CHARACTERIZATION OF SPONTANEOUS AND INDUCED PUBERTY IN GIRLS WITH TURNER SYNDROME.

OBJECTIVE: To characterize puberty in girls with Turner syndrome (TS) and determine whether specific patient characteristics are associated with the timing of menarche. We also sought to compare spontaneous versus induced puberty in these patients. METHODS: Medical records of girls followed in our Pediatric Endocrine clinic for TS from 2007 to 2015 were reviewed. RESULTS: Fifty-three girls were included, of whom 10 (19%) achieved menarche spontaneously and 43 (81%) received hormone replacement therapy (HRT). Of girls receiving HRT, a younger age at estrogen initiation correlated with a longer time to menarche (P = .02), and a mosaic karyotype was associated with a shorter time to menarche (P = .02), whereas no relationship was seen for body mass index, estrogen regimen, or maternal age at menarche. Nineteen girls (44%) receiving HRT had bleeding on estrogen alone at a wide dose range and were more likely to be on transdermal than oral preparations (P = .01). Girls with spontaneous puberty achieved menarche at a younger age (P<.01) and were more likely to have mosaic TS (P = .02). CONCLUSION: Significant variability in the timing of menarche exists among girls with TS. However, age at pubertal induction and karyotype were significantly correlated with age at menarche in our patients. A wide range of estrogen doses is seen in girls who bleed prior to progesterone, suggesting extreme variability in estrogen sensitivity among patients with TS. Girls achieving spontaneous menarche are younger and more likely to have a mosaic karyotype than those with induced menarche. Large-scale prospective studies are needed to confirm these results. ABBREVIATIONS: BMI = body mass index; HRT = hormone replacement therapy; TS = Turner syndrome.

Hyperphosphatemic familial tumoral calcinosis: genetic models of deficient FGF23 action.

Hyperphosphatemic familial tumoral calcinosis (hFTC) is a rare disorder of phosphate metabolism defined by hyperphosphatemia and ectopic calcifications in various locations. To date, recessive mutations have been described in three genes involving phosphate metabolism: FGF23, GALNT3, and α-Klotho, all of which result in the phenotypic presentation of hFTC. These mutations result in either inadequate intact fibroblast growth factor-23 (FGF23) secretion (FGF23 or GALNT3) or resistance to FGF23 activity at the fibroblast growth factor receptor/α-Klotho complex (α-Klotho). The biochemical consequence of limitations in FGF23 activity includes increased renal tubular reabsorption of phosphate, hyperphosphatemia, and increased production of 1,25-dihydroxyvitamin D. The resultant ectopic calcifications can be painful and debilitating. Medical treatments are targeted toward decreasing intestinal phosphate absorption or increasing phosphate excretion; however, results have been variable and generally limited. Treatments that would increase FGF23 levels or signaling would more appropriately target the genetic etiologies of this disease and perhaps be more effective.

Germ cell neoplasia in situ complicating 17ß-hydroxysteroid dehydrogenase type 3 deficiency.

17ß-hydroxysteroid dehydrogenase type 3 (17ßHSD3) deficiency is an autosomal recessive disorder of male sex development that results in defective testosterone biosynthesis. Although mutations in the cognate HSD17B3 gene cause a spectrum of phenotypic manifestations, the majority of affected patients are genetic males having female external genitalia. Many cases do not present until puberty, at which time peripheral conversion of androgen precursors causes progressive virilization. Measurement of the testosterone-to-androstenedione ratio is useful to screen for 17ßHSD3 deficiency, and genetic analysis can confirm the diagnosis. As some individuals with 17ßHSD3 deficiency transition from a female sex assignment to identifying as males, providers should ensure stable gender identity prior to recommending irreversible treatments. Gonadectomy is indicated to prevent further virilization if a female gender identity is established. The risk of testicular neoplasia is unknown, a point which should be discussed if patients elect to transition into a male gender role.

Collaboration Is Key for Successful Treatment of Youth-Onset Type 2 Diabetes.

Type 2 diabetes (T2D) is increasing in U.S. adolescents, particularly those of ethnic and racial minority groups. Risk factors for youth-onset T2D include obesity, family history of T2D, poor diet, lack of exercise, and poverty. The onset of diabetes-related complications is accelerated in adolescents with T2D compared to adults, and knowledge regarding the optimal way to prevent and slow complications is lacking. Existing treatment options are limited, and research into novel pharmacologic treatments is hindered by lack of sufficient patient population for clinical trials. Health care providers and investigators should collaborate both with each other, and with patients and their communities to build networks that will allow comprehensive evaluation of this disease in order to offer optimal, comprehensive care for these adolescents.

Reproductive Issues in Women with Turner Syndrome.

Turner syndrome is one of the most common chromosomal abnormalities affecting female infants. The severity of clinical manifestations varies and it affects multiple organ systems. Women with Turner syndrome have a 3-fold increase in mortality, which becomes even more pronounced in pregnancy. Reproductive options include adoption or surrogacy, assisted reproductive techniques, and in rare cases spontaneous pregnancy. Risks for women with Turner syndrome during pregnancy include aortic disorders, hepatic disease, thyroid disease, type 2 diabetes, and cesarean section delivery. Providers must be familiar with the risks and recommendations in caring for women with Turner syndrome of reproductive age.