Parathyroid carcinoma: Report of 10 patients and literature review.

OBJECTIVE: Parathyroid carcinoma (PC) is a rare disease with high rates of misdiagnosis and recurrence. This report summarized the clinical and pathological characteristics of 10 patients with PC at our hospital, to improve the early recognition and prognosis of PC. METHODS: The clinical manifestations, imaging findings, pathological features, treatments, and prognostic data of 10 patients diagnosed with PC at the First Medical Center, Chinese PLA General Hospital from 2003 to 2021 were analyzed. RESULTS: There were 7 male and 3 female patients with PC whose average age was 41.4 ± 9.4 years. All patients had bone involvement (bone pain and/or osteoporosis), meanwhile 6 patients had kidney stones and 7 patients had palpable neck masses. Five patients presented with tumor metastasis, invading lymph nodes, lung, liver, or bone. Laboratory examinations revealed elevated serum total calcium (4.15 ± 0.81 mmol/L), parathyroid hormone (PTH, 1236.1 ± 519.9 pg/mL) and alkaline phosphatase (405.8 ± 219.0 IU/L) levels. Especially, hypercalcemic crisis occurred in 9 patients. The diagnosis of PC depended on histopathological features of the parathyroid tumor, including capsular and/or vascular invasion. All patients underwent at least en bloc resection. In the follow-up, six patients with relatively high preoperative PTH levels (1519.5 ± 436.8 pg/mL) relapsed postoperatively. Two patients with the Ki-67 index ≥ 10% in parathyroid tumor tissue and distant metastasis died within 2 years after the operation. CONCLUSION: Severe bone pain, kidney stones, hypercalcemic crisis, and markedly elevated PTH usually indicate PC. A markedly elevated PTH level, tumor metastasis, and the Ki-67 index ≥ 10% may be indicators of poor prognosis.

Clinical data analysis of 22 cases with hypoparathyroidism misdiagnosed as epilepsy.

OBJECTIVE: Patients with hypoparathyroidism always present with recurrent tetany caused by hypocalcemia. These patients are usually misdiagnosed with epilepsy and incorrectly treated with anti-epileptic drugs. This research analyzed clinical data about 22 patients with hypoparathyroidism misdiagnosed as epilepsy and summarized the clinical experience for reducing misdiagnosis and incorrect therapy about hypoparathyroidism. METHOD: Totally 160 patients with hypoparathyroidism, administrated to the First Medical Center of Chinese PLA General Hospital from January 1st, 2008, to July 1st, 2021, were enrolled in this report. Clinical data about 22 patients initially misdiagnosed with epilepsy were analyzed. RESULTS: Of the 160 cases with hypoparathyroidism, 22 patients (12 males and 10 females) were misdiagnosed with epilepsy in local hospitals. The misdiagnosis rate was 13.75% and the median duration of misdiagnosis was 8.0 (2.0, 14.8) years. The clinical manifestations of the 22 patients misdiagnosed as epilepsy included tetany 81.8% (18/22), disturbance of consciousness 27.3% (6/22), limb numbness 13.6% (3/22), limb weakness 27.3% (6/22), mental and behavioral abnormality 9.1% (2/22), and memory impairment 13.6% (3/22), etc. Electroencephalogram (EEG) was performed in 9 cases, which presented as slow wave and spike-slow complex wave in 3 cases, slowing down of Î¸ and δ band background in 2 cases and normal EEG in 4 cases. Out of the 15 cases that underwent head computed tomography (CT) scan, in which 13 cases had intracranial calcification. Anti-epileptic drugs were used to treat 22 patients, of which 17 patients were treated with two kinds of drugs. With calcium and calcitriol supplement in all these 22 patients, the anti-epileptic drugs were gradually reduced and withdrawn in 17 cases. In the other 5 cases with secondary epilepsy, the type of anti-epileptic drugs was reduced to one and the clinical condition improved obviously. CONCLUSION: The clinical manifestations of hypoparathyroidism are complex and usually be misdiagnosed as primary epilepsy. Detection of serum calcium, phosphorus and parathyroid hormone is very important to avoid misdiagnosis and incorrect therapy about hypoparathyroidism.

Paget's disease of bone: Report of 11 cases.

