The response to gonadotropin releasing hormone (GnRH) stimulation test does not predict the progression to true precocious puberty in girls with onset of premature thelarche in the first three years of life

J Clin Endocrinol Metab. 2014 Feb;99(2):433-9. doi: 10.1210/jc.2013-3292. Epub 2013 Dec 2.


Context: Premature thelarche in early childhood may evolve into true precocious puberty. The individuation of cases progressing to precocious puberty is challenging.

Objective: We analyzed the parameters predictive for progression in girls younger than 3 years.

Design and setting: We conducted a retrospective longitudinal study.

Patients and methods: A total of 450 girls referred for premature thelarche were initially evaluated, 353 were clinically monitored at 3-month intervals, and 97 underwent endocrine and imaging assessment. Central precocious puberty (CPP) was diagnosed in girls showing LH peak response to GnRH testing >5 mU/mL with tuber cinereum hamartoma at magnetic resonance imaging, or with normal magnetic resonance imaging but progression of puberty during follow-up.

Main outcome measure: We measured the progression to precocious puberty.

Results: Idiopathic premature thelarche (IPT) was diagnosed in 85 of the 97 girls who underwent extensive evaluation, CPP in nine girls, and peripheral precocious puberty in three girls. The uterus was >34 mm in six (7%) IPT girls and six (66.6%) CPP girls. Basal LH was >0.2 mU/mL in one (1.17%) IPT girl and eight (88.8%) CPP girls. LH peak was >5 mU/mL in 31 (36.4%) IPT girls and nine (100%) CPP girls. LH peak/FSH peak ratio was >1 in six (66.6%) CPP girls.

Conclusions: None of the available tests alone allows identification of girls who will progress to precocious puberty. Elevated LH responses to GnRH are common but are not related to progression toward puberty. The combined measurement of basal LH and longitudinal diameter of the uterus represents a reliable screening approach to identify subjects who should undergo GnRH testing.

MeSH terms

  • Child, Preschool
  • Diagnostic Techniques, Endocrine*
  • Disease Progression
  • Female
  • Follicle Stimulating Hormone / blood*
  • Gonadotropin-Releasing Hormone*
  • Humans
  • Infant
  • Longitudinal Studies
  • Luteinizing Hormone / blood*
  • Puberty, Precocious / blood
  • Puberty, Precocious / diagnosis*
  • Retrospective Studies


  • Gonadotropin-Releasing Hormone
  • Luteinizing Hormone
  • Follicle Stimulating Hormone