Characteristics of a nationwide cohort of patients presenting with Isolated Hypogonadotropic Hypogonadism (IHH)

2018

EUROPEAN JOURNAL OF ENDOCRINOLOGY

Characteristics of a nationwide cohort of patients presenting with Isolated Hypogonadotropic Hypogonadism (IHH)

01 Pubblicazione su rivista

Bonomi, Marco, Vezzoli, Valeria, Krausz, Csilla Gabriella, Guizzardi, Fabiana, Vezzani, Silvia, Simoni, Manuela, Bassi, Ivan, Duminuco, Paolo, Di Iorgi, Natascia, Giavoli, Claudia, Pizzoccaro, Alessandro, Russo, Gianni, Moro, Mirella, Fatti, Letizia Maria, Ferlin, Alberto, Mazzanti, Laura, Zatelli, Maria Chiara, Cannavò, Salvatore, Isidori Andrea M, Pincelli, Angela I, Prodam, Flavia, Mancini, Antonio, Limone, Paolo, Tanda, Maria Laura, Gaudino, Rossella, Salerno, Mariacarolina, Pregnolato, Francesca, Maghnie, Mohammad, Maggi, Mario, Persani, Luca, Aimaretti, G, Altobelli, M, Ambrosio, Mr, Andrioli, M, Angeletti, G, Arecco, F, Arnaldi, G, Arosio, M, Balsamo, A, Baldassarri, M, Bartalena, L, Bazzoni, N, Beccaria, L, Beck-Peccoz, P, Bellastella, G, Bellizzi, M, Benedicenti, F, Bernasconi, S, Bizzarri, C, Bona, G, Bonadonna, S, Borretta, G, Boschetti, M, Brunani, A, Brunelli, V, Buzi, F, Cacciatore, C, Cangiano, B, Cappa, M, Casalone, R, Cassio, A, Cavarzere, P, Cherubini, V, Ciampani, T, Cicognani, D, Cignarelli, A, Cisternino, M, Colombo, P, Corbetta, S, Corciulo, N, Corona, G, Cozzi, R, Crivellaro, C, Dalle Mule, I, Danesi, L, D', Elia, Av, Degli Uberti, E, De Leo, S, Della Valle, E, De Marchi, M, Di Iorgi, N, Di Mambro, A, Fabbri, A, Foresta, C, Forti, G, Franceschi, Ar, Garolla, A, Ghezzi, M, Giacomozzi, C, Giusti, M, Grosso, E, Guabello, G, Guarneri, Mp, Grugni, G, Isidori Am, Lanfranco, F, Lania, A, Lanzi, R, Larizza, L, Lenzi A, Loche, S, Loli, P, Lombardi, V, Maggio, Mc, Mandrile, G, Manieri, C, Mantovani, G, Marelli, S, Marzullo, M, Mencarelli, Ma, Migone, N, Motta, G, Neri, G, Padova, G, Parenti, G, Pasquino, B, Pia, A, Piantanida, E, Pignatti, E, Pilotta, A, Pivetta, B, Pollazzon, M, Pontecorvi, A, Porcelli, P, Pozzan, Gb, Pozzobon, G, Radetti, G, Razzore, P, Rocchetti, L, Roncoroni, R, Rossi, G, Sala, E, Salvatoni, A, Salvini, F, Secco, A, Segni M, Selice, R, Sgaramella, P, Sileo, F, Sinisi, Aa, Sirchia, F, Spada, A, Tresoldi, A, Vigneri, R, Weber, G, Zucchini, S.

DOI: 10.1530/EJE-17-0065

ISSN: 0804-4643

IHH is a rare disorder with pubertal delay, normal (normoosmic-IHH, nIHH) or defective sense of smell (Kallmann syndrome, KS). Other reproductive and non-reproductive anomalies might be present altough information on their frequency are scanty, particularly according to the age of presentation.
DESIGN:
Observational cohort study carried out between January 2008-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 upon 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 classified as PPO and 10% as AO. Typical midline and olfactory defects, bimanual synkinesis and familiarity for pubertal delay were found also among the AO-IHH. Mean age at diagnosis was significantly earlier and more frequently associated with congenital hypogonadism stigmata in KS patients. Synkinesis, renal and male genital tract anomalies were enriched in KS. Overweight/obesity are significantly associated with AO-IHH rather than PPO-IHH.
CONCLUSIONS:
KS patients 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 findings improve the understanding of IHH and may have a positive impact on the management of patients and their families.

complex diagnosis disease genetic-basis genotype gnrh deficiency gonadotropin-deficiency heterogeneity linked kallmann-syndrome phenotype