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Central hypogonadism in Klinefelter syndrome: report of two cases and review of the literature
Purpose Klinefelter syndrome (KS) is characterized by late adolescence/young adulthood onset of primary hypogonadism. Hypogonadotropic hypogonadism (HH), when congenital, is usually associated with absent/incomplete puberty and low/normal gonadotropins. We report the clinical and genetic features of...
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Published in: | Journal of endocrinological investigation 2021-03, Vol.44 (3), p.459-470 |
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container_title | Journal of endocrinological investigation |
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creator | Cangiano, Biagio Indirli, Rita Profka, Eriselda Castellano, Elena Goggi, Giovanni Vezzoli, Valeria Mantovani, Giovanna Arosio, Maura Persani, Luca Borretta, Giorgio Ferrante, Emanuele Bonomi, Marco |
description | Purpose
Klinefelter syndrome (KS) is characterized by late adolescence/young adulthood onset of primary hypogonadism. Hypogonadotropic hypogonadism (HH), when congenital, is usually associated with absent/incomplete puberty and low/normal gonadotropins. We report the clinical and genetic features of two subjects with KS and an unexpected HH hormone profile.
Methods
Magnetic resonance imaging (MRI) of hypothalamus-pituitary region and next generation sequencing (NGS) of congenital HH-associated genes were obtained. A narrative review of the literature was conducted.
Results
Patients were diagnosed with Klinefelter syndrome following karyotype analysis. Nevertheless, they showed unusual features: both had incomplete puberty, low gonadotropins and testosterone levels, and the first one was anosmic. Sellar lesions were excluded by MRI, and NGS was negative in both subjects. Our data add to those of the only 14 similar cases reported so far. Unexplained HH rarely occurs in KS and is variably associated with anosmia, other pituitary hormones deficiencies and heterogeneous karyotypes. However, most cases show an early, pre-pubertal onset of hypogonadism. If the causes behind this gonadotropins defect are largely unknown, hereby we provide the first review of the literature on this topic and propose some pathogenetic hypotheses, including the coexistence of KS and congenital HH as suggested by overlapping clinical features in some of these patients.
Conclusion
HH is an exceptional occurrence in Klinefelter syndrome and is associated with heterogeneous phenotypes and, probably, aetiologies. Moreover, KS could underlie HH nonresponsive to gonadotropins. An exhaustive diagnostic workup and a tailored clinical management are advisable in these rare forms. |
doi_str_mv | 10.1007/s40618-020-01324-3 |
format | article |
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Klinefelter syndrome (KS) is characterized by late adolescence/young adulthood onset of primary hypogonadism. Hypogonadotropic hypogonadism (HH), when congenital, is usually associated with absent/incomplete puberty and low/normal gonadotropins. We report the clinical and genetic features of two subjects with KS and an unexpected HH hormone profile.
Methods
Magnetic resonance imaging (MRI) of hypothalamus-pituitary region and next generation sequencing (NGS) of congenital HH-associated genes were obtained. A narrative review of the literature was conducted.
Results
Patients were diagnosed with Klinefelter syndrome following karyotype analysis. Nevertheless, they showed unusual features: both had incomplete puberty, low gonadotropins and testosterone levels, and the first one was anosmic. Sellar lesions were excluded by MRI, and NGS was negative in both subjects. Our data add to those of the only 14 similar cases reported so far. Unexplained HH rarely occurs in KS and is variably associated with anosmia, other pituitary hormones deficiencies and heterogeneous karyotypes. However, most cases show an early, pre-pubertal onset of hypogonadism. If the causes behind this gonadotropins defect are largely unknown, hereby we provide the first review of the literature on this topic and propose some pathogenetic hypotheses, including the coexistence of KS and congenital HH as suggested by overlapping clinical features in some of these patients.
