Normal Reference Ranges of Serum Testosterone and Gonadotropins in Thai Fertile Men: A Cross-sectional Study in a Single Tertiary Center

Objective: To identify the normal reference ranges of serum testosterone and gonadotropins in Thai fertile men, compare these levels among different age groups, and assess their relationships with body mass index (BMI). Material and Methods: One hundred and twenty men aged 18-65 years whose wives had conceived within the past year were recruited at Songklanagarind Hospital and stratified into 3 age groups: 18-29, 30-39, and 40-65 years. Serum total testosterone (TT) was measured by electrochemiluminescence immunoassay. Bioavailable testosterone (BT) and free testosterone (FT) were calculated using a validated formula. Results: The mean serum TT levels of the 18-29, 30-39, and 40-65 age groups were 520±200, 456±160, and 478±166 nanograms per deciliter (ng/dL), respectively. There were no significant differences in TT levels among the age groups. The overall mean TT was 481±174 ng/dL and the normal TT reference range was 211-970 ng/dL. Both calculated FT and calculated BT significantly decreased in line with increased follicular stimulating hormone with increased age, while luteinizing hormone levels remained similar. BMI had a weakly negative correlation with TT levels (correlation coefficient=-0.33, p-value<0.001) and small correlations with other measures. Conclusion: Normal ranges of serum testosterone and gonadotropins determined in Thai fertile men with various ages are useful as a reference for clinical practice. Serum TT levels which are negatively correlated with BMI should be interpreted cautiously in obese men

Factors influencing the presence of peripheral arterial disease among Thai patients with type 2 diabetes

Background: Little is known about factors predicting peripheral arterial disease (PAD) development in Thai type 2 diabetes patients. This study aims to identify factors related to PAD in type 2 diabetes and the best predictors for PAD development. Methods and results: A case-control study was conducted in which 405 type 2 diabetes patients were recruited from four tertiary care hospitals in Bangkok, Thailand. Cases were type 2 diabetes patients with PAD who were compared to those without PAD. An ankle-brachial index (ABI) 70 years, having coronary heart disease as a comorbid illness, and having a body mass index of 25–29.9 kg/m2 were predictive for PAD development (all p < 0.05). These three variables explained 12.3% of the variance in the incidence of PAD among type 2 diabetes patients. The demographic and clinical factors were the best predictors for PAD development. Conclusion: Thai type 2 diabetes patients who are elderly, have coronary heart disease as a comorbid condition, or have a normal weight should be considered at risk for PAD development

Efficacy and safety of osilodrostat in patients with Cushing's disease (LINC 3): a multicentre phase III study with a double-blind, randomised withdrawal phase

