Premature thelarche: clinical and laboratorial assessment by immunochemiluminescent assay

Abstract

In order to establish cut-off limits and to distinguish isolated premature thelarche (IPT) from precocious puberty (PP), we evaluated data from 79 girls with premature thelarche, comparing basal and stimulated LH and FSH serum concentrations with those from 91 healthy girls. A GnRH stimulation test was performed in 10 normal girls and in 42 with premature thelarche. Comparison among groups was performed by Kruskal-Wallis and Dunn's tests. LH values were significantly greater in girls with IPT than in control groups. Basal gonadotropin concentrations were higher in patients with PP than in controls, but not different from patients with IPT. Peak LH levels after GnRH stimulation distinguished those two groups, with a cut-off value of 4.0 IU/L, but still with minimal overlap. In conclusion, a girl with premature thelarche and LH peak value above 4.5 IU/L has, indeed, PP, but values between 3.5 and 4.5 IU/L point to careful follow-up. RESUMOTelarca precoce: avaliação clínica e laboratorial pelo método imunoquimioluminescente. Com o objetivo de estabelecer o valor de corte e distinguir telarca precoce isolada (TPI) de puberdade precoce (PP), avaliamos 79 meninas com telarca precoce, comparando as dosagens basais e pós-estímulo de LH e FSH com grupo-controle. O teste de estímulo com GnRH foi realizado em 10 meninas normais e em 42 com telarca precoce. Os testes de Kruskal-Wallis and Dunn foram usados na comparação dos grupos. Os níveis de LH foram significativamente mais elevados no grupo com TPI, quando comparados com controles. As gonadotrofinas basais foram mais elevadas naquelas com PP que nos controles, mas não diferiram do grupo com TPI. O pico de LH após GnRH distinguiu estes dois grupos, com valor de corte de 4,0 UI/L, apesar de pequena sobreposição. Concluímos que uma menina com telarca precoce e LH pós-estímulo acima de 4,5 UI/L apresenta PP, mas valores entre 3,5 e 4,5 UI/L requerem seguimento cuidadoso. SUBJECTS AND METHODS SubjectsThe research protocol was approved by the Ethics Committee of the Faculdade de Medicina da Universidade Federal do Triângulo Mineiro, Uberaba, (Brazil). Written consent to participate in this study was obtained from the subjects in the healthy control group and their parents. We compared, retrospectively, data from 79 records of girls presenting PT with 91 healthy pre-pubertal girls.Patients were distributed into two groups ( Figure 1): a) Isolated premature thelarche (IPT) -58 girls with breast enlargement and absence of other signs of pubertal development were divided into two subgroups according to the age at onset of thelarche: 40 girls ages 0.9-2.9 yr (IPT 1 ) and 18 girls between 3 and 8 years of age (IPT 2 ). b) Precocious puberty (PP) -21 girls with PT were selected and divided into two subgroups according to the time of activation of HPG axis: 9 girls ages 1.5-7.7 yr initially presented HPG axis inactivated (phase I-PP 1 ,), but during the follow-up they developed pubarche, acceleration of growth velocity, and a second GnRH test disclosed an active HPG axisThe...

Factors to Predict Positive Results of Gonadotropin Releasing Hormone Stimulation Test in Girls with Suspected Precocious Puberty

“…Other previous studies suggested that the IGF-I level was increased in girls with CPP, compared to those with premature thelarche (20-22). Another study suggested that the peak LH level after GnRH stimulation test was useful, therefore, girls with early breast budding and peak LH values between 3.5 and 4.5 IU/L should be carefully followed-up (23). …”

Diagnosis of Diseases of Steroid Hormone Production, Metabolism and Action

“…Some girls present with isolated breast development (premature thelarche) and no growth acceleration (135). Increased oestrogen production in girls with premature thelarche is a benign condition not to be confused with central precocious puberty.…”

Interpretation des GnRH (LHRH)-Tests bei der Abklärung der Pubertas praecox

“…Bei Erhöhung des Wertes auf 0,3 IU/l erhöhten sich der positive Vorhersagewert und die Spezifität sogar auf 100 % bei verminderter Sensitivität (16). Da Mädchen mit isolierter prematurer Thelarche in einer anderen Untersuchung jedoch höhere basale LH-Werte bis 0,7 IU/l aufwiesen, sollte zur Differenzierung gegenüber einer Pubertas praecox ein GnRH-Test durchgeführt werden (17).…”

“…Nach (17). Aufgrund der Überlappung der stimulierten LH-Werte bei Mädchen im frühen Pubertätsstadium müssen diese bei unauffälligem GnRH-Test und weiter bestehendem klinischen Verdacht auf eine Pubertas praecox bei fortschreitendem Pubertätsverlauf erneut getestet werden (17).…”

“…Bei Mädchen mit Pubertas praecox und GnRH-stimulierten LH-Werten >5 IU/l lagen die medianen stimulierten LH-Werte bei 7,5 IU/l und die medianen GnRH-stimulierten FSH-Werte bei 9,5 IU/l, sodass sich daraus ergibt, dass bei einem nicht unerheblichen Anteil der Mädchen mit Pubertas praecox ein GnRH-stimulierter LH/ FSH-Quotient von <1 vorgelegen haben muss (17).…”