Classes and predictors of reversal in male patients with congenital hypogonadotropic hypogonadism: a cross-sectional study of six international referral centres
Authors' conclusion
Applying LCMM to a large cohort of male patients with CHH reversal uncovered two distinct classes of reversal. Genetic investigation combined with careful clinical phenotyping could help surveillance of reversal after withdrawing treatment, representing the first tailored management approach for male patients with this rare endocrine disorder.
Study context
- Population
- Adult men with congenital hypogonadotropic hypogonadism (CHH) (absent or incomplete spontaneous puberty by age 18 years, low serum testosterone, no identifiable cause of HPG axis dysfunction), referral centres in Brazil, Finland, France, Italy, the UK and the USA
- Participants
- 75 / 12 / 87 / 108
- Exposure
- CHH reversal vs no CHH reversal; reversal class 1 vs class 2
- Class 1n = 75reference
- Class 2n = 12
- CHH reversaln = 87
- Without CHH reversaln = 108reference
- Outcome
- Presence of at least two distinct classes of reversal
Methodological detailsmulticentre, six international CHH referral centres, latent class mixture modelling
- Multicentre
- Six international CHH referral centres
- Latent class mixture modelling
Main finding
As reported in the abstract
Distinct reversal classes (LCMM)
| Group | Value | Classification probability |
|---|---|---|
| Class 1 | 86% | 0.998 |
| Class 2 | 14% | 0.838 |
Value
Class 186%
Class 214%
Classification probability
Class 10.998
Class 20.838
- Entropy (modelling uncertainty low)
- 0.90
Observational data: associations, not effects.
Further findings
| Outcome | CHH reversal | Without CHH reversal | P value |
|---|---|---|---|
| Rare pathogenic ANOS1 variant (genetically tested) | 0 events | 11% | |
| Tested | 75 | 95 | |
| Rare variants in GNRHR (genetically tested)CHH reversal vs Without CHH reversal · significantly higher with CHH reversal | 12% | 3% | P = 0.025 |
| Tested | 75 | 95 |
- Class 2 vs class 1 phenotype · significantly larger with class 2
- P < 0.0001
- Class 2 vs class 1 phenotype · higher with class 2
- P = 0.041
- Predictors: features more likely without CHH reversal · Without CHH reversal vs CHH reversal · more likely without reversal
- P = 0.016
- Predictors: features more likely without CHH reversal · Without CHH reversal vs CHH reversal · more likely without reversal
- P = 0.0012
- Predictors: features more likely without CHH reversal · Without CHH reversal vs CHH reversal · more likely without reversal
- P = 0.0016
- Predictors: features more likely without CHH reversal · Without CHH reversal vs CHH reversal · more likely without reversal
- P = 0.0001
Class 2 vs class 1 phenotype
- No micropenis in class 2; consistent with Pasqualini syndrome (fertile eunuch) subtype
Original publication
Classes and predictors of reversal in male patients with congenital hypogonadotropic hypogonadism: a cross-sectional study of six international referral centres. Lancet Diabetes Endocrinol. Published 1 March 2024. doi:10.
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