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Insulinoma is a rare pancreatic neuroendocrine tumor that can spontaneously produce excess endogenous insulin, resulting in recurrent and serious hypoglycemia. Patients with insulinoma always have intermittent neuroglycopenia, which has been frequently reported as being misdiagnosed as epilepsy. In this report, we analyzed the clinical data of patients with confirmed insulinoma who had ever been misdiagnosed to have epilepsy.The retrospective review was performed on 266 patients with confirmed insulinoma at the First Medical Center of Chinese PLA General Hospital between January 2000 and July 2020.1. The diagnosis of insulinoma was confirmed in 266 patients. Forty-four patients [male/female=1/1.8, aged (41.25±12.30) years old] were misdiagnosed to have epilepsy, with a misdiagnosis rate of 16.5%. 2. Thirty-eight patients presented with consciousness disorder. Eleven patients presented with palpitation, sweating, and anxiety. Five patients presented with convulsion and 6 patients presented with abnormal behavior and delirium. 3. Twenty-two patients underwent EEG examination. EEG showed spike wave or spike-slow complex wave in 5 patients, decreased α wave and increased slow wave in θ and δ band in 7 patients, and was normal in 10 patients. 4. Thirty-five patients were incorrectly prescribed with AEDs and 22 patients were even misdiagnosed to have refractory epilepsy. 5. All these 44 patients underwent successful surgery, and hypoglycemia symptoms were relieved after insulinoma resection.Patients with insulinoma sometimes share common clinical characteristics with epilepsy. To patients with epilepsy or suspected epilepsy, especially with poor response to ADEs, hypoglycemia caused by insulinoma should be emphasized in the differential diagnosis.

A multicenter, open-label, randomized, controlled superiority trial with 18 months of follow-up was conducted to investigate whether oral zinc supplementation could further promote spermatogenesis in males with isolated hypogonadotropic hypogonadism (IHH) receiving sequential purified urinary follicular-stimulating hormone/human chorionic gonadotropin (uFSH/hCG) replacement. Sixty-seven Chinese male IHH patients were recruited from the Departments of Endocrinology in eight tertiary hospitals and randomly allocated into the sequential uFSH/hCG group (Group A, n = 34) or the sequential uFSH plus zinc supplementation group (Group B, n = 33). In Group A, patients received sequential uFSH (75 U, three times a week every other 3 months) and hCG (2000 U, twice a week) treatments. In Group B, patients received oral zinc supplementation (40 mg day-1 ) in addition to the sequential uFSH/hCG treatment given to patients in Group A. The primary outcome was the proportion of patients with a sperm concentration ≥1.0 × 106 ml-1 during the 18 months. The comparison of efficacy between Groups A and B was analyzed. Nineteen of 34 (55.9%) patients receiving sequential uFSH/hCG and 20 of 33 (60.6%) patients receiving sequential uFSH/hCG plus zinc supplementation achieved sperm concentrations ≥1.0 × 106 ml-1 by intention to treat analyses. No differences between Group A and Group B were observed as far as the efficacy of inducing spermatogenesis (P = 0.69). We concluded that the sequential uFSH/hCG plus zinc supplementation regimen had a similar efficacy to the sequential uFSH/hCG treatment alone. The additional improvement of 40 mg day-1 oral zinc supplementation on spermatogenesis and masculinization in male IHH patients is very subtle.

Pituitary stalk interruption syndrome (PSIS) is a rare congenital disease which results in hypopituitarism. Patients with PSIS often exhibit short stature due to their deficiency of growth hormone (GH).Here, we present two rare cases of adults males with PSIS, in which the patients were of normal height and did not take any GH supplements. Sterility and multiple hormone deficiencies including GH were seen in both of them. Through whole exome sequencing of their DNA, we found novel mutations they shared, three in MUC4 (c.7815GT, c.3548CT, c.3399CG) and one in NBPF10 (c.536CA).The present cases suggest that there are exceptions in GH deficient patients where a select few can attain normal heights without GH therapy. Genetic screening can be a predictor for prognoses of rare types of hypopituitarism.

