S D Joustra, C A Heinen, N Schoenmakers, M Bonomi, B E P B Ballieux, M-O Turgeon, D J Bernard, E Fliers, A S P van Trotsenburg, M Losekoot, L Persani, J M Wit, N R Biermasz, A M Pereira, W Oostdijk
{"title":"IGSF1 缺乏症：从广泛的病例系列中汲取的教训和临床管理建议。","authors":"S D Joustra, C A Heinen, N Schoenmakers, M Bonomi, B E P B Ballieux, M-O Turgeon, D J Bernard, E Fliers, A S P van Trotsenburg, M Losekoot, L Persani, J M Wit, N R Biermasz, A M Pereira, W Oostdijk","doi":"10.1210/jc.2015-3880","DOIUrl":null,"url":null,"abstract":"<p><strong>Context: </strong>Mutations in the immunoglobulin superfamily, member 1 (IGSF1) gene cause the X-linked IGSF1 deficiency syndrome consisting of central hypothyroidism, delayed pubertal testosterone rise, adult macroorchidism, variable prolactin deficiency, and occasionally transient partial GH deficiency. Since our first reports, we discovered 20 new families with 18 new pathogenic IGSF1 mutations.</p><p><strong>Objective: </strong>We aimed to share data on the largest cohort of patients with IGSF1 deficiency to date and formulate recommendations for clinical management.</p><p><strong>Methods: </strong>We collected clinical and biochemical characteristics of 69 male patients (35 children, 34 adults) and 56 female IGSF1 mutation carriers (three children, 53 adults) from 30 unrelated families according to a standardized clinical protocol. At evaluation, boys were treated with levothyroxine in 89%, adult males in 44%, and females in 5% of cases.</p><p><strong>Results: </strong>Additional symptoms in male patients included small thyroid gland volume (74%), high birth weight (25%), and large head circumference (20%). In general, the timing of pubertal testicular growth was normal or even premature, in contrast to a late rise in T levels. Late adrenarche was observed in patients with prolactin deficiency, and adult dehydroepiandrosterone concentrations were decreased in 40%. Hypocortisolism was observed in 6 of 28 evaluated newborns, although cortisol concentrations were normal later. Waist circumference of male patients was increased in 60%, but blood lipids were normal. Female carriers showed low free T4 (FT4) and low-normal FT4 in 18% and 60%, respectively, delayed age at menarche in 31%, mild prolactin deficiency in 22%, increased waist circumference in 57%, and a negative correlation between FT4 concentrations and metabolic parameters.</p><p><strong>Conclusion: </strong>IGSF1 deficiency represents the most common genetic cause of central hypothyroidism and is associated with multiple other characteristics. Based on these results, we provide recommendations for mutational analysis, endocrine work-up, and long-term care.</p>","PeriodicalId":39865,"journal":{"name":"中国肿瘤临床","volume":"2 1","pages":"1627-36"},"PeriodicalIF":0.0000,"publicationDate":"2016-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880178/pdf/","citationCount":"0","resultStr":"{\"title\":\"IGSF1 Deficiency: Lessons From an Extensive Case Series and Recommendations for Clinical Management.\",\"authors\":\"S D Joustra, C A Heinen, N Schoenmakers, M Bonomi, B E P B Ballieux, M-O Turgeon, D J Bernard, E Fliers, A S P van Trotsenburg, M Losekoot, L Persani, J M Wit, N R Biermasz, A M Pereira, W Oostdijk\",\"doi\":\"10.1210/jc.2015-3880\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Context: </strong>Mutations in the immunoglobulin superfamily, member 1 (IGSF1) gene cause the X-linked IGSF1 deficiency syndrome consisting of central hypothyroidism, delayed pubertal testosterone rise, adult macroorchidism, variable prolactin deficiency, and occasionally transient partial GH deficiency. Since our first reports, we discovered 20 new families with 18 new pathogenic IGSF1 mutations.</p><p><strong>Objective: </strong>We aimed to share data on the largest cohort of patients with IGSF1 deficiency to date and formulate recommendations for clinical management.</p><p><strong>Methods: </strong>We collected clinical and biochemical characteristics of 69 male patients (35 children, 34 adults) and 56 female IGSF1 mutation carriers (three children, 53 adults) from 30 unrelated families according to a standardized clinical protocol. At evaluation, boys were treated with levothyroxine in 89%, adult males in 44%, and females in 5% of cases.