Comparison of the therapeutic effects of 15 mg and 30 mg initial daily prednisolone doses in patients with subacute thyroiditis: a multicenter, randomized, open-label, parallel-controlled trial.

INTRODUCTION: Current guidelines recommendations for the initial dose of prednisolone (PSL) in the treatment of subacute thyroiditis (SAT) are based on low-quality studies. We designed a randomized controlled trial (RCT) to compare the efficacy and safety of using a low initial dose of PSL with a standard initial dose of PSL in SAT patients. PATIENTS AND METHODS: This open-label RCT was conducted at five hospitals in China from June 2019 to January 2022. SAT patients with moderate-to-severe pain or a poor response to non-steroidal anti-inflammatory drugs (NSAIDs) were randomly assigned in a 1:1 ratio to the experimental and control groups. The initial dose of PSL was 15 mg/d in the experimental group and 30 mg/d in the control group. The primary outcome was the total duration of PSL treatment, with non-inferiority prespecified with a margin of 7 days. Clinical trial registration number: ChiCTR1900023884. RESULTS: The full analysis set included 60 patients (30 in each group). The mean duration of PSL treatment in the experimental and control group was 34.62 ± 14.12 and 41.18 ± 16.89 days, respectively, meeting the non-inferiority criterion (pnon-inferiority = 0.0006). The total dose of PSL used in the experimental group was lower than in the control groups (330 vs 595 mg, p < 0.0001). There were no differences in the mean time to pain relief and complete resolution, the occurrence of recurrence, hypothyroidism, or adverse events between the groups. CONCLUSIONS: The initial dose of 15 mg/d of PSL was not inferior to the dose of 30 mg/d in terms of efficacy and showed a similar safety profile. A low initial dose of PSL could be recommended for Chinese adult SAT patients who have a suboptimal response using NSAIDs or experience moderate-to-severe pain.KEY MESSAGESLow initial dose (15 mg/d) of prednisolone was non-inferior to the standard initial dose of prednisolone (30 mg/d) in treatment duration, time to pain relief, or the prevalence of hypothyroidism, recurrence, and adverse reactions in the treatment of subacute thyroiditis.Patients with subacute thyroiditis administered a low initial dose of prednisolone had a lower total dose of prednisolone compared to those receiving the standard dose of prednisolone.

Normal weight obesity and the risk of diabetes in Chinese people: a 9-year population-based cohort study.

We evaluated the risk of developing diabetes in Chinese individuals with normal weight obesity (NWO). This 9-year population-based cohort study was based on the China National Diabetes and Metabolic Disorders Survey. A total of 1128 subjects without diabetes were included. Body fat percentage (BF%) was assessed by electrical bioimpedance. NWO was defined as subjects with a normal BMI (< 24 kg/m2) and an excess BF% (≥ 24% in men; ≥ 33% in women). Of 1128 individuals, 528 individuals were normal weight non-obese (NWNO), 118 (10.5%) were normal weight obese (NWO), 63 were overweight non-obese (OWNO), and 419 were overweight obese (OWO). During a follow-up of 9.0 years (interquartile range: 8.9-9.3), 113 (10.0%) individuals developed diabetes. The incidence rates of diabetes in NWNO, NWO, OWNO and OWO people were 5.69 (27 cases), 11.30 (12 cases), 3.53 (2 cases) and 19.09 (72 cases) per 1000 person-years, respectively. Cox regression analyses indicated multivariate-adjusted hazard ratios of diabetes in NWO, OWNO and OWO people were 2.110 (95% CI 1.026-4.337, p = 0.025), 0.441 (95% CI 0.101-1.928, p = 0.232) and 3.465 (95% CI 2.163-5.551, p < 0.001), respectively, relative to NWNO people. Chinese people with NWO are at increased risk of developing diabetes. We strongly suggest the incorporation of BF% measurement into the regular physical examination in Chinese medical practice.

Thyrotoxicosis and osteomalacia: from symptom to pathogenesis.