BACKGROUND: Paget's disease of bone (PDB) is a rare metabolic bone disease in China and is characterized by increased bone resorption and disorganized bone formation. The main clinical symptoms of PDB are focal or multiple bone pain and deformity with high disability. The disease has high missed diagnosis and misdiagnosis rates. This report summarizes the clinical manifestations, imaging and pathological features, and treatments of 11 patients with PDB at our hospital from 1993 to 2020 in order to improve the recognition and prognosis of PDB. CASE SUMMARY: There were eight male and three female patients whose average age was 48.7 ± 11.0 years with a PDB course of 1-16 years. Nine patients had bone pain and bone deformities in different parts of the body, the majority of which involved the long bones. Laboratory examinations revealed elevated serum alkaline phosphatase (ALP) in all patients with an average of 618 ± 460 IU/L (normal range 0-130 IU/L), and serum calcium and phosphorus levels were in the normal range. Imageology showed that osteolysis was usually combined with osteosclerosis and/or bone deformities in single or multiple bones. 99mTc-methylene diphosphonate bone scintigraphy revealed increased radionuclide uptake in the bone lesions. Six patients underwent bone tissue biopsy, and the typical pathological changes were a mosaic structure of the bone trabeculae with irregularly arranged cement lines and multinuclear osteoclasts. Ten of the 11 patients were effectively treated with bisphosphonates. CONCLUSION: Early diagnosis of the rare disease PDB can be made through elevated ALP levels and typical presentations on bone X-ray and from bone tissue biopsy.

Insulinoma misdiagnosed as epilepsy in 44 Chinese patients.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Diffuse large B cell lymphoma with bilateral adrenal and hypothalamic involvement: A case report and literature review.

BACKGROUND: Non-Hodgkin's lymphoma (NHL) can involve extralymphatic organs, resulting in diverse clinical manifestations, especially if the endocrine organs are affected. This type of involvement can often be difficult to detect accurately. Until now, no patients with NHL and concomitant bilateral adrenal and hypothalamic involvement have been reported. The purpose of this article is to discuss the diagnosis and treatment of lymphoma with bilateral adrenal gland and hypothalamic involvement so as to help physicians avoid misdiagnosis and missed diagnosis. CASE SUMMARY: We describe a case of a 52-years-old male patient with bilateral adrenal masses, who presented with a fever of unknown origin on admission. Subsequently, hypopituitarism of the anterior pituitary followed by posterior pituitary developed. 18fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) showed lesions with a high metabolism in both adrenal glands, hypothalamus, left supraclavicular lymph nodes, and other organs. The etiological diagnosis was determined based on a left supraclavicular lymph node biopsy. The patient, who eventually present with panhypopituitarism, was finally diagnosed with diffuse large B cell lymphoma with bilateral adrenal gland and hypothalamic involvement. After immunochemotherapy, glucocorticoids administration and desmopressin acetate replacement therapy, the symptoms of fever and panhypopituitarism improved, and all the lesions reduced in size. CONCLUSION: This report demonstrates that, although synchronous involvement of two endocrine organs is rare in NHL, extra caution should be taken when dysfunction occurs in multiple endocrine organs.

Bilateral adrenocortical adenomas causing adrenocorticotropic hormone-independent Cushing's syndrome: A case report and review of the literature.

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.

Microarray-based differential expression profiling of long noncoding RNAs and messenger RNAs in formalin-fixed paraffin-embedded human papillary thyroid carcinoma samples.

BACKGROUND: Long noncoding RNAs (lncRNAs) can regulate the expression of genes at almost every level. The altered expression of lncRNAs was observed in many kinds of cancers. Until recently, few studies have focused on the function of lncRNAs in the context of papillary thyroid carcinoma (PTC). METHODS: In the current study, we collected seven PTC and nodular goiter tissue samples and explored mRNA and lncRNA expression patterns in these samples by microarray. RESULTS: We observed aberrant expression of 94 lncRNAs and 99 mRNAs in the seven PTC samples as compared to the nodular goiter tissue [fold change (FC) ≥2.0; P<0.01]. To confirm these microarray results, quantitative polymerase chain reaction (q-PCR) was performed to assess the expression of three randomly selected differentially expressed mRNAs and lncRNAs, confirming our microarray findings significantly. We then performed gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses to systematically characterize the twelve significantly differential genes. A co-expression analysis revealed that the lncRNAs n382996, n342483, and n409114 were closely related to the regulation of MT1G, MT1H, and MT1F. CONCLUSIONS: In the present study a string of novel lncRNAs associated with PTC were identified. Further study of these lncRNAs should be performed to identify novel target molecules which may improve diagnosis and treatment of PTC.

Cardiovascular disease outcomes in metabolically healthy obesity in communities of Beijing cohort study.

