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.

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.

Telmisartan increases lipoprotein lipase expression via peroxisome proliferator-activated receptor-alpha in HepG2 cells.

In addition to their hypotensive properties, angiotensin receptor blockers (ARBs) have been shown to exert clinical antidyslipidemic effects. The mechanism underlying these ARB lipid metabolic effects remains unclear. Some ARBs, for example, telmisartan, activate peroxisome proliferator-activated activated receptor-gamma (PPAR-gamma). We hypothesized that PPAR-gamma-activating ARBs might exert antidyslipidemic effects via PPAR-alpha. In this study, we assessed the effect of telmisartan on the expression of PPAR-alpha and lipoprotein lipase (LPL). PPAR-alpha expression was detected by reverse-transcription polymerase chain reaction and Western blot in HepG2 hepatocytes as well as differentiated C2C12 myocytes treated with increasing concentrations of telmisartan (0.1-10 µmol/L) for 48 h. Results showed that 1 µmol/L and 10 µmol/L telmisartan significantly increased the expression of PPAR-alpha mRNA and protein in HepG2 cells (p < 0.01). No effect was shown in differentiated C2C12 cells. Similarly, 1 µmol/L and 10 µmol/L telmisartan significantly increased the expression of LPL mRNA and protein in HepG2 cells (p < 0.01), and this increase was significantly (p < 0.01) inhibited by the PPAR-alpha-specific antagonist MK886. These results indicate that certain of the antidyslipidemic effects of telmisartan might be mediated via increased PPAR-alpha-dependent induction of LPL expression.

Effectiveness of different waist circumference cut-off values in predicting metabolic syndrome prevalence and risk factors in adults in China.

OBJECTIVE: To study the effectiveness of waist circumference cut-off values in predicting the prevalence of metabolic syndrome (MetS) and risk factors in adults in China. METHODS: A cross-sectional survey was condcuted in 14 provinces (autonomous region, municipality) in China. A total of 47,325 adults aged⋝20 years were selected by multistage stratified sampling, and questionnaire survey and physical and clinical examination were conducted among them. MetS was defined according to the International Diabetes Federation (IDF) criteria and modified IDF criteria. RESULTS: The age-standardized prevalence of MetS was 24.2% (22.1% in men and 25.8% in women) and 19.5% (22.1% in men and 18.0% in women) according to the IDF criteria and modified IDF criteria respectively. The age-standardized prevalence of pre-MetS was 8.1% (8.6% in men and 7.8% in women) according to the modified IDF criteria. The prevalence of MetS was higher in urban residents than rural residents and in northern China residents than in southern China residents. The prevalence of central obesity was about 30% in both men and women according to the ethnicity-specific cut-off values of waist circumference for central obesity (90 cm for men and 85 cm for women). Multivariate regression analysis revealed no significant difference in risk factors between the two MetS definitions. CONCLUSION: Using both the modified IDF criteria and ethnicity-specific cut-off values of waist circumference can provide more useful information about the prevalence of MetS in China. Conclusion Using both the modified IDF criteria and ethnicity-specific cut-off values of waist circumference can provide more useful information about the prevalence of MetS in China.

Pituitary stalk interruption syndrome in 58 Chinese patients: clinical features and genetic analysis.

