ArticleThe Journal of clinical endocrinology and metabolism2023
Reproductive Phenotypes and Genotypes in Men With IHH.
Article in The Journal of clinical endocrinology and metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Reversal of Congenital Hypogonadotropic Hypogonadism.The Journal of clinical endocrinology and metabolism · 2026Pooled it
- Genetic landscape of a neonatal hypogonadotropic hypogonadism series: Novel variants and phenotypic spectrum.Journal of neuroendocrinology · 2026Article
- The Pathogenicity Analysis of a Hypogonadotropic Hypogonadism Patient With the Novel Variant in the Deep Intronic Region of the PROK2 Gene.Molecular genetics & genomic medicine · 2026Article
- Reversible congenital hypogonadotropic hypogonadism: keys for clinical management.Archives of endocrinology and metabolism · 2026Review
- From patients to partners: evaluating a co-designed website for congenital hypogonadotropic hypogonadism.Endocrine connections · 2026Article
- Predictors of early response to GnRH and gonadotropin therapy in pediatric patients with suspected dual congenital hypogonadotropic hypogonadism: a retrospective single-center study.Frontiers in endocrinology · 2026Article
- Clinical and genetic basis of congenital gonadotropin deficiency.Human reproduction open · 2026Article
- Nursing's Role in Advancing Care for Rare Genetic Diseases.The Nursing clinics of North America · 2025Review
- Current landscape of fertility induction in males with congenital hypogonadotropic hypogonadism.Annals of the New York Academy of Sciences · 2024Review
- Lack of a genetic risk continuum between pubertal timing in the general population and idiopathic hypogonadotropic hypogonadism.Journal of neuroendocrinology · 2024Article
- Classes and predictors of reversal in male patients with congenital hypogonadotropic hypogonadism: a cross-sectional study of six international referral centres.The lancet. Diabetes & endocrinology · 2024Article
- Case report: Novel SIN3A loss-of-function variant as causative for hypogonadotropic hypogonadism in Witteveen-Kolk syndrome.Frontiers in genetics · 2024Article
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10 authors at 2 institutions in 1 country.
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Abstract
contextIsolated hypogonadotropic hypogonadism (IHH) is phenotypically and genetically heterogeneous.
objectiveThis work aimed to determine the correlation between genotypic severity with pubertal and neuroendocrine phenotypes in IHH men.
methodsA retrospective study was conducted (1980-2020) examining olfaction (Kallmann syndrome [KS] vs normosmic IHH [nHH]), baseline testicular volume (absent vs partial puberty), neuroendocrine profiling (pulsatile vs apulsatile luteinizing hormone [LH] secretion), and genetic variants in 62 IHH-associated genes through exome sequencing (ES).
resultsIn total, 242 men (KS: n = 131 [54%], nHH: n = 111 [46%]) were included. Men with absent puberty had significantly lower gonadotropin levels (P < .001) and were more likely to have undetectable LH (P < .001). Logistic regression showed partial puberty as a statistically significant predictor of pulsatile LH secretion (R2 = 0.71, P < .001, OR: 10.8; 95% CI, 3.6-38.6). Serum LH of 2.10 IU/L had a 95% true positive rate for predicting LH pulsatility. Genetic analyses in 204 of 242 IHH men with ES data available revealed 36 of 204 (18%) men carried protein-truncating variants (PTVs) in 12 IHH genes. Men with absent puberty and apulsatile LH were enriched for oligogenic PTVs (P < .001), with variants in ANOS1 being the predominant PTV in this genotype-phenotype association. Men with absent puberty were enriched for ANOS1 PTVs compared to partial puberty counterparts (P = .002). PTVs in other IHH genes imparted more variable reproductive phenotypic severity.
conclusionPartial puberty and LH greater than or equal to 2.10 IU/L are proxies for pulsatile LH secretion. ANOS1 PTVs confer severe reproductive phenotypes. Variable phenotypic severity in the face of severe genetic variants in other IHH genes point to significant neuroendocrine plasticity of the HPG axis in IHH men.
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