OBJECTIVE: The objective of this study was to investigate the association between metabolically healthy obese (MHO) phenotype and the risk of cardiovascular disease (CVD). METHODS: A total of 9393 subjects aged ≥40 years were enrolled in the cohort study (2011-2015). The participants were stratified by body mass index category and metabolic risk at baseline, and incidence of CVD was ascertained at follow-up. RESULTS: The MHO accounted for 6.7%. Compared with the metabolically healthy normal weight (MHNW) group, MHO subjects demonstrated increased risk of CVD events (HR = 1.91; 95% CI, 1.13-3.24). In people with obesity, there was no significant difference on increasing risk of incidence of CVD in the metabolically unhealthy individuals compared with metabolically healthy individuals (HR = 1.19; 95% CI, 0.74-1.91). Female (OR = 1.97; 95% CI, 1.06-3.64), smoking (OR = 2.09; 95% CI, 1.06-4.10), a larger waist circumference (OR = 1.07; 95% CI, 1.03-1.10) and higher LDL cholesterol levels (OR = 1.55; 95% CI, 1.20-2.00) were independent risk factors of the development of the MHO to the metabolically unhealthy obese (MUO) phenotype. CONCLUSIONS: The risk of CVD events of MHO phenotypes is similar to MUO phenotypes; both are higher than the MHNW phenotypes.

Thyrotrophic status in patients with pituitary stalk interruption syndrome.

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 ±â€Š3.40 vs 1.67 ±â€Š1.20 mU/L, P < .05). TSH elevation (8.79 ±â€Š3.17 mU/L) was noticed in 29 of 71 (40.85%) hypothyroid PSIS patients but not in the 24 hypothyroid SS patients. The TSH levels in the hypothyroid PSIS patients were significantly higher in comparison with the euthyroid PSIS patients (5.42 ±â€Š3.67 vs 3.66 ±â€Š1.50 mU/L). Thyroid hormone replacement significantly reduced the TSH levels in the PSIS patients with elevated TSH levels from 7.24 ±â€Š0.98 to 1.67 ±â€Š1.51 mU/L (P < .05). The logistic regression analysis suggested that TSH level was not significantly associated with pituitary stalk status and height of the anterior pituitary gland.PSIS is a newly recognized cause of central hypothyroidism. The proportion and amplitude of TSH elevations are higher in PSIS than in other causes of central hypothyroidism.

Whole-genome sequencing revealed armadillo repeat containing 5 (ARMC5) mutation in a Chinese family with ACTH-independent macronodular adrenal hyperplasia.

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 <1% of all endogenous cases of CS. In order toidentify the pathogenic mutations in the causative gene of (AIMAH pedigrees, Whole-genome sequencing of three patients in family I was used to retrieve candidate causative genes. Meanwhile, the causative gene was identified by Sanger sequencing from the two pedigrees. Sequencing of ARMC5 exons of three patients was carried out to identify somatic mutations. Moreover, haploid clone of one tumor DNA sample was conducted. ARMC5 was the causative gene of two pedigrees confirmed by whole-genome sequencing (WGA) and Sanger sequencing. The variant sites of the two families were c.C943T (p.R315W) and c.C1960T (p.R654X), respectively. Autosomal dominant inheritance of AIMAH was confirmed by genotypes of one family member. Several somatic mutations were discovered in tumor DNA samples. In addition, haploid clone of tumor DNA was confirmed by germline mutation and somaticmutation, which suggested the pathogenic mechanism of "two-hit-model." ARMC5 was the causative gene of AIMAH pedigrees. This AIMAH in this study presented autosomal dominant inheritance, fitting to Mendelian inheritance law. However, the pathogenic mode of this disease showed as compound heterozygote.

Dynamic profile of differentiated thyroid cancer in male and female patients with thyroidectomy during 2000-2013 in China: a retrospective study.

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 < 0.001). The proportion of thyroid cancer was dominated in blood type B and the lowest incidence in blood type A in male, the difference was not statistically significant. The results showed that age, nodule number, BMI and serum TSH were the related factors for DTC. More aggressive behaviors of DTC were observed in male patients, and more attention should be focused on the timely diagnosis and treatment of these patients.

Multi-genic pattern found in rare type of hypopituitarism: a whole-exome sequencing study of Han Chinese with pituitary stalk interruption syndrome.

