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.

Characteristics of a nationwide cohort of patients presenting with isolated hypogonadotropic hypogonadism (IHH) / M. Bonomi, V. Vezzoli, C. Krausz, F. Guizzardi, S. Vezzani, M. Simoni, I. Bassi, P. Duminuco, N. Di Iorgi, C. Giavoli, A. Pizzocaro, G. Russo, M. Moro, L. Fatti, A. Ferlin, L. Mazzanti, M.C. Zatelli, S. Cannavò, A. M Isidori, A.I. Pincelli, F. Prodam, A. Mancini, P. Limone, M.L. Tanda, R. Gaudino, M. Salerno, F. Pregnolato, M. Maghnie, M. Maggi, L. Persani. - In: EUROPEAN JOURNAL OF ENDOCRINOLOGY. - ISSN 0804-4643. - 178:1(2018 Jan), pp. 23-32. [10.1530/EJE-17-0065]

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

M. Bonomi;V. Vezzoli;F. Guizzardi;I. Bassi;C. Giavoli;L. Fatti;L. Persani
Writing – Review & Editing
2018

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.
adolescent; adult; age of onset; cohort studies; female; gonadal steroid hormones; gonadotropins; humans; hypogonadism; italy; male; obesity; olfaction disorders; overweight; phenotype; pituitary hormones; synkinesis; young adult; endocrinology, diabetes and metabolism; endocrinology
Settore MED/13 - Endocrinologia
   Idiopathic Central Hypogonadism (ICH) as an emerging clinical problem: Investigations on the disrupted signals underlying its pathogenesis and generation of an efficient national network for its diagnosis and management
   ICH
   MINISTERO DELLA SALUTE
   GR-2008-1137632
gen-2018
Article (author)
File in questo prodotto:
File Dimensione Formato  
Bonomi_M_EJE_2018.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 584.36 kB
Formato Adobe PDF
584.36 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/551152
Citazioni
  • ???jsp.display-item.citation.pmc??? 41
  • Scopus 67
  • ???jsp.display-item.citation.isi??? 68
social impact