Endocrine Practice最新文献

Background

While clinical features of KCNJ5-mutated aldosterone-producing adenoma (APA) have been reported, evidence of its clinical outcomes is lacking. We aimed to synthesize available literature about the associations between KCNJ5 mutation with cardiovascular and metabolic outcomes among patients with APA.

Methods

In this systematic review of observational studies, MEDLINE and Embase were searched through August 2022. Two independent authors screened the search results and extracted data from eligible observational studies investigating cardiovascular or metabolic outcomes between KCNJ5-mutated APAs and KCNJ5-non-mutated APAs. Risk of Bias In Non-randomized Studies of Interventions was used to assess the quality of the included studies.

Results

A total of 573 titles/abstracts were screened and after the expert opinion of the literature, full text was read in 20 titles/abstracts, of which 12 studies were included. Across 3 studies comparing the baseline or change in the cardiac function between KCNJ5-mutated APAs and KCNJ5-non-mutated APAs, all studies reported the association between impaired cardiac functions and KCNJ5 mutation status. Among 6 studies evaluating the cure of hypertension after surgery, all studies showed that KCNJ5 mutation was significantly associated with the cure of hypertension. In quality assessment, 7 studies were at serious risk of bias, while the remaining studies were at moderate risk of bias.

Conclusions

This systematic review provided evidence of the significant association between KCNJ5 mutation and unfavorable cardiovascular outcomes in patients with primary aldosteronism. Further research is needed to improve the quality of evidence on this topic and elucidate the underlying mechanisms of the potential burden of KCNJ5 mutation.

Objective

To assess the diagnostic value of combining plasma steroid profiling with machine learning (ML) in differentiating between mild autonomous cortisol secretion (MACS) and nonfunctioning adenoma (NFA) in patients with adrenal incidentalomas.

Methods

The plasma steroid profiles data in the laboratory information system were screened from January 2021 to December 2023. EXtreme Gradient Boosting was applied to establish diagnostic models using plasma 24-steroid panels and/or clinical characteristics of the subjects. The SHapley Additive exPlanation (SHAP) method was used for explaining the model.

Results

Seventy-six patients with MACS and 86 patients with NFA were included in the development and internal validation cohort while the external validation cohort consisted of 27 MACS and 21 NFA cases. Among 5 ML models evaluated, eXtreme Gradient Boosting demonstrated superior performance with an area under the curve of 0.77 using 24 steroid hormones. The SHAP method identified 5 steroids that exhibited optimal performance in distinguishing MACS from NFA, namely dehydroepiandrosterone, 11-deoxycortisol, 11β-hydroxytestosterone, testosterone, and dehydroepiandrosteronesulfate. Upon incorporating clinical features into the model, the area under the curve increased to 0.88, with a sensitivity of 0.77 and specificity of 0.82. Furthermore, the results obtained through SHAP revealed that lower levels of testosterone, dehydroepiandrosterone, low-density lipoprotein cholesterol, body mass index, and adrenocorticotropic hormone along with higher level of 11-deoxycortisol significantly contributed to the identification of MACS in the model.

Conclusions

We have elucidated the utilization of ML-based steroid profiling to discriminate between MACS and NFA in patients with adrenal incidentalomas. This approach holds promise for distinguishing these 2 entities through a single blood collection.

Short stature in children is a common reason for referral to a pediatric endocrinologist. Many genetic, nutritional, psychological, illness-related, and hormonal causes must be excluded before labeling as idiopathic. Idiopathic short stature is not a diagnosis, but rather describes a large, heterogeneous group of children, who are short and often slowly growing. As new testing paradigms become available, the pool of patients labeled as idiopathic will shrink, although most will have a polygenic cause. Given that many of the new diagnoses are involved in growth plate biology, physical examination should assess for subtle dysmorphology or disproportion of the skeleton that may indicate a heterozygous mutation that in its homozygous state would be apparent. When laboratory evaluations are negative, one may consider genetic testing, such as targeted gene or gene panel, comparative genomic hybridization, or whole exome or whole genome sequencing (respectively). With a known genetic diagnosis, targeted therapy may be possible rather than recombinant human growth hormone, where response is generally poorer than that for children with growth hormone deficiency, because the variety of diagnoses may have varying growth hormone sensitivity. A firm diagnosis has heuristic value: to truncate further diagnostic evaluation, alert the clinician to other possible comorbidities, inform the family for genetic counseling, and direct appropriate targeted therapy, if available.

Background

Resmetirom, a liver-directed, thyroid hormone receptor beta-selective agonist, has recently been approved to treat nonalcoholic steatohepatitis (NASH). This meta-analysis aimed to summarize the efficiency and safety of resmetirom in treating NASH.

Methods

Electronic databases were searched for randomized controlled trials (RCTs) of resmetirom vs placebo in patients with NASH. The primary outcomes were the changes from baseline in hepatic fat content, liver histology, including NASH resolution, and noninvasive markers of hepatic fibrosis.

Results

Three randomized controlled trials (n = 2231) met the inclusion criteria. Compared to placebo, resmetirom achieved greater reductions from baseline in hepatic fat content assessed by magnetic resonance imaging proton density fat fraction (for resmetirom 80 mg: MD −27.76% [95%CI: −32.84, −22.69]; for resmetirom 100 mg: MD −36.01% [95%CI: −41.54, −30.48]; P < .00001 for both) and FibroScan controlled attenuation parameter (for resmetirom 80 mg: MD −21.45 dBm [95%CI: −29.37, −13.52]; for resmetirom 100 mg: MD −25.51 dBm [95%CI: −33.53, −17.49]; P < .00001 for both). Resmetirom 80 mg outperformed placebo in NASH resolution and ≥2-point nonalcoholic fatty liver disease activity score reduction. Moreover, resmetirom 80 mg and 100 mg were superior to placebo in cytokeratin-18 (M30) reduction. Greater reductions in liver enzymes, lipids, and reverse triiodothyronine were observed in the resmetirom arms with no impact on triiodothyronine. Nausea and diarrhea were more common with resmetirom than with placebo; other adverse events were comparable.

Conclusion

Resmetirom improves hepatic fat content, liver enzymes, and fibrosis biomarkers in NASH patients. Resmetirom generally does not affect thyroid function and is well-tolerated.