Apparent Mineralocorticoid Excess in the Pediatric Population: Report of a Novel Pathogenic Variant of the 11ß-HSD2 Gene and Systematic Review of the Literature.

Apparent mineralocorticoid excess (AME) is a rare inherited disorder caused by pathogenic variants in the 11ß-HSD2 gene resulting in a deficiency of the 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) enzyme catalyzing the conversion of cortisol to its inactive metabolite, cortisone. Impaired cortisol metabolism results in a mineralocorticoid excess-like state presenting as low renin, low aldosterone hypertension (HTN) and hypokalemia. Typically, AME is diagnosed in early childhood. Medical treatment to control HTN and hypokalemia often is only partially successful. Herein, we systematically review previously reported AME cases in the pediatric population, focusing on presentation, genetic basis, treatment and outcomes. We demonstrate a negative correlation between the ratio of urinary cortisol to cortisone metabolites, and the age of diagnosis (p=0.0051). We also report a novel causative variant of the 11ß-HSD2 gene and propose an explanation for failure of the mineralocorticoid receptor antogonist, spironolactone, to control hypertension and hypokalemia in a subgroup of patients.

Update on central precocious puberty: from etiologies to outcomes.

INTRODUCTION: Precocious puberty (PP) is one of the most common reasons for referral to pediatric endocrinologists. Gonadotropin-releasing hormone analogs (GnRHas) are the gold standard for the treatment of central precocious puberty (CPP) and have an impressive record of safety and efficacy. However, ongoing refinements in diagnosis and management continue to lead to important advancements in clinical care. AREAS COVERED: The aim of this review is to cover current considerations and controversies regarding the diagnosis of CPP, as well as new findings in regards to etiology and treatment modalities. EXPERT COMMENTARY: There is emerging evidence of monogenic etiologies of CPP and significant progress in the expansion of newer formulations of GnRHas. Despite these exciting developments, areas of uncertainty in the diagnosis and treatment of CPP remain. While long-term outcomes of patients treated for CPP are encouraging, only short-term follow-up is available with respect to the newer extended release GnRHa preparations, and how they compare with historically used formulations is unknown. A particular shortage of information exists pertaining to CPP in boys and regarding the psychological implications of PP in girls, and more research is needed. Continued investigation will yield new insights into the underlying genetics and optimal treatment strategies for CPP.

Prevalence of cranial MRI findings in girls with central precocious puberty: a systematic review and meta-analysis.

Background Some pediatric endocrinologists recommend that girls with central precocious puberty (CPP) have cranial magnetic resonance imaging (MRI) performed only if they are younger than 6 years of age. However, no practice guidelines exist. The objective of this review was to assess the frequency of intracranial lesions in girls with CPP. Content We searched six electronic databases (PubMed, Cochrane, Web of Science, SCOPUS, ProQuest, and Dissertation & Theses) from 1990 through December 2015. We included studies on girls with CPP and MRI data. Case reports, case series, studies from the same author/group with the same patient population, and studies with conditions predisposing to CPP were excluded. Two physicians independently reviewed the search results and extracted data. A random-effects model was used to obtain pooled prevalence of positive MRI's across studies. Heterogeneity among studies was evaluated with the Q-statistic. Publication bias was assessed with funnel plots and Egger's test. Pooled prevalence was computed by age group. A linear regression assessed the relationship between intracranial lesion prevalence and healthcare availability. We included 15 studies with a total of 1853 girls <8 year old evaluated for CPP. Summary The pooled prevalence from all studies was 0.09 [95% confidence interval (CI) 0.06-0.12]. There was a significant heterogeneity, indicating the appropriateness of a random effects model in computing pooled prevalence. In the few studies stratified by age group, pooled prevalence was 25% in girls <6 years vs. 3% in girls 6-8 of age. Outlook Our results support that the benefit of routine MRIs in girls with CPP older than 6 years of age without any neurological concerns is not clear-cut.