Outcomes of Patients with Central Precocious Puberty Due to Loss-of-Function Mutations in the MKRN3 Gene after Treatment with Gonadotropin-Releasing Hormone Analog.

INTRODUCTION: Loss-of-function mutation of MKRN3 represents the most frequent genetic cause of familial central precocious puberty (CPP). The outcomes of gonadotropin-releasing hormone analog (GnRHa) treatment in CPP patients with MKRN3 defects are unknown. OBJECTIVE: To describe the clinical and hormonal features of patients with CPP with or without MKRN3 mutations after GnRHa treatment. Anthropometric, metabolic and reproductive parameters were evaluated. PATIENTS AND METHODS: Twenty-nine female patients with CPP due to loss-of-function mutations in the MKRN3 and 43 female patients with idiopathic CPP were included. Their medical records were retrospectively evaluated for clinical, laboratory, and imaging study, before, during, and after GnRHa treatment. All patients with idiopathic CPP and 11 patients with CPP due to MKRN3 defects reached final height (FH). RESULTS: At the diagnosis, there were no significant differences between clinical and laboratory features of patients with CPP with or without MKRN3 mutations. A high prevalence of overweight and obesity was observed in patients with CPP with or without MKRN3 mutations (47.3 and 50%, respectively), followed by a significant reduction after GnRHa treatment. No significant differences in the values of mean FH and target height were found between the 2 CPP groups after GnRHa treatment. Menarche occurred at the expected age in patients with or without CPP due to MKRN3 mutations (11.5 ± 1.3 and 12 ± 0.6 years, respectively). The prevalence of polycystic ovarian syndrome was 9.1% in patients with CPP due to MKRN3 mutations and 5.9% in those with idiopathic CPP. CONCLUSION: Anthropometric, metabolic, and reproductive outcomes after GnRHa treatment were comparable in CPP patients, with or without MKRN3 mutations, suggesting the absence of deleterious effects of MKRN3 defects in young female adults' life.

Premature Pubarche due to Exogenous Testosterone Gel or Intense Diaper Rash Prevention Cream Use: A Case Series.

BACKGROUND/AIMS: Premature pubarche is associated with conditions such as virilizing congenital adrenal hyperplasia, androgen-secreting tumors, and exogenous exposure to androgen products. We describe the clinical and hormonal features of a series of children who were referred to endocrine evaluation due to premature pubarche. METHODS: This is a retrospective case series study of 14 children with premature pubarche and/or virilization. Five were unintentionally exposed to testosterone gel (parental use). Nine patients were intensely exposed to diaper rash prevention creams. Clinical and laboratory data were revised. RESULTS: Moderate to severe virilization was detected in the 5 patients (2 boys and 3 girls) who were exposed to testosterone gel. These patients had pubic hair development associated with clitoromegaly (3/3), penile enlargement (2/2), and accelerated growth (5/5). Testosterone levels were elevated in 4/5 patients associated with normal prepubertal gonadotropin levels and adrenal androgen precursors. The 9 children who were intensely exposed to diaper rash prevention creams had mild pubarche (intermediate hair) without any other clinical manifestation of pubertal development. Three of them exhibited pubic hair thinning after cream withdrawal. CONCLUSION: Unintentional topical androgen exposure or the intense use of diaper rash prevention cream should be ruled out in children with precocious pubarche and/or virilization signs to avoid misdiagnosis and expendable investigation.