INSL3 in 268 male patients with congenital hypogonadotropic hypogonadism (CHH): effects of different modalities of hormonal treatment

Abstract Context Men with Congenital Hypogonadotropic Hypogonadism (CHH) and Kallmann syndrome (KS) have both low circulating testosterone and estradiol levels. Whether bone structure is affected remains unknown. Objective To characterize bone geometry, volumetric density and microarchitecture in CHH/KS. Design Cross-sectional study. Setting One tertiary academic French center. Patients and Controls 51 genotyped CHH/KS patients and 40 healthy volunteers were included. Ninety-eight percent of CHH/KS men had received testosterone and/or combined gonadotropins. Intervention(s) High-resolution Peripheral Quantitative Computed Tomography (HR-pQCT), Dual X-ray absorptiometry (DXA) and measurement of serum bone markers. Main Outcome Volumetric bone mineral density (vBMD), cortical and trabecular microarchitecture. Results CHH and controls did not differ for age, BMI, vitamin D and PTH levels. Despite long-term hormonal treatment (10.8 ± 6.8 years), DXA showed lower areal BMD in CHH/KS at lumbar spine, total hip, femoral neck and distal radius. Consistent with persistently higher serum bone markers, HR-pQCT revealed lower cortical and trabecular vBMD as well as cortical thickness at the tibia and the radius. CHH/KS men had altered trabecular microarchitecture with a predominant decrease of trabecular thickness. Moreover, CHH/KS men exhibited lower cortical bone area, whereas total and trabecular areas were higher only at the tibia. Earlier treatment onset (before the age of 19 years) conferred a significant advantage for trabecular bone volume/tissue volume and trabecular vBMD at the tibia. Conclusion Both vBMD and bone microarchitecture remain impaired in CHH/KS men despite long-term hormonal treatment. Treatment initiation during adolescence is associated with enhanced trabecular outcomes, highlighting the importance of early diagnosis.

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Faculty Opinions recommendation of Correlations among genotype and outcome in chinese male patients with congenital hypogonadotropic hypogonadism under HCG treatment.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.737572702.793583848 ◽

2021 ◽

Author(s):

Roberto Maggi

Keyword(s):

Hypogonadotropic Hypogonadism ◽

Congenital Hypogonadotropic Hypogonadism ◽

Male Patients ◽

Chinese Male

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Insulin-like Peptide 3 (INSL3) in Men With Congenital Hypogonadotropic Hypogonadism/Kallmann Syndrome and Effects of Different Modalities of Hormonal Treatment: A Single-Center Study of 281 Patients

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2013-2288 ◽

2014 ◽

Vol 99 (2) ◽

pp. E268-E275 ◽

Cited By ~ 30

Author(s):

Séverine Trabado ◽

Luigi Maione ◽

Hélène Bry-Gauillard ◽

Hélène Affres ◽

Sylvie Salenave ◽

...

Keyword(s):

Hypogonadotropic Hypogonadism ◽

Hormonal Treatment ◽

Kallmann Syndrome ◽

Single Center ◽

Congenital Hypogonadotropic Hypogonadism ◽

Single Center Study ◽

Center Study

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Faculty Opinions recommendation of Efficacy of follitropin-alpha versus human menopausal gonadotropin for male patients with congenital hypogonadotropic hypogonadism.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.739748018.793583850 ◽

2021 ◽

Author(s):

Roberto Maggi

Keyword(s):

Hypogonadotropic Hypogonadism ◽

Human Menopausal Gonadotropin ◽

Congenital Hypogonadotropic Hypogonadism ◽

Male Patients

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Congenital hypogonadotropic hypogonadism/Kallmann syndrome is associated with statural gain in both men and women: a monocentric study

Acta Endocrinologica ◽

10.1530/eje-19-0537 ◽

2020 ◽

Vol 182 (2) ◽

pp. 185 ◽

Cited By ~ 4

Author(s):

Luigi Maione ◽

Giovanna Pala ◽

Claire Bouvattier ◽

Séverine Trabado ◽

Georgios Papadakis ◽

...

Keyword(s):

General Population ◽

Hypogonadotropic Hypogonadism ◽

Genetic Defect ◽

Hormonal Treatment ◽

Rare Condition ◽

Kallmann Syndrome ◽

Age At Diagnosis ◽

Individual Growth ◽

Men And Women ◽

Congenital Hypogonadotropic Hypogonadism

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.

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