著者

Nobutake Matsuo Tomohiro Ishii John I Takayama Masayuki Miwa Tomonobu Hasegawa

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ14-0069, (Released:2014-06-13)

被引用文献数

4 21

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The present study set forth the reference values for penile size and determined the prevalence of buried penis in Japanese full-term newborns. The stretched penile length was measured and the presence of buried penis was assessed at 1-7 days of age in 547 Japanese full-term newborn infants born between 2008 and 2012 in Tokyo. The stretched penile lengths were compared at 1-12 hours and 1-7 days of age in 63 infants and by two observers in 73 infants to estimate postnatal changes and interobserver variation, respectively. The mean stretched penile length was 3.06 cm (SD, 0.26; 95% confidence interval [CI], 3.04-3.08) and the mean ratio of penile length to body length was 6.24×100-1 (SD, 0.55×100-1), both of which were significantly smaller than those in Caucasian newborn infants. Buried penis was identified in 20 of 547 infants (3.7%; 95% CI, 2.1-5.2%). The first measurements of penile length at 1-12 hours were significantly smaller than the next measurements at 1-7 days (95% CI of the difference, 0.22-0.34). The 95% CI for the limits of agreement in the penile lengths measured by the two observers was -0.58 to -0.40 for the lower limit and 0.33 to 0.51 for the upper limit. These findings indicate that the penile length should be assessed after 24 hours of age by the reference standard of the same ethnicity for identifying micropenis and that buried penis is not uncommon in Japanese full-term newborns.

著者

Goro Sasaki Tomohiro Ishii Naoaki Hori Naoko Amano Keiko Homma Seiji Sato Tomonobu Hasegawa

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.66, no.9, pp.837-842, 2019 (Released:2019-09-28)

参考文献数

30

被引用文献数

3 11

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Steroid 5α-reductase type 2 deficiency (5αRD2) is a congenital disorder of sex development caused by impairment of conversion from testosterone (T) to 5α-dihydrotestosterone (DHT). DHT deficiency leads to various degrees of undervirilized external genitalia including micropenis, primarily correlated with mutations of the SRD5A2 gene that encodes 5α-reductase type 2. Four Japanese boys with isolated micropenis were diagnosed as 5αRD2 by elevated ratios of serum T/DHT, and decreased ratios of urinary 5α/5β-reduced steroid metabolites. Genetic analyses for SRD5A2 identified that the four patients shared a hypomorphic mutation R227Q that has a residual activity related to the mild-form of 5αRD2. For prepubertal micropenis, DHT was transdermally applied to the four patients at the ages of 4–11 year, increasing a median of stretched penile lengths (SPLs) from 2.6 cm (–2.5 SD) to 4.4 cm (–0.2 SD). Nevertheless, the post-pubertal penile growth was apparently retarded, despite normal levels of T secreted from well-developed testes. The second course of DHT treatment underwent at ages of 12–18 year, but unable to normalize SPLs at a range of 6.0 to 7.0 cm (–3.4 to –2.4 SD). The prostate volumes of two patients were variable at 8.1 and 21 cm3, and a sperm cell count of one patient was normal as young adult. DHT treatment contributes to development of the penis and prostate, which are favorable for the potential fertility of 5αRD2 adults. Meanwhile, the retarded penile growth and a risk of prostate overgrowth may complicate the post-pubertal management with DHT for 5αRD2 males.

著者

Satoshi Narumi Larry A Fox Keisuke Fukudome Zenichi Sakaguchi Chiho Sugisawa Kiyomi Abe Kaori Kameyama Tomonobu Hasegawa

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ17-0194, (Released:2017-09-01)

