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Neuroimaging in 205 consecutive Children Diagnosed with Central Precocious Puberty in Denmark

Pediatric Research (2022)Cite this article

Abstract

Introduction

A brain magnetic resonance image (MRI) is considered part of routine evaluation in children diagnosed with central precocious puberty (CPP) to rule out intracranial pathology. We evaluated the occurrence of pathological findings on neuroimaging among children diagnosed with CPP.

Methods

A retrospective study based on an evaluation of 1544 children referred with early signs of puberty from 2009–2019. Of these, 205 children (29 boys) with confirmed CPP had a brain MRI performed, and we report MRI results, pubertal stage, bone age, and hormonal analyses. All abnormal MRI results were re-evaluated by a trained neuroradiologist.

Results

A new intracranial pathology was found by brain MRI in 6 out of 205 patients aged 1.5 to 6.1 years. The occurrence of intracranial pathology was 3/162 (1.8%) and 3/24 (12.5 %) in girls and boys respectively.

Conclusion

Organic causes of precocious puberty are more frequent in boys with CPP than in girls. No cases of organic CPP were seen above age 6.1 years of age. The age cut off value for routine brain MRI could be lowered to seven or perhaps even six years of age for girls, except in rapidly progressing puberty or presence of neurological symptoms.

Impact

In our study of children with central precocious puberty (CPP), intracranial pathology is a rare cause and occurs only in younger children. It supports the general trend, that younger children are at higher risk of having organic causes to CPP and supports the clinical practice, that only high-risk patients with CPP should undergo routine brain MRI.

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Fig. 1: MRI of the brain of the six subjects with intracranial pathology with marking around pathological finding.

References

  1. Eckert-lind C. et al. Worldwide Secular Trends in Age at Pubertal Onset Assessed by Breast Development Among Girls A Systematic Review and Meta-analysis. Published online 2020:1–12. https://doi.org/10.1001/jamapediatrics.2019.5881.

  2. Bräuner, E. V. et al. Trends in the incidence of central precocious puberty and normal variant puberty among children in Denmark, 1998 to 2017. JAMA Netw. Open. 3, e2015665 (2020).

    Article  Google Scholar 

  3. Day, F. R., Elks, C. E., Murray, A., Ong, K. K. & Perry, J. R. B. Puberty timing associated with diabetes, cardiovascular disease and also diverse health outcomes in men and women: the UK Biobank study. Sci. Rep. 5, 11208 (2015).

    Article  Google Scholar 

  4. Carel, J. C. & Léger, J. Precocious puberty. N. Engl. J. Med. 358, 2366–2377 (2008).

    CAS  Article  Google Scholar 

  5. Herman-Giddens, M. E. et al. 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 LP–505512 (1997).

    Article  Google Scholar 

  6. Teilmann, G., Pedersen, C. B., Jensen, T. K., Skakkebæk, N. E. & Juul, A. Prevalence and incidence of precocious pubertal development in Denmark: An epidemiologic study based on national registries. Pediatrics 116, 1323–1328 (2005).

    Article  Google Scholar 

  7. Cantas-Orsdemir, S., Garb, J. L. & Allen, H. F. Prevalence of cranial MRI findings in girls with central precocious puberty: A systematic review and meta-analysis. J. Pediatr. Endocrinol. Metab. 31, 701–710 (2018).

    Article  Google Scholar 

  8. Alikasifoglu, A., Vuralli, D., Gonc, E. N., Ozon, A. & Kandemir, N. Changing etiological trends in male precocious puberty: Evaluation of 100 cases with central precocious puberty over the last decade. Horm. Res. Paediatrics. 83, 340–344 (2015).

    CAS  Article  Google Scholar 

  9. Mogensen S. S. et al. Pathological and incidental findings on brain MRI in a single-center study of 229 consecutive girls with early or precocious puberty. PLoS ONE. 2012;7. https://doi.org/10.1371/journal.pone.0029829.

  10. Tinggaard, J. et al. The 2014 Danish references from birth to 20 years for height, weight and body mass index. Acta Paediatrica, Int. J. Paediatrics. 103, 214–224 (2014).

    Article  Google Scholar 

  11. Marshall W. A., Tanner J. M. Variations in Pattern of Pubertal Changes in Girls. Published online 1969.

  12. Marshall, W. A. & Tanner, J. M. Variations in the Pattern of Pubertal Changes in Boys. Arch. Dis. Child. 45, 13 LP–13 23 (1970).

    Article  Google Scholar 

  13. Thodberg, H. H., Kreiborg, S., Juul, A. & Pedersen, K. D. The BoneXpert method for automated determination of skeletal maturity. IEEE Trans. Med. Imaging 28, 52–66 (2009).

    Article  Google Scholar 

  14. Søeborg T. et al. Sex, age, pubertal development and use of oral contraceptives in relation to serum concentrations of DHEA, DHEAS, 17α-hydroxyprogesterone, Δ4-androstenedione, testosterone and their ratios in children, adolescents and young adults. Clinica Chimica Acta. 2014;437. https://doi.org/10.1016/j.cca.2014.06.018.

  15. Pedicelli, S., Alessio, P., Scirè, G., Cappa, M. & Cianfarani, S. 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, 4455–4461 (2014).

    CAS  Article  Google Scholar 

  16. Ng, S. M., Kumar, Y., Cody, D., Smith, C. S. & Didi, M. Cranial MRI scans are indicated in all girls with central precocious puberty. Arch. Dis. Child. 88, 414–417 (2003).

    CAS  Article  Google Scholar 

  17. Oh, Y. J., Park, H. K., Yang, S., Song, J. H. & Hwang, I. T. Clinical and radiological findings of incidental Rathke’s cleft cysts in children and adolescents. Ann. Pediatr. Endocrinol. Metab. 19, 20–26 (2014).

    Article  Google Scholar 

  18. Chalumeau, M. et al. Selecting girls with precocious puberty for brain imaging: Validation of European evidence-based diagnosis rule. J. Pediatrics. 143, 445–450 (2003).

    Article  Google Scholar 

  19. Yoon, J. S., So, C. H., Lee, H. S., Lim, J. S. & Hwang, J. S. The prevalence of brain abnormalities in boys with central precocious puberty may be overestimated. PLoS One. 13, 1–9 (2018).

    CAS  Google Scholar 

  20. Yoon, J. S., So, C. H., Lee, H. S., Lim, J. S. & Hwang, J. S. Prevalence of pathological brain lesions in girls with central precocious puberty: Possible overestimation? J. Korean Med. Sci. 33, 1–9 (2018).

    Article  Google Scholar 

  21. Chemaitilly, W. et al. Central precocious puberty: Clinical and laboratory features. Clin. Endocrinol. 54, 289–294 (2001).

    CAS  Article  Google Scholar 

  22. Chalumeau, M. et al. Central precocious puberty in girls: An evidence-based diagnosis tree to predict central nervous system abnