Objective To evaluate osteoporosis and the bone turnover markers in patients with Graves′ disease(GD) and the association of bone turnover markers including serum osteocalcin ( OCN ),I procollagen Nterminal propeptide( PINP),serum alkaline phosphatase ( ALP),and β- I collagen carboxyl-terminal peptide ( β-CTX)with thyroid hormone levels.Methods A total of 163 patients with Graves′ disease were enrolled.Serum thyroid hormone,OCN,PINP,and β-CTX levels were measured by the method of ethchemiluminescence.Serum ALP,calcium,phosphorus,and urinary calcium/creatinine ratio were measured by automatic biochemical system.Bone mineral density ( BMD ) of lumbar spines 1-4 ( L 1-4 ) and the proximal left femur was detected by dual energy xray absorptiometry.Results GD cases enrolled were composed of 43 men (26.4％ )and 120 women ( 73.6％ ),with an average age of ( 47 ± 1 ) years.There were 126 cases ( 77.3％ ) with normal BMD,and 37 cases ( 22.7％ ) with osteoporosis.OCN,ALP,PINP,β-CTX,and free T3 levels were significantly higher in the group of osteoporosis than those in the group with normal BMD( P＜0.05 or P＜0.01 ) after adjusting for sex,age,and BMI.The levels of OCN,P1NP,and β-CTX were positively correlated with serum FT3 level ( all P＜0.01 ) and were also progressively increased according to the quartile groups of FT3 levels ( P＜0.01 ) after sex,age,and BMI were adjusted.Conclusion Patients with Graves′ disease had a high incidence of osteoporosis with characristic high rate of bone turnover,which is related to the raised thyroid hormone levels.

Thirty-three patients with new-onset type 1 diabetes from Zhongshan Hospital, Fudan University were recruited from 2013 to 2014. Relevant clinical data were collected for the statistical analysis. Among the 33 patients with type 1 diabetes, there were 7 with fulminant type 1 diabetes (FT1DM), 12 acute onset type 1 diabetes (AT1DM), and 14 with slowly progressive type 1 diabetes (SPIDDM). The fasting and stimulated C-peptide levels were significantly lower while glycated albumin (GA)/HbA1C and mean amplitude of glucose excursions (MAGE) levels were significantly higher in FT1DM group compared with other two groups(all P<0.05). Pearson correlation analysis in all patients with type 1 diabetes revealed that GA/HbA1C was correlated with fasting C-peptide, MAGE, and difference of the peak blood glucose to the lowest blood glucose (ΔBG) levels (all P<0.05). Stepwise multivariate analysis showed that GA/HbA1C was independently correlated with MAGE and ΔBG (P<0.05). Logistic regression model indicated that GA, HbA1C, and GA/HbA1C were independently correlated with FT1DM.

Objective To explore the distribution change and antimicrobial resistance of pathogens causing catheter associat‐ed urinary tract infection in ICU .Methods 500 cases of patients received by emergency department ICU in our hospital from 2012 April~ 2014 June were collected ,urine samples were collected by closed drainage bag after indwelling catheter in 3 ,7 ,14 ,21ds .By culture ,separation ,purification ,screening and identification and antimicrobial disc diffusion experiments ,distribution changes and resistantance of pathogens causing catheter related infections were analyzed .Results 358 strains were found in catheter associated urinary tract infections ,in which 175 strains were Gram‐positive bacteria ,mainly were Staphylococcus aureus (48 .57% ) and en‐terococci (46 .86% ) ,137 were Gram‐negative bacteria ,mainly were E .coli (56 .93% ) ,46 fungi ,mainly were Candida albicans (47 .83% );Gram‐positive bacteria showed a decreasing trend ,while Gram‐negative bacteria increased every year;resistance rates of Staphylococcus aureus and enterococci to penicillins ,cephalosporins and quinolones were more than 50% ;Escherichia coli and Kleb‐siella pneumoniae had strong resistance to penicillins ,cephalosporins and quinolones ;resistance rate of Pseudomonas aeruginosa to ampicillin ,sulbactam and ampicillin cefazolin up to 100% .Conclusion Escherichia coli is the major pathogens causing ICU catheter associated urinary tract infections;pathogens resistance are strong ,clinical monitoring should be strengthened .

