Electrocardiographic Findings in Children Treated with Leuprolide Acetate for Precocious Puberty: Does it Cause Prolonged QT?

Introduction: Central precocious puberty is treated with long-acting GnRH analogues. Some adult patients undergoing GnRHa treatment experienced prolonged QT syndrome, which is associated with an increased risk of serious cardiac events such as myocardial infarction, stroke, arrhythmias, and sudden cardiac death. Method: Seventy-four patients, aged between 5 and 11 years and diagnosed with central precocious puberty but with no other concomitant disease or medication use, underwent electrocardiogram assessment. They had been receiving 3.75 mg leuprolide acetate (Lucrin® Depot) injections every 28 days for at least three months. Results: The electrocardiograms of all patients showed a QTc interval within normal limits, consistent with the data of healthy Turkish children of the same age and gender. No other pathological physical examination or ECG findings were observed. Furthermore, there was no significant difference in QTc interval in relation to age, anthropometric data, or the duration or cumulative dose of the treatment. Conclusion: The study found no correlation between QTc interval values and age, treatment duration, total cumulative dose, and anthropometric data. The findings suggest that cardiovascular adverse events associated with GnRHa may be related to age and other underlying physiopathological conditions rather than the drug.

Familial early-onset obesity in Turkish children: variants and polymorphisms in the melanocortin-4 receptor (MC4R) gene.

OBJECTIVES: Genetic factors have a key role in childhood obesity with higher rates in children than adults. Among the monogenic types of non-syndromic obesity, melanocortin-4 receptor (MC4R) deficiency is the most frequent cause. Beside pathogenic variants, single-nucleotide polymorphisms in MC4R gene are also associated with lower energy expenditure. The aim of this study was to estimate the frequency of MC4R variants and polymorphisms in a cohort of Turkish children and adolescents with severe early-onset obesity, and to understand the clinical features of patients. METHODS: Patients, 1-17 years of age, with the onset of obesity before 10 years of age and a body mass index (BMI) standard deviation score (SDS) of >2.3, and who had a family history of early-onset obesity in at least one of their first-degree relatives were included in the study. Beside routine blood tests genetic analyses for MC4R gene were performed. RESULTS: Analyses of MC4R revealed previously known variations in three (3.5%) patients, and pathogenic polymorphisms related with obesity in four (4.7%) patients. BMI SDS values were between 2.8 and 5.5 SDS in the pathogenic variant carrier group, and 2.8-4.9 SDS in the polymorphism group. Mean BMI SDS in variant-negative group was 3.4 ± 0.82. CONCLUSIONS: Investigation of the MC4R in individuals with early-onset obesity and presence of obesity first-degree relatives is important. Hypertension is a rare comorbidity compared to other causes. Contrary to studies reporting that insulin resistance was absent or very rare, we found it as a frequent finding in both pathogenic variants and polymorphisms of MC4R.