Pituitary stalk interruption syndrome (PSIS) is a rare type of hypopituitarism manifesting various degrees of pituitary hormone deficiency. Although mutations have been identified in some familial cases, the underpinning mechanisms of sporadic patients with PSIS who are in a vast majority remain elusive, necessitating a comprehensive study using systemic approaches. We postulate that other genetic mechanisms may be responsible for the sporadic PSIS. To test this hypothesis, we conducted a study in 24 patients with PSIS of Han Chinese with no family history using whole-exome sequencing (WES) and bioinformatic analysis. We identified a group of heterozygous mutations in 92% (22 of 24) of the patients, and these genes are mostly associated with Notch, Shh, Wnt signalling pathways. Importantly, 83% (20 of 24) of the patients had more than one mutation in those pathways suggesting synergy of compound mutations underpin the pathogenesis of sporadic PSIS.

Effect of Negative Pressure Wound Therapy on Cellular Fibronectin and Transforming Growth Factor-ß1 Expression in Diabetic Foot Wounds.

BACKGROUND: Chronic diabetic foot wounds are a leading cause of amputation, morbidity, and hospitalization for patients with diabetes. Negative-pressure wound therapy (NPWT) can putatively facilitate wound healing, but the underlying mechanisms remain unclear. Cellular fibronectin (cFN) and transforming growth factor-ß1 (TGF-ß1) play an important role in wound healing. This prospective randomized controlled trial evaluated the effects of NPWT on the production of cFN and the expression of TGF-ß1 in diabetic foot wounds of patients. METHODS: From January 2012 to January 2015, 40 patients with diabetic foot wounds were randomly and equally apportioned to receive either NPWT or advanced moist wound therapy (control) for 7 days. Granulation tissue was harvested before and after treatment. Immunohistochemistry and Western blot were performed to evaluate protein levels of cFN and TGF-ß1, and real-time polymerase chain reaction (PCR) to measure corresponding mRNA expressions. RESULTS: NPWT facilitated the expression of cFN and TGF-ß1 in diabetic foot wounds. Immunohistochemical analysis revealed higher levels of cFN and TGF-ß1 in the NPWT group than in the control group. Western blot and real-time PCR analysis further showed that protein and mRNA levels of cFN or TGF-ß1 were higher in the NPWT group than that in the control group ( P < .01, both). CONCLUSION: Our results showed that NPWT facilitated the production of cFN and the expression of TGF-ß1 in granulation tissue in diabetic foot ulcers. LEVEL OF EVIDENCE: Level I, randomized controlled study.

Association between Self-reported Snoring and Prediabetes among Adults Aged 40 Years and Older without Diabetes.

BACKGROUND: Several previous studies have shown that snoring is associated with glucose metabolism and the development of diabetes, but rare study has shown the association between snoring frequency and prediabetes, particularly in China. We hypothesized that individuals who snore might have a higher risk of prediabetes. This study aimed to investigate the association between self-reported snoring and prediabetes in a Chinese population. METHODS: A cross-sectional study was performed in three large communities of Beijing from December 2011 to August 2012 by recruiting individuals aged ≥40 years old. All participants were requested to complete a detailed questionnaire and undergo anthropometric measurements. A 75 g oral glucose tolerance test was performed in individuals without diabetes. Blood samples of all participants were collected; blood glucose and blood fat levels were measured. Multivariate logistic regression models were built to assess the association between snoring frequency and prediabetes. RESULTS: A total of 13,592 participants (female: 66.56%; mean age: 56.8 ± 7.9 years; mean body mass index: 25.5 ± 3.4 kg/m2) were included in the final analysis. Of these, 30.9% were diagnosed with prediabetes, while 41.3% and 25.4% had occasional and habitual snoring, respectively. Habitual snoring was associated with an increased risk of prediabetes (odds ratio [OR]: 1.3, 95% confidence interval [CI]: 1.1-1.4, P< 0.001), after adjusting for diabetes and sleep-related confounders in the multivariable models. Habitual snoring was also associated with isolated impaired fasting glucose (IFG; OR: 1.3, 95% CI: 1.0-1.6; P< 0.001) and isolated impaired glucose tolerance (IGT; OR: 1.3, 95% CI: 1.2-1.5; P< 0.001), but not IFG + IGT (OR: 1.1, 95% CI: 0.9-1.4; P = 0.281). When stratified by total cholesterol (TC) levels, this association between habitual snoring and prediabetes was observed only in individuals with TC <5.6 mmol/L (OR: 1.4, 95% CI: 1.2-1.6; P< 0.001). CONCLUSIONS: Habitual snoring is associated with prediabetes, but only in individuals with TC <5.6 mmol/L. Further prospective studies are needed to confirm this finding.

