Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult men
BackgroundDelayed puberty in males is almost invariably associated with constitutional delay of growth and puberty (CDGP) or congenital hypogonadotrophic hypogonadism (CHH). Establishing the cause at presentation is challenging, with “red flag” features of CHH commonly overlooked. Thus, several mark...
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.1076984/full |
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| author | Ali Abbara Ali Abbara Kanyada Koysombat Maria Phylactou Maria Phylactou Pei Chia Eng Pei Chia Eng Sophie Clarke Sophie Clarke Alexander N. Comninos Alexander N. Comninos Lisa Yang Lisa Yang Chioma Izzi-Engbeaya Chioma Izzi-Engbeaya Simon Hanassab Simon Hanassab Neil Smith Channa N. Jayasena Channa N. Jayasena Cheng Xu Cheng Xu Richard Quinton Richard Quinton Nelly Pitteloud Nelly Pitteloud Gerhard Binder Ravinder Anand-Ivell Richard Ivell Waljit S. Dhillo Waljit S. Dhillo |
| author_facet | Ali Abbara Ali Abbara Kanyada Koysombat Maria Phylactou Maria Phylactou Pei Chia Eng Pei Chia Eng Sophie Clarke Sophie Clarke Alexander N. Comninos Alexander N. Comninos Lisa Yang Lisa Yang Chioma Izzi-Engbeaya Chioma Izzi-Engbeaya Simon Hanassab Simon Hanassab Neil Smith Channa N. Jayasena Channa N. Jayasena Cheng Xu Cheng Xu Richard Quinton Richard Quinton Nelly Pitteloud Nelly Pitteloud Gerhard Binder Ravinder Anand-Ivell Richard Ivell Waljit S. Dhillo Waljit S. Dhillo |
| author_sort | Ali Abbara |
| collection | DOAJ |
| description | BackgroundDelayed puberty in males is almost invariably associated with constitutional delay of growth and puberty (CDGP) or congenital hypogonadotrophic hypogonadism (CHH). Establishing the cause at presentation is challenging, with “red flag” features of CHH commonly overlooked. Thus, several markers have been evaluated in both the basal state or after stimulation e.g. with gonadotrophin releasing hormone agonist (GnRHa).Insulin-like peptide 3 (INSL3) is a constitutive secretory product of Leydig cells and thus a possible candidate marker, but there have been limited data examining its role in distinguishing CDGP from CHH. In this manuscript, we assess INSL3 and inhibin B (INB) in two cohorts: 1. Adolescent boys with delayed puberty due to CDGP or CHH and 2. Adult men, both eugonadal and having CHH.Materials and methodsRetrospective cohort studies of 60 boys with CDGP or CHH, as well as 44 adult men who were either eugonadal or had CHH, in whom INSL3, INB, testosterone and gonadotrophins were measured.Cohort 1: Boys with delayed puberty aged 13-17 years (51 with CDGP and 9 with CHH) who had GnRHa stimulation (subcutaneous triptorelin 100mcg), previously reported with respect to INB.Cohort 2: Adult cohort of 44 men (22 eugonadal men and 22 men with CHH), previously reported with respect to gonadotrophin responses to kisspeptin-54.ResultsMedian INSL3 was higher in boys with CDGP than CHH (0.35 vs 0.15 ng/ml; p=0.0002). Similarly, in adult men, median INSL3 was higher in eugonadal men than CHH (1.08 vs 0.05 ng/ml; p<0.0001). However, INSL3 more accurately differentiated CHH in adult men than in boys with delayed puberty (auROC with 95% CI in adult men: 100%, 100-100%; boys with delayed puberty: 86.7%, 77.7-95.7%).Median INB was higher in boys with CDGP than CHH (182 vs 59 pg/ml; p<0.0001). Likewise, in adult men, median INB was higher in eugonadal men than CHH (170 vs 36.5 pg/ml; p<0.0001). INB performed better than INSL3 in differentiating CHH in boys with delayed puberty (auROC 98.5%, 95.9-100%), than in adult men (auROC 93.9%, 87.2-100%).ConclusionINSL3 better identifies CHH in adult men, whereas INB better identifies CHH in boys with delayed puberty. |
| first_indexed | 2024-04-13T13:47:42Z |
| format | Article |