ObjectiveTo evaluate the priority application of thin adrenal CT scanning in out-patients with hypertension for early diagnosis of adrenal hypertension.MethodsThe patients with hypertension were collected from January to August 2009,in whom the secondary hypertension ( including endocrine and renal hypertension) and malignant cancers were excluded.All patients accepted the adrenal CT scan firstly,and then the patients with the positive result of morphological abnormalities in the adrenal CT( including adenoma and hyperplasia)were evaluated for endocrine function of adrenal glands.Results A total 362 cases of hypertension were studied,in.cluding 162 males and 200 females.The average age was (60.9 ±9.3 ) year-old,the average duration of hypertension was ( 13.8 ±5.3 ) year.After adrenal thin layer scanner CT scan,35 patients ( 9.6％ ) with adrenal abnormalities were found.Endocrine functional assessments of adrenal glands were carried out among these patients,17 cases (4.7％) with functional lesions were diagnosed,including 14 cases(3.9％ )with primary hyperaldosteronism,2 cases(0.6％ )with Cushing's syndrome,and 1 case ( 0.3％ ) with pheochromocytoma.Conclusion This study revealed that the percentage of adrenal lesions in outpatients with hypertension was 9.6％.The percentage of adrenal hypertension was 4.7％.Thin layer CT scan seems to effectively screen the adrenal hypertension with adrenal lesions,and would be helpful to the diagnosis of endocrine hypertension.

Objective With a computer-assisted program,retinal vascular calibers were measured quantitatively.In this study the relationship between retinal vascular calibers and components of the metabolic syndrome was examined.Methods A total of 450 hypertensive patients were collected.Medical history,physical examination,blood tests,and retinal photographs were taken.Retinal vascular calibers were measured quantitatively from digital retinal photographs.In the hypertensive population the associations of retinal vascular calibers with components of the metabolic syndrome were described,and the factors that influenced retinal vascular calibers were analyzed.Results In the enrolled population,mean age was (57.53 ± 10.01) years,mean systolic blood pressure (138 ± 17) mm Hg(1 mm Hg =0.133 kPa),diastolic blood pressure (84 ± 10) mm Hg.Mean central retinal arteriolar equivalent(CRAE) was(129.26 ± 12.68) μm,and mean central retinal venular equivalent (CRVE) (198.25 ± 18.37) μm.After adjusting for age,gender,etc,CRAE in group with poor blood pressure control was smaller than that in the group with good blood pressure control [(126.45 ± 15.74) μm vs (130.30 ± 11.30) μm,P =0.029].CRAE tended to be narrower with worsened blood pressure control (P =0.075).CRVE was smaller in patients with normal high density lipoprotein-cholesterol (HDL-C) than in those with abnormal level [(197.36 ±17.62) μm vs (203.07 ± 21.52) μm,P =0.040].The diastolic blood pressure was raised along with the decreasing CRAE(P=0.009).And the HDL-C level was reduced as CRVE was increasing(P=0.042).Old age (r =-0.090,P=0.013) and poor blood pressure control(r=-0.098,P=0.038) were independent risk factors for narrow CRAE,while lowered HDL-C (r =0.105,P =0.024) and smoking (r =0.141,P =0.010) were independent risk factors for wide CRVE.Conclusions Narrow CRAE was related to poor blood pressure control,while wide CRVE was related to lowed HDL-C.Aging and poor blood pressure control were independent risk factors for narrow CRAE,while lowed HDL-C and smoking were independent risk factors for wide CRVE in the hypertensive patients.

This article reported a case of type 1 diabetes caused by a programmed death-1 ( PD-1) inhibitor. The patient was a 52-year-old man with metastatic renal cell carcinoma who received the combined therapy of PD-1 inhibitor Nivolumab and vascular endothelial growth factor ( VEGF) inhibitor Bevacizumab. He presented with thirst, polydipsia, polyuria, repeated vomiting, and fatigue 9 weeks after initiation of the therapy and developed into diabetic ketoacidosis (DKA) about 2 weeks later, with blood glucose 50.9 mmol/L, HbA1C8.4％, serum fasted and glucose-loaded C peptide<0.01 ng/ml, arginine test negative, and autoantibodies negative. The patient was diagnosed as type 1 diabetes caused by the PD-1 inhibitor and was given intensive glucose lowering treatment with insulin, water and electrolyte disorders were also corrected. His symptoms improved but he had to continue insulin treatment. It is recommended to check baseline glucose level prior to the initiation of treatment with PD-1 inhibitor, and should carefully monitor the clinical symptoms and glucose levels during the treatment. Timely detection, correct diagnosis and treatment are important to ensure patients' safety and to improve their prognosis.

Objective:To investigate the clinical features of multiple endocrine gland dysfunction in patients with tumors after using immune checkpoint inhibitors(ICIs).Methods:Cases with two or more abnormalities of endocrine gland function after immunotherapy were collected from the Department of Endocrinology, Zhongshan Hospital, Fudan University between January 2019 and January 2022. Clinical manifestations, laboratory tests, imaging, treatment and prognosis were analyzed.Results:A total of 12 patients were included, 6 males and 6 females, aged(61.2±10.0) years old. All patients received programmed cell death protein-1(PD-1) monoclonal antibody therapy, and the time to endocrine abnormality ranged from 9 to 94 weeks after administration. All patients developed primary hypothyroidism, 11 of them had isolated adrenocorticotropic hormone deficiency, and 1 had primary adrenal insufficiency.Conclusion:ICIs can involve multiple endocrine glands simultaneously or successively, mainly manifested as primary hypothyroidism and isolated adrenocorticotropic hormone deficiency. It is essential to assess the function of the pituitary and target glands in patients treated with ICIs to improve the safety of immunotherapy.