OBJECTIVES: Pituitary stalk interruption syndrome (PSIS) is rare and its clinical features and pathogenesis are poorly understood. This study characterized the clinical and genetic features of PSIS in Chinese patients. DESIGN AND PATIENTS: Clinical data of 58 patients with PSIS and 46 patients with GH deficiency but a normal pituitary stalk (NPS) were retrospectively analysed. HESX1, LHX4, OTX2 and SOX3 polymorphisms were screened in 33 PSIS patients, and GH1 and GHRHR in 4 NPS patients. RESULTS: Deficiency of GH was 100% in both PSIS and NPS groups. Other deficiency rates for PSIS and NPS groups were as follows: ACTH, 77·6% and 23·9%; TSH, 43·1% and 10·9%; LH/FSH, 94·2% and 47·4%; and combined pituitary hormone, 93·1% and 41·3% respectively. In PSIS and NPS patients, the percentages of anterior pituitary hypoplasia were 98·3% and 54·3%, pituitary stalk abnormality were 100% and 0%, and ectopic neurohypophysis were 91·4% and 0%. A novel heterozygous sequence variant (c.142A>T, p.T48S) was found in HESX1 in one PSIS patient, 3 polymorphisms (c.63T>C, p.G21G; c.450C>T, p.N150N; and c.983A>G, p.N328S) in LHX4 in 7, 1 and 31 PSIS patients, respectively, and a hemizygous polymorphism (c.157G>C, p.V53L) in SOX3 in one PSIS patient. No OTX2 abnormality was detected in PSIS patients, and no GH1 or GHRHR polymorphisms in NPS patients. CONCLUSIONS: Compared with NPS, PSIS patients had more severe anterior pituitary hormone deficiency, lower anterior pituitary hormone secretion and higher probability of abnormal pituitary morphology. HESX1, LHX4 and SOX3 polymorphisms may be associated with PSIS.

Efficacy and safety of combination therapy with vildagliptin and metformin versus metformin up-titration in Chinese patients with type 2 diabetes mellitus: study design and rationale of the vision study.

BACKGROUND AND AIM: Limitations of the currently recommended stepwise treatment pathway for type 2 diabetes mellitus (T2DM), especially the failure of monotherapies to maintain good glycemic control, have prompted use of early, more aggressive combination therapies.The VISION study is designed to explore the efficacy and safety of vildagliptin as an add-on to metformin therapy compared with up-titration of metformin monotherapy in Chinese patients with T2DM. METHODS: VISION, a 24-week, phase 4, prospective, randomized, multicenter, open-label, parallel-group study, will include 3312 Chinese T2DM patients aged ≥18 years who are inadequately controlled (6.5% >HbA1c ≤9%) by metformin (750-1000 mg/day). Eligible patients will be randomized to receive either vildagliptin plus metformin or up-titration of metformin monotherapy (5:1). Patients will also be subgrouped (1:1:1:1) based on their age and body mass index (BMI): <60 years and <24 kg/m²; <60 years and ≥24 kg/m²; ≥60 years and <24 kg/m²; and ≥60 years and ≥24 kg/m². CONCLUSION: The VISION study will test the hypothesis that early use of combination therapy with vildagliptin and metformin will provide good glycemic control and will be better tolerated than up-titration of metformin monotherapy. The study will also correlate these benefits with age and BMI.

Glycemic control among patients in China with type 2 diabetes mellitus receiving oral drugs or injectables.

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) is increasing rapidly among Chinese adults, and limited data are available on T2DM management and the status of glycemic control in China. We assessed the efficacy of oral antidiabetes drugs (OADs), glucagon-like peptide-1 (GLP-1) receptor agonists, and insulin for treatment of T2DM across multiple regions in China. METHODS: This was a multicenter, cross-sectional survey of outpatients conducted in 606 hospitals across China. Data from all the patients were collected between April and June, 2011. RESULTS: A total of 238,639 patients were included in the survey. Eligible patients were treated with either OADs alone (n=157,212 [65.88%]), OADs plus insulin (n=80,973 [33.93%]), or OADs plus GLP-1 receptor agonists (n=454 [0.19%]). The OAD monotherapy, OAD + insulin, and OAD + GLP-1 receptor agonist groups had mean glycosylated hemoglobin (HbA1c) levels (±SD) of 7.67% (±1.58%), 8.21% (±1.91%), and 7.80% (±1.76%), respectively. Among those three groups, 34.63%, 26.21%, and 36.12% met the goal of HbA1c <7.0%, respectively. Mean HbA1c and achievement of A1c <7.0% was related to the duration of T2DM. CONCLUSIONS: Less than one third of the patients had achieved the goal of HbA1c <7.0%. Glycemic control decreased and insulin use increased with the duration of diabetes.

Effects of a multivitamin/multimineral supplement on young males with physical overtraining: a placebo-controlled, randomized, double-blinded cross-over trial.

