The use of stimulation tests for the differential diagnosis of delayed puberty in boys. How to increase the specificity of the method?

BACKGROUND: In patients with a constitutional delay of puberty starts and ends completely without any medical intervention. In adolescents with hypogonadotropic hypogonadism puberty is absent or does not continue its development. Differential diagnosis of the conditions is complicated due to lack of standard recommendations for the selection, conducting and assessment of stimulation tests.

AIM: To assess the information content and find ways to increase the specificity of stimulation tests with triptorelin and corionic gonadotropin in relation to hypogonadotropic hypogonadism.

MATERIALS AND METHODS: We examined 44 adolescent boys aged 13.5–17 years with delayed puberty. Sexual development was assessed according to Tanner scale, bone age (X-ray of the non-dominant hand according to the Greulich atlas). All boys were tested with triptorelin. The test with one- and three-day intramuscular injection of human chorionic gonadotropin was performed in 26 and 35 patients, respectively. Statistical analysis was performed using the StatTech v. 2.6.1 (developer — Stattech LLC, Russia). To assess the diagnostic significance of quantitative signs in predicting a certain outcome the ROC-curve analysis was performed.

RESULTS: It was revealed that a negative test with triptorelin was observed in some patients with constitutional delay of puberty. Threshold stimulated luteinizing hormone and follicle stimulating hormone levels were set (8.90 and 5.90 IU/l respectively). Gonadotropins values equal to or lower than selected thresholds allow diagnosing of hypogonadotropic hypogonadism with high sensitivity and specificity. Threshold testosterone levels stimulated by one- and three-day administration of human chorionic gonadotropin were determined (2.11 and 5.84 nmol/l respectively). Testosterone values equal to or lower than selected thresholds allow diagnosing of hypogonadotropic hypogonadism with high sensitivity and specificity. A high degree of positive correlation was found between stimulated luteinizing hormone levels and stimulated testosterone levels during a three-day test with human chorionic gonadotropin.

CONCLUSIONS: A negative test with triptorelin is observed in some patients with constitutional delay of puberty. The specificity of the test can be improved by using threshold stimulated levels of luteinizing hormone and follicle stimulating hormone (8.90 and 5.90 IU/L, respectively). The use of the threshold levels of testosterone (2.11 and 5.84 nmol/l within the one- and three-day functional tests of the testicles respectively) can help to increase the specificity of the considered outdated stimulation tests with human chorionic gonadotropin.