High Diagnostic Accuracy of Subcutaneous Triptorelin Test Compared With GnRH Test for Diagnosing Central Precocious Puberty in Girls

Analía Verónica Freire; María Eugenia Escobar; Mirta Graciela Gryngarten; Andrea Josefina Arcari; María Gabriela Ballerini; Ignacio Bergadá; María Gabriela Ropelato


Clin Endocrinol. 2013;78(3):398-404. 

In This Article

Abstract and Introduction


Context The GnRH test is the gold standard to confirm the diagnosis of central precocious puberty (CPP); however, this compound is not always readily available. Diagnostic accuracy of subcutaneous GnRH analogues tests compared to classical GnRH test has not been reported.

Objective To evaluate the diagnostic accuracy of Triptorelin test (index test) compared to the GnRH test (reference test) in girls with suspicion of CPP.

Design A prospective, case–control, randomized clinical trial was performed. CPP or precocious thelarche (PT) was diagnosed according to maximal LH response to GnRH test and clinical characteristics during follow-up.

Patients and Interventions Forty-six girls with premature breast development randomly underwent two tests: (i) intravenous GnRH 100 μg, (ii) subcutaneous Triptorelin acetate (0·1 mg/m2, to a maximum of 0·1 mg) with blood sampling at 0, 3 and 24 h for LH, FSH and estradiol ascertainment.

Measurements Gonadotrophins and estradiol responses to Triptorelin test were measured by ultrasensitive assays.

Results Clinical features were similar between CPP (n = 33) and PT (n = 13) groups. Using receiver operating characteristic curves, maximal LH response (LH-3 h) under Triptorelin test ≥7 IU/l by immunofluorometric assay (IFMA) or ≥8 IU/l by electrochemiluminescence immunoassay (ECLIA) confirmed the diagnosis of CPP with specificity of 1·00 (95% CI: 0·75–1·00) and sensitivity 0·76 (95% CI: 0·58–0·89). Considering either LH-3 h or maximal estradiol response at 24 h (cut-off value, 295 PM), maintaining the specificity at 1·00, the test sensitivity increased to 0·94 (95% CI: 0·80–0·99) and the diagnostic efficiency to 96%.

Conclusion The Triptorelin test had high accuracy for the differential diagnosis of CPP vs PT in girls providing a valid alternative to the classical GnRH test. This test also allowed a comprehensive evaluation of the pituitary–ovarian axis.


Central precocious puberty (CPP) in girls is characterized by an activation of the hypothalamic–pituitary–ovarian (HPO) axis before 8 years of age.[1] Given the gradual awakening of the GnRH pulse generator, a spectrum of presentations has been found among girls with premature sexual development.[2] Earliest clinical features of CPP are not easily distinguished from idiopathic precocious thelarche (PT) or other intermediate positions along this spectrum where the gonadotrophic axis is not completely activated.[1] These conditions do not always warrant therapy with GnRH agonists.[2,3] Diagnostic confirmation of CPP at early stages of pubertal development, through the demonstration of the activation of the HPO axis, is desirable to consider treatment to optimize outcome.[4,5] Lost to follow-up or inadequate interventions may lead to shorter final height as well as to psychosocial disturbances caused by earlier and inappropriate physical maturation to the age of the girl. These could be prevented with timely treatment.

For the last decades, the GnRH stimulation test has been the gold standard to assess the status of the hypothalamic–pituitary–gonadal axis in children with pubertal disorders.[1] However, GnRH is not readily available worldwide, and GnRH agonists (GnRHa) have been used, albeit not systematically, as an alternative.[1,6] While depot Triptorelin acetate formulation is used as a therapeutic regimen to suppress the gonadotrophic axis, the rapid-acting, aqueous formulation of Triptorelin acetate has an acute stimulatory effect on the gonadotrophs when given as single dose, with gonadotrophins reaching maximum levels 3 h after administration.[7] Owing to its longer half-life, this effect lasts at least 24 h, making possible to additionally evaluate the sex-hormone secretion by the gonads.[7,8]

To date, no reports are available on the diagnostic accuracy of stimulation tests with subcutaneous aqueous GnRH analogues compared to the gold standard GnRH test, assessed with ultrasensitive gonadotrophin assays, for the diagnosis of CPP in girls. The aim of this study was to evaluate the diagnostic accuracy of a Triptorelin test, based on the administration of a single dose of a rapid-acting, aqueous formulation of Triptorelin acetate, followed by serum gonadotrophins and estradiol (E2) determination, to ascertain the diagnosis of CPP in girls compared to the classical GnRH test.