OBJECTIVE: To investigate the effects of vitamin-mineral supplement on young males with physical overtraining. METHODS: Two hundred and forty male Chinese field artillery personnel who undertook large scale and endurance military training and were on ordinary Chinese diet were randomized to receive a multivitamin/multimineral supplement or a placebo for 1 week. After a 1-week wash-out period, a cross-over with 1 week course of a placebo or multivitamin/multimineral supplement was conducted. Blood and urine samples were analyzed for adrenal, gonadal and thyroid hormones. In addition, cellular immune parameters (CD3+, CD3+CD4+, CD3+CD8+, CD4/CD8, CD3-CD56+, CD3-CD19+) were examined and psychological tests were performed before and after the training program and nutrition intervention. RESULTS: After a large scale and endurance military training, the participants showed significantly increased thyroid function, decreased adrenal cortex, testosterone and immunological function, and significantly increased somatization, anger and tension. Compared to placebo, multivitamin/ multimineral intervention showed significant effects on functional recovery of the pituitary - adrenal axis, pituitary-gonadal axis, pituitary- thyroid axis and immune system as well as psychological parameters. CONCLUSION: High-intensity military operations have significant impacts on the psychology, physical ability and neuroendocrine-immune system in young males. Appropriate supplementation of multivitamin/multimineral can facilitate the recovery of the psychology, physical ability and neuroendocrine-immune system in young males who take ordinary Chinese diet.

[The clinical characteristics of multi-detector computed tomography of congenital adrenal hyperplasia].

OBJECTIVE: To explore the imaging features of congenital adrenal cortex hyperplasia (CAH). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[The safety and effectiveness of once daily detemir in patients with type 2 diabetes previously failing oral agents: the Chinese cohort from SOLVE(TM) observational study].

OBJECTIVE: Study of Once-daily LeVEmir(®) (SOLVE(TM)) was a 24-week international observational study to evaluate the safety and effectiveness of initiating once-daily insulin detemir (Levemir) as add-on therapy in patients with type 2 diabetes mellitus (T2DM) who failed treatment of oral anti-diabetic drugs (OAD). METHODS: The present study was derived from the data of Chinese cohort. A total of 3272 patients with T2DM failing OAD were enrolled in the study. Determir were prescribed to the patients by the decision of the physician. Clinical data were collected at baseline, week 12 and week 24 to evaluate the safety and effectiveness of detemir. RESULTS: The age of the patients was (56.2 ± 10.8) years with a diabetes duration of (7.1 ± 5.2) years. Their BMI was (25.3 ± 3.3) kg/m(2). No patient experienced any major or nocturnal hypoglycaemic event during the study. After 24 weeks of treatment, the glycosylated hemoglobin A1c (HbA1c) decreased from (8.33 ± 1.69)% to (7.16 ± 1.18)% with a mean change of -1.17%, the fasting plasma glucose decreased from (9.52 ± 2.59) mmol/L to (6.84 ± 1.42) mmol/L with a mean change of -2.7 mmol/L, and the 7-point blood glucose profile improved overall. Totally 49.1% of patients achieved HbA1c < 7%. The mean body weight decreased by 0.15 kg. CONCLUSIONS: Insulin detemir administered once daily as add-on therapy in patients with T2DM failing OAD regimen significantly reduces the risk of major hypoglycemia, improves glycemic control, increases the percentage of patients achieving treatment target with neutral effect on body weight.

[The design and baseline characteristics of a phase III study to evaluate the efficacy and safety of alogliptin versus placebo in type 2 diabetes mellitus in Mainland China].

OBJECTIVE: To assess the design and the Mainland China subgroup baseline characteristics of the study to evaluate the efficacy and safety of alogliptin versus placebo in subjects with type 2 diabetes (T2DM) as monotherapy, add-on to metformin or add-on to pioglitazone. METHODS: This was a multi-center, randomized, double-blind, placebo-controlled, 16-week study comparing alogliptin (ALO, 25 mg, 1/d) versus placebo (PLA) as monotherapy (A), add-on to metformin (B) or add-on to pioglitazone ± metformin (C). The T2DM subjects with glycosylated hemoglobin A1c(HbA1c) between 7% and 10% and aged between 18 years and 75 years were enrolled and randomized to the alogliptin group and the placebo group in 1: 1 ratio with 16 weeks treatment. All patients were followed up every 4 weeks. The safety endpoints consisted of the incidence of hypoglycemia and other adverse events. RESULTS: A total of 491 patients were enrolled in the Mainland China subgroup of the study (181 in group A, 186 in group B and 124 in group C). In each treatment group, the baseline characteristics including age, gender, body mass index, diabetes duration, HbA1c, fasting plasma glucose, body weight, daily dosage of metformin and daily dosage of pioglitazone were all well balanced. CONCLUSION: The demographic data, medical history, glycemic profile and treatment regimen at baseline in Mainland China subgroup are well balanced. The result of this study will provide the clinical evidence for the use of alogliptin in Chinese T2DM patients.

