ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: J Pediatr Endocrinol Metab. 2018 Jul 26;31(7):701–710.

This meta-analysis assesses the prevalence of intracranial lesions in girls with central precocious puberty and hence evaluates the benefit of routine MRIs in girls with puberty onset at age 6–8 years.

Central precocious puberty (CPP) is defined as the development of secondary sexual characteristics before age 8 years in girls and 9 years in boys (1) and is due to premature activation of the hypothalamic-pituitary gonadal axis. It can be idiopathic, genetic or associated with central nervous system (CNS) abnormalities (3). Girls with CPP have a lower incidence of CNS abnormalities than boys, but this rate varies between studies (3–7). Moreover, the incidence of CNS abnormalities seems to increase with younger ages at puberty onset (1), although data are inconsistent (8). In light of ongoing discussions regarding the decreasing age of normal puberty (9, 10), the utility of brain MRI in girls with CPP is still a matter of debate.

This paper reports the first systematic review and meta-analysis to provide an overall estimate of the prevalence of CNS lesions in girls with CPP, with a particular focus on CPP in girls aged 6–8 years old. The authors identified 15 studies from six electronic databases from 1990 through December 2015, describing a total of 1853 girls with CPP aged <8 years. Across all studies, the overall incidence of positive MRI was 7% (excluding lesions with questionable relationship with CPP). From the five studies that stratified data by age, the pooled prevalence of positive MRI was 25% in girls <6 years vs. 3% in girls aged 6–8 years. A similar trend was observed in CPP girls aged <7 vs. 7–8 years old. The most common CNS lesion was hypothalamic hamartoma, which in most cases does not require surgical intervention. Across all CPP girls, the incidence of CNS tumours was 1.6%.

Thus, MRI should be performed in girls with CPP before 6 years old (1, 11, 12). However, there is no clear benefit of routine MRI in girls with CPP older than 6 years without any neurological concern; such decisions require a consideration of the likelihood of detecting an intracranial lesion requiring intervention.

References: 1. Carel JC, Eugster EA, Rogol A, Ghizzoni L, Palmert MR. 2009 Consensus statement on the use of gonadotropin-releasing hormone analgos in children. Pediatrics 123: e752–62.

2. Brito VN, Latronico AC, Arnhold IJ, Mendonça BB. 2008 Update on the etiology, diagnosis and therapeutic management of sexual precocity. Arq Bras Endocrinol Metab. 52: 18–31.

3. Chalumeau M, Chemaitilly W, Trivin C, Adan L, Breart G & Brauner R. 2002 Central precocious puberty in girls: an evidence-based diagnosis tree to predict central nervous system abnormalities. Pediatrics. 109:61–7.

4. Pedicelli S, Alessio P, Scirè G, Cappa M, Cianfarani S. 2014 Routine screening by brain magnetic resonance imaging is not indicated in every girl with onset of puberty between the ages of 6 and 8 years. J Clin Endocrinol Metab.; 99: 4455–61.

5. De Sanctis V, Corrias A, Rizzo V, Bertelloni S, Urso L, Galluzzi F, Pasquino AM, Pozzan G, Guarneri MP, Cisternino M, De Luca F, Gargantini L, Pilotta A, Sposito M, Tonini G. 2000 Etiology of central prococious puberty in males: the results of the Italian Study Group for Physiopathology of Puberty. J Pediatr Endocrinol Metab; 13:687–93.

6. Choi KH, Chung SJ, Kang MJ, Yoon JY, Lee JE, Shin CH, Yang SW. 2013 Boys with precocious or early puberty: incidence of pathological brain magnetic resonance imaging findings and factors related to newly developed brain lesions”. Ann Pediatr Endocrinol Metab. 18:183–90.

7. Ng SM, Kumar Y, Cody D, Smith CD, Didi M. 2003 Cranial MRI scans are indiated in all girls with central precocious puberty. Arch Dis Child. 88:414–8.

8. Mogensen SS, Aksglaede L, Mouritsen A, Sørensen K, Main KM, Gideon P, Juul A. 2012 Pathological and incidental findings on brain MRI in a single-center study of 229 consecutive girls with early or precocious puberty. PLoS One 7:e29829.

9. Herman-Giddens ME, Slora EJ, Wasserman RC, Bourdony CJ, Bhapkar MV, Koch GG, Hasemeier CM. 1997 Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research in Office Settings network. Pediatrics 99:505–12.

10. Kaplowitz PB, Oberfield SE. 1999 Reexamination of the age limit for defining when puberty is precocious in girls in the United States: implications for evaluation and treatment. Drug and Therapeutics and Executive Committees of the Lawson Wilkins Pediatric Endocrine Society. Pediatrics 104(Pt 1):936–41.

11. Kaplowitz PB. 2016 Do 6–8 year old girls with central precocious puberty need routine brain imaging? Int J Pediatr Endocrinol. 2016:19.

12. Chalumeau M, Hadjiathanasiou CG, Ng SM, Cassio A, Mul D, Cisternino M, Partsch CJ, Theodoridis C, Didi M, Cacciari E, Oostdijk W, Borghesi A, Sippell WG, Bréart G, Brauner R. 2003 Selecting girls with precocious puberty for brain imaging: validation of European evidence-based diagnosis rule. J Pediatr. 143:445–50