</p><p><strong>Results: </strong>Additional symptoms in male patients included small thyroid gland volume (74%), high birth weight (25%), and large head circumference (20%). In general, the timing of pubertal testicular growth was normal or even premature, in contrast to a late rise in T levels. Late adrenarche was observed in patients with prolactin deficiency, and adult dehydroepiandrosterone concentrations were decreased in 40%. Hypocortisolism was observed in 6 of 28 evaluated newborns, although cortisol concentrations were normal later. Waist circumference of male patients was increased in 60%, but blood lipids were normal. Female carriers showed low free T4 (FT4) and low-normal FT4 in 18% and 60%, respectively, delayed age at menarche in 31%, mild prolactin deficiency in 22%, increased waist circumference in 57%, and a negative correlation between FT4 concentrations and metabolic parameters.</p><p><strong>Conclusion: </strong>IGSF1 deficiency represents the most common genetic cause of central hypothyroidism and is associated with multiple other characteristics. Based on these results, we provide recommendations for mutational analysis, endocrine work-up, and long-term care.</p>\",\"PeriodicalId\":39865,\"journal\":{\"name\":\"中国肿瘤临床\",\"volume\":\"2 1\",\"pages\":\"1627-36\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2016-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880178/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"中国肿瘤临床\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1210/jc.2015-3880\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2016/2/3 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"中国肿瘤临床","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1210/jc.2015-3880","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2016/2/3 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"Medicine","Score":null,"Total":0}
IGSF1 Deficiency: Lessons From an Extensive Case Series and Recommendations for Clinical Management.
Context: Mutations in the immunoglobulin superfamily, member 1 (IGSF1) gene cause the X-linked IGSF1 deficiency syndrome consisting of central hypothyroidism, delayed pubertal testosterone rise, adult macroorchidism, variable prolactin deficiency, and occasionally transient partial GH deficiency. Since our first reports, we discovered 20 new families with 18 new pathogenic IGSF1 mutations.
Objective: We aimed to share data on the largest cohort of patients with IGSF1 deficiency to date and formulate recommendations for clinical management.
Methods: We collected clinical and biochemical characteristics of 69 male patients (35 children, 34 adults) and 56 female IGSF1 mutation carriers (three children, 53 adults) from 30 unrelated families according to a standardized clinical protocol. At evaluation, boys were treated with levothyroxine in 89%, adult males in 44%, and females in 5% of cases.
Results: Additional symptoms in male patients included small thyroid gland volume (74%), high birth weight (25%), and large head circumference (20%). In general, the timing of pubertal testicular growth was normal or even premature, in contrast to a late rise in T levels. Late adrenarche was observed in patients with prolactin deficiency, and adult dehydroepiandrosterone concentrations were decreased in 40%. Hypocortisolism was observed in 6 of 28 evaluated newborns, although cortisol concentrations were normal later. Waist circumference of male patients was increased in 60%, but blood lipids were normal. Female carriers showed low free T4 (FT4) and low-normal FT4 in 18% and 60%, respectively, delayed age at menarche in 31%, mild prolactin deficiency in 22%, increased waist circumference in 57%, and a negative correlation between FT4 concentrations and metabolic parameters.
Conclusion: IGSF1 deficiency represents the most common genetic cause of central hypothyroidism and is associated with multiple other characteristics. Based on these results, we provide recommendations for mutational analysis, endocrine work-up, and long-term care.
期刊介绍：
CHINESE JOURNAL OF CLINICAL ONCOLOGY has become a good teacher and companion for guiding the workers of medical oncology, with high creativity, science, practice and readability. Relying on the Chinese edition of CJCO and with first class international publication as its object, the staff of the English edition editorial office fully exert their own predominance, and highlight the principle and characteristics of the journal. Under the guidance and support of senior oncologists and their many colleagues, the English edition of CJCO will, we hope, provide a way for the English speaking would to learn about Chinese research in the field of Oncology.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
