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, Andrea M Isidori, Angela Ida PincelliFlavia Prodam, Antonio Mancini, Paolo Limone, Maria Laura Tanda, Rossella Gaudino, Mariacarolina Salerno, Pregnolato Francesca, Mohamad Maghnie, Mario Maggi, Luca Persani, Italian Network on Central Hypogonadism

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 non-reproductive 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.

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

Keywords

  • 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
  • Journal Article
  • Observational Study

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  • Cite this

    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, M. C., Cannavò, S., Isidori, A. M., ... Italian Network on Central Hypogonadism (2018). Characteristics of a nationwide cohort of patients presenting with isolated hypogonadotropic hypogonadism (IHH). European Journal of Endocrinology, 178(1), 23-32. https://doi.org/10.1530/EJE-17-0065