Characteristics of a nationwide cohort of patients presenting with isolated hypogonadotropic hypogonadism (IHH)

Marco Bonomi, Valeria Vezzoli, Csilla Krausz, Fabiana Guizzardi, Silvia Vezzani, Manuela Simoni, Ivan Bassi, Paolo Duminuco, Natascia Di Iorgi, Claudia Giavoli, Alessandro Pizzocaro, Gianni Russo, Mirella Moro, Letizia Fatti, Alberto Ferlin, Laura Mazzanti, Maria Chiara Zatelli, Salvo Cannavò, A. M. Isidori, Angela Ida PincelliFlavia Prodam, Antonio Mancini, Mohamad Maghnie, Luca Persani, M. Arosio, A. Balsamo, P. Beck-Peccoz, C. Bizzarri, M. Boschetti, A. Brunani, V. Brunelli, M. Cappa, P. Colombo, S. Corbetta, G. Corona, Natascia Di Iorgi, A. Fabbri, M. Ghezzi, E. Grosso, G. Grugni, A. Lania, L. Larizza, V. Lombardi, G. Mantovani, M. A. Mencarelli, P. Porcelli, G. Rossi, E. Sala, A. Spada, G. Weber, on behalf of the Italian Network on Central Hypogonadism (NICe group)

Research output: Contribution to journalArticle

Abstract

Objective: Isolated hypogonadotropic hypogonadism (IHH) is a rare disorder with pubertal delay, normal (normoosmic-IHH, nIHH) or defective sense of smell (Kallmann syndrome, KS). Other reproductive and nonreproductive anomalies might be present although information on their frequency are scanty, particularly according to the age of presentation. Design: Observational cohort study carried out between January 2008 and June 2016 within a national network of academic or general hospitals. Methods: We performed a detailed phenotyping of 503 IHH patients with: (1) manifestations of hypogonadism with low sex steroid hormone and low/normal gonadotropins; (2) absence of expansive hypothalamic/pituitary lesions or multiple pituitary hormone defects. Cohort was divided on IHH onset (PPO, pre-pubertal onset or AO, adult onset) and olfactory function: PPO-nIHH (n = 275), KS (n = 184), AO-nIHH (n = 36) and AO-doIHH (AO-IHH with defective olfaction, n = 8). Results: 90% of patients were classifed as PPO and 10% as AO. Typical midline and olfactory defects, bimanual synkinesis and familiarity for pubertal delay were also found among the AO-IHH. Mean age at diagnosis was signifcantly earlier and more frequently associated with congenital hypogonadism stigmata in patients with Kallmann's syndrome (KS). Synkinesis, renal and male genital tract anomalies were enriched in KS. Overweight/obesity are signifcantly associated with AO-IHH rather than PPO-IHH. Conclusions: Patients with KS are more prone to develop a severe and complex phenotype than nIHH. The presence of typical extra-gonadal defects and familiarity for PPO-IHH among the AO-IHH patients indicates a common predisposition with variable clinical expression. Overall, these fndings improve the understanding of IHH and may have a positive impact on the management of patients and their families.

Original languageEnglish
Pages (from-to)23-32
Number of pages10
JournalEuropean Journal of Endocrinology
Volume178
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

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Hypogonadism
Kallmann Syndrome
Synkinesis
Smell
Christianity
Pituitary Hormones
Gonadal Steroid Hormones
Gonadotropins
General Hospitals
Observational Studies
Cohort Studies
Obesity

