From Bariatric Surgery to Conception: The Ideal Timing to Optimize Fetal Weight.

PURPOSE: Bariatric surgery (BS) increases the risk of small for gestational age (SGA) neonates. Guidelines recommend postponing pregnancy for 12-24 months, but optimal surgery-to-conception interval (BSCI) remains uncertain. We aimed to evaluate the impact of BSCI on birth weight and SGA. MATERIALS AND METHODS: Retrospective cohort study of 42 pregnancies following BS, including Roux-en-Y gastric bypass, gastric sleeve, adjustable gastric banding and biliopancreatic diversion. Neonates were classified as SGA if birth weight < 10th percentile. Optimal BSCI was obtained from the analysis of ROC curves, and pregnancies were compared by that cut-off. RESULTS: There was a linear association between BSCI and birth weight and an inverse association with SGA, with each additional month of BSCI translating into additional 4.5 g (95%CI: 2.0-7.0) on birth weight and -6% risk of SGA (95%CI: 0.90-0.99). We established a cut-off of 24.5 months of BSCI for lower risk of SGA. Pregnancies conceived in the first 24 months had a more than tenfold increased risk of SGA (OR 12.6, 95%CI: 2.4-66.0), even when adjusted for maternal age, gestational diabetes and inadequate gestational weight gain. CONCLUSION: BSCI was associated with birth weight and SGA. Our results are in line with the recommendations of BSCI of at least 24 months to reduce the risk of SGA.

A Novel FGFR1 Missense Mutation in a Portuguese Family with Congenital Hypogonadotropic Hypogonadism.

Congenital hypogonadotropic hypogonadism (CHH) is a rare reproductive endocrine disorder characterized by complete or partial failure of pubertal development and infertility due to deficiency of the gonadotropin-releasing hormone (GnRH). CHH has a significant clinical heterogeneity and can be caused by mutations in over 30 genes. The aim of this study was to investigate the genetic defect in two siblings with CHH. A woman with CHH associated with anosmia and her brother with normosmic CHH were investigated by whole exome sequencing. The genetic studies revealed a novel heterozygous missense mutation in the Fibroblast Growth Factor Receptor 1 (FGFR1) gene (NM_023110.3: c.242T>C, p.Ile81Thr) in the affected siblings and in their unaffected father. The mutation affected a conserved amino acid within the first Ig-like domain (D1) of the protein, was predicted to be pathogenic by structure and sequence-based prediction methods, and was absent in ethnically matched controls. These were consistent with a critical role for the identified missense mutation in the activity of the FGFR1 protein. In conclusion, our identification of a novel missense mutation of the FGFR1 gene associated with a variable expression and incomplete penetrance of CHH extends the known mutational spectrum of this gene and may contribute to the understanding of the pathogenesis of CHH.

Late diagnosis of classic congenital adrenal hyperplasia: long-term consequences during adulthood.

SUMMARY: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders related to enzyme deficiencies in the adrenal steroidogenesis pathway leading to impaired corticosteroid biosynthesis. Depending on the extension of enzyme defect, there may be variable severities of CAH - classic and non-classic. We report the case of a 37-year-old male patient with a previously unknown diagnosis of classic CAH referred to Endocrinology evaluation due to class III obesity and insulin resistance. A high diagnostic suspicion was raised at the first Endocrinology consultation after careful past medical history analysis especially related to the presence of bilateral adrenal myelolipomas and primary infertility. A genetic test confirmed the presence of a variant of the CYP21A2 in homozygous with an enzymatic activity of 0-1%, corresponding to a classic and severe CAH form. Our case represents an unusually late definitive diagnose of classic CAH since the definition was established only during adulthood in the fourth decade of life. The missing diagnosis of classic 21 hydroxylase deficiency during infancy led to important morbidity, with a high impact on patients' quality of life. LEARNING POINTS: Congenital adrenal hyperplasia (CAH) refers to a group of autosomal recessive enzyme disorders responsible for an impaired cortical adrenal hormonal synthesis. CAH may be divided into two major forms: classic and non-classic CAH. If untreated, CAH may be fatal or may be responsible for important multi-organ long-term consequences that can be undervalued during adulthood. Adrenal myelolipomas are associated with chronic exposure to high ACTH levels and continuous androgen hyperstimulation typically found in undertreated CAH patients. Testicular adrenal rest tumours (TART) and primary infertility can be the first manifestation of the disease during adulthood.