Clinical Pediatric Endocrinology最新文献

Thyroid function in patients with chronic thyroiditis (CT) varies depending on the clinical course. Serum antithyroglobulin antibody (TgAb) and antithyroid peroxidase antibody (TPOAb) levels may be used to predict hypothyroidism in CT. In this retrospective cohort study, patients with CT, defined as having a high TgAb or TPOAb value, were divided into a hypothyroid group (HG) and euthyroid group (EG), after a mean follow-up of 2.5 years. The definitions of the two groups was based on the maximum TSH value from the initial measurement to the most recent follow-up: HG was defined as TSH 10.0 μIU/mL or higher, and EG was defined as TSH < 10.0 μIU/mL. There were 20 and 113 patients in the HG and EG, respectively. There were no significant differences in age, sex, underlying diseases, or TgAb and TPOAb levels between the groups. Receiver operating characteristic curve analyses of TgAb and TPOAb values for predicting thyroid function showed areas under the curve of 0.714 and 0.757, respectively. The value with the highest diagnostic accuracy was 106 IU/mL for TgAb and 16 IU/mL for TPOAb. Thus, TgAb > 106 IU/mL and TPOAb > 16 IU/mL may predict hypothyroidism in children and young adults with CT.

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.

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.

11-Oxyandrogens, such as 11-ketotestosterone (11-KT), 11-ketodihydrotestosterone (11-KDHT), 11β-hydroxytestosterone (11-OHT), 11β-hydroxyandrostenedione (11-OHA4), and 11-KA4, are newly specified human androgens. These 11-oxyandrogens are present in the cord blood and placenta, as well as in the blood of men and women of various ages, and are produced primarily in the adrenal gland. Accumulating evidence suggests that these steroids contribute to androgen excess in patients with 21-hydroxylase deficiency or polycystic ovary syndrome. More importantly, unlike classic androgens, 11-oxyandrogens produced in maternal tumors can pass through the placenta without being converted into estrogens, and cause severe virilization of female fetuses. Thus, overproduction of 11-oxyandrogens represents a new mechanism of 46,XX disorders of sex development. On the other hand, the physiological roles of 11-oxyandrogens remain to be clarified. This mini-review introduces the current understanding of 11-oxyandrogens, from the perspective of pediatric endocrinology.

In Japan, a pituitary-extracted human GH (phGH), Crescormon®, was approved for the treatment of pituitary dwarfism in 1975. The Study Group of Pituitary Dysfunction was organized by the Ministry of Health and Welfare (MHW) in 1973 and prepared the "Diagnostic Handbook: Pituitary Dwarfism" guidelines in 1974. Eligibility assessments for phGH treatment were conducted by the research group on pituitary dwarfism (later the Foundation for Growth Science [FGS] GH Treatment Eligibility Assessment Committee); however, there were 200-300 patients on the waiting list. GH treatment has been financially supported by the Grant-in-Aid Program for Chronic Diseases in Childhood, MHW, since 1974. In 1984, phGH was discontinued in the United States due to reports of the onset of Creutzfeldt-Jakob disease in patients treated with phGH. Japan approved the use of methionyl hGH in 1986 and recombinant hGH in 1988. As a result, the phGH disappeared from the market. The role of the Eligibility Assessment Committee of the FGS shifted to the provision of second opinions about diagnoses and treatment appropriateness. Since then, the indications for GH treatment of pediatric growth disorders have expanded to include other pediatric growth disorders such as Turner syndrome, achondroplasia/hypochondroplasia, etc.

The health-related quality of life is reduced in patients with achondroplasia (ACH) and hypochondroplasia (HCH); however, the detailed inconveniences in the daily living and individual adaptations have not been elucidated. This study aimed to evaluate the inconvenience and adaptation in patients with ACH/HCH. A cross-sectional study was conducted in patients with ACH/HCH aged 20 yr or older. Questionnaires were sent to 567 patients (described 86) with a medical history at the co-authors' institutions or who were registered at the patients' association with ACH in Japan. The questionnaire included a free description format for the inconveniences and adaptations in daily living; a content analysis was performed. The recorded inconveniences included 148 physical, 84 mental, and 52 social problems. Patients who underwent spine surgery had significantly more recorded physical problems than those who did not (p < 0.05). Pain and numbness were significantly higher in patients aged ≥ 50 yr (p < 0.05). The 160 and 1 adaptations were for physical and social problems, respectively. No patient adaptation was found for mental health problems. Individual adaptations by ACH/HCH patients can improve only some aspects of physical and social problems. Multilateral social support is needed to resolve patients' issues.

Recent studies have indicated that heterozygous loss-of-function variants in fibroblast growth factor receptor 1 (FGFR1) are involved in the development of congenital hypogonadotropic hypogonadism and combined pituitary hormone deficiency (CPHD). We encountered a Japanese boy with short stature and pubertal failure. Endocrine studies showed GH, TSH, and LH/FSH deficiencies, and brain magnetic resonance imaging delineated hypoplastic anterior pituitary and ectopic posterior pituitary. The patient was treated with GH, l-thyroxine, and hCG/rFSH. Next-generation sequencing panel for pituitary dysfunction identified a probably weak disease-associated heterozygous missense variant in FGFR1 (NM_023110.3:c.176A>T:p.(Asp59Val)), together with a probably non-deleterious heterozygous missense variant in KISS1R (NM_032551.5:c.769G>C:p.(Val257Leu)). We also review six previously reported CHPD patients with probably deleterious FGFR1 variants. The data, in conjunction with the previously reported cases, argue for the relevance of FGFR1 variants to the development of CPHD.

[This corrects the article DOI: 10.1297/cpe.25.71.].