| id | doaj.art-65865504228c43389686a6059514ae8a |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-13T13:47:42Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-65865504228c43389686a6059514ae8a2022-12-22T02:44:25ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-11-011310.3389/fendo.2022.10769841076984Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult menAli Abbara0Ali Abbara1Kanyada Koysombat2Maria Phylactou3Maria Phylactou4Pei Chia Eng5Pei Chia Eng6Sophie Clarke7Sophie Clarke8Alexander N. Comninos9Alexander N. Comninos10Lisa Yang11Lisa Yang12Chioma Izzi-Engbeaya13Chioma Izzi-Engbeaya14Simon Hanassab15Simon Hanassab16Neil Smith17Channa N. Jayasena18Channa N. Jayasena19Cheng Xu20Cheng Xu21Richard Quinton22Richard Quinton23Nelly Pitteloud24Nelly Pitteloud25Gerhard Binder26Ravinder Anand-Ivell27Richard Ivell28Waljit S. Dhillo29Waljit S. Dhillo30Section of Investigative Medicine, Imperial College London, London, United KingdomDepartment of Endocrinology, Imperial College Healthcare National Health Service (NHS) Trust, London, United KingdomSection of Investigative Medicine, Imperial College London, London, United KingdomSection of Investigative Medicine, Imperial College London, London, United KingdomDepartment of Endocrinology, Imperial College Healthcare National Health Service (NHS) Trust, London, United KingdomSection of Investigative Medicine, Imperial College London, London, United KingdomDepartment of Endocrinology, Imperial College Healthcare National Health Service (NHS) Trust, London, United KingdomSection of Investigative Medicine, Imperial College London, London, United KingdomDepartment of Endocrinology, Imperial College Healthcare National Health Service (NHS) Trust, London, United KingdomSection of Investigative Medicine, Imperial College London, London, United KingdomDepartment of Endocrinology, Imperial College Healthcare National Health Service (NHS) Trust, London, United KingdomSection of Investigative Medicine, Imperial College London, London, United KingdomDepartment of Endocrinology, Imperial College Healthcare National Health Service (NHS) Trust, London, United KingdomSection of Investigative Medicine, Imperial College London, London, United KingdomDepartment of Endocrinology, Imperial College Healthcare National Health Service (NHS) Trust, London, United KingdomSection of Investigative Medicine, Imperial College London, London, United KingdomDepartment of Computing, Imperial College London, London, United KingdomKallmann Syndrome Patient Support Group, London, United KingdomSection of Investigative Medicine, Imperial College London, London, United KingdomDepartment of Endocrinology, Imperial College Healthcare National Health Service (NHS) Trust, London, United KingdomService of Endocrinology, Diabetology & Metabolism, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SwitzerlandFaculty of Biology and Medicine, University of Lausanne, Lausanne, SwitzerlandTranslational & Clinical Research Institute, University of Newcastle-upon-Tyne, Newcastle, United KingdomThe Newcastle upon Tyne Hospitals National Health Service (NHS) Foundation Trust, Newcastle, United KingdomService of Endocrinology, Diabetology & Metabolism, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SwitzerlandFaculty of Biology and Medicine, University of Lausanne, Lausanne, SwitzerlandDepartment of Paediatric Endocrinology, University Children’s Hospital, Tübingen, Germany0School of Biosciences, University of Nottingham, Nottingham, United Kingdom0School of Biosciences, University of Nottingham, Nottingham, United KingdomSection of Investigative Medicine, Imperial College London, London, United KingdomDepartment of Endocrinology, Imperial College Healthcare National Health Service (NHS) Trust, London, United KingdomBackgroundDelayed puberty in males is almost invariably associated