IMPE2023 Free Communications Endocrinology of Sex Differences 1 (4 abstracts)
The combination of FSH and markers of Sertoli cell function provides a high accuracy strategy to differentiate central hypogonadism from constitutional delay of puberty in boys: a longitudinal prospective study.
Sebastián Castro 1 , Lourdes Correa Brito 1 , Patricia Bedecarrás 1 , María Gabriela Ropelato 1 , Ana Keselman 1 , Fernando Cassorla 2 , Ignacio Bergadá 1 , Rodolfo A. Rey 1 & Romina P. Grinspon 1
1Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET – FEI – División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina. 2Instituto de Investigaciones Materno Infantil (IDIMI), Universidad de Chile, Santiago, Chile
Constitutional delay of puberty (CDP) and congenital central hypogonadism (CH) show great overlap in clinical features and in gonadotrophin and testosterone serum concentrations in boys. The gold standard to distinguish both entities relies on the assessment of pubertal stage beyond 18 years of age. The long lasting insufficient FSH activity in boys with congenital CH may result in lower AMH and inhibin B serum concentrations compared with boys with CDP.
Aim of this study: To determine whether the assessment of the FSH-Sertoli cell axis could distinguish between CDP and CH in boys referred for pubertal delay. 62 boys with delay of puberty, median age at referral 14.2 years (CDP) and 15.3 years (CH), were prospectively evaluated until 18 years of age to ascertain the definitive diagnosis: CDP (n:32): testes >15 ml, CH (n:30): testes <15 ml, bilaterally. 8/13 (61%) CH patients studied by NGS carried a (likely) pathogenic variant. Median basal hormone levels at referral were significantly lower in CH compared with CDP (FSH IU/L: 0.56 vs 2.53; P<0.0001. LH IU/L: 0.10 vs 0.73; P<0.0001. AMH pmol/L: 172 vs 375; P<0.0001. Inhibin B pg/ml: 20 vs 82; P<0.0001). Median testosterone was similar in both groups (<10 ng/dL). For the selected cut-off values, serum FSH <1.4 IU/L showed the highest sensitivity (97%) and good specificity (87%) for CH, whereas Inhibin B <35 pg/mL showed the highest specificity (100%), with 65% sensitivity. Their combination, FSH (IU/L) x inhibin B (pg/mL) exhibited 100% sensitivity and 92% specificity. AMH alone or in combination with FSH showed a slightly lower performance.
| Cut-off value | Sensitivity (%,95%CI) | Specificity (%,95%CI) | PPV (%) | NPV (%) | + LR | |
| FSH (IU/L) | 1.4 | 97 (83-100) | 87 (70-96) | 97 | 96 | 7.5 |
| Inhibin B (pg/ml) | 35 | 65 (44-83) | 100 (87-100) | 100 | 75 | >19.7 |
| FSH (IU/L) x Inhibin B (pg/mL) | 90 | 100 (86-100) | 92 (75-99) | 93 | 100 | 13.0 |
| AMH (pmol/L) | 200 | 53 (34-72) | 91 (75-98) | 84 | 67 | 5.7 |
| FSH (IU/L) x AMH (pmol/L) | 630 | 100 (88-100) | 84 (66-94) | 85 | 100 | 6.2 |
| LH (IU/L) | 0.3 | 77 (58-90) | 71 (52-86) | 72 | 77 | 2.6 |
| Testosterone (ng/dL) | 20 | 89 (72-98) | 19 (7-36) | 49 | 67 | 1.1 |
Conclusion: the assessment of the FSH-Sertoli cell axis, especially by determining serum FSH in association with inhibin B, provides an accurate tool to differentiate CH and CDP in boys referred for pubertal delay.
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