GnRH stimulation testing and serum inhibin B in males: insufficient specificity for discriminating between congenital hypogonadotropic hypogonadism from constitutional delay of growth and puberty

2021 ◽  
Author(s):  
Mosbah H ◽  
Bouvattier C ◽  
Maione L ◽  
Trabado S ◽  
De Filippo G ◽  
...  
Keyword(s):  
Hypogonadotropic Hypogonadism ◽  
Inhibin B ◽  
Congenital Hypogonadotropic Hypogonadism ◽  
Constitutional Delay

scholarly journals GnRH stimulation testing and serum inhibin B in males: insufficient specificity for discriminating between congenital hypogonadotropic hypogonadism from constitutional delay of growth and puberty

2020 ◽  
Vol 35 (10) ◽  
pp. 2312-2322
Author(s):  
Héléna Mosbah ◽  
Claire Bouvattier ◽  
Luigi Maione ◽  
Séverine Trabado ◽  
Gianpaolo De Filippo ◽  
...  
Keyword(s):  
Hypogonadotropic Hypogonadism ◽  
International Study ◽  
Serum Testosterone ◽  
Diagnostic Procedures ◽  
Inhibin B ◽  
Ministry Of Health ◽  
Recherche Clinique ◽  
Congenital Hypogonadotropic Hypogonadism ◽  
Specificity And Sensitivity ◽  
Constitutional Delay

Abstract STUDY QUESTION Are GnRH tests and serum inhibin B levels sufficiently discriminating to distinguish transient constitutional delay of growth and puberty (CDGP) from congenital hypogonadotropic hypogonadism (CHH) that affects reproductive health for life? SUMMARY ANSWER Both parameters lack the specificity to discriminate CDGP from CHH. WHAT IS KNOWN ALREADY GnRH tests and inhibin B levels have been proposed to differentiate CDGP from CHH. However, their diagnostic accuracies have been hampered by the small numbers of CHH included and enrichment of CHH patients with more severe forms. STUDY DESIGN, SIZE, DURATION The aim of this study was to assess the diagnostic performance of GnRH tests and inhibin B measurements in a large cohort of CHH male patients with the whole reproductive spectrum. From 2008 to 2018, 232 males were assessed: 127 with CHH, 74 with CDGP and 31 healthy controls. PARTICIPANTS/MATERIALS, SETTING, METHODS The participants were enrolled in two French academic referral centres. The following measurements were taken: testicular volume (TV), serum testosterone, inhibin B, LH and FSH, both at baseline and following the GnRH test. MAIN RESULTS AND THE ROLE OF CHANCE Among CHH patients, the LH response to the GnRH test was very variable and correlated with TV. Among CDGP patients, the LH peak was also variable and 47% of CHH patients had peak LH levels overlapping with the CDGP group. However, no patients with CDGP had an LH peak below 4.0 IU/l, while 53% CHH patients had LH peak below this threshold. Among CHH patients, inhibin B levels were also variable and correlated with TV and peak LH. Inhibin B was significantly lower in CHH patients than in CDGP patients but 50% of CHH values overlapped with CDGP values. Interestingly, all patients with CDGP had inhibin B levels above 35 pg/ml but 50% of CHH patients also had levels above this threshold. LIMITATIONS, REASONS FOR CAUTION As CHH is very rare, an international study would be necessary to recruit a larger CHH cohort and consolidate the conclusion reached here. WIDER IMPLICATIONS OF THE FINDINGS Peak LH and basal inhibin B levels are variable in both CHH and CDGP with significant overlap. Both parameters lack specificity and sensitivity to efficiently discriminate CHH from CDGP. This reflects the varying degree of gonadotropin deficiency inherent to CHH. These two diagnostic procedures may misdiagnose partial forms of isolated (non-syndromic) CHH, allowing them to be erroneously considered as CDGP. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by Agence Française de Lutte contre le Dopage: Grant Hypoproteo AFLD-10 (to J.Y.); Agence Nationale de la Recherche (ANR): Grant ANR-09-GENO-017-01 (to J.Y.); European Cooperation in Science and Technology, COST Action BM1105; Programme Hospitalier de Recherche Clinique (PHRC), French Ministry of Health: PHRC-2009 HYPO-PROTEO (to J.Y.); and Programme Hospitalier de Recherche Clinique (PHRC) “Variété”, French Ministry of Health, N° P081216/IDRCB 2009-A00892-55 (to P.C.). There are no competing interests. TRIAL REGISTRATION NUMBER N/A

scholarly journals Serum inhibin B for differentiating between congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty: a systematic review and meta-analysis

Endocrine ◽  
2021 ◽  
Author(s):  
Yuting Gao ◽  
Qin Du ◽  
Liyi Liu ◽  
Zhihong Liao
Keyword(s):  
Systematic Review ◽  
Study Design ◽  
Meta Analysis ◽  
Hypogonadotropic Hypogonadism ◽  
Inhibin B ◽  
Testicular Volume ◽  
Assay Method ◽  
Cochrane Library ◽  
Congenital Hypogonadotropic Hypogonadism ◽  
Constitutional Delay