with constitutional delay of growth and puberty (CDGP) or congenital hypogonadotrophic hypogonadism (CHH). Establishing the cause at presentation is challenging, with “red flag” features of CHH commonly overlooked. Thus, several markers have been evaluated in both the basal state or after stimulation e.g. with gonadotrophin releasing hormone agonist (GnRHa).Insulin-like peptide 3 (INSL3) is a constitutive secretory product of Leydig cells and thus a possible candidate marker, but there have been limited data examining its role in distinguishing CDGP from CHH. In this manuscript, we assess INSL3 and inhibin B (INB) in two cohorts: 1. Adolescent boys with delayed puberty due to CDGP or CHH and 2. Adult men, both eugonadal and having CHH.Materials and methodsRetrospective cohort studies of 60 boys with CDGP or CHH, as well as 44 adult men who were either eugonadal or had CHH, in whom INSL3, INB, testosterone and gonadotrophins were measured.Cohort 1: Boys with delayed puberty aged 13-17 years (51 with CDGP and 9 with CHH) who had GnRHa stimulation (subcutaneous triptorelin 100mcg), previously reported with respect to INB.Cohort 2: Adult cohort of 44 men (22 eugonadal men and 22 men with CHH), previously reported with respect to gonadotrophin responses to kisspeptin-54.ResultsMedian INSL3 was higher in boys with CDGP than CHH (0.35 vs 0.15 ng/ml; p=0.0002). Similarly, in adult men, median INSL3 was higher in eugonadal men than CHH (1.08 vs 0.05 ng/ml; p<0.0001). However, INSL3 more accurately differentiated CHH in adult men than in boys with delayed puberty (auROC with 95% CI in adult men: 100%, 100-100%; boys with delayed puberty: 86.7%, 77.7-95.7%).Median INB was higher in boys with CDGP than CHH (182 vs 59 pg/ml; p<0.0001). Likewise, in adult men, median INB was higher in eugonadal men than CHH (170 vs 36.5 pg/ml; p<0.0001). INB performed better than INSL3 in differentiating CHH in boys with delayed puberty (auROC 98.5%, 95.9-100%), than in adult men (auROC 93.9%, 87.2-100%).ConclusionINSL3 better identifies CHH in adult men, whereas INB better identifies CHH in boys with delayed puberty.https://www.frontiersin.org/articles/10.3389/fendo.2022.1076984/fullinsulin-like peptide 3INSL3inhibin Bcongenital hypogonadotrophic hypogonadismCHHconstitutional delay of growth and puberty |
| spellingShingle | Ali Abbara Ali Abbara Kanyada Koysombat Maria Phylactou Maria Phylactou Pei Chia Eng Pei Chia Eng Sophie Clarke Sophie Clarke Alexander N. Comninos Alexander N. Comninos Lisa Yang Lisa Yang Chioma Izzi-Engbeaya Chioma Izzi-Engbeaya Simon Hanassab Simon Hanassab Neil Smith Channa N. Jayasena Channa N. Jayasena Cheng Xu Cheng Xu Richard Quinton Richard Quinton Nelly Pitteloud Nelly Pitteloud Gerhard Binder Ravinder Anand-Ivell Richard Ivell Waljit S. Dhillo Waljit S. Dhillo Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult men Frontiers in Endocrinology insulin-like peptide 3 INSL3 inhibin B congenital hypogonadotrophic hypogonadism CHH constitutional delay of growth and puberty |
| title | Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult men |
| title_full | Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult men |
| title_fullStr | Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult men |
| title_full_unstemmed | Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult men |
| title_short | Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult men |
| title_sort | insulin like peptide 3 insl3 in congenital hypogonadotrophic hypogonadism chh in boys with delayed puberty and adult men |
| topic | insulin-like peptide 3 INSL3 inhibin B congenital hypogonadotrophic hypogonadism CHH constitutional delay of growth and puberty |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.1076984/full |
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