Background: Cushing's disease is a rare endocrine disorder characterised by cortisol overproduction with severe complications. Therapies for cortisol reduction are often necessary. Here we report the outcomes from the pivotal phase III study of osilodrostat (a potent oral inhibitor of cytochrome P450 11B1, mitochondrial [11β-hydroxylase]; Novartis Pharma AG, Basel, Switzerland) in patients with Cushing's disease. Methods: LINC 3 was a prospective, multicentre, open-label, phase III study with a double-blind randomised withdrawal period, that comprised four periods. Patients aged 18–75 years, with confirmed persistent or recurrent Cushing's disease (defined as mean 24-h urinary free cortisol [UFC] concentration >1·5 times the upper limit of normal [ULN] and morning plasma adrenocorticotropic hormone above the lower limit of normal) who had previously had pituitary surgery or irradiation, or were newly diagnosed and who refused surgery or were not surgical candidates, were recruited from 66 hospital sites and private clinical practices in 19 countries. In period 1, open-label osilodrostat was initiated in all participants and adjusted every 2 weeks (1–30 mg twice daily; film-coated tablets for oral administration) on the basis of mean 24-h UFC concentration and safety until week 12. In period 2, weeks 13–24, osilodrostat was continued at the therapeutic dose determined during period 1. In period 3, beginning at week 26, participants who had a mean 24-h UFC concentration of less than or equal to the ULN at week 24, without up-titration after week 12, were randomly assigned (1:1), via an interactive-response technology, stratified by osilodrostat dose at week 24 and history of pituitary irradiation, to continue osilodrostat or switch to placebo for 8 weeks. Participants and investigators were masked to treatment assignment. Ineligible participants continued open-label osilodrostat. In period 4, weeks 35–48, all participants were given open-label osilodrostat until core-study end. The primary objective was to compare the efficacy of osilodrostat versus placebo at the end of period 3. The primary endpoint was the proportion of participants who had been randomly assigned to treatment or placebo with a complete response (ie, mean 24-h UFC concentration of ≤ULN) at the end of the randomised withdrawal period (week 34), without up-titration during this period. The key secondary endpoint was the proportion of participants with a complete response at the end of the single-arm, open-label period (ie, period 2, week 24) without up-titration during weeks 13–24. Analysis was by intention-to-treat for all patients who received at least one dose of osilodrostat (full analysis set; key secondary endpoint) or randomised treatment (randomised analysis set; primary endpoint) and safety was assessed in all enrolled patients who received at least one dose of osilodrostat and had at least one post-baseline safety assessment. LINC 3 is registered with ClinicalTrials.gov, NCT02180217, and is now complete. Findings: Between Nov 12, 2014, and March 22, 2017, 202 patients were screened and 137 were enrolled. The median age was 40·0 years (31·0–49·0) and 106 (77%) participants were female. 72 (53%) participants were eligible for randomisation during the withdrawal phase, of whom 36 were assigned to continue osilodrostat and 35 were assigned to placebo; one patient was not randomly assigned due to investigator decision and continued open-label osilodrostat. More patients maintained a complete response with osilodrostat versus with placebo at week 34 (31 [86%] vs ten [29%]; odds ratio 13·7 [95% CI 3·7–53·4]; p25% of participants) were nausea (57 [42%]), headache (46 [34%]), fatigue (39 [28%]), and adrenal insufficiency (38 [28%]). Hypocortisolism occurred in 70 (51%) patients and adverse events related to adrenal hormone precursors occurred in 58 (42%) patients. One patient died, unrelated to study drug, after the core study phase. Interpretation: Twice-daily osilodrostat rapidly reduced mean 24-h UFC and sustained this reduction alongside improvements in clinical signs of hypercortisolism; it was also generally well tolerated. Osilodrostat is an effective new treatment option that is approved in Europe for the treatment of endogenous Cushing's syndrome and in the USA for Cushing's disease. Funding: Novartis Pharma AG

Complication profiles and their associated factors in Malaysian adult type 2 diabetes mellitus—an analysis of ADCM registry

Early detection and treatment of risk factors in type 2 diabetes mellitus (T2D) have been proven in reducing complications, improving survival and quality of life. This study aimed to examine an overall diabetes-related complication profiles and their associated factors in adult T2D. Adult diabetes control and management (ADCM) is a prospective registry that included patients with T2D in 2009. Complication profiles were reported descriptively. Multivariate analyses adjusted for differences in patient characteristics were used to determine the associated factors for diabetes-related complications categorised as microvascular complication (microCx) such as retinopathy and nephropathy and macrovascular complication (macroCx) such as ischaemic heart disease and cerebrovascular accident and both complications (combined microCx and macroCx). Complete data were available for 57,780 patients (81.5 %) with a mean age of 58.3 (SD 11.27) years; 59.7 % were female. About one fifth (10,834/57,780) of T2D patients were diagnosed with at least one complication. Ethnicity, gender, duration of T2D and co-morbids, under hospitals with specialist (HS) care, glycaemic and low-density lipoprotein-cholesterol (LDL-C) targets were associated with complications. When compared to T2D patients without complication, patients who were older (OR 1.03), male (OR 1.48), had longer duration of diabetes (OR 1.04) and hypertension (OR 1.03) and under the care HS (OR 13.64) were more likely to have both complications. T2D patients had moderate morbidity burden. Older age and male gender were two main risk factors of all types of complications. T2D patients with these associated factors should be monitored for prevention, screening and early treatment of diabetes-related complications. T2D patients under the HS care were noted to have also more complications could be due to HS had been centres of referral for advanced diabetes care rather than the result of HS care itself