Prolactinoma is an estrogen-related tumor and leukemia-related protein 16 (LRP16) is correlated with the progression of estrogen-related tumors, but the regulatory mechanism between LRP16 and prolactinoma remain unclear. This study demonstrates a variation in LRP16 with estrogen receptor α (ERα) in prolactinoma models and the up and downregulation effects of LRP16 on prolactin secretion of pituitary adenomas cells (GH3 cells). In our study, 50 male SD rats (30-day-old) were randomly divided into five groups of 10 rats each. After 120 days of treatment, the rats were sacrificed, and the expression of LRP16 and ERα were examined by Western blot and immunohistochemistry to explore the changes in ERα, LRP16, and prolactin. After siRNA transfection of the respective genes, the GH3 cells were cultured, and their secretory function as well as the expression of ERα mRNA and prolactin were analyzed by enzyme-linked immunosorbent assay and real-time-polymerase chain reaction analysis. The results show that secretion of prolactin by GH3 cells can be affected by up and downregulating LRP16 expression, which may provide a novel medical therapy in clinical trials.

Excessively deep sedation is prevalent in mechanically ventilated patients and often considered suboptimal. We hypothesized that the bispectral index (BIS), a quantified electroencephalogram instrument, would accurately detect deep levels of sedation.We prospectively enrolled 90 critically ill mechanically ventilated patients who were receiving sedation. The BIS was monitored for 24 hours and compared with the Richmond Agitation Sedation Scale (RASS) evaluated every 4 hours. Deep sedation was defined as a RASS of -3 to -5. Threshold values of baseline BIS (the lowest value before RASS assessment) and stimulated BIS (the highest value after standardized assessment) for detecting deep sedation were determined in a training set (45 patients, 262 RASS assessments). Diagnostic accuracy was then analyzed in a validation set (45 patients, 264 RASS assessments).Deep sedation was only prescribed in 6 (6.7%) patients, but 76 patients (84.4%) had at least 1 episode of deep sedation. Thresholds for detecting deep sedation of 50 for baseline and 80 for stimulated BIS were identified, with respective areas under the receiver-operating characteristic curve of 0.771 (95% confidence interval, 0.714-0.828) and 0.805 (0.752-0.857). The sensitivity and specificity of baseline BIS were 94.0% and 66.5% and of stimulated BIS were 91.0% and 66.5%. When baseline and stimulated BIS were combined, the sensitivity, specificity, and clinical utility index were 85.0% (76.1%-91.1%), 85.9% (79.5%-90.7%), and 66.9% (57.8%-76.0%), respectively.Combining baseline and stimulated BIS may help detect deep sedation in mechanically ventilated patients.

Objective To analyze the clinical characteristics of pituitary stalk interruption syndrome(PSIS). Methods The clinical data including clinical manifestations,laboratory tests,and imaging findings of 114 PSIS patients in our hospital were retrospectively analyzed. Results Of these 114 PSIS patients,102 cases (89.4%) were male. The average age was 21.1?6.1 years. A history of breech delivery was documented in 91 cases (91.9%). Short stature was found in 89 cases (71.8%) and bone age delayed (6.1?5.1) years. Secondary sex characteristics were poor or undeveloped in most patients. The prevalence of deficiencies in growth hormone,gonadotropins,corticotropin,and thyrotropin were 100.0%,94.0%,84.2%,and 74.6%,respectively. Hyperprolactinemia was found in 28.1% of patients. Three or more pituitary hormone abnormalities were found in 105 cases(92.1%). Compared with the 5 cases with history of cephalic delivery,no difference were found in the aspects of height(t=0.297,P=0.634),penile length(t=1.205,P=0.882),testicular volume (U=99.000,P=0.348),growth hormone peak (U=89.000,P=0.186),adrenocorticotropic hormone peak(U=131.000,P=0.967),luteinizing hormone peak(U=98.500,P=0.582),thyroid-stimulating hormone (U=82.000,P=0.162),and the height of anterior pituitary (t=1.676,P=0.107) in the 53 cases with history of breech delivery. Conclusions The clinical manifestations,symptoms,hormone deficiencies were severe in our series. The condition severities were not remarkably different in patients with different delivery ways.

Patients with malignant insulinoma always present with symptoms of severe hypoglycemia and have poor life expectancy. In addition, inoperable metastatic malignant insulinomas are very difficult to manage. The aim of this report is to present our successful experiences in diagnosis and treatment of this disease in 6 patients.Six patients (male 2, female 4) with malignant insulinomas were admitted into our hospital. Their clinical histories, including clinical presentations, endocrine evaluations, radiological images, pathological examination and treatments, were reviewed.The diagnosis of malignant insulinoma combined with liver metastases was confirmed in all patients by endocrine evaluation and radiological images. Patients 1-3 underwent surgical management. The primary and metastasized tumors were completely resected. After successful surgery, no hypoglycemia recurred. Patients 4-6 did not undergo surgery because of systemic disease and poor health. Instead, they were administrated with diazoxide 50 mg Three Times a Day (TID), with final doses up to 200-300 mg TID. These 3 patients had good responses to diazoxide administration. After treatment, the frequency and severity of hypoglycemia were improved significantly. All 6 patients had better life quality than previously expected.Combination of surgical and medical approaches can improve life quality and prolong survival of patients with malignant insulinomas.