Pathophysiology of peripheral arterial disease in diabetes mellitus.

Peripheral arterial disease (PAD) increases the risk of lower extremity amputation. It is also an independent predictor of cardiovascular and cerebrovascular ischemic events, affecting both the quality and expectancy of life. Many studies have demonstrated that the prevalence of PAD in patients with diabetes mellitus (DM) is higher than in non-diabetic patients. In diabetic patients, PAD occurs early with rapid progression, and is frequently asymptomatic. Multiple metabolic aberrations in DM, such as advanced glycation end-products, low-density lipoprotein cholesterol, and abnormal oxidative stress, have been shown to worsen PAD. However, the role of DM in PAD is not completely understood. The purpose of the present article is to review and discuss the pathophysiology of PAD in DM.

Clinical Features of Pituitary Stalk Interruption Syndrome in 114 Cases.

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.

Malignant insulinoma: Report of 6 patients and literature review.

OBJECTIVE: 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. PATIENTS/METHODS: 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. RESULTS: 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. CONCLUSION: Combination of surgical and medical approaches can improve life quality and prolong survival of patients with malignant insulinomas.

Candesartan cilexetil prevents diet-induced insulin resistance via peroxisome proliferator-activated receptor-γ activation in an obese rat model.

Angiotensin II type 1 receptor (AT1R) blockers (ARBs) have been shown to reduce the incidence of type 2 diabetes mellitus; however, the underlying molecular mechanism is unknown. Peroxisome proliferator-activated receptor γ (PPARγ) is the central regulator of insulin and glucose metabolism, which improves insulin sensitivity. Whether candesartan cilexetil, as a prodrug of the AT1R blocker candesartan, has PPARγ-activating properties remains to be elucidated. The aim of the present study was to investigate the effects of oral administration of candesartan cilexetil on glucose tolerance and the actions of PPARγ on liver and adipose tissue in the insulin-resistant obese rat induced by high-fat diet. Animals treated with candesartan cilexetil showed an improved glucose tolerance after oral glucose challenge. Whole-body insulin sensitivity was evaluated using the hyperinsulinemic-euglycemic clamp technique. During high-fat feeding in high-fat diet (HF) rats, the glucose infusion rate (GIR) was 52.3% lower than that in normal chow (NC) rats. However, the GIR was significantly enhanced following candesartan cilexetil treatment. Angiotensin II receptor antagonism also resulted in significant increases in PPARγ protein expression in adipose and liver tissue. These results indicate that PPARγ activation by candesartan cilexetil may provide novel therapeutic options in the treatment of patients with metabolic syndrome.

Type B insulin resistance syndrome with Scleroderma successfully treated with multiple immune suppressants after eradication of Helicobacter pylori infection: a case report.

BACKGROUND: Type B insulin resistance is a rare autoimmune disease characterized by the presence of autoantibodies against the insulin receptor. Helicobacter pylori (H pylori) infection may play a causative role in the autoimmune diseases. CASE PRESENTATION: Here, we present a rare case of a 48-year old female patient, who had type B insulin resistance with systemic scleroderma and was successfully treated with multiple immune suppressants after eradication of Helicobacter pylori infection. CONCLUSION: The present case suggests H pylori infection-related pathological mechanism may contribute to type B insulin resistance syndrome and autoimmune disorders. Treatment toward H pylori may be helpful to relieve syndrome of type B insulin resistance for H pylori positive patients.

Correlation between Pituitary Stalk Interruption Syndrome and Prokineticin Receptor 2 and Prokineticin 2 Mutations.

OBJECTIVE: To analyze the correlation between pituitary stalk interruption syndrome (PSIS) and prokineticin receptor 2 (PROKR2) and prokineticin 2 (RROK2) mutations. METHODS: PROKR2 and RROK2 genotypes were identified by multiplex polymerase chain reaction analysis with exon-flanking primers and by automated sequencing techniques with peripheral blood DNA samples from 59 patients with PSIS. RESULTS: Of these 59 PSIS patients, 6 showed intragenic deletions at the PROKR2 locus. Of them, 5 patients exhibited intragenic subsititution of exon 2 (c.991G>A), and the remaining one patient exhibited intragenic subsititution of exon 2 (c.1057C>T). No PROK2 mutation was found in these PSIS patients. CONCLUSION: PROKR2 may be the susceptibility gene of PSIS.