Precocious Puberty or Premature Thelarche: Analysis of a Large Patient Series in a Single Tertiary Center with Special Emphasis on 6- to 8-Year-Old Girls.

Tero Varimo,Laura Kariola,Päivi Johanna Miettinen,Annika Tarkkanen,Taneli Raivio,Matti Hero,Johanna Hietamäki,Heta Huttunen

doi:10.3389/fendo.2017.00213

Tero Varimo, Laura Kariola + Show 6 more

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https://doi.org/10.3389/fendo.2017.00213

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Abstract

We describe the etiology, MRI findings, and growth patterns in girls who had presented with signs of precocious puberty (PP), i.e., premature breast development or early menarche. Special attention was paid to the diagnostic findings in 6- to 8-year-olds. We reviewed the medical records of 149 girls (aged 0.7-10.3 years) who had been evaluated for PP in the Helsinki University Hospital between 2001 and 2014. In 6- to 8-year-old girls, PP was most frequently caused by idiopathic gonadotropin-releasing hormone (GnRH)-dependent PP (60%) and premature thelarche (PT; 39%). The former subgroup grew faster (8.7 ± 2.0 cm/year, n = 58) than the girls with PT (7.0 ± 1.1 cm/year, n = 32) (P < 0.001), and the best discrimination for GnRH-dependent PP was achieved with a growth velocity cut-off value of 7.0 cm/year (sensitivity 92% and specificity 58%) [area under the curve 0.82, 95% confidence interval (CI) 0.73-0.91, P < 0.001]. Among asymptomatic and previously healthy 6- to 8-year-old girls with GnRH-dependent PP, one (1.7%, 95% CI 0.3-9.7%) had a pathological brain MRI finding requiring surgical intervention (craniopharyngioma). In girls younger than 3 years, the most frequent cause of breast development was PT, and, in 3- to 6-year-olds, GnRH-dependent PP. In 6- to 8-year-old girls, analysis of growth velocity is helpful in differentiating between PT and GnRH-dependent PP. Although the frequency of clinically relevant intracranial findings in previously healthy, asymptomatic 6- to 8-year-old girls was low, they can present without any signs or symptoms, which favors routine MRI imaging also in this age group.

Highlights

During the last 50 years, there has been a continuing downward trend toward an earlier timing of puberty, evidenced in girls by an earlier mean age of breast development and, to lesser extent, menarche [1, 2]
The Lawson Wilkins Pediatric Endocrine Society (LWPES) and European Society of Pediatric Endocrinology (ESPE) recommended that in girls with gonadotropin-releasing hormone (GnRH)-dependent precocious puberty (PP), a brain MRI should be performed in all subjects less than 6 years of age; whereas in girls aged 6–8 years, brain MRI may be reserved to those who show a rapid progression of puberty or neurologic signs or symptoms [12]
We evaluated the etiology of PP in a large series of girls with a special focus on those aged 6–8 years, as their optimal management has been debated [9, 12, 14, 27]

Summary

Introduction

During the last 50 years, there has been a continuing downward trend toward an earlier timing of puberty, evidenced in girls by an earlier mean age of breast development and, to lesser extent, menarche [1, 2]. Puberty is considered to be precocious when it occurs before the age of 8 years [3,4,5], and when precocious puberty (PP) manifests secondary to the activation of the hypothalamic–pituitary–gonadal (HPG) axis, the condition is considered to be gonadotropin-releasing hormone (GnRH) dependent. Secondary sexual characteristics can occur without the activation of the HPG axis. The premature activation of the HPG axis is caused by an abnormality in the central nervous system (CNS), which emphasizes the need to identify these subjects as early as possible. Incidental findings in brain MRI are relatively common and their role in GnRH-dependent PP are not always clear [10, 11]. The suggested guideline has been supported by some studies [10, 13, 14], whereas others have questioned it, and currently no consensus or evidence-based criteria for brain imaging exist for 6- to 8-year-old girls [9, 11, 12]

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