Gonadotropin therapy using a human chorionic gonadotropin (hCG) and FSH preparation is an effective regimen in inducing masculinization and spermatogenesis in men with idiopathic hypogonadotropic hypogonadism (IHH). However, the high cost of medication and frequent injections affect compliance.The aim of this study was to determine the efficacy of sequential use of highly purified urinary FSH (uFSH)/hCG in men with IHH.A randomized, open-label, prospective, controlled noninferiority trial with an 18-month follow-up was conducted in 9 tertiary hospitals.A total of 67 Chinese men with IHH were randomly allocated into group A receiving continual uFSH (75 U, 3 times a week) and hCG (2000 U, twice a week) injection and group B receiving sequential uFSH (75 U, 3 times a week every other 3 months) and hCG (2000 U, twice a week) injection.The primary outcome was the proportion of subjects with a sperm concentration of ≥ 1.0 × 10(6)/mL during the 18 months. The efficacy between groups A and B was compared for noninferiority.Of the patients, 17/33 (51.5%) receiving continual uFSH/hCG and 19/34 (55.9%) receiving sequential uFSH/hCG achieved sperm concentrations of ≥ 1.0 × 10(6)/mL. The efficacy in the sequential uFSH/hCG group was not inferior to that in the continual uFSH/hCG group (noninferiority, P = .008) by intention-to-treat analysis.The efficacy of the sequential uFSH/hCG regimen is not inferior to that of the continual uFSH/hCG regimen in inducing spermatogenesis and masculinization of patients with IHH.

Objective The aim of this study was to assess the levels of serum lipid and awareness, treatment, and control of dyslipidemia in type 2 diabetes mellitus (T2DM) patients from top-ranked endocrinology clinics in large cities of China. Materials and Methods A cross-sectional study in a representative sample of 4807 Chinese adults 40 to 75 years of age was conducted during 2010 to 2011 at 20 endocrinology clinics in top-ranked hospitals covering most of the major cities of China. Serum lipid levels were measured, and treatment of dyslipidemia was recorded and assessed. Results In the present study, the prevalence of dyslipidemia was 67.1% in T2DM subjects. Among those with dyslipidemia, the proportion of awareness and treatment was 68.7% and 55.9%. Among participants with lipid-lowering therapy, 686 subjects achieved the low-density lipoprotein cholesterol (LDL-C) control less than 2.60 mmol/L, with the rate being 39.4%. In those patients with previous cardiovascular disease, the percentage of participants who achieved LDL-C goal (1.80 mmol/L) was 15.3%. Conclusion The prevalence of dyslipidemia is high, and the awareness, treatment, and control of dyslipidemia are relatively low in Chinese T2DM patients. This calls for the awareness and intervention of dyslipidemia in these patients.

To explore the imaging features of congenital adrenal cortex hyperplasia (CAH).A total of 45 patients clinically confirmed as CAH were retrospectively analyzed to investigate the imaging features and strengthening way of the multi-detector-row Computed tomography.The imaging features of all the cases presented as following: 25 with bilateral adrenal hyperplasia, 6 with unilateral adrenal hyperplasia, 6 with adrenal nodular hyperplasia, 2 with adrenal hyperplasia and unilateral solid cystic lesion, 2 with adrenal hyperplasia and double side real cystic lesion, 1 with adrenal hyperplasia and unilateral cystic changes and 3 with normal adrenal. The unilateral or bilateral hyperplasia adrenal could be homogeneously enhanced, while the enhanced performance of other cases was inequitable.The adrenal imaging features of CAH by multi-detector-row CT are variable, with the bilateral adrenal hyperplasia as the main form, which could be restored to normal morphology after hormone replacement therapy.No regression of the tumor size is observed in cases with adrenal mass. CT scanning combined with clinical manifestation and biochemical examination could facilitate the diagnosis of CAH.

