Clinical Endocrinology最新文献

Introduction

Hypogonadotropic hypogonadism (HH) is a treatable cause of nonobstructive azoospermic male infertility. Gonadotropin treatment can successfully induce spermatogenesis in most patients, although comprehensive quantitative summary data on spermatogenic outcomes like those required to induce pregnancy is lacking in the literature.

Materials and Methods

Systematic review and meta-analysis of outcomes related to male reproductive function following gonadotropin treatment.

Results

Our search strategy identified 41 studies encompassing 1673 patients with a mean age of 25 (± 5) years. Average sperm concentration achieved after a median of 18 months of gonadotropin treatment was 11.6 M/mL of ejaculate (95% CI 8.4–14.9). Sperm concentrations > 0, > 1, > 5, > 10 and > 20 M/mL were achieved by 78%, 55%, 36%, 24% and 15% of patients, respectively. Mean sperm output and the proportion of patients achieving all sperm thresholds were significantly greater following combined hCG/FSH treatment compared with hCG monotherapy. When compared by diagnosis, patients with congenital HH (CHH) had significantly lower mean sperm output compared with patients with hypopituitarism or mixed patient cohorts that did not differentiate between CHH and hypopituitarism. Treatment-related increases in testosterone and testicular volume (TV) were not different between hCG and combined hCG/FSH treated patients, although increases in TV were lower in men with CHH compared with those with hypopituitarism.

Conclusions

Gonadotropin treatment successfully induced spermatogenesis in most men with pathological gonadotropin deficiency. Sperm outputs more consistent with those typically needed to induce a natural pregnancy were less commonly achieved. Despite similar effects on serum testosterone and TV, combined hCG/FSH appeared more efficacious than hCG alone at inducing spermatogenesis.

Objective

Despite the generally favourable long-term prognosis of low-risk differentiated thyroid cancer (DTC), questions remain about disease-free survival (DFS) after initial treatment, particularly regarding the use of radioactive iodine (RAI). Although there are RCT trial confirming that RAI ablation therapy is not superior to follow-up in terms of the 3-year DFS rate in low-risk thyroid cancer, its longer-term prognosis remains to be established. The objective of this study was to assess the impact of RAI ablation on the presence of structural persistent/recurrent disease in patients with low-risk DTC.

Methods

We retrospectively identified 720 low-risk DTC patients who had undergone total or near-total thyroidectomy (TT) at a tertiary medical centre between January 2008 and July 2018. Propensity scores were calculated using a multivariable logistic regression model that accounted for age, sex, tumour size, neck dissection, multifocality, capsular invasion and lymph node (LN) metastasis. We compared DFS between patients who received RAI and those who did not using log-rank tests and multivariate Cox analyses. Subgroup analyses were also conducted.

Results

Of the total cohort, 180 (25.0%) patients received RAI, while 540 (75.0%) did not before matching. The median follow-up duration was 59.5 months. After matching, the RAI group comprised 135 (39.8%) patients and the non-RAI group comprised 204 (60.2%) patients. In the entire cohort, the 5-year DFS rate was 97.6% for patients receiving RAI compared to 96.8% for those not receiving RAI (p = 0.704). In the matched cohort, the rates were 98.5% and 95.6%, respectively (p = 0.090). Matched multivariate Cox analysis demonstrated that RAI was neither significantly nor independently associated with DFS (hazard ratio [HR] = 0.29; 95% CI 0.06–1.37; p = 0.118). Further subgroup analyses reaffirmed that RAI ablation did not significantly reduce the risk of developing structural persistent/recurrent disease.

Conclusion

Administering RAI ablation following TT did not result in improved DFS for low-risk DTC patients. Our findings suggest that decisions regarding RAI should be made judiciously to avoid overtreatment in this clinical scenario.

Context

Treating overt hyperthyroidism prevents atrial fibrillation (AF). Though subclinical hyperthyroidism (SH) has been associated with AF, it is unknown whether treating SH prevents AF.

Objective

We aimed to identify the association between treating SH and incident AF.

Design

In a pharmacoepidemiologic retrospective cohort study, patients diagnosed with SH between 2000 and 2021 were followed.

Patients

Outpatients ≥ 18 years with biochemical SH and without prior AF, hypothyroidism, thyroid cancer, pituitary disease, or pregnancy were included.

Main Outcomes

The primary outcome was incident AF. Secondary outcomes were ECG and echocardiographic features associated with AF.

Results

Of 2169 patients screened, 360 (131 treated and 229 untreated) were followed up for a mean of 4.27 years. In the treated and untreated groups, AF occurred in 4 (3.1%) and 15 (6.6%) patients (p = 0.15), and AF incidence was 0.8% and 1.4%/year (p = 0.31), respectively. The hazard ratio (HR) for treatment as a time-dependent variable was 0.60 (95% CI 0.19–1.92; p = 0.39). As some cases of AF were documented nearly simultaneously with SH treatment, a sensitivity analysis was performed reassigning two patients diagnosed with AF < 30 days after starting SH treatment to the untreated group. Here, in the treated and untreated groups, AF occurred in 1.6% and 7.4% (p = 0.02), and AF incidence was 0.4% and 1.8%/year (p = 0.02), respectively. The HR was 0.25 (0.06–1.13; p = 0.07). There were no differences in ECG or echocardiographic features.

Conclusion

There was an overall trend towards lower incidence and prevalence of AF following treatment of SH, supporting the need for larger scale studies.