被引用文献数

10

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Thyroid peroxidase (TPO) deficiency, caused by biallelic TPO mutations, is a well-established genetic form of congenital hypothyroidism (CH). More than 100 patients have been published, and the patients have been diagnosed mostly in the frame of newborn screening (NBS) programs. Correlation between clinical phenotypes and TPO activity remains unclear. Here, we report clinical and molecular findings of two unrelated TPO mutation-carrying mildly hypothyroid patients. The two patients were born at term after an uneventful pregnancy and delivery, and were NBS negative. They sought medical attention due to goiter at age 8 years. Evaluation of the thyroid showed mild elevation of serum TSH levels, normal or slightly low serum T4 levels, high serum T3 to T4 molar ratio, high serum thyroglobulin levels, and high thyroidal 123I uptake. We performed next-generation sequencing-based genetic screening, and found that one patient was compound heterozygous for two novel TPO mutations (p.Asp224del; c.820-2A>G), and the other was homozygous for a previously known mutation (p.Trp527Cys). In vitro functional analyses using HEK293 cells showed that the two amino acid-altering mutations (p.Asp224del and p.Trp527Cys) caused partial loss of the enzymatic activity. In conclusion, we report that TPO mutations with residual activity are associated with mild TPO deficiency, which is clinically characterized by marked goiter, mild TSH elevation, high serum T3 to T4 molar ratio, and high serum thyroglobulin levels. Our findings illuminate the hitherto under-recognized correlation between clinical phenotypes and residual enzymatic activity among patients with TPO deficiency.

著者

Satoshi Narumi Tomonobu Hasegawa

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ15-0131, (Released:2015-03-21)

被引用文献数

1 9

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Genetic defects of hormone receptors are the most common form of end-organ hormone resistance. One example of such defects is TSH resistance, which is caused by biallelic inactivating mutations in the TSH receptor gene (TSHR). TSH, a master regulator of thyroid functions, affects virtually all cellular processes involving thyroid hormone production, including thyroidal iodine uptake, thyroglobulin iodination, reuptake of iodinated thyroglobulin and thyroid cell growth. Resistance to TSH results in defective thyroid hormone production from the neonatal period, namely congenital hypothyroidism. Classically, clinical phenotypes of TSH resistance due to inactivating TSHR mutations were thought to vary depending on the residual mutant receptor activity. Nonfunctional mutations in the two alleles produce severe thyroid hypoplasia with overt hypothyroidism (uncompensated TSH resistance), while hypomorphic mutations in at least one allele produce normal-sized thyroid gland with preserved hormone-producing capacity (compensated TSH resistance). More recently, a new subgroup of TSH resistance (nonclassic TSH resistance) that is characterized by paradoxically high thyroidal iodine uptake has been reported. In this article, the pathophysiology and clinical features of TSH resistance due to inactivating TSHR mutations are reviewed, with particular attention to the nonclassic form.

著者

Yoshihiro Miyake Keiko Tanaka Tetsuo Nishikawa Mitsuhide Naruse Ryoichi Takayanagi Hironobu Sasano Yoshiyu Takeda Hirotaka Shibata Masakatsu Sone Fumitoshi Satoh Masanobu Yamada Hajime Ueshiba Takuyuki Katabami Yasumasa Iwasaki Hirotoshi Tanaka Yusuke Tanahashi Shigeru Suzuki Tomonobu Hasegawa Noriyuki Katsumata Toshihiro Tajima Toshihiko Yanase

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ13-0353, (Released:2013-09-28)

被引用文献数

7 36

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The Research Committee of Disorders of Adrenal Hormones, Japan, undertook a nationwide epidemiological study of primary aldosteronism (PA). The present study was undertaken as a part of this study to reveal the relationship between type of treatment and the prognosis of PA. In the primary survey, 4161 patients with PA during the period January 1, 2003-December 31, 2007 were reported from 3252 departments of internal medicine, pediatrics and urology. In the secondary survey, a questionnaire that requested detailed clinical information on individual patients was sent to those departments reporting patients in the primary survey. In total, data on 1706 patients with PA were available in the present study. Among patients with bilateral or unilateral aldosterone-producing adenoma, after adjustment for age at which prognosis was examined, sex, surgical treatment and medical treatment, surgical treatment was significantly associated with amelioration of hypertension (adjusted odds ratio [OR]: 0.47 [95% confidence interval (CI): 0.29–0.77]) and hypokalemia (adjusted OR: 0.17 [95% CI: 0.11–0.29]). No significant relationship was observed between medical treatment and such prognosis in this group of patients. Among patients with bilateral or unilateral adrenal hyperplasia, surgical, but not medical, treatment was significantly associated with amelioration of hypokalemia (adjusted OR: 0.23 [95% CI: 0.06–0.74]), while there was no relationship between surgical or medical treatment and the prognosis of hypertension. In conclusion, surgery offered a better prognosis of PA than medication with regards to hypertension and hypokalemia, with the limitation that a new anti-aldosterone drug, eplerenone, was not available during the study period.