Luigi Maione1,2,3, Giovanna Pala2,4,5, Claire Bouvattier1,4,3, Séverine Trabado1,3,6, Georgios Papadakis2,7, Philippe Chanson1,2,3, Jérôme Bouligand1,3,6, Nelly Pitteloud7, Andrew A Dwyer8, Mohamad Maghnie5, Jacques Young1,2,3. 1. Paris-Saclay University, Paris-Saclay Medical School, Le Kremlin-Bicêtre, France. 2. Endocrinology and Reproductive Diseases Department, Assistance Publique-Hôpitaux de Paris, Bicêtre Hospital, Le Kremlin-Bicêtre, France. 3. INSERM U1185, Le Kremlin-Bicêtre, France. 4. Paediatric Endocrinology, Assistance Publique-Hôpitaux de Paris, Bicêtre Hospital, Le Kremlin-Bicêtre, France. 5. Paediatric Department, Istituto Giannina Gaslini, Istituto Pediatrico di Ricovero e Cura a Carattere Scientifico, Università di Genova, Genova, Italy. 6. Molecular Genetics, Pharmacogenomics, and Hormonology, Assistance Publique-Hôpitaux de Paris, Bicêtre Hospital, Le Kremlin-Bicêtre, France. 7. Endocrinology, Diabetes, and Metabolism Service, University Hospital of Lausanne, Lausanne, Switzerland. 8. Boston College, William F. Connell School of Nursing, Chestnut Hill, Massachusetts, USA.
Abstract
CONTEXT: Congenital hypogonadotropic hypogonadism/Kallmann syndrome (CHH/KS) is a rare condition characterized by gonadotropin deficiency and pubertal failure. Adult height (AH) in patients with CHH/KS has not been well studied. OBJECTIVE: To assess AH in a large cohort of patients with CHH/KS. PATIENTS: A total of 219 patients (165 males, 54 females). Parents and siblings were included. METHODS: AH was assessed in patients and family members. AH was compared to the general French population, mid parental target height (TH) and between patients and same-sex siblings. Delta height (∆H) was considered as the difference between AH and parental TH. ∆H was compared between patients and siblings, normosmic CHH and KS (CHH with anosmia/hyposmia), and according to underlying genetic defect. We examined the correlations between ∆H and age at diagnosis and therapeutically induced individual statural gain. RESULTS: Mean AH in men and women with CHH/KS was greater than that in the French general population. Patients of both sexes had AH > TH. Males with CHH/KS were significantly, albeit moderately, taller than their brothers. ∆H was higher in CHH/KS compared to unaffected siblings (+6.2 ± 7.2 cm vs +3.4 ± 5.2 cm, P < 0.0001). ∆H was positively correlated with age at diagnosis. Neither olfactory function (normosmic CHH vs KS) nor specific genetic cause impacted ∆H. Individual growth during replacement therapy inversely correlated with the age at initiation of hormonal treatment (P < 0.0001). CONCLUSIONS: CHH/KS is associated with higher AH compared to the general population and mid-parental TH. Greater height in CHH/KS than siblings indicates that those differences are in part independent of an intergenerational effect.
CONTEXT: Congenital hypogonadotropic hypogonadism/Kallmann syndrome (CHH/KS) is a rare condition characterized by gonadotropin deficiency and pubertal failure. Adult height (AH) in patients with CHH/KS has not been well studied. OBJECTIVE: To assess AH in a large cohort of patients with CHH/KS. PATIENTS: A total of 219 patients (165 males, 54 females). Parents and siblings were included. METHODS: AH was assessed in patients and family members. AH was compared to the general French population, mid parental target height (TH) and between patients and same-sex siblings. Delta height (∆H) was considered as the difference between AH and parental TH. ∆H was compared between patients and siblings, normosmic CHH and KS (CHH with anosmia/hyposmia), and according to underlying genetic defect. We examined the correlations between ∆H and age at diagnosis and therapeutically induced individual statural gain. RESULTS: Mean AH in men and women with CHH/KS was greater than that in the French general population. Patients of both sexes had AH > TH. Males with CHH/KS were significantly, albeit moderately, taller than their brothers. ∆H was higher in CHH/KS compared to unaffected siblings (+6.2 ± 7.2 cm vs +3.4 ± 5.2 cm, P < 0.0001). ∆H was positively correlated with age at diagnosis. Neither olfactory function (normosmic CHH vs KS) nor specific genetic cause impacted ∆H. Individual growth during replacement therapy inversely correlated with the age at initiation of hormonal treatment (P < 0.0001). CONCLUSIONS: CHH/KS is associated with higher AH compared to the general population and mid-parental TH. Greater height in CHH/KS than siblings indicates that those differences are in part independent of an intergenerational effect.
Authors: Vassos Neocleous; Pavlos Fanis; Meropi Toumba; George A Tanteles; Melpo Schiza; Feride Cinarli; Nicolas C Nicolaides; Anastasis Oulas; George M Spyrou; Christos S Mantzoros; Dimitrios Vlachakis; Nicos Skordis; Leonidas A Phylactou Journal: Front Endocrinol (Lausanne) Date: 2020-08-28 Impact factor: 5.555
Authors: B Cangiano; G Goggi; S Federici; C Bresesti; L Cotellessa; F Guizzardi; V Vezzoli; P Duminuco; L Persani; M Bonomi Journal: J Endocrinol Invest Date: 2021-03-18 Impact factor: 4.256