To investigate the relationship between -308 genotype polymorphism in the promoter region of the tumor necrosis factor alpha (TNFalpha) gene and asthenospermia in infertile men.Allele-specific polymerase chain reaction (ASPCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to analyze the genotype at position -308 in the promoter region of the TNFalpha gene in 187 infertile male patients, who were divided into Groups A (asthenospermia, n = 60), B (oligoasthenozoospermia, n = 65) and C (infertile patients with normal sperm, n = 62). The levels of TNFalpha in the seminal plasma from these patients were measured by radioimmunoassay, and all the data were statistically analyzed by SPSS16.0.Groups A and B exhibited significant differences from C in the frequency of GA/AA at position 308 in the promoter region of the TNFalpha gene (21.67% and 26.15% versus 8.06%, P0.05). Spearman analysis showed a negative correlation between the GA + AA type of the TNFalpha-308 allele and the percentage of grade a + b sperm (r = -0.690, P0.05). The level of TNFalpha in the seminal plasma was significantly elevated in Groups A ([4.23 +/- 0.45] ng/ml) and B ([4.29 +/- 0.47] ng/ml) as compared with C ([4.03 +/- 0.66] ng/ml, P0.05), but with no significant differences between Groups A and B (P0.05). It was also significantly higher in the GA+AA ([4.61 +/- 0.29] ng/ml) than in the GGtype ([4.06 +/- 0.45] ng/ml, P0.05).Regardless of sperm density, the frequently of TNFalpha-308 GA/AA is negatively correlated with the percentage of grade a + b sperm, which may be associated with the level of TNFalpha in the seminal plasma. Accordingly, anti-TNFalpha therapy might be effective for asthenospermia, and the measurement of the TNFalpha level in the seminal plasma can be an auxiliary diagnostic marker for male infertility.

To study the cerebrospinal fluid (CSF) and serum level of human chorionic gonadotropin (HCG) in patients with intracranial germinoma and to evaluate its diagnostic and therapeutic value.Thirty-one patients with intracranial germinoma receiving estimation of HCG in CSF and serum in our hospital were retrospectively analyzed in terms of HCG level, its influencing factors and the relationship of HCG with clinical features.HCG levels in CSF of the 31 cases ranged from 0.17 IU/L to 5316.98 IU/L with a median value of 3.44 IU/L. The sensitivity of diagnosis increased from 80.6% to 90.3%, when the cut point of HCG in CSF changed from 0.60 IU/L to 0.50 IU/L. The sensitivity increased from 83.9% to 93.5% when the cut point of the ratio of CSF/serum HCG decreased from 1.8 to 1.7. HCG level of germinoma located in pineal region was higher than that in basal ganglia region, while it is lowest in sellar region. The ratio of CSF/serum HCG in different parts showed no difference. Multiple risk factors analysis revealed that serum HCG (r = 0.886, P = 0.0001) and tumor size (r = 0.748, P = 0.0211) were positively correlated with the HCG level in CSF, while course of the disease, age and gender were not correlated. After radiation therapy, HCG in CSF and serum decreased dramatically as compared with those before radiation.The HCG level and its dynamic change were sensitive marker of intracranial germinomas. Based on our analysis, HCG in CSF over 0.50 IU/L and the its ratio in CSF/serum over 1.7 were highly indicative of the possibility of intracranial germinomas.

To investigate the clinical characteristics of multiple endocrine neoplasia type 1 (MEN1) patients presenting with hypoglycemic coma as chief manifestation and the related clinical experience in diagnosis and therapy.We analyzed the clinical data of 4 patients who were hospitalized because of recurrent hypoglycemic coma and diagnosed as having MEN1 by endocrinological, radiological and pathological examinations.In the 4 cases of Whipple trilogy, radiological examination showed occupying lesion in the pancreas and pathological examination confirmed the diagnosis of insulinoma. In 2 cases the insulinomas were multiple. In this series, one case was complicated with pituitary adenoma, parathyroidoma (recurrent after operation) and adrenocortical adenoma, one case with pituitary adenoma, parathyroidoma (2 tumors) and adrenal nodular hyperplasia, one case with pituitary adenoma and parathyroidoma, and the remaining one with pituitary adenoma and suspectible parathyroidoma.For patients with insulinoma, MEN1 should be considered. In patients with MEN1, the presence of multiple or ectopic parathyroid adenomas (or hyperplasia) and insulinomas should be inspected during operation. After operation, examinations should be regularly performed to identify whether the diseases relapse or new endocrine neoplasias occur.