Conclusion
HH is an exceptional occurrence in Klinefelter syndrome and is associated with heterogeneous phenotypes and, probably, aetiologies. Moreover, KS could underlie HH nonresponsive to gonadotropins. An exhaustive diagnostic workup and a tailored clinical management are advisable in these rare forms.</description><identifier>ISSN: 1720-8386</identifier><identifier>ISSN: 0391-4097</identifier><identifier>EISSN: 1720-8386</identifier><identifier>DOI: 10.1007/s40618-020-01324-3</identifier><identifier>PMID: 32537678</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Anosmia ; Coexistence ; Endocrinology ; Gonadotropins ; Hypogonadism ; Hypothalamus ; Internal Medicine ; Karyotypes ; Klinefelter's syndrome ; Literature reviews ; Magnetic resonance imaging ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Next-generation sequencing ; Original Article ; Phenotypes ; Pituitary ; Pituitary (anterior) ; Pituitary hormones ; Puberty ; Testosterone</subject><ispartof>Journal of endocrinological investigation, 2021-03, Vol.44 (3), p.459-470</ispartof><rights>Italian Society of Endocrinology (SIE) 2020</rights><rights>Italian Society of Endocrinology (SIE) 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-6903560cdc289100ed20da5fd23ebaf7cd5ef49d83b16ff1c950a809df72d2643</citedby><cites>FETCH-LOGICAL-c375t-6903560cdc289100ed20da5fd23ebaf7cd5ef49d83b16ff1c950a809df72d2643</cites><orcidid>0000-0003-3988-3616 ; 0000-0002-2658-744X ; 0000-0002-0556-7650 ; 0000-0001-5454-6074 ; 0000-0003-2068-9581 ; 0000-0001-5642-0563 ; 0000-0002-9065-3886</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32537678$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cangiano, Biagio</creatorcontrib><creatorcontrib>Indirli, Rita</creatorcontrib><creatorcontrib>Profka, Eriselda</creatorcontrib><creatorcontrib>Castellano, Elena</creatorcontrib><creatorcontrib>Goggi, Giovanni</creatorcontrib><creatorcontrib>Vezzoli, Valeria</creatorcontrib><creatorcontrib>Mantovani, Giovanna</creatorcontrib><creatorcontrib>Arosio, Maura</creatorcontrib><creatorcontrib>Persani, Luca</creatorcontrib><creatorcontrib>Borretta, Giorgio</creatorcontrib><creatorcontrib>Ferrante, Emanuele</creatorcontrib><creatorcontrib>Bonomi, Marco</creatorcontrib><title>Central hypogonadism in Klinefelter syndrome: report of two cases and review of the literature</title><title>Journal of endocrinological investigation</title><addtitle>J Endocrinol Invest</addtitle><addtitle>J Endocrinol Invest</addtitle><description>Purpose
Klinefelter syndrome (KS) is characterized by late adolescence/young adulthood onset of primary hypogonadism. Hypogonadotropic hypogonadism (HH), when congenital, is usually associated with absent/incomplete puberty and low/normal gonadotropins. We report the clinical and genetic features of two subjects with KS and an unexpected HH hormone profile.
Methods
Magnetic resonance imaging (MRI) of hypothalamus-pituitary region and next generation sequencing (NGS) of congenital HH-associated genes were obtained. A narrative review of the literature was conducted.
Results
Patients were diagnosed with Klinefelter syndrome following karyotype analysis. Nevertheless, they showed unusual features: both had incomplete puberty, low gonadotropins and testosterone levels, and the first one was anosmic. Sellar lesions were excluded by MRI, and NGS was negative in both subjects. Our data add to those of the only 14 similar cases reported so far. Unexplained HH rarely occurs in KS and is variably associated with anosmia, other pituitary hormones deficiencies and heterogeneous karyotypes. However, most cases show an early, pre-pubertal onset of hypogonadism. If the causes behind this gonadotropins defect are largely unknown, hereby we provide the first review of the literature on this topic and propose some pathogenetic hypotheses, including the coexistence of KS and congenital HH as suggested by overlapping clinical features in some of these patients.