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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Characteristics of a nationwide cohort of patients presenting with isolated hypogonadotropic hypogonadism (IHH). / Bonomi, Marco; Vezzoli, Valeria; Krausz, Csilla; Guizzardi, Fabiana; Vezzani, Silvia; Simoni, Manuela; Bassi, Ivan; Duminuco, Paolo; Di Iorgi, Natascia; Giavoli, Claudia; Pizzocaro, Alessandro; Russo, Gianni; Moro, Mirella; Fatti, Letizia; Ferlin, Alberto; Mazzanti, Laura; Zatelli, Maria Chiara; Cannavò, Salvo; Isidori, A. M.; Pincelli, Angela Ida; Prodam, Flavia; Mancini, Antonio; Maghnie, Mohamad; Persani, Luca; Arosio, M.; Balsamo, A.; Beck-Peccoz, P.; Bizzarri, C.; Boschetti, M.; Brunani, A.; Brunelli, V.; Cappa, M.; Colombo, P.; Corbetta, S.; Corona, G.; Di Iorgi, Natascia; Fabbri, A.; Ghezzi, M.; Grosso, E.; Grugni, G.; Lania, A.; Larizza, L.; Lombardi, V.; Mantovani, G.; Mencarelli, M. A.; Porcelli, P.; Rossi, G.; Sala, E.; Spada, A.; Weber, G.; on behalf of the Italian Network on Central Hypogonadism (NICe group).

In: European Journal of Endocrinology, Vol. 178, No. 1, 01.01.2018, p. 23-32.

Research output: Contribution to journalArticle

Bonomi, M, Vezzoli, V, Krausz, C, Guizzardi, F, Vezzani, S, Simoni, M, Bassi, I, Duminuco, P, Di Iorgi, N, Giavoli, C, Pizzocaro, A, Russo, G, Moro, M, Fatti, L, Ferlin, A, Mazzanti, L, Zatelli, MC, Cannavò, S, Isidori, AM, Pincelli, AI, Prodam, F, Mancini, A, Maghnie, M, Persani, L, Arosio, M, Balsamo, A, Beck-Peccoz, P, Bizzarri, C, Boschetti, M, Brunani, A, Brunelli, V, Cappa, M, Colombo, P, Corbetta, S, Corona, G, Di Iorgi, N, Fabbri, A, Ghezzi, M, Grosso, E, Grugni, G, Lania, A, Larizza, L, Lombardi, V, Mantovani, G, Mencarelli, MA, Porcelli, P, Rossi, G, Sala, E, Spada, A, Weber, G & on behalf of the Italian Network on Central Hypogonadism (NICe group) 2018, 'Characteristics of a nationwide cohort of patients presenting with isolated hypogonadotropic hypogonadism (IHH)', European Journal of Endocrinology, vol. 178, no. 1, pp. 23-32. https://doi.org/10.1530/EJE-17-0065
Bonomi, Marco ; Vezzoli, Valeria ; Krausz, Csilla ; Guizzardi, Fabiana ; Vezzani, Silvia ; Simoni, Manuela ; Bassi, Ivan ; Duminuco, Paolo ; Di Iorgi, Natascia ; Giavoli, Claudia ; Pizzocaro, Alessandro ; Russo, Gianni ; Moro, Mirella ; Fatti, Letizia ; Ferlin, Alberto ; Mazzanti, Laura ; Zatelli, Maria Chiara ; Cannavò, Salvo ; Isidori, A. M. ; Pincelli, Angela Ida ; Prodam, Flavia ; Mancini, Antonio ; Maghnie, Mohamad ; Persani, Luca ; Arosio, M. ; Balsamo, A. ; Beck-Peccoz, P. ; Bizzarri, C. ; Boschetti, M. ; Brunani, A. ; Brunelli, V. ; Cappa, M. ; Colombo, P. ; Corbetta, S. ; Corona, G. ; Di Iorgi, Natascia ; Fabbri, A. ; Ghezzi, M. ; Grosso, E. ; Grugni, G. ; Lania, A. ; Larizza, L. ; Lombardi, V. ; Mantovani, G. ; Mencarelli, M. A. ; Porcelli, P. ; Rossi, G. ; Sala, E. ; Spada, A. ; Weber, G. ; on behalf of the Italian Network on Central Hypogonadism (NICe group). / Characteristics of a nationwide cohort of patients presenting with isolated hypogonadotropic hypogonadism (IHH). In: European Journal of Endocrinology. 2018 ; Vol. 178, No. 1. pp. 23-32.