Protective effects of Salvianolic acid B on Schwann cells apoptosis induced by high glucose.

Diabetic peripheral neuropathy (DPN) is one of the most common and debilitating microvascular complications of diabetes, and there is no effective therapy for the prevention or treatment of DPN. Oxidative stress triggers several pathways of injury and may be the unifying factor of hyperglycemia. The aim of this study was to investigate protective effect of Salvianolic acid B (Sal B) on the high glucose (HG)-induced oxidative stress-induced mitochondrial pathway activation and Schwann cells (SCs) apoptosis in vitro. We found that Sal B inhibited the HG-induced oxidative stress by reducing ROS and 8-hydroxy-2-deoxy Guanosine (8-OHdG) production, and mitochondrial depolarization and apoptosis in SCs in a dose-dependent manner. Furthermore, Sal B down-regulated the HG-mediated Bax expression and AIF nuclear translocation and the release of cytochrome c, but up-regulated the HG-induced BcL-2 expression in SCs. In addition, Sal B attenuated the HG-induced activation of caspase 3 and 9 and minimized the cleavage of PARP in SCs. Our results indicated that Sal B antagonized the HG-induced oxidative stress, activation of the mitochondrial pathway and apoptosis in SCs.

Albuminuria independently predicts cardiovascular and all-cause mortality in a middle-aged and elderly Chinese population.

AIM: To investigate the relationship between albuminuria and mortality in a middle-aged-to-elderly Chinese population. METHODS: A total of 2,344 individuals aged over 40 in the same district were interviewed and followed up for 4 years. Information on survival or cause of death was recorded. A total of 2,181 participants with detailed information were finally recruited. Baseline overnight urine samples were obtained to measure urinary albumin and creatinine. The urinary albumin excretion rate was expressed as albumin-to-creatinine ratio (ACR). Participants were divided into three groups, according to their ACR: normoalbuminuria (ACR < 30 mg/g), microalbuminuria (≥ 30 - < 300 mg/g ACR) and macroalbuminuria (ACR ≥ 300 mg/g). The Cox proportional hazard model was used to analyze the relationships between albuminuria and cardiovascular and all-cause mortalities. RESULTS: Seventy-seven deaths with known causes were registered. The prevalences of microalbuminuria and macroalbuminuria at baseline were 8.3% and 1.6%, respectively. Cardiovascular mortalities in the normoalbuminuria, microalbuminuria and macroalbuminuria groups were 2.4, 11.0, and 36.8/1,000 person years (pyrs) respectively, and all-cause mortalities were 6.9, 20.6, and 58.8/1,000 pyrs. After adjusting for confounding factors, the relative risks (RR) of cardiovascular mortality were 2.72 (95% CI, 1.06-4.20) in the microalbuminuria group, and 4.87 (95% CI, 2.46-9.45) in the macroalbuminuria group. Adjusted RRs for all-cause mortality were 2.01 (95% CI, 0.96-4.77) and 3.76 (95% CI, 1.52-7.15) in the two groups, respectively. CONCLUSION: Albuminuria is a useful predictor of cardiovascular mortality and all-cause mortality in the general population.

Clinical and genetic analysis of three Chinese patients with steroid 5α-reductase type 2 deficiency.

