Andrea Salzano1,2, Roberta D'Assante3, Liam M Heaney2, Federica Monaco1, Giuseppe Rengo1, Pietro Valente1, Daniela Pasquali4, Eduardo Bossone5, Daniele Gianfrilli6, Andrea Lenzi6, Antonio Cittadini7, Alberto M Marra3, Raffaele Napoli1. 1. Department of Translational Medical Sciences, Federico II University School of Medicine, Naples, Italy. 2. Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, Glenfield Hospital, Leicester, UK. 3. IRCCS S.D.N., Via Gianturco 113, 80143, Naples, Italy. 4. Department of Neurological, Metabolic, and Geriatric Science, Endocrinology Unit, University of Campania "Luigi Vanvitelli", Caserta, Italy. 5. Department of Cardiology and Cardiac Surgery, University Hospital "Scuola Medica Salernitana", Salerno, Italy. 6. Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy. 7. Department of Translational Medical Sciences, Federico II University School of Medicine, Naples, Italy. antonio.cittadini@unina.it.
Abstract
PURPOSE: Klinefelter syndrome (KS), the most frequent chromosomic abnormality in males, is associated with hypergonadotropic hypogonadism and an increased risk of cardiovascular diseases (CVD). The mechanisms involved in increasing risk of cardiovascular morbidity and mortality are not completely understood. This review summarises the current understandings of the complex relationship between KS, metabolic syndrome and cardiovascular risk in order to plan future studies and improve current strategies to reduce mortality in this high-risk population. METHODS: We searched PubMed, Web of Science, and Scopus for manuscripts published prior to November 2017 using key words "Klinefelter syndrome" AND "insulin resistance" OR "metabolic syndrome" OR "diabetes mellitus" OR "cardiovascular disease" OR "testosterone". Manuscripts were collated, studied and carried forward for discussion where appropriate. RESULTS: Insulin resistance, metabolic syndrome, and type 2 diabetes are more frequently diagnosed in KS than in the general population; however, the contribution of hypogonadism to metabolic derangement is highly controversial. Whether this dangerous combination of risk factors fully explains the CVD burden of KS patients remains unclear. In addition, testosterone replacement therapy only exerts a marginal action on the CVD system. CONCLUSION: Since fat accumulation and distribution seem to play a relevant role in triggering metabolic abnormalities, an early diagnosis and a tailored intervention strategy with drugs aimed at targeting excessive visceral fat deposition appear necessary in patients with KS.
PURPOSE:Klinefelter syndrome (KS), the most frequent chromosomic abnormality in males, is associated with hypergonadotropic hypogonadism and an increased risk of cardiovascular diseases (CVD). The mechanisms involved in increasing risk of cardiovascular morbidity and mortality are not completely understood. This review summarises the current understandings of the complex relationship between KS, metabolic syndrome and cardiovascular risk in order to plan future studies and improve current strategies to reduce mortality in this high-risk population. METHODS: We searched PubMed, Web of Science, and Scopus for manuscripts published prior to November 2017 using key words "Klinefelter syndrome" AND "insulin resistance" OR "metabolic syndrome" OR "diabetes mellitus" OR "cardiovascular disease" OR "testosterone". Manuscripts were collated, studied and carried forward for discussion where appropriate. RESULTS:Insulin resistance, metabolic syndrome, and type 2 diabetes are more frequently diagnosed in KS than in the general population; however, the contribution of hypogonadism to metabolic derangement is highly controversial. Whether this dangerous combination of risk factors fully explains the CVD burden of KS patients remains unclear. In addition, testosterone replacement therapy only exerts a marginal action on the CVD system. CONCLUSION: Since fat accumulation and distribution seem to play a relevant role in triggering metabolic abnormalities, an early diagnosis and a tailored intervention strategy with drugs aimed at targeting excessive visceral fat deposition appear necessary in patients with KS.
Authors: Andrea Salzano; Alberto Maria Marra; Francesco Ferrara; Michele Arcopinto; Emanuele Bobbio; Pietro Valente; Roberto Polizzi; Carlo De Vincentiis; Margherita Matarazzo; Lavinia Saldamarco; Francesco Saccà; Raffaele Napoli; Maria Gaia Monti; Roberta D'Assante; Andrea M Isidori; Jorgen Isgaard; Nicola Ferrara; Pasquale Perrone Filardi; Francesco Perticone; Carlo Vigorito; Eduardo Bossone; Antonio Cittadini Journal: Int J Cardiol Date: 2016-09-26 Impact factor: 4.164
Authors: Stephanie Cung; Laura Pyle; Kristin Nadeau; Dana Dabelea; Melanie Cree-Green; Shanlee M Davis Journal: J Investig Med Date: 2021-09-07 Impact factor: 2.895
Authors: Shanlee M Davis; Sophia DeKlotz; Kristen J Nadeau; Megan M Kelsey; Philip S Zeitler; Nicole R Tartaglia Journal: Am J Med Genet C Semin Med Genet Date: 2020-06-16 Impact factor: 3.908
Authors: M Spaziani; S Granato; N Liberati; F M Rossi; N Tahani; C Pozza; D Gianfrilli; G Papi; A Anzuini; A Lenzi; L Tarani; A F Radicioni Journal: J Endocrinol Invest Date: 2020-05-06 Impact factor: 4.256
Authors: Piotr Jarecki; Waldemar A Herman; Elżbieta Pawliczak; Katarzyna Lacka Journal: Diabetes Metab Syndr Obes Date: 2019-10-21 Impact factor: 3.168
Authors: D Pasquali; P Chiodini; V Simeon; A Ferlin; L Vignozzi; G Corona; F Lanfranco; V Rochira; A E Calogero; M Bonomi; R Pivonello; G Balercia; A Pizzocaro; V A Giagulli; P Salacone; A Aversa; G Accardo; M Maggi; A Lenzi; A Isidori; C Foresta; E A Jannini; A Garolla Journal: J Endocrinol Invest Date: 2022-05-24 Impact factor: 5.467