Thyroid hormones have a direct effect on bone mineral homeostasis, leading to increased bone mineral resorption and calcium loss through the kidneys. Osteomalacia is conceptualized as a disorder of bone tissue characterized by inadequate or delayed mineralization of osteoid in mature cortical and spongy bone, and is associated with thyrotoxicosis. This article assessed the impact of thyrotoxicosis on the occurrence and development of osteomalacia for better diagnosis and treatment of the disease. We searched databases such as Pubmed with "osteomalacia" and "thyrotoxicosis", 15 papers were found; with "osteopenia" or "osteomalacia" or "osteoporosis" and "thyrotoxicosis", 129 papers were found. The causes of osteomalacia include insufficient intake of calcium, phosphorus and vitamin D, impaired absorption and metabolism of vitamin D, kidney diseases (nephrotic syndrome, chronic renal failure, renal tubular acidosis, Fanconi syndrome, etc.), hereditary and neoplastic hypophosphatemia, and other diseases such as heavy metal poisoning, high fluoride intake. At present, the pathogenesis of osteomalacia caused by thyrotoxicosis are mainly attributed to catabolism of vitamin D, vitamin D deficiency and mechanisms underlying calcium metabolism disorder. Since thyrotoxicosis can cause osteopenia and may coexist with osteomalacia, attention should be given to the changes of alkaline phosphatase, liver function and clinical symptoms. If necessary, chest X-ray and pelvic X-ray should be carried out to find out potential osteomalacia for timely treatment to avoid the occurrence of fracture and even deformity.

Endometrial adenocarcinoma metastatic to the pituitary gland: a case report and literature review.

Pituitary metastases are rare, and metastatic pituitary lesions originating from endometrial adenocarcinoma are extremely rare. These lesions can be mistaken for pituitary adenomas and their diagnosis can be very difficult. Pituitary metastases mostly affect the posterior lobe and patients may develop diabetes insipidus. Patients with endometrial cancer complicated with diabetes, including poor glycemic control, may also suffer from thirst, making it more difficult to diagnose diabetes insipidus. A 68-year-old woman who was being followed-up for primary endometrial adenocarcinoma was admitted for gradually worsened polyuria and polydipsia. Her laboratory findings were compatible with diabetes insipidus. Magnetic resonance imaging revealed thickening of the pituitary stalk, involvement of the superior pituitary gland, and disappearance of hyperintensity in the posterior lobe, indicating pituitary metastasis. Increased urine output and oral fluid intake in a patient with a diagnosis of carcinoma may indicate possible pituitary metastasis, and the hormonal insufficiency should be corrected to improve the patient's quality of life.

Comparison of the therapeutic effects of 15 mg and 30 mg initial dosage of prednisolone daily in patients with subacute thyroiditis: protocol for a multicenter, randomized, open, parallel control study.

BACKGROUND: Subacute thyroiditis (SAT) is the most common cause of thyroid pain. Several clinical guidelines recommend that patients who fail to respond to full doses of non-steroidal anti-inflammatory drugs (NSAIDs) should be treated instead with oral corticosteroid therapy. However, albeit strong recommendations, the treatment protocol is based on low-quality evidence and high-quality clinical trials are lacking with respect to the optimal initiation dosage and usage of corticosteroid. We aimed to evaluate whether 15 mg/day of prednisolone (PSL) as the initial dosage could provide non-inferiority effectiveness but with lower risk and more safety compared with 30 mg/day of PSL as the initial dosage. METHODS/DESIGN: This is a multicenter, open-label, randomized, parallel trial that will be conducted at five academic hospitals in China. A total of 90 adult patients diagnosed with SAT who present moderate to severe pain or fail to respond to full doses of NSAIDs will be randomly assigned with a 1:1 ratio to the low initial PSL dosage group (15 mg daily) and standard initial PSL dosage group (30 mg daily). The primary endpoint is the time period (days) required for PSL treatment (including PSL treatment for recurrence). DISCUSSION: Our randomized controlled trial will try to determine the optimal protocol in the treatment of SAT by providing high-quality evidence. TRIALS REGISTRATION: Chinese Clinical Trial Register, ChiCTR1900023884. Registered on 15 June 2019.

Fasting triglycerides and glucose index is more suitable for the identification of metabolically unhealthy individuals in the Chinese adult population: A nationwide study.