Steroid 5α-reductase type 2 deficiency (5α-RD2) is a rare autosomal recessive inherited disorder caused by mutations in the SRD5A2 gene. Its clinical features and pathogenesis in Chinese patients are poorly understood. This study aimed to characterize the clinical features and genetically analyze the SRD5A2 gene in three Chinese 5α-RD2 patients. The patients were characterized by ambiguous genitalia and spontaneous virilization without breast development at puberty. Elevated post-human chorionic gonadotropin stimulation T/DHT ratios were useful indicators of 5α-RD2 (with ratios of 20.4, 20.1, and 26.6 in the three patients, respectively). Two compound heterozygous mutations in the SRD5A2 gene were identified: p.G203S/p.R246Q in patients 1 and 2 and p.G203S/c.655delT in patient 3. The father and the mother of patients 1 and\xa02 were carriers of p.R246Q and p.G203S, respectively. p.G203S appears to be common in Chinese 5α-RD2 patients. Early genetic analysis should be performed in suspected patients to improve prognosis.

Laparoscope resection of ectopic corticosteroid-secreting adrenal adenoma.

Tumors originating from ectopic adrenal tissue are relatively rare. In this article, we describe a case with Cushing's syndrome caused by an ectopic adrenal adenoma. A 38 year-old male patient presenting with cushingoid appearance for 2 years was diagnosed to have ACTH-independent Cushing's syndrome based on endocrinological evaluation. Mutiple radiological examinations detected bilateral adrenal atrophy. When the images were investigated in a more expanded scope, a 3.0×3.5×5.3 cm mass was detected in the anterior of left renal hilum and left renal vein. The mass was successfully resected with intraoperative endoscopy and pathological evaluation revealed an ectopic adrenal tumor. It is suggested that when the endocrinlogically confirmed adrenal neoplasm could not be well and definitely localized, the possibility of ectopic adrenal should be presumed and further radiography examinations should extend to the field where ectopic adrenal usually presents.

[The baseline characteristics of patients with type 2 diabetes initiating insulin detemir : the Chinese cohort from the SOLVE(TM) study].

OBJECTIVE: To characterize the baseline status of Chinese diabetic patients based on data derived from Chinese cohort from SOLVE(TM) study. METHODS: Patients with type 2 diabetes initiating basal insulin detemir at the decision of the physician were eligible for the study. Data on demographics, medical history, glycemic profile and treatment regimen at baseline were collected by physicians. RESULTS: A total of 3272 patients [female 42%, male 58%, mean age (56.2 ± 10.8) years] were included in the study. Their BMI was (25.3 ± 3.3) kg/m(2). The duration of diabetes was 4.0 (0.1 - 27.0) years, and the duration of treatment with oral antidiabetic drugs (OADs) was 3.0 (0.0 - 20.2) years. The proportions of subjects with diabetic macro- and micro-vascular complications were 15.8% (515 cases) and 27.1% (866 cases), respectively. The hemoglobin A1c (HbA1c) at baseline was (8.33 ± 1.70)%, and the fasting blood glucose (FPG) was (9.5 ± 2.6) mmol/L. CONCLUSIONS: A large proportion of patients with type 2 diabetes remain in poor glycemic control, and the prevalence of diabetic complications is high, which requires optimal therapeutic strategy for the patients with suboptimal glycemic control.

A young boy with diffuse hyperpigmentation and delayed puberty.

An 18-year-old male patient had presented with diffuse hyperpigmentation after birth and with adrenal insufficiency syndrome since childhood. After puberty, no secondary sexual signs developed. Laboratory examination showed an extremely high concentration of serum triglycerides (9.14 mmol/L) and plasma adrenocorticotropic hormone (>275 pmol/L), however, a low concentration of plasma free cortisone (<25.1-67.6 nmol/L). Abdomen computed tomography detected atrophy of both adrenals glands.

Recurrent autoimmune hypophysitis successfully treated with glucocorticoids plus azathioprine: a report of three cases.

