Epidemiology of thyroid-stimulating immunoglobulin in recent-onset symptomatic thyroid eye disease.

Purpose: This study aims to report correlations between thyroid-stimulating immunoglobulin (TSI) and both clinical and radiological parameters in recent-onset symptomatic thyroid eye disease (TED) patients. Methods: A prospective cohort study of TED patients managed at the Chinese University of Hong Kong from January 2014 to May 2022. Serum TSI levels were determined with the functional assay. Outcomes included the Clinical Activity Score (CAS), marginal reflex distance1 (MRD1), extraocular muscle motility restriction (EOMy), exophthalmos, and diplopia. The radiological assessment included cross-sectional areas and signal of extraocular muscles on STIR-sequence MRI. Results: A total of 255 (197 female) treatment-naive patients, with an average onset age of 50 ± 14 years (mean ± s.d.), were included. Elevated pre-treatment TSI level was observed in 223 (88%) patients. There was a weak positive correlation between TSI and CAS (r = 0.28, P = 0.000031), MRD1 (r = 0.17, P = 0.0080), and the size of the levator palpebrae superioris/superior rectus complex (r = 0.25, P = 0.018). No significant correlation existed between TSI and STIR signals. The AUC and optimal cut-off value for clinical active TED were 0.67 (95% CI: 0.60-0.75) and 284% (specificity: 50%, sensitivity: 85%). In total, 64 patients received intravenous methylprednisolone (IVMP) during the study interval, and they had a higher baseline TSI level than those who did not have IVMP (P = 0.000044). Serial post-IVMP TSI among the 62 patients showed a significant reduction compared to the baseline level (P < 0.001). Both the baseline and post-IVMP TSI levels, and percentages of TSI changes were comparable between patients who responded and did not respond to the first course of IVMP. Conclusion: TSI can be a serum biomarker for the diagnosis, prognosis, and treatment response of TED. Further validation should be warranted.

Declining Trends of Cardiovascular-Renal Complications and Mortality in Type 2 Diabetes: The Hong Kong Diabetes Database.

OBJECTIVE: Nationwide studies on secular trends of diabetes complications are not available in Asia. We examined changes in risk factor control and incidence of complications from diabetes and death in a large longitudinal cohort of Chinese adults with type 2 diabetes in Hong Kong. RESEARCH DESIGN AND METHODS: Between 1 January 2000 and 31 December 2012, 338,908 Chinese adults with type 2 diabetes underwent metabolic and complication assessment in 16 diabetes centers operated by Hong Kong Hospital Authority that provided care to a large majority of diagnosed patients. Patients were followed for incident acute myocardial infarction (AMI), stroke, end-stage renal disease (ESRD), and death until 31 December 2012. Risk factor levels between enrollment periods were compared. Incidence of clinical events, stratified by diabetes duration, was examined over time. RESULTS: Incidence of complications from diabetes and death declined over the observation period in patients at varying disease duration. Among the high-risk group with diabetes for at least 15 years, crude incidence of AMI decreased from 8.7 to 5.8, stroke from 13.5 to 10.1, ESRD from 25.8 to 22.5, and death from 29.0 to 26.6 per 1,000 person-year between the periods 2000 to 2002 and 2010 to 2012. Improvements in levels of metabolic risk factors were detected. Proportion of patients achieving HbA1c <7.0% (53 mmol/mol) was increased from 32.9 to 50.0%, blood pressure ≤130/80 mmHg from 24.7 to 30.7%, and LDL cholesterol <2.6 mmol/L from 25.8 to 38.1%. CONCLUSIONS: From this territory-wide Hong Kong Diabetes Database, we observed decreases in incidence of cardiovascular-renal complications and death and corresponding improvements in risk factor control over a 13-year period.

Pharmacokinetics of testosterone undecanoate injected alone or in combination with norethisterone enanthate in healthy men.

Long-acting injectable testosterone undecanoate (TU) is a promising androgen for male hormonal contraception. As a prerequisite for a planned multicenter male contraceptive efficacy study, we studied the pharmacokinetics of 2 doses of TU alone or in combination with norethisterone enanthate (NETE) in a prospective 2-center study, randomized for TU dose in each center. Twenty healthy male volunteers in each center were administered intramuscular injections of 750 or 1000 mg TU alone or in combination with 200 mg of NETE IM every 8 weeks for 3 injections. There were no significant differences in maximum concentration and area under the curve (AUC) for serum total and free testosterone (T) between the TU 750 and 1000 mg groups, irrespective of whether TU was administered with 200 mg of NETE. TU 1000 mg IM alone or with NETE at 8-weekly intervals resulted in linear increases in average concentration and AUC of serum total and free T with each injection. Accumulation ratios of serum total and free T levels (calculated as 8 weeks post- to preinjection levels) for each period showed significant increases in the TU+ NETE groups. Serum gonadotropins levels and sperm concentration were more consistently suppressed in the TU 1000 mg + NETE group. We conclude that despite some accumulation of T, TU 1000 mg + NETE 200 mg administered every 8 weeks may be preferable for the future contraceptive efficacy study because of more complete suppression of gonadotropins and spermatogenesis.