Abstract Purpose The distinction between congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth and puberty (CDGP) in patients with delayed puberty is difficult to distinguish, but important for timely treatment. The aim of this study is to perform a systematic review and meta-analysis to determine the diagnostic performance of serum inhibin B (INHB) levels for differentiating CHH and CDGP. Methods PubMed, EMBASE, and Cochrane Library databases were systematically searched from the date of database inception to November 10, 2019 for studies examining the use of serum INHB to discriminate between CHH and CDGP. Pooled odds ratios (OR), sensitivity, specificity, and 95% confidence intervals (CI) were calculated. The Quality Assessment of Diagnostic Studies-2 (QUADAS-2) was used to assess the quality of the included studies. Sub-analyses were performed including that based on testicular volume (TV) and study design. Results Seven studies, comprising of 349 patients (96 CHH and 253 CDGP), were included in the meta-analysis. For differentiating between CHH and CDGP, INHB level exhibited good diagnostic accuracy with a pooled sensitivity of 92% (95% confidence interval [CI]: 0.86–0.96, I2 = 0.4%, p = 0.4343), specificity of 92% (95% CI: 0.88–0.94, I2 = 68.1%, p = 0.0009), and pooled area under the receiver operating characteristic curve (AUC) of 0.9619. The cut-off values of INHB for boys were 56, 66, 80, 96, 94.7, 111, and 113 pg/ml (assay method standardized to Gen II ELISA). Sub-analyses showed that testicular volume and study design could be a source of statistically significant heterogeneity in specificity. In boys with a testicular volume of ≤3 ml, INHB performed well with a sensitivity of 92%, specificity of 98%, and AUC of 0.9956. Conclusion INHB exhibits excellent diagnostic efficiency in distinguishing CHH from CDGP, especially in boys with severe puberty deficiency (TV ≤ 3 ml).

scholarly journals Congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures

2018 ◽  
Vol 178 (4) ◽  
pp. 377-388 ◽  
Author(s):  
Daniele Cassatella ◽  
Sasha R Howard ◽  
James S Acierno ◽  
Cheng Xu ◽  
Georgios E Papadakis ◽  
...  
Keyword(s):  
Genetic Basis ◽  
Rare Variants ◽  
Hypogonadotropic Hypogonadism ◽  
Delayed Puberty ◽  
Sequencing Data ◽  
Congenital Hypogonadotropic Hypogonadism ◽  
Constitutional Delay ◽  
Genetic Profiles ◽  
And Control ◽  
Shared Genetic

Objective Congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth and puberty (CDGP) represent rare and common forms of GnRH deficiency, respectively. Both CDGP and CHH present with delayed puberty, and the distinction between these two entities during early adolescence is challenging. More than 30 genes have been implicated in CHH, while the genetic basis of CDGP is poorly understood. Design We characterized and compared the genetic architectures of CHH and CDGP, to test the hypothesis of a shared genetic basis between these disorders. Methods Exome sequencing data were used to identify rare variants in known genes in CHH (n = 116), CDGP (n = 72) and control cohorts (n = 36 874 ExAC and n = 405 CoLaus). Results Mutations in at least one CHH gene were found in 51% of CHH probands, which is significantly higher than in CDGP (7%, P = 7.6 × 10−11) or controls (18%, P = 5.5 × 10−12). Similarly, oligogenicity (defined as mutations in more than one gene) was common in CHH patients (15%) relative to CDGP (1.4%, P = 0.002) and controls (2%, P = 6.4 × 10−7). Conclusions Our data suggest that CDGP and CHH have distinct genetic profiles, and this finding may facilitate the differential diagnosis in patients presenting with delayed puberty.

Gonadotropins for testicular descent in cryptorchid congenital hypogonadotropic hypogonadism males beyond infancy

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Shreya Sharma ◽  
Ravikumar Shah ◽  
Virendra Patil ◽  
Anurag R. Lila ◽  
Vijaya Sarathi ◽  
...  
Keyword(s):  
Semen Analysis ◽  
Hypogonadotropic Hypogonadism ◽  
Sperm Concentration ◽  
Inhibin B ◽  
Testicular Descent ◽  
Total Testosterone ◽  
Human Menopausal Gonadotropin ◽  
Beneficial Effects ◽  
Congenital Hypogonadotropic Hypogonadism

Abstract Objectives To study the effect of combined gonadotropin therapy (CGT) on testicular descent ± spermatogenesis in congenital hypogonadotropic hypogonadism (CHH) patients with cryptorchidism beyond infancy. Methods This retrospective cohort study included CHH patients with cryptorchidism [bilateral (n=5) or unilateral (n=1)] treated with CGT for testicular descent ± pubertal induction. All participants were treated with CGT [human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG)] with hMG pretreatment in three and monitored for changes in testicular volume (TV), serum total testosterone (T), serum inhibin-B, and sperm concentration. Results Complete testicular descent to the scrotal position was achieved in 5/6 patients (10/11 testes) after 4.7 ± 1.6 months of treatment. There was 44 ± 18%, 97.5% (IQR: 44–195), 10-fold (IQR: 3–19.6), and two-fold (IQR: 1.7–9.3) increase in stretched penile length, ultrasound measured TV, T level, and serum inhibin-B from baseline, respectively. In two pediatric cases, testicular descent occurred with isolated hMG therapy. At the last follow up (median: 23.5, IQR: 10.5–38.7 months), all the descended testes remained in scrotal position. In four pubertal/postpubertal age patients, continuous CGT (18–60 months) yielded T and inhibin-B levels of 16.64 ± 1.46 nmol/l and 106 ± 32.6 pg/mL, respectively. All the three patients with available semen analysis had sperm concentration of ≥5 million/mL and one of them achieved paternity. Conclusions A trial of CGT before orchiopexy may be considered in CHH males with cryptorchidism even beyond the narrow age-window of infancy. CGT may also have beneficial effects on future spermatogenesis and fertility outcomes in these patients.

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