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

被引:79
作者
Bonomi, Marco [1 ,2 ,3 ]
Vezzoli, Valeria [2 ,3 ]
Krausz, Csilla [4 ]
Guizzardi, Fabiana [2 ,3 ]
Vezzani, Silvia [5 ,6 ,7 ]
Simoni, Manuela [5 ,6 ,7 ]
Bassi, Ivan [2 ,3 ]
Duminuco, Paolo [2 ,3 ]
Di Iorgi, Natascia [8 ]
Giavoli, Claudia [1 ,9 ]
Pizzocaro, Alessandro [10 ]
Russo, Gianni [11 ]
Moro, Mirella [2 ,3 ]
Fatti, Letizia [2 ,3 ]
Ferlin, Alberto [12 ]
Mazzanti, Laura [13 ]
Zatelli, Maria Chiara [14 ]
Cannavo, Salvo [15 ]
Isidori, Andrea M. [16 ]
Pincelli, Angela Ida [17 ]
Prodam, Flavia [18 ]
Mancini, Antonio [19 ]
Limone, Paolo [20 ]
Tanda, Maria Laura [21 ]
Gaudino, Rossella [22 ]
Salerno, Mariacarolina [23 ]
Francesca, Pregnolato [24 ]
Maghnie, Mohamad [8 ]
Maggi, Mario [4 ]
Persani, Luca [1 ,2 ,3 ]
机构
[1] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy
[2] IRCCS, Ist Auxol Italiano, Div Endocrine & Metab Dis, Milan, Italy
[3] Lab Endocrine & Metab Res, Milan, Italy
[4] Univ Florence, Dept Biomed Expt & Clin Sci Mario Serio, Florence, Italy
[5] Univ Modena & Reggio Emilia, Unit Endocrinol, Dept Biomed Metab & Neural Sci, Modena, Italy
[6] Azienda USL Modena, Dept Med Endocrinol Metab & Geriatr, Modena, Italy
[7] Univ Modena & Reggio Emilia, Ctr Genom Res, Modena, Italy
[8] Univ Genoa, IRCCS Giannina Gaslini, Dept Pediat, Genoa, Italy
[9] Fdn IRCCS, Endocrinol & Metab Dis Unit, Ca Granda Osped Maggiore Policlin, Milan, Italy
[10] IRCCS, Humanitas Res Hosp, Endocrinol Unit, Milan, Italy
[11] IRCCS, Hosp San Raffaele, Dept Pediat, Milan, Italy
[12] Univ Padua, Unit Androl & Reprod Med, Dept Med, Padua, Italy
[13] Alma Mater Studiourm Univ Bologna, Dept Med & Surg Sci, Bologna, Italy
[14] Univ Ferrara, Dept Med Sci, Sect Endocrinol & Internal Med, Ferrara, Italy
[15] Univ Messina, Endocrinol Unit, Dept Clin & Expt Med, Messina, Italy
[16] Sapienza Univ Rome, Dept Expt Med, Rome, Italy
[17] Univ Milano Bicocca, San Gerardo Hosp, Endocrinol & Diabetol Unit, Div Internal Med, Monza, Italy
[18] Univ Piemonte Orientale, Dept Hlth Sci, Novara, Italy
[19] Univ Cattolica Sacro Cuore, Operat Unit Endocrinol, Rome, Italy
[20] AO Ordine Mauriziano Torino, Endocrinol Diabet & Metab Dis Unit, Turin, Italy
[21] Univ Insubria Sede Varese, Dipartimento Med Clin & Sperimentale, Varese, Italy
[22] Univ Verona, Dept Surg Sci Dent Gynecol & Pediat, Verona, Italy
[23] Univ Naples Federico II, Dept Translat Med Sci, Naples, Italy
[24] IRCCS, Ist Auxol Italiano, Expt Lab Immunol & Rheumatol Res, Milan, Italy
关键词
LINKED KALLMANN-SYNDROME; GENETIC-BASIS; GONADOTROPIN-DEFICIENCY; GNRH DEFICIENCY; HETEROGENEITY; PHENOTYPE; DIAGNOSIS; GENOTYPE; DISEASE; COMPLEX;
D O I
10.1530/EJE-17-0065
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 classified 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 significantly 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 significantly 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 findings improve the understanding of IHH and may have a positive impact on the management of patients and their families.
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收藏
页码:23 / 32
页数:10
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