18 research outputs found
Contour of the GnRH Pulse Independently Modulates Gonadotropin Secretion in the Human Male
Role of Seminiferous Tubular Development in Determining the FSH versus LH Responsiveness to GnRH in Early Sexual Maturation
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Comparison of Short and Long-Term Outcomes of Metabolic and Bariatric Surgery in Adolescents and Adults
Objective: We sought to compare the short and long-term outcomes of MBS in adolescents vs. adults who have undergone a Roux-en-Y gastric bypass (RYGB) or Sleeve gastrectomy (SG). Design: Retrospective cohort study. Setting: Single tertiary care academic referral center. Participants: One hundred fifty adolescent (≤ 21-years) and adult (>21-years) subjects with severe obesity between 15 and 70 years of age who underwent RYGB or SG. Outcomes: Metabolic parameters, weight and height measures were obtained pre-and post-surgery (at 3 and 6 months, and then annually for 4 years). Results: Median pre-surgical body mass index (BMI) was higher in adolescents (n = 76) vs. adults (n = 74): 50 (45-57) vs. 44 (40-51) kg/m2 (p < 0.0001). However, obesity related complications were greater in adults vs. adolescents: 66 vs. 21% had hypertension, 68 vs. 28% had dyslipidemia, and 42 vs. 21% had type 2 diabetes mellitus (all p < 0.010). % BMI reduction and % weight loss (WL) were greater in adolescents vs. adults at all time points (p < 0.050). %WL was higher in adolescents who underwent SG at each time point (p < 0.050), and trended higher among adolescents who underwent RYGB (p = 0.060), compared to adults with the respective procedure. Follow-up data showed greater resolution of type 2 diabetes and hypertension in adolescents than adults (87.5 vs. 54.8%; p = 0.04, and 68.7 vs. 35.4%; p = 0.040). Conclusion: Adolescents compared to adults had greater reductions in BMI and weight, even at 4 years, and greater resolution of type 2 diabetes and hypertension. Earlier intervention in the treatment of severe obesity with MBS may lead to better outcomes.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes
BACKGROUND: Kallmann's syndrome (KS) is a clinically and genetically heterogeneous disorder consisting of idiopathic hypogonadotropic hypogonadism (IHH) and anosmia. Mutations in KAL1 causing the X-linked form of KS have been identified in 10% of all KS patients and consistently result in a severe reproductive phenotype. KAL1 gene encodes for anosmin-1, a key protein involved in olfactory and GnRH neuronal migration through a putative interaction with FGFR1. Heterozygous mutations in the FGFR1 gene accompanied by a high frequency of cleft palate and other facial dysmorphisms were recently identified in 8% of a large KS cohort, yet the reproductive phenotype of KS patients harboring FGFR1 mutations has not been described. RESULTS: One hundred and fifty probands with KS (130 males and 20 females) were studied to determine the frequency and distribution of FGFR1 mutations and their detailed reproductive phenotypes. Fifteen heterozygous mutations in unrelated probands were identified. Twelve missense mutations (p.R78C, p.V102I, p.D224H, p.G237D, p.R254Q, p.V273M, p.E274G, p.Y339C, p.S346C, p.I538V, p.G703S and p.G703R) were distributed among the first, second and third immunoglobulin-like domains (D1-D3), as well as the tyrosine kinase domain (TKD). The mutations Y339C and S346C are located in exon 8B and code for the isoform FGFR1c. Additionally, two nonsense mutations (p.T585X and p.R622X) were documented in the TKD of the protein. A wide spectrum of reproductive function was observed among KS probands including: (1) a severe phenotype demonstrated by microphallus, cryptorchidism, no pubertal development, undetectable serum gonadotropins and low serum testosterone (T) and inhibin B; (2) partial pubertal development; (3) the fertile eunuch variant of IHH with normal testicular size and active spermatogenesis with a reversal of HH after T therapy. In addition, we found an even wider spectrum of reproductive function within pedigrees carrying an FGFR1 mutation ranging from IHH to delayed puberty to normal reproductive function (anosmia only or asymptomatic carriers). These observations strongly suggest a role for other genes that modify the phenotype of FGFR1 mutations. CONCLUSION: KS patients and family members carrying an FGFR1 mutation present a broad spectrum of pubertal development in contrast to the almost uniform severe clinical phenotype described in KS subjects with a KAL1 mutation. Additionally, this report implicates the isoform FGFR1c in the pathogenesis of K