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abstract = "Objective: Isolated hypogonadotropic hypogonadism (IHH) is a rare disorder with pubertal delay, normal (normoosmic-IHH, nIHH) or defective sense of smell (Kallmann syndrome, KS). Other reproductive and nonreproductive anomalies might be present although information on their frequency are scanty, particularly according to the age of presentation. Design: Observational cohort study carried out between January 2008 and June 2016 within a national network of academic or general hospitals. Methods: We performed a detailed phenotyping of 503 IHH patients with: (1) manifestations of hypogonadism with low sex steroid hormone and low/normal gonadotropins; (2) absence of expansive hypothalamic/pituitary lesions or multiple pituitary hormone defects. Cohort was divided on IHH onset (PPO, pre-pubertal onset or AO, adult onset) and olfactory function: PPO-nIHH (n = 275), KS (n = 184), AO-nIHH (n = 36) and AO-doIHH (AO-IHH with defective olfaction, n = 8). Results: 90{\%} of patients were classifed as PPO and 10{\%} as AO. Typical midline and olfactory defects, bimanual synkinesis and familiarity for pubertal delay were also found among the AO-IHH. Mean age at diagnosis was signifcantly earlier and more frequently associated with congenital hypogonadism stigmata in patients with Kallmann's syndrome (KS). Synkinesis, renal and male genital tract anomalies were enriched in KS. Overweight/obesity are signifcantly associated with AO-IHH rather than PPO-IHH. Conclusions: Patients with KS are more prone to develop a severe and complex phenotype than nIHH. The presence of typical extra-gonadal defects and familiarity for PPO-IHH among the AO-IHH patients indicates a common predisposition with variable clinical expression. Overall, these fndings improve the understanding of IHH and may have a positive impact on the management of patients and their families.",
author = "Marco Bonomi and Valeria Vezzoli and Csilla Krausz and Fabiana Guizzardi and Silvia Vezzani and Manuela Simoni and Ivan Bassi and Paolo Duminuco and {Di Iorgi}, Natascia and Claudia Giavoli and Alessandro Pizzocaro and Gianni Russo and Mirella Moro and Letizia Fatti and Alberto Ferlin and Laura Mazzanti and Zatelli, {Maria Chiara} and Salvo Cannav{\`o} and Isidori, {A. M.} and Pincelli, {Angela Ida} and Flavia Prodam and Antonio Mancini and Mohamad Maghnie and Luca Persani and M. Arosio and A. Balsamo and P. Beck-Peccoz and C. Bizzarri and M. Boschetti and A. Brunani and V. Brunelli and M. Cappa and P. Colombo and S. Corbetta and G. Corona and {Di Iorgi}, Natascia and A. Fabbri and M. Ghezzi and E. Grosso and G. Grugni and A. Lania and L. Larizza and V. Lombardi and G. Mantovani and Mencarelli, {M. A.} and P. Porcelli and G. Rossi and E. Sala and A. Spada and G. Weber and {on behalf of the Italian Network on Central Hypogonadism (NICe group)}",
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TY - JOUR