Conclusion
HH is an exceptional occurrence in Klinefelter syndrome and is associated with heterogeneous phenotypes and, probably, aetiologies. Moreover, KS could underlie HH nonresponsive to gonadotropins. An exhaustive diagnostic workup and a tailored clinical management are advisable in these rare forms.</description><subject>Anosmia</subject><subject>Coexistence</subject><subject>Endocrinology</subject><subject>Gonadotropins</subject><subject>Hypogonadism</subject><subject>Hypothalamus</subject><subject>Internal Medicine</subject><subject>Karyotypes</subject><subject>Klinefelter's syndrome</subject><subject>Literature reviews</subject><subject>Magnetic resonance imaging</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Next-generation sequencing</subject><subject>Original Article</subject><subject>Phenotypes</subject><subject>Pituitary</subject><subject>Pituitary (anterior)</subject><subject>Pituitary hormones</subject><subject>Puberty</subject><subject>Testosterone</subject><issn>1720-8386</issn><issn>0391-4097</issn><issn>1720-8386</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kE9P3DAQxa0KVP60X6AHZIlLLyljO7Gd3qpVC6hIXOBayxuPISixFzthtd8el6UFceBke_x7b2YeIV8YfGMA6iTXIJmugEMFTPC6Eh_IPlPlqYWWO6_ue-Qg5zsAoYRWH8me4I1QUul98meBYUp2oLebVbyJwbo-j7QP9PfQB_Q4TJho3gSX4ojfacJVTBONnk7rSDubMVMbXKk_9Lh-qt8iHfqistOc8BPZ9XbI-Pn5PCTXv35eLc6qi8vT88WPi6oTqpkq2YJoJHSu47otu6Hj4GzjHRe4tF51rkFft06LJZPes65twGponVfccVmLQ_J167tK8X7GPJmxzx0Ogw0Y52x4zWoADUwW9PgNehfnFMp0hdJatsWvLRTfUl2KOSf0ZpX60aaNYWD-pm-26ZuSvnlK34giOnq2npcjuv-Sf3EXQGyBXL7CDaaX3u_YPgIEBJAD</recordid><startdate>20210301</startdate><enddate>20210301</enddate><creator>Cangiano, Biagio</creator><creator>Indirli, Rita</creator><creator>Profka, Eriselda</creator><creator>Castellano, Elena</creator><creator>Goggi, Giovanni</creator><creator>Vezzoli, Valeria</creator><creator>Mantovani, Giovanna</creator><creator>Arosio, Maura</creator><creator>Persani, Luca</creator><creator>Borretta, Giorgio</creator><creator>Ferrante, Emanuele</creator><creator>Bonomi, Marco</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-3988-3616</orcidid><orcidid>https://orcid.org/0000-0002-2658-744X</orcidid><orcidid>https://orcid.org/0000-0002-0556-7650</orcidid><orcidid>https://orcid.org/0000-0001-5454-6074</orcidid><orcidid>https://orcid.org/0000-0003-2068-9581</orcidid><orcidid>https://orcid.org/0000-0001-5642-0563</orcidid><orcidid>https://orcid.org/0000-0002-9065-3886</orcidid></search><sort><creationdate>20210301</creationdate><title>Central hypogonadism in Klinefelter syndrome: report of two cases and review of the literature</title><author>Cangiano, Biagio ; Indirli, Rita ; Profka, Eriselda ; Castellano, Elena ; Goggi, Giovanni ; Vezzoli, Valeria ; Mantovani, Giovanna ; Arosio, Maura ; Persani, Luca ; Borretta, Giorgio ; Ferrante, Emanuele ; Bonomi, Marco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-6903560cdc289100ed20da5fd23ebaf7cd5ef49d83b16ff1c950a809df72d2643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Anosmia</topic><topic>Coexistence</topic><topic>Endocrinology</topic><topic>Gonadotropins</topic><topic>Hypogonadism</topic><topic>Hypothalamus</topic><topic>Internal Medicine</topic><topic>Karyotypes</topic><topic>Klinefelter's syndrome</topic><topic>Literature reviews</topic><topic>Magnetic resonance imaging</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Next-generation sequencing</topic><topic>Original Article</topic><topic>Phenotypes</topic><topic>Pituitary</topic><topic>Pituitary (anterior)</topic><topic>Pituitary hormones</topic><topic>Puberty</topic><topic>Testosterone</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cangiano, Biagio</creatorcontrib><creatorcontrib>Indirli, Rita</creatorcontrib><creatorcontrib>Profka, Eriselda</creatorcontrib><creatorcontrib>Castellano, Elena</creatorcontrib><creatorcontrib>Goggi, Giovanni</creatorcontrib><creatorcontrib>Vezzoli, Valeria</creatorcontrib><creatorcontrib>Mantovani, Giovanna</creatorcontrib><creatorcontrib>Arosio, Maura</creatorcontrib><creatorcontrib>Persani, Luca</creatorcontrib><creatorcontrib>Borretta, Giorgio</creatorcontrib><creatorcontrib>Ferrante, Emanuele</creatorcontrib><creatorcontrib>Bonomi, Marco</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of