To prospectively evaluate the current situation of blood pressure control in the type 2 diabetics in some regions of China.Totally 5063 consecutive patients with hypertension were investigated. Among them 1993 with diabetes underwent baseline survey. Individualized target blood pressures were set by physicians. Four follow-up visits, in weeks 2, 4, 8, and 12 were performed to monitor the achievements of these targets and the reasons for not modifying antihypertensive treatments were analyzed when the blood pressure goals were not reached.The prevalence of diabetes among the hypertensive patients was 39.2%. The target blood pressure values defined by the physicians at baseline survey varied with the grade and degree of hypertension. 31.4% of the patients reached the target blood pressure goals (BP130/80 mm Hg) at week 12. The reasons for not intensifying antihypertensive treatment when the blood pressure targets were not achieved were manifold. The main reasons were as follows: the physicians considered that the BP value was close to the target, longer treatment and waiting for full drug effect were needed, etc. On average, 2 different antihypertensive agents were used to achieve BP target and some patients used 4-5 different drugs. The most frequent agents used were angiotensin II receptor antagonist and calcium channel blockers. The use of thiazide-type diuretics increased from the first visit to the last visit (weeks 12).The co-prevalence of hypertension and diabetes in China is high and the target blood pressure set by physician is almost 130/80 mm Hg as defined in guidelines. Only about 31.4% of patients have reached their goals 12 weeks after treatment. There are many subjective and objective reasons responsible for not intensifying antihypertensive treatment when the blood pressure targets are not achieved. Hypertension in diabetes is poorly controlled compared with that in the whole population.

To explore non-invasive therapy for treatment of Bell palsy.Two hundred and seventy-six were randomly divided into two groups, a treatment group and a control group, 138 cases in each group. The treatment group were treated with non-invasive electrode pulse electric stimulation at Taiyang (EX-HN 5), Sibai (ST 2), Qianzheng (Extra), Dicang (ST 4), and the control group with routine medicine (prednisone, dibazol, vitamine B complex and Qianzheng Powder), once each day, 10 days constituting one course. After two courses, their therapeutic effects were compared.The cured rate and the effective rate were 83.3% and 99.3% in the treatment group, and 48.5% and 88.4% in the control group respectively with a significant difference between the two groups (P0.05).Non-invasive electrode pulse electric stimulation at facial points has obvious therapeutic effect on Bell palsy.

To investigate the molecular diagnosis method and possible molecular mechanism of the etiology of a hereditary genetic hypercholesterolemia family by scanning and analyzing the related genes of hereditary hypercholesterolemia in a clinically diagnosed proband and his family members.Molecular diagnosis was performed with PCR and then DNA sequencing of the promoter and 18 exons of low-density lipoprotein receptor (LDLR) gene and 3500 - 3531 fragment of apolipoprotein B-100 gene was carried out. The sequencing results were compared with the normal nucleotide sequence queried from the GeneBank database to discover the mutations.Familial defective apolipoprotein B-100 was excluded, as no mutation was detected in the apolipoprotein B 3500 - 3531 fragment. Two new point mutations were detected in the exon 4 of the proband's LDLR gene, they were heterozygous 685delA (Del A at 685) and 386AG. The sequencing in his parents and other family members showed that the two mutations were paternal origin (685delA) and maternal origin (386AG) respectively and should be located in different alleles of the proband.Molecular diagnosis in the family shows that the proband is a compound heterozygote and the newly detected LDLR gene mutations of 685delA and 386AG are the possible molecular etiological basis of the disease in this family.

To study the expression of matrix metalloproteinase-9 (MMP-9) in diabetic nephropathy of Kkay mice with hyperhomocysteinemia.Sixteen Kkay mice were divided into two groups with 8 in each:diabetes group (KA) and methionine-diet group (KB). C57BL/6 mice were used as normal control (C57). Four months after being treated with two different diets, the mice were sacrificed and serum homocysteine (Hcy) was assayed with fluorescence polarization immunoassay. Renal pathological change was examined with periodic acid Schiff (PAS). The expression of MMP-9 protein and mRNA was detected with immunohistochemical staining and reverse transcriptase-PCR respectively.It was shown that induction of hyperhomocysteinemia in Kkay mice (KB) with a diet enriched in methionine aggravated diabetic nephropathy as compared with the KA group (P0.05). The expression of MMP-9 protein and mRNA in KB group was also enhanced and the mean positive area of MMP-9 in KB group was higher than that in KA group (15.90% vs 11.14%, P0.05).The increased level of Hcy could worsen the nephropathy; this may be related to a higher expression of MMP-9.

To study the genes differentially expressed in the liver of Kkay diabetic and normal mice by genomic-scale gene expression analysis.cDNA microarray chips containing 8,192 cDNAs were used to explore the gene expression pattern of Kkay mouse liver.One hundred and fifty-four genes were screened out, including 68 complete cDNAs and expressed sequence tags, and among them 40 genes were up-regulated and 114 genes were down-regulated respectively.Most of the gene expression analysis results were consistent with previous study, and the gene expression pattern of Kkay mouse based on cDNA microarray could be used for high-throughout screening out the genes associated with type 2 diabetes.