Transient testicular warming enhances the suppressive effect of testosterone on spermatogenesis in adult cynomolgus monkeys (Macaca fascicularis).

CONTEXT: The context of the study was to examine whether combined testosterone (T) and heat (H) treatment have additive or synergistic effects on suppression of spermatogenesis. OBJECTIVE: The objective of the study was to determine whether T+H induces a greater suppression of spermatogenesis than either treatment alone in monkeys. DESIGN: The study was a randomized, placebo-controlled study. SETTING: The study was conducted at a primate center in China. PARTICIPANTS: The study population was comprised of 32 adult cynomolgus monkeys. INTERVENTIONS: Groups of eight adult monkeys were treated for 12 wk with: 1) two empty implants (C); 2) two T implants (T); 3) daily testicular heat exposure (43 C for 30 min) for 2 consecutive days (H); or 4) two T implants plus testicular heat exposure (T+H). Treatment was followed by an 8-wk recovery period. MAIN OUTCOME MEASURES: Measures included sperm counts and germ cell apoptosis. RESULTS: Serum T levels were elevated in both the T and T+H groups during treatment but not in the C or H group. Sperm counts were transiently suppressed after heat to 16.4% of baseline at 4 wk and then returned to pretreatment levels. Sperm counts were suppressed slowly after T treatment to nadir of 6.4% of pretreatment levels at 12 wk. T+H rapidly suppressed sperm output as early as 4 wk to 3.9% of pretreatment levels that was maintained throughout treatment. The decreased sperm counts were due to increased germ cell apoptosis in all treatment groups. Sperm counts recovered to the pretreatment levels in all groups by 8 wk after treatment. CONCLUSION: This proof-of-concept study demonstrates that transient testicular warming enhances and hastens the effect of T implant on the suppression of spermatogenesis in monkeys.

The use of aldosterone-renin ratio as a diagnostic test for primary hyperaldosteronism and its test characteristics under different conditions of blood sampling.

Recent reviews recommended the use of the aldosterone/renin ratio (ARR) to screen for primary hyperaldosteronism. However, widely different cutoff levels have been proposed, and test characteristics of ARR under different conditions of sampling are not known. We conducted a retrospective review among 45 subjects with carefully validated diagnoses of primary hyperaldosteronism and 17 subjects with essential hypertension to study the utility of ARR. Sixty-two patients with 75 sets of plasma renin activity (PRA), aldosterone, and ARR values from a postural study and 48 sets of values from a saline suppression test were analyzed. Ninety-four percent of these subjects underwent investigations because of hypokalemic hypertension.ARR yielded larger areas under the curve in the receiver-operating-characteristics curve than PRA or aldosterone under all conditions of testing. Our results confirmed the superiority of ARR to either aldosterone or PRA alone as a diagnostic test for primary hyperaldosteronism.ARR cutoff levels were significantly affected by the condition of testing. Depending on posture and time of day, it varied from 13.1-35.0 ng/dl per ng/ml.h in our study population. When using ARR for screening primary hyperaldosteronism, posture and time of sampling should be standardized both within and between centers to minimize variability in cutoff levels.

The role of carnitine in the male reproductive system.

Carnitine is highly concentrated in the epididymis and spermatozoa, where it may serve as an intramitochondrial vehicle for the acyl group, which in the form of acyl CoA acts as a substrate for the oxidation process producing energy for sperm respiration and motility. To date, studies in rodents and humans suggest that sperm count, motility, and maturation are related to epididymal free carnitine concentrations. Moreover, supplementation with carnitine improves sperm quality and/or quantity in testes of mice exposed to physical insults, such as heat and X-irradiation, and in men with idiopathic oligoasthenospermia. These benefits may be due to increased mitochondrial fatty acid oxidation resulting in improvement in motility of epididymal sperm. The antiapoptotic effect(s) of carnitine in the testes may also contribute, but this remains speculative and requires further investigation. Research to uncover the many characteristics and mechanisms of action of carnitine in somatic and germ cells may provide insights into the pathophysiology of germ cell apoptosis, the prevention of germ cell death, and possibly specific therapy of some forms of infertility. Further well-controlled, carefully designed, larger-scale studies are necessary and desirable before widespread clinical use as an infertility therapy can be contemplated.