Objective:To analyze the clinical features of type 2 diabetic patients with insulin autoimmune syndrome after treatment with exogenous insulin.Methods:A total of 106 patients with type 2 diabetes diagnosed with exogenous insulin-related insulin autoimmune syndrome (EIAS) were included from September 2017 to March 2019 in the Department of Endocrinology, Zhongshan Hospital, Fudan University. The clinical data, physical examination, and laboratory examination results of patients were collected.Results:Of the 106 patients, 84 (79.24%) used premixed human insulin or premixed insulin analogs, and 18 patients (16.98%) presented recurrent hypoglycemia. The arginine stimulation test showed that the median value of the baseline insulin was 73.40 (23.07-146.75) μU/ml, and the median ratio of 4 minute insulin to 0 minute insulin was 1.27 (1.03-1.85), with the mean of the ratio 1.72±1.47. The ratio of baseline insulin (μU/ml) to C-peptide (ng/ml) was 44.60 (14.92-87.93), with an average of 81.92±130.93. Taking the two-fold upper limit of fasting insulin reference value (49.8 μU/ml) as the cut-off point, the subjects were divided into insulin accumulation group (baseline insulin≥49.8 μU/ml) and insulin non-accumulation group (baseline insulin <49.8 μU/ml). Among the 66 patients in the insulin accumulation group, 14 patients had hypoglycemia (21.21%) and 4 patients in the insulin non-accumulation group presented hypoglycemia (10%). The ratio of 4 minute insulin to baseline insulin, ratio of baseline insulin to C-peptide, blood glucose level standard deviation (SDBG) and maximum blood glucose fluctuation amplitude (LAGE) in the insulin accumulation group were significantly higher than those in the insulin non-accumulation group (all P<0.05). Among 66 patients in the insulin accumulation group, 36 patients changed the type of insulin preparafion (insulin treatment group), 30 patients were changed from insulin to oral hypoglycemic agents (oral medication group). After treatment, both SDBG and LAGE in the two groups were significantly lower than before treatment ( P<0.05). Conclusions:With the aggravation of exogenous insulin accumulation, the fluctuation of blood glucose and the proportion of hypoglycemia were significantly increased. There was a characteristic change in islet function in patients with insulin autoimmune syndrome. After arginine stimulation, there was no significant peak of insulin secretion, showing a " high-level" curve. The baseline insulin/C-peptide ratio was significantly increased. The prognosis of EIAS patients is good after timely diagnosis and adjustment of treatment.

Objective:To identify the association of sex hormone and sex hormone-binding globulin (SHBG) levels in patients with Graves′ disease.Methods:Between December 2017 and July 2019, 152 patients with Graves′ disease were enrolled in the Department of Endocrinology and Metabolism of Zhongshan Hospital, Fudan University. Parameters such as height, weight, thyroid function, sex hormone, fasting blood glucose, insulin, C-peptide, glycosylated albumin, HbA 1C, and liver function were collected. The associations between SHBG and bioclinical characteristics were analyzed. Results:The glycosylated albumin level was negatively associated with SHBG in all subjects ( β=-0.308, P<0.01), while this association was not significant after the adjustment for thyroid hormones. Male patients had significantly lower SHBG level than female patients ( P<0.01). In male patients, SHBG was associated with luteinizing hormone ( r=0.465, P<0.01), estradiol ( r=0.629, P<0.01), testosterone ( r=0.786, P<0.01). While in female patients, SHBG was also associated with testosterone ( r=0.191, P<0.05). In multivariate linear regression analysis, estradiol was independently associated with SHBG ( β=0.329, P<0.01) in male subjects. Conclusion:The hypogonadism and infertility in Graves′ disease patients could partially be attributed to the association between SHBG and Graves′ disease.

Objective:To analyze clinical characteristics of 17α-hydroxylase deficiency, and to facilitate the understanding and management of the disease.Methods:A retrospective analysis of the clinical characteristics and biochemical results of 5 cases with 17α-hydroxylase deficiency diagnosed and treated from 2018 to 2020.Results:All 5 patients were female as social gender, and reached adulthood upon first clinic visit to our department and got diagnosed. All 5 cases had hypertension, hypokalemia, bilateral adrenal hyperplasia or adenoma, osteoporosis, and typical hormone changes related to steroid synthesis.Conclusion:Steroid hormone tests with liquid chromatography tandem mass spectrometry(LC-MS/MS) enable early diagnosis of 17α-hydroxylase deficiency, assessment of the type and degree of enzyme deficiency, and choice of treatment. For such patients, it is necessary to give appropriate anti-osteoporosis therapy.