endocrinological investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cangiano, Biagio</au><au>Indirli, Rita</au><au>Profka, Eriselda</au><au>Castellano, Elena</au><au>Goggi, Giovanni</au><au>Vezzoli, Valeria</au><au>Mantovani, Giovanna</au><au>Arosio, Maura</au><au>Persani, Luca</au><au>Borretta, Giorgio</au><au>Ferrante, Emanuele</au><au>Bonomi, Marco</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Central hypogonadism in Klinefelter syndrome: report of two cases and review of the literature</atitle><jtitle>Journal of endocrinological investigation</jtitle><stitle>J Endocrinol Invest</stitle><addtitle>J Endocrinol Invest</addtitle><date>2021-03-01</date><risdate>2021</risdate><volume>44</volume><issue>3</issue><spage>459</spage><epage>470</epage><pages>459-470</pages><issn>1720-8386</issn><issn>0391-4097</issn><eissn>1720-8386</eissn><abstract>Purpose
Klinefelter syndrome (KS) is characterized by late adolescence/young adulthood onset of primary hypogonadism. Hypogonadotropic hypogonadism (HH), when congenital, is usually associated with absent/incomplete puberty and low/normal gonadotropins. We report the clinical and genetic features of two subjects with KS and an unexpected HH hormone profile.
Methods
Magnetic resonance imaging (MRI) of hypothalamus-pituitary region and next generation sequencing (NGS) of congenital HH-associated genes were obtained. A narrative review of the literature was conducted.
Results
Patients were diagnosed with Klinefelter syndrome following karyotype analysis. Nevertheless, they showed unusual features: both had incomplete puberty, low gonadotropins and testosterone levels, and the first one was anosmic. Sellar lesions were excluded by MRI, and NGS was negative in both subjects. Our data add to those of the only 14 similar cases reported so far. Unexplained HH rarely occurs in KS and is variably associated with anosmia, other pituitary hormones deficiencies and heterogeneous karyotypes. However, most cases show an early, pre-pubertal onset of hypogonadism. If the causes behind this gonadotropins defect are largely unknown, hereby we provide the first review of the literature on this topic and propose some pathogenetic hypotheses, including the coexistence of KS and congenital HH as suggested by overlapping clinical features in some of these patients.
Conclusion
HH is an exceptional occurrence in Klinefelter syndrome and is associated with heterogeneous phenotypes and, probably, aetiologies. Moreover, KS could underlie HH nonresponsive to gonadotropins. An exhaustive diagnostic workup and a tailored clinical management are advisable in these rare forms.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>32537678</pmid><doi>10.1007/s40618-020-01324-3</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-3988-3616</orcidid><orcidid>https://orcid.org/0000-0002-2658-744X</orcidid><orcidid>https://orcid.org/0000-0002-0556-7650</orcidid><orcidid>https://orcid.org/0000-0001-5454-6074</orcidid><orcidid>https://orcid.org/0000-0003-2068-9581</orcidid><orcidid>https://orcid.org/0000-0001-5642-0563</orcidid><orcidid>https://orcid.org/0000-0002-9065-3886</orcidid></addata></record> |
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subjects | Anosmia Coexistence Endocrinology Gonadotropins Hypogonadism Hypothalamus Internal Medicine Karyotypes Klinefelter's syndrome Literature reviews Magnetic resonance imaging Medicine Medicine & Public Health Metabolic Diseases Next-generation sequencing Original Article Phenotypes Pituitary Pituitary (anterior) Pituitary hormones Puberty Testosterone |
title | Central hypogonadism in Klinefelter syndrome: report of two cases and review of the literature |
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