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Noonan syndrome (NS) is caused by pathogenic variants in genes encoding components of the RAS/MAPK pathway and presents with a number of symptoms, including characteristic facial features, congenital heart diseases, and short stature. Advances in genetic analyses have contributed to the identification of pathogenic genes in NS as well as genotype-phenotype relationships; however, updated evidence for the detection rate of pathogenic genes with the inclusion of newly identified genes is lacking in Japan. Accordingly, we examined the genetic background of 116 individuals clinically diagnosed with NS and the frequency of short stature. We also investigated genotype-phenotype relationships in the context of body mass index (BMI). Genetic testing revealed the responsible variants in 100 individuals (86%), where PTPN11 variants were the most prevalent (43%) and followed by SOS1 (12%) and RIT1 (9%). The frequency of short stature was the lowest in subjects possessing RIT1 variants. No genotype-phenotype relationships in BMI were observed among the genotypes. In conclusion, this study provides evidence for the detection rate of pathogenic genes and genotype-phenotype relationships in Japanese patients with NS, which will be of clinical importance for accelerating our understanding of the genetic backgrounds of Japanese patients with NS. [ABSTRACT FROM AUTHOR]

As evidenced by the intact histology of the testes during infancy, testicular differentiation during the prenatal period occurs normally in individuals with 5 alpha-reductase type 2 deficiency (5αRD); however, a majority of these individuals suffer from azoospermia or oligospermia during adulthood, indicating that impaired spermatogenesis occurs postnatally. Although the accompanying cryptorchidism may be partly responsible for this process, the underlying mechanisms remain largely unknown. To address this issue, we retrospectively compared the histological findings of descended testes in a 3-mo-old patient and undescended testes in an 18-yr-old patient with 5αRD. In the latter, testicular histology was compared to that of cryptorchid testes obtained from five adolescent patients without endocrinological abnormalities. Histological findings of a 3-mo-old patient revealed normal number of germ cells with intact seminiferous tubules. In contrast, an 18-yr-old patient showed marked reduction in germ cell number and atrophic seminiferous tubules. The findings were very similar to those observed in cryptorchid testes without endocrinological abnormalities. These findings suggest that the decrease in germ cells in 5αRD patients may be at least partly caused by accompanying cryptorchidism. As the number of germ cells did not decrease during the infantile period, early orchiopexy is recommended to prevent a decrease in germ cell number and preserve fertility. [ABSTRACT FROM AUTHOR]

Congenital adrenal hyperplasia is a category of disorders characterized by impaired adrenocortical steroidogenesis. The most frequent disorder of congenital adrenal hyperplasia is 21-hydroxylase deficiency, which is caused by pathogenic variants of CAY21A2 and is prevalent between 1 in 18,000 and 20,000 in Japan. The clinical guidelines for 21-hydroxylase deficiency in Japan have been revised twice since a diagnostic handbook in Japan was published in 1989. On behalf of the Japanese Society for Pediatric Endocrinology, the Japanese Society for Mass Screening, the Japanese Society for Urology, and the Japan Endocrine Society, the working committee updated the guidelines for the diagnosis and treatment of 21-hydroxylase deficiency published in 2014, based on recent evidence and knowledge related to this disorder. The recommendations in the updated guidelines can be applied in clinical practice considering the risks and benefits to each patient. [ABSTRACT FROM AUTHOR]

Selenium (Se) is an essential trace element that is involved in numerous biological processes in the form of a selenoprotein such as iodothyronine deiodinase (DIO). Se deficiency may prevent the conversion of T4 to T3 through reducing DIO expression and thereby affecting thyroid hormone status. However, this has not been well documented in humans. In this study, to clarify the association between Se and thyroid hormone status, we investigated the thyroid hormone levels in patients with severe Se deficiency (< 2 μg/dl). Severe Se deficiency was associated with increases in free T4 levels, but not with decreases and increases in free T3 and thyroid stimulating hormone (TSH) levels, respectively. Increases in free T4 levels during Se deficiency were reduced with Se supplementation; however, neither free T3 nor TSH levels were affected. Taken together, these findings indicate that free T4 may be a useful biomarker for Se status when serum Se levels are severely low. [ABSTRACT FROM AUTHOR]

Congenital hyperinsulinism is a rare condition and following recent advances in diagnosis and treatment, it was considered necessary to formulate evidence-based clinical practice guidelines reflecting the most recent progress, to guide the practice of neonatologists, pediatric endocrinologists, general pediatricians and pediatric surgeons. These guidelines cover a range of aspects, including general features of congenital hyperinsulinism, diagnostic criteria and tools for diagnosis, first-and second-line medical treatment, criteria for and details of surgical treatment, and future perspectives. These guidelines were generated as a collaborative effort between The Japanese Society for Pediatric Endocrinology and The Japanese Society of Pediatric Surgeons and followed the official procedures of guideline generation to identify important clinical questions, perform a systematic literature review (April 2016), assess the evidence level of each paper, formulate the guidelines and obtain public comments. [ABSTRACT FROM AUTHOR]

The presence of Y chromosome material in patients with disorders of sex development (DSD) has been associated with a high risk of gonadoblastoma. Therefore, gonadectomy is recommended in females with bilateral streak gonads and Y chromosome material. The aim of this study was to present our experience with prophylactic gonadectomy in those patients and evaluate their risk of gonadal tumors. We reviewed the charts of 11 female patients who had bilateral gonadectomy (by laparoscopically in 9 patients, by laparotomy in 2 patients) between 1991 and 2012 at our hospital. Seven patients with Turner syndrome (TS) who carry a Y mosaic karyotype in peripheral blood, 3 patients with Swyer syndrome and one patient with Frasier syndrome were included. All patients had an unambiguous female phenotype. Age at surgery and follow-up ranged from 2 to 23 (mean 11) and 0.5 to 20 (mean 8) yr, respectively. Pathologic examination revealed gonadal tumors in 6 of 11 patients (56%), including 4 with TS, the youngest of which was 2 yr old, one with Swyer syndrome and one with Frasier syndrome. A gonadoblastoma was detected in 8 gonads, and an association of dysgerminoma with gonadoblastoma was detected in 2 gonads. Imaging studies showed no metastasis, and the postoperative course was uneventful in all patients. In our series of DSD patients with bilateral streak gonads and Y chromosome material, the risk of gonadal tumor was high. Considering the early occurrence of gonadoblastoma and its high potential for malignant transformation, early prophylactic gonadectomy is strongly recommended. [ABSTRACT FROM AUTHOR]

CHARGE syndrome is a congenital disorder caused by mutation of the chromodomain helicase DNA binding protein 7 (CHD7) gene and is characterized by multiple anomalies including ocular coloboma, heart defects, choanal atresia, retarded growth and development, genital and/ or urological abnormalities, ear anomalies, and hearing loss. In the present study, 76% of subjects had some type of endocrine disorder: short stature (72%), hypogonadotropic hypogonadism (60%), hypothyroidism (16%), and combined hypopituitarism (8%). A mutation in CHD7 was found in 80% of subjects. Here, we report the phenotypic spectrum of 25 Japanese patients with CHARGE syndrome, including their endocrinological features. [ABSTRACT FROM AUTHOR]