AIMS/INTRODUCTION: Metabolic unhealth can be defined by the components of metabolic syndrome, which is closely connected to insulin resistance. We aimed to determine a simple index to identify metabolic unhealth in the Chinese adult population. MATERIALS AND METHODS: A total of 30,291 individuals were screened from the China National Diabetes and Metabolic Disorders Study carried out from June 2007 to May 2008. Metabolic unhealth was defined using components of metabolic syndrome, except waist circumference. We compared the three surrogate indices of insulin resistance: the product of fasting triglycerides and glucose (TyG), triglycerides divided by high-density lipoprotein cholesterol and the metabolic score for insulin resistance for the evaluation of metabolic status. RESULTS: All indices had high sensitivity and specificity for the identification of metabolic unhealth, especially the TyG index with an area under the curve of 0.863 for men and 0.867 for women. Participants were divided into subgroups for further analysis. The TyG index also showed high diagnostic values, especially for younger individuals and men with normal waist circumference. Sex-specific cut-offs for three indices were also used to define metabolic unhealth. The TyG index showed the highest agreement with κ values of 0.603 and 0.605 for men and women between the components of metabolic syndrome and three indices. CONCLUSIONS: We propose that the TyG index, just read in one blood laboratory test report, is simpler and more suitable for the identification of metabolically unhealthy individuals as well as who have high risk of cardiometabolic diseases of the Chinese adult population.

Differences between the perspectives of physicians and patients on the potential barriers to optimal diabetes control in China: a multicenter study.

BACKGROUND: To investigate the potential barriers to optimal diabetes control by evaluating the different perspectives of physicians and patients on such matters in China. METHODS: This multi-center survey was conducted from December 2015 to March 2016. A multi-stage stratified random sampling method was used to sample representative diabetes physicians and patients in 18 hospitals in Shaanxi province, China. A self-designed questionnaire was used. The questionnaire mainly consisted of 2 questions for physicians and 1 question for patients of which the participants were required to rank in priority of 3 (for physicians) and 2 (for patients) choices from a list of barriers. The strategies to improve diabetes control were only in the questionnaire for physicians. RESULTS: A total of 85 physicians and 584 patients completed the questionnaire. Physicians and patients differed regarding the patients' awareness of the risk of diabetes: over 70% of the physicians believed that the patients had no sufficient understanding of the harm and risk of diabetes, whereas the patients believed otherwise. Both physicians and patients considered self-monitoring of blood glucose to be an important link of glucose control; unfortunately, most of the patients failed to do so in practice. In addition, physicians considered "improving health insurance coverage for diabetes" as the first important measure and "providing more and easy-to-use diabetes brochures or educational materials for patients" as the second important measure to improve diabetes control. CONCLUSION: The survey revealed differences between the perspectives of physicians and patients on the potential barriers to optimal diabetes control. The main potential barriers to optimal diabetes control were patient's poor lifestyle interventions, limited understanding of the danger of diabetes, and poor self-monitoring of blood glucose. From the physicians' perspective, China's primary focus about diabetes control in the future should still be put on diabetes education, particular the importance of lifestyle interventions.

RFamide-related peptide-3 promotes alpha TC1 clone 6 cell survival likely via GPR147.

Type 2 diabetes mellitus (T2DM) is closely related to islet alpha cell mass and viability. Several types of RFamide-related peptides (RFRPs) are involved in regulating proliferation and function of islet cells. However, current understanding of the role of RFamide-related peptide-3 (RFRP-3) in pancreatic alpha cells is limited. Therefore, we investigated the expression of the RFRP-3 receptor, G protein-coupled receptor 147 (GPR147), in mouse islets and alpha TC1 clone 6 cells, and evaluated the function of RFRP-3 on alpha cells. We show that GPR147 is expressed in mouse islets and alpha cell lines. In addition, RFRP-3 promotes survival of alpha cells under conditions of hyperglycemia and serum starvation. Mechanistic evidence demonstrates that RFRP-3 activated PI3K/AKT and ERK1/2 signaling cascades and treatment with an antagonist of GPR147, 1-adamantanecarbonyl-Arg-Phe-NH2 (RF9) blocked this function. These findings indicate a novel effect of RFRP-3 in promoting alpha cell survival, likely via GPR147.

Body fat percentage cutoffs for risk of cardiometabolic abnormalities in the Chinese adult population: a nationwide study.