Remission of acromegaly is defined by normalization of GH/IGF-1 values according to age and gender. While treatment strategies, biochemical cut-off to reach, and morbidities related to the persistence of the disease are well described in the literature, there is little data focusing on the delay to reach remission and its consequences. In this commentary, the authors discussed the results obtained from the UK acromegaly registry showing that the time to biochemical remission predicts the overall survival of patients in acromegaly.

Objectives

Anaemia is a key cause of morbidity in chronic kidney disease (CKD). Androgen deficiency (AD) in males can contribute to anaemia of all causes, including in CKD. We sought to examine the prevalence of AD in men with CKD, the extent to which it contributed to anaemia and whether it was independently associated with long-term survival.

Methods

This cross-sectional observational study was conducted among males aged 18 years and over with CKD stages 4 and 5. The study analysed morning blood samples with regard to their full blood count, urea and electrolytes, albumin, lipids, testosterone (T) and sex hormone binding globulin, with calculation of free testosterone by mass action equation. Mortality data were obtained 15 years later for survival analysis.

Results

Among 322 patients with a mean age of 63 years, the overall prevalence of AD was 68.9%. There was a statistically significant negative correlation between erythropoiesis stimulating agent (ESA) dose and testosterone concentrations (Pearson correlation −0.193, p = 0.05). There was a positive correlation between haemoglobin (Hb) and free testosterone level among patients not on ESA therapy (Pearson correlation 0.331, p < 0.001). Kaplan-Meier plots showed p < 0.001 on log-rank analysis, indicating that AD was significantly associated with worse survival. However, in Cox regression analysis, free testosterone was not associated with survival (95% CI for free testosterone 0.997–1.000).

Conclusions

AD is highly prevalent among this population, and increases further with older age and more severe CKD warranting haemodialysis. Association of lower Hb and higher ESA dose with lower T concentration might be causative, which has important pharmaco-economic as well as clinical implications. Lower survival in men with low T, more likely reflects overall poor health rather than causation. A properly constituted randomised controlled study evaluating the effect of native T replacement is warranted in men with CKD and AD.

Objective

A link between maternal thyroid function and the placental biomarkers, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), has been brought forward. This study aimed to describe their association in early pregnancy.

Design

Retrospective cohort study.

Participants

Eight hundred and fifty-eight pregnant women from the North Denmark Region, 2013, with blood samples drawn in early pregnancy.

Measurements

Thyroid-stimulating hormone (TSH), free thyroxine (fT4), thyroid-peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers), sFlt-1 and PlGF (Kryptor Compact, ThermoFisher Scientific) were measured. The association between maternal TSH and fT4 and percentile (pc) levels of sFlt-1 and PlGF (< 25th pc, 25–75th pc, > 75th pc) was evaluated using regression analysis and reported as adjusted beta coefficient (aβ). The frequency of maternal thyroid autoantibodies (TPO-Ab > 60 U/mL or Tg-Ab > 33 U/mL) by pc levels of sFlt-1 and PlGF was compared using chi-squared test.

Results

Higher levels (> 75th pc) of sFlt-1 associated with lower TSH (aβ 0.62, 95% CI: 0.51–0.76) and higher fT4 (aβ 1.03, 95% CI: 1.01–1.05). Higher levels of PlGF associated with lower TSH (aβ 0.82, 95% CI: 0.69–0.98), but not with levels of fT4 (aβ 1.00, 95% CI: 0.97–1.02). No association with maternal thyroid autoantibodies was found (TPO-Ab: sFlt-1: p-value 0.5 and PlGF: p-value 0.1; Tg-Ab: sFlt-1: p-value 0.7 and PlGF: p-value 0.1).

Conclusions

In a large cohort of Danish pregnant women, higher levels of sFlt-1 and PlGF associated with maternal thyroid function in early pregnancy, while there was no association with maternal thyroid autoantibodies.

Context

Congenital Hyperinsulinism (CHI) is associated with inappropriately high levels of C-peptide in the context of hypoglycemia.

Objective

We aimed to better clarify a diagnostic threshold value of C-peptide for children presenting with CHI.

Design

This was a retrospective case-control analysis, examining all hypoglycemia screens, undertaken between 2009 and 2019 at a quaternary paediatrics unit. Plasma C-peptide, insulin, free fatty acid (FFA) and B-hydroxybutyrate (BHOB) concentrations in children diagnosed with CHI were compared with concentrations in children diagnosed with other conditions.

Patients

All patients requiring hypoglycaemic screens at the quaternary children's hospital were analysed.

Results

Median [C-peptide] were statistically significantly different between CHI (147) and non-CHI (72) patients, p < 0.05. The Youden Index indicated that a [C-peptide] value of 291.5 pmol/L would give the greatest optimization of sensitivity (82%) and specificity (99%) for detecting CHI. Median [insulin] differed significantly between the cohorts with a level of 64 pmol/L for CHI patients compared with 0 pmol/L with non-CHI patients (p < 0.01). Median [BOHB] was 0 μmol/L in CHI patients as compared with 2378 μmol/L for non-CHI patients (p < 0.01). Median [FFA] levels were 1910 μmol/L in the non-CHI cohort, compared with 0 in the CHI cohort (p < 0.01).

Conclusions

This study suggests that a C-peptide concentration greater than 291.5 pmol/L is diagnostic of CHI in children. C-peptide appears to offer the greatest utility as a biochemical diagnostic test for CHI and could be prioritised for laboratory analysis.