T1 - Characteristics of a nationwide cohort of patients presenting with isolated hypogonadotropic hypogonadism (IHH)

AU - Bonomi, Marco

AU - Vezzoli, Valeria

AU - Krausz, Csilla

AU - Guizzardi, Fabiana

AU - Vezzani, Silvia

AU - Simoni, Manuela

AU - Bassi, Ivan

AU - Duminuco, Paolo

AU - Di Iorgi, Natascia

AU - Giavoli, Claudia

AU - Pizzocaro, Alessandro

AU - Russo, Gianni

AU - Moro, Mirella

AU - Fatti, Letizia

AU - Ferlin, Alberto

AU - Mazzanti, Laura

AU - Zatelli, Maria Chiara

AU - Cannavò, Salvo

AU - Isidori, A. M.

AU - Pincelli, Angela Ida

AU - Prodam, Flavia

AU - Mancini, Antonio

AU - Maghnie, Mohamad

AU - Persani, Luca

AU - Arosio, M.

AU - Balsamo, A.

AU - Beck-Peccoz, P.

AU - Bizzarri, C.

AU - Boschetti, M.

AU - Brunani, A.

AU - Brunelli, V.

AU - Cappa, M.

AU - Colombo, P.

AU - Corbetta, S.

AU - Corona, G.

AU - Di Iorgi, Natascia

AU - Fabbri, A.

AU - Ghezzi, M.

AU - Grosso, E.

AU - Grugni, G.

AU - Lania, A.

AU - Larizza, L.

AU - Lombardi, V.

AU - Mantovani, G.

AU - Mencarelli, M. A.

AU - Porcelli, P.

AU - Rossi, G.

AU - Sala, E.

AU - Spada, A.

AU - Weber, G.

AU - on behalf of the Italian Network on Central Hypogonadism (NICe group)

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Objective: Isolated hypogonadotropic hypogonadism (IHH) is a rare disorder with pubertal delay, normal (normoosmic-IHH, nIHH) or defective sense of smell (Kallmann syndrome, KS). Other reproductive and nonreproductive anomalies might be present although information on their frequency are scanty, particularly according to the age of presentation. Design: Observational cohort study carried out between January 2008 and June 2016 within a national network of academic or general hospitals. Methods: We performed a detailed phenotyping of 503 IHH patients with: (1) manifestations of hypogonadism with low sex steroid hormone and low/normal gonadotropins; (2) absence of expansive hypothalamic/pituitary lesions or multiple pituitary hormone defects. Cohort was divided on IHH onset (PPO, pre-pubertal onset or AO, adult onset) and olfactory function: PPO-nIHH (n = 275), KS (n = 184), AO-nIHH (n = 36) and AO-doIHH (AO-IHH with defective olfaction, n = 8). Results: 90% of patients were classifed as PPO and 10% as AO. Typical midline and olfactory defects, bimanual synkinesis and familiarity for pubertal delay were also found among the AO-IHH. Mean age at diagnosis was signifcantly earlier and more frequently associated with congenital hypogonadism stigmata in patients with Kallmann's syndrome (KS). Synkinesis, renal and male genital tract anomalies were enriched in KS. Overweight/obesity are signifcantly associated with AO-IHH rather than PPO-IHH. Conclusions: Patients with KS are more prone to develop a severe and complex phenotype than nIHH. The presence of typical extra-gonadal defects and familiarity for PPO-IHH among the AO-IHH patients indicates a common predisposition with variable clinical expression. Overall, these fndings improve the understanding of IHH and may have a positive impact on the management of patients and their families.

AB - Objective: Isolated hypogonadotropic hypogonadism (IHH) is a rare disorder with pubertal delay, normal (normoosmic-IHH, nIHH) or defective sense of smell (Kallmann syndrome, KS). Other reproductive and nonreproductive anomalies might be present although information on their frequency are scanty, particularly according to the age of presentation. Design: Observational cohort study carried out between January 2008 and June 2016 within a national network of academic or general hospitals. Methods: We performed a detailed phenotyping of 503 IHH patients with: (1) manifestations of hypogonadism with low sex steroid hormone and low/normal gonadotropins; (2) absence of expansive hypothalamic/pituitary lesions or multiple pituitary hormone defects. Cohort was divided on IHH onset (PPO, pre-pubertal onset or AO, adult onset) and olfactory function: PPO-nIHH (n = 275), KS (n = 184), AO-nIHH (n = 36) and AO-doIHH (AO-IHH with defective olfaction, n = 8). Results: 90% of patients were classifed as PPO and 10% as AO. Typical midline and olfactory defects, bimanual synkinesis and familiarity for pubertal delay were also found among the AO-IHH. Mean age at diagnosis was signifcantly earlier and more frequently associated with congenital hypogonadism stigmata in patients with Kallmann's syndrome (KS). Synkinesis, renal and male genital tract anomalies were enriched in KS. Overweight/obesity are signifcantly associated with AO-IHH rather than PPO-IHH. Conclusions: Patients with KS are more prone to develop a severe and complex phenotype than nIHH. The presence of typical extra-gonadal defects and familiarity for PPO-IHH among the AO-IHH patients indicates a common predisposition with variable clinical expression. Overall, these fndings improve the understanding of IHH and may have a positive impact on the management of patients and their families.

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