Recurrent autoimmune hypophysitis is a rare autoimmune endocrine disease involving lymphocytic infiltration and chronic pituitary inflammation. It is even more rare than primary hypophysitis. The objective of the study was to evaluate the efficacy of glucocorticoid treatment combined with azathioprine for treating three cases of recurrent autoimmune lymphocytic hypophysitis encountered within a two-year period. The clinical features and follow-up data of these cases were analyzed, including results of treatment with glucocorticoids combined with azathioprine. All three patients were female and presented with the following clinical characteristics: case 1 was a 22-year-old with headache and diplopia; case 2 was a 70-year-old with dry mouth, polydipsia, and polyuria; case 3, a 32-year-old, with polydipsia, polyuria and menstrual disorders with headache and dizziness. Regarding recurrence, case 1 recurred 4 months after surgery and again 14 months after discontinuing prednisone; case 2 relapsed 16 months after receiving high-dose methylprednisolone pulse therapy; and case 3 recurred during the period of prednisone dose reduction. The patients were treated with glucocorticoids plus azathioprine, and positive responses were seen in all three cases. Symptoms were relieved, and MRI revealed significant reduction of lesions during follow-up. Pituitary function resumed in cases 1 and 3; permanent hypopituitarism was present in case 2. At last follow-up, MRI showed no further recurrence of disease in any patient. Treatment and responses of these patients with autoimmune hypophysitis suggest that glucocorticoid therapy combined with azothioprine is effective treatment for recurrent autoimmune hypophysitis. Endocrine and radiologic studies are an essential part of follow-up.

Medullar thyroid carcinoma in mediastinum initially presenting as Ectopic ACTH syndrome. A case report.

A rare case with ectopic adrenocorticotrophic hormone syndrome (EAS) caused by medullar thyroid carcinoma (MTC) in mediastinum was reported. This 49 year-old male patient initially presented with serious and intractable hypokalemia. Endocrine evaluations showed increased levels of adrenocorticotrophic hormone (ACTH) and urinary free cortisol, which could not be suppressed more than 50% by high-dose dexamethasone suppression test. Computed tomography (CT) scan detected a 5×5×5 cm mass at the bottom of thyroid in anterior mediastinum. The patient underwent total thyroidectomy with central compartment and ipsilateral modified radical neck dissection. Pathological examination showed an infiltrating thyroid medullary carcinoma with abundant amyloid deposition, meanwhile immunohistochemical positive for ACTH. After surgery, serum levels of kalium, as well as cortisol and ACTH returned to normal range. During follow-up, the patient's clinical manifestation of Cushing syndrome relieved.

[A randomized, double blind, placebo-controlled, parallel and multicenter study to evaluate the safety and efficacy of pioglitazone with sulphonylurea in type 2 diabetic patients].

OBJECTIVE: To evaluate the safety and efficacy of 30 mg pioglitazone hydrochloride combined with sulphonylurea in the treatment of type 2 diabetic patients. METHODS: A randomized, double blind, placebo-controlled, parallel group, multicenter study was performed. A total of 236 patients, who had fasting plasma glucose (FPG) 7.5 - 13.0 mmol/L and glycosylated hemoglobin A1c (HbA1c) 7.0% - 12.0%, treated with stable dosage of a sulphonylurea for at least 30 days previously, were randomized to receive placebo or pioglitazone 30 mg once daily for 16 weeks. The sulphonylurea and dosage remained unchanged. RESULTS: The patients who had been treated with pioglitazone 30 mg showed significant decrease than that in the placebo group on the average from baseline in FPG [(1.48 ± 2.08) mmol/L vs (-0.17 ± 1.92) mmol/L, P < 0.05], and in HbA1c [(0.92 ± 0.10)% vs (0.28 ± 0.11)%, P < 0.05]. Since fasting plasma insulin (FIns) levels decreased (0.24 ± 0.04) mU/L and (0.09 ± 0.04) mU/L in the two groups. The homeostatic model assessment insulin resistant (HOMA-IR) decreased 1.42 ± 2.90 and 0.46 ± 3.53 in two groups. The triglyceride level was decreased 0.36 mmol/L and 0.14 mmol/L, and the HDL-C level increased 0.17 mmol/L and 0.05 mmol/L in two groups. There were significant differences in two groups (all P < 0.05). CONCLUSIONS: The 16-week clinical study demonstrated that pioglitazone hydrochloride with a dosage of 30mg daily, could significantly improve the blood glucose control and enhance the insulin sensitivity, lower triglyceride and raise HDL-C level as an additional therapy to a stable-dose sulphonylurea in Chinese type 2 diabetic patients previously poorly controlled by single sulphonylurea therapy, and furthermore had good safety and compliance.