Clinical and molecular analyses of isolated central congenital hypothyroidism based on a survey conducted in Japan

IF 1.3 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM Endocrine journal Pub Date : 2024-03-08 DOI:10.1507/endocrj.ej23-0391
Nao Shibata, Chikahiko Numakura, Takashi Hamajima, Kenichi Miyako, Ikuma Fujiwara, Jun Mori, Akihiko Saitoh, Keisuke Nagasaki
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Abstract

Central congenital hypothyroidism (CH) can occur as an isolated deficiency or as part of combined pituitary hormone deficiency. Unlike primary CH, central CH cannot be detected by newborn screening (NBS) using dry filter paper blood TSH levels, and early diagnosis remains challenging. In this study, the clinical and genetic backgrounds of patients with isolated central CH were determined through a questionnaire-based survey among members of the Japanese Society for Pediatric Endocrinology. The known causes of isolated central CH were studied in 14 patients, including six with previously reported patient data. The results revealed IGSF1 and TBL1X pathogenic variants in nine and one patient, respectively. All six patients with low free thyroxine (FT4) levels detected in NBS carried IGSF1 pathogenic variants. Five patients with isolated central CH diagnosed after 3 months of age were variant-negative, except for one female patient with a heterozygous IGSF1 variant. Two of the four variant-negative patients and a variant-positive patient were diagnosed with pituitary hypoplasia. One and two patients with IGSF1 variant had obesity and intellectual disability, respectively. Left amblyopia was identified in the patient with a TBL1X variant. The study revalidated that IGSF1 variants comprise the most frequent pathogenic variant in patients with isolated central CH in Japan. The neonatal period is the optimal time for the diagnosis of central CH, particularly IGSF1 abnormalities, and the introduction of T4 screening should be considered in the future, taking cost-effectiveness into consideration.

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基于日本调查的孤立性中枢性先天性甲状腺功能减退症的临床和分子分析
中枢性先天性甲状腺功能减退症(CH)可能是一种孤立的甲状腺功能缺乏症,也可能是合并垂体激素缺乏症的一部分。与原发性先天性甲状腺功能减退症不同,中枢性先天性甲状腺功能减退症无法通过新生儿筛查(NBS)的干滤纸血TSH水平检测出来,因此早期诊断仍具有挑战性。本研究通过对日本儿科内分泌学会成员进行问卷调查,确定了孤立性中枢性CH患者的临床和遗传背景。研究了14例孤立性中枢性CH患者的已知病因,其中6例患者的数据此前已有报道。结果显示,分别有9名和1名患者存在IGSF1和TBL1X致病变体。在NBS中检测到游离甲状腺素(FT4)水平较低的6名患者均携带IGSF1致病变体。除了一名女性患者携带杂合子IGSF1变异体外,5名3个月后确诊的孤立性中枢性CH患者均为变异体阴性。四名变异阴性患者中的两名和一名变异阳性患者被诊断为垂体发育不全。一名和两名IGSF1变异体患者分别患有肥胖症和智力障碍。TBL1X变异体患者出现左侧弱视。该研究再次证实,IGSF1变异是日本孤立性中枢性CH患者中最常见的致病变异。新生儿期是诊断中枢性CH,尤其是IGSF1异常的最佳时期,未来应考虑引入T4筛查,并将成本效益考虑在内。
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来源期刊
Endocrine journal
Endocrine journal 医学-内分泌学与代谢
CiteScore
4.30
自引率
5.00%
发文量
224
审稿时长
1.5 months
期刊介绍: Endocrine Journal is an open access, peer-reviewed online journal with a long history. This journal publishes peer-reviewed research articles in multifaceted fields of basic, translational and clinical endocrinology. Endocrine Journal provides a chance to exchange your ideas, concepts and scientific observations in any area of recent endocrinology. Manuscripts may be submitted as Original Articles, Notes, Rapid Communications or Review Articles. We have a rapid reviewing and editorial decision system and pay a special attention to our quick, truly scientific and frequently-citable publication. Please go through the link for author guideline.
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