tested in 70 sporadic Kallmann syndrome cases and 200 Chinese healthy controls. In pedigrees 1, 2, and 7, the secondary sex characteristics were poorly developed and the patients’ sense of smell was severely or completely lost. We detected a genetic mutation in five of the seven pedigrees: homozygous KAL1 p.R191ter (pedigree 1); homozygous KAL1 p.C13ter (pedigree 2; a novel mutation); heterozygous FGFR1 p.R250W (pedigree 3); and homozygous PROKR2 p.Y113H (pedigrees 4 and 5). No genetic change of the assayed genes was detected in pedigrees 6 and 7. Among the 70 sporadic cases, we detected one homozygous and one heterozygous PROKR2 p.Y113H mutation. This mutation was also detected heterozygously in 2/200 normal controls and its pathogenicity is likely questionable. The genetics and genotype–phenotype relationships in Kallmann syndrome are complicated. Classical monogenic inheritance does not explain the full range of genetic inheritance of Kallmann syndrome patients. Because of stochastic nature of genetic mutations, exome analyses of Kallmann syndrome patients may provide novel insights.

Objective: To investigate the association between serum ALT level within reference range (≤40 U/L) and morbidity of MetS in a large middle-aged and elderly Chinese community population. Methods: Our study was a community-based cross-sectional survey which used cluster sampling method. From November 2011 to August 2012 a total of 16,539 subjects (males 5184, females 11,355) with serum ALT levels in the normal range aged ≥40 years from Shijingshan District (Beijing, China) were included in the study. Data on demographic information, lifestyle, history of diabetes mellitus, hypertension, dyslipidemia and liver disease were collected. Body height, body weight, waist circumference, hip circumference, and blood pressure were recorded. The oral glucose tolerance test or a standard meal test and blood lipid test was performed. The determination of metabolic syndrome was according to the unified criteria published in 2009. The association between serum ALT level and metabolic syndrome was evaluated by logistic regression. The association between serum ALT level and all components of metabolic syndrome was evaluated by multiple linear regression. p &lt, 0.05 was regarded as statistically significant. Results: The prevalence of metabolic syndrome was 41.4% in males and 40.6% in females. We found ALT level was positively associated with odds of metabolic syndrome after adjustment for age, smoking, and alcohol intake. The odds ratio values of MetS in the ALT quartiles 2–4 groups were 1.920 (95%CI: 1.619–2.277), 2.853 (95%CI: 2.407–3.381), and 4.171 (95%CI: 3.510–4.956) in males, 1.889 (95%CI: 1.671–2.136), 3.490 (95%CI: 3.095–3.935), and 5.593 (95%CI: 4.957–6.311) in females, respectively, compared with the ALT quartile 1 group. Conclusions: Higher serum ALT level within the reference range was associated with increased odds of MetS in middle-aged and elderly Chinese men and women.

Rationale: An accessory ovary is a rare structure containing normal ovarian tissue, which has a direct or ligamentous connection with a normal and eutopic ovary. Patient concerns: In the study, we reported a 46-year-old woman presented with secondary amenorrhea and virilization symptoms for 1 year. Diagnoses: Endocrine evaluation revealed slightly elevated serum cortisol, extremely elevated 24-hour urinary-free cortisol and serum testosterone. Clinical assessment exhibited a large solid mass with heterogeneous enhancement in the left adnexauteri compounded with hypercortisolism and hyperandrogenemia. An accessory ovarian tumor attached to the infundibulum of the left fallopian tube was found, and a separate normal ovary was present on the same side. Interventions: The patient underwent a left adnexectomy. Outcomes: During surgery, a 12 cm × 8 cm, gray-red, and well-circumscribed solid mass was be identified. The tumor had ligamentous attachment with the infundibulum of left fallopian tube. The sectioned surface was gray-brown, lobulated and did not exhibit either significant necrosis or hemorrhage. Pathological findings demonstrated that tumor cells had small round nuclei, mild atypia, no mitosis were arranged in a diffuse pattern of columns or nests separated by a rich vascular network and no crystals of Reinke were found. It was diagnosis ovarian steroid cell tumor (NOS) without malignant behavior by immunohistochemical staining. The patient was finally diagnosed as accessory ovarian steroid. The patient was discharged from the hospital on the seventeenth day after surgery. During postoperative follow-up, the first postoperative menstrual flow recovered and blood pressure regained 1 month after surgery. Furthermore, her Cushing syndrome regressed and hirsutism disappeared completely 4 months after surgery cell tumor. Lessons: It is vitally important to establish a final diagnosis according to the clinical manifestations and laboratory values in addition to imaging studies and laparoscopic examination of a rare coexistence of hyperandrogenemia and Cushing syndrome based on the accessory ovarian pathology.