BACKGROUND/OBJECTIVES: The direct assessment of body fat (BF) by using simple methods might be an alternative index of obesity. We aim to investigate the optimal cutoffs of the %BF relating to metabolic disorders and cardiovascular risks in China. SUBJECTS/METHODS: The data were from the 2007-2008 China National Diabetes and Metabolic Disorders Study. Participants with age of 20-75 years and with a BF measurement record were included. The %BF was measured using a foot-to-foot bioelectrical impedance analysis. Receiver operating characteristic curve was used to decide the optimal %BF cutoffs for predicting the risk of diabetes, hypertension, metabolic syndrome (MetS), and 10-year cardiovascular events (estimated by Framingham risk score (FRS)). RESULTS: A total of 23,769 participants were enrolled with the mean age of 44.88 years, the male percentage of 40.59%, and the mean %BF of 25.22%. The mean %BFs of subjects who had diabetes, hypertension, metabolic syndrome, and FRS ≥ 10% were higher than those without diabetes, hypertension, metabolic syndrome, and FRS ≥ 10%, respectively. In men, the optimal %BF cutoffs for these four endpoints were 24.50%, 24.90%, 24.21%, and 22.10%, respectively. In women, they were 35.69%, 32.50%, 32.60%, and 32.31%, respectively. On the basis of the weights of these endpoints, the pooled optimal %BF cutoff was 23.67% and 32.88% in men and women, respectively. CONCLUSIONS: We suggest the optimal foot-to-foot BIA-measured %BF cutoffs for predicting risk of cardiometabolic abnormalities to be 24% and 33% in Chinese men and women, respectively.

Effectiveness and safety of bifidobacteria and berberine in people with hyperglycemia: study protocol for a randomized controlled trial.

BACKGROUND: Berberine is one of the most important examples of a Chinese traditional medicine that has hypoglycemic effects but there have been no randomized controlled trials of the drug in a larger sample. In addition, the use of probiotic biotherapy to maintain an appropriate intestinal flora may represent an effective early intervention for hyperglycemia. Unfortunately, there has been a shortage of relevant research on this possibility at the population level. This study was designed to determine the hypoglycemic effect and safety of both bifidobacteria and berberine administration to newly diagnosed patients with pre-diabetes or diabetes mellitus. METHODS/DESIGN: This is a multicenter, double-blind, randomized, and parallel-controlled study that includes a run-in period of 2 weeks and a treatment period of 16 weeks, which will be conducted between June 2015 and October 2018. The 300 randomized patients will be assigned to the following four groups for 16 weeks' treatment: Bifidobacterium, berberine, Bifidobacterium combined berberine, and placebo control groups. The primary outcome is the absolute value of fasting plasma glucose compared with baseline after 16 weeks of treatment. DISCUSSION: This is the first randomized controlled trial to determine the hypoglycemic effect and safety of both bifidobacteria and berberine administration to newly diagnosed patients with pre-diabetes or diabetes mellitus. It may provide support for the use of berberine and bifidobacteria in the treatment of diabetes. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03330184 . Retrospectively registered on 18 October 2017.

Recommendations for revision of Chinese diagnostic criteria for metabolic syndrome: A nationwide study.

BACKGROUND: Diagnostic criteria for metabolic syndrome (MS) proposed by the Chinese Diabetes Society (CDS) may have limitations because an additional 2-h postprandial plasma glucose (2-h PPG) test is required to diagnose hyperglycemia. The aim of this study was to revise the CDS-MS criteria by removing the 2-h PPG test and determining the optimal fasting plasma glucose (FPG) cut-off for a diagnosis of hyperglycemia in the Chinese population. METHODS: The study population was from the 2007-08 China Diabetes and Metabolic Disorders Study. The optimal FPG diagnostic cut-off value was determined using receiver operating characteristic curves. Hyperglycemia defined using CDS-MS criteria was the end-point. Agreement between different diagnostic methods was assessed using κ values. RESULTS: The study enrolled 46 239 participants (mean age 44.95 years). The optimal diagnostic cut-off for FPG was found to be 5.62 mmol/L, which showed a sensitivity of 66.92%, a specificity of 89.09%, and an area under the curve of 0.848. Using this diagnostic criterion, the standardized prevalence of MS was similar to that using the CDS-MS criteria (18.26% vs 17.89%, respectively), with both values being lower than those obtained using conventional international criteria (20.64-26.67%). Compared with the CDS-MS criteria, the recommended FPG cut-off showed better agreement (κ) with international criteria: 0.695, 0.774, and 0.730 with the International Diabetes Federation (IDF), revised Adult Treatment Panel III, and Joint Interim Statement of the IDF criteria, respectively. CONCLUSIONS: We recommend eliminating the 2-h PPG blood test and lowering the FPG diagnostic cut-off value to 5.6 mmol/L in the CDS-MS diagnostic criteria.

Inhaled antibiotics in non-cystic fibrosis bronchiectasis: A meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of inhaled antibiotics for the treatment of non-cystic fibrosis bronchiectasis (NCFB). METHODS: Pubmed, Cochrane library, Embase, Elsevier, OVID, Springerlink, Web of knowledge and NEJM were searched for randomized controlled trials (RCTs) on inhaled antibiotics in treatment of NCFB from inception until April 2015. Meta-analysis was conducted to assess the efficacy and safety of inhaled antibiotics in the treatment of NCFB. RESULTS: Twelve RCTs involving 1154 participants were included. They showed that inhaled antibiotics were more effective in reduction of sputum bacterial density, eradication of P. aeruginosa, prolonged time to exacerbation and reduction of new pathogens emergence with no significant difference in adverse events compared with control groups. However, we did not find significant benefits of inhaled antibiotics in reducing the risk of acute exacerbation, improving health-related quality of life and reduction of P. aeruginosa resistance. Moreover, inhaled antibiotics exerted a statistically significant reduction in FEV1%. CONCLUSIONS: Inhaled antibiotics may be an alternative pathway to inhibit airway inflammation with no more adverse events in patients with NCFB.

Clinical and pathological analysis of 116 cases of adult adrenal cortical adenoma and literature review.

BACKGROUND: The aim of this study is to investigate origin, gross features, microscopic features, immunohistochemical properties, and differential diagnosis of adrenal cortical adenoma (ACA) in patients ≥20 years old. METHODS: The clinicopathological features of 116 cases of ACA and the immunohistochemical features of 50 cases of ACA were evaluated, and the relevant literature was reviewed. RESULTS: In our cohort, 76.72% (89/116) of the cases were functional, and 27 cases had non-functional, benign adrenal adenomas. ACA presented as an island tumor with an envelope, and the mean tumor size was 3.6 cm (range 1-5 cm), with a mean tumor weight of 9.28 g (range 5-113 g). The shape of the tumor cells was consistent, and mitosis was rarely observed. Forty of the 46 patients with cortisol-secreting ACA had tumors containing granule cells. Primary aldosteronism was observed in 43 cases. Thirty-eight cases had endoscopically visible tumors, with clear cells and lipid-rich cytoplasm arranged in irregular patches or strips. Cortisol-producing ACAs were associated with atrophy of the non-tumorous cortex. Adrenocortical adenomas displayed positive immunohistochemical staining for MELAN-A, Syn (46 of 50 cases of ACA), NSE (44 of 50 cases of ACA), Vim (42 of 50 cases of ACA) and Ki-67 <5% (24 of 50 cases of ACA; the remaining 26 cases were negative for Ki-67). CONCLUSION: Prediction of endocrine syndrome in functional ACA was possible based on its structure and morphologic features, which could prevent an unanticipated postoperative crisis. However, a clinical study is needed to validate these findings.

Ectopic cortisol-producing adrenocortical adenoma in the renal hilum: histopathological features and steroidogenic enzyme profile.

Ectopic cortisol-producing adrenocortical adenomas (CPA) are extremely rare, and only four cases have previously been reported so far but the tumors were not ultrastructurally studied. Presented in this paper is the fifth case with ectopic CPA which was extensively examined to gain deeper insights in terms of the histopathological features and steroidogenic enzyme profile of the tumor. A 53-year-old woman complained of accidental discovery of left renal mass. She had a 5-year history of hypertension, weight gain, moon face, thin skin and systemic edema. These symptoms completely relieved after the tumor removal. Two years later, the above symptoms recurred, and a recurrent tumor was revealed in left renal hilum. The tumor was removed completely with relief of her symptoms of Cushing's syndrome. Histologically and ultrastructurally, the tumor was composed of compact cells and clear cells, and the former was prominent, suggesting an active secretory function of the tumor. The adenoma tissue showed a strong immunostaining for Melan-A, 3beta-hydroxysteroid dehydrogenase (HSD3B2) and 17alpha-hydroxylase1 (CYP17A1). Expression pattern for 11beta-hydroxylase 1 (CYP11B1), 11beta-hydroxylase 2 (CYP11B2), CYP17 and HSD3B2 mRNA in ectopic CPA was similar to that in the adrenal CPA. In conclusion, in terms of histopathological characteristic and steroidogenic enzyme profile, ectopic CPA is similar to adrenal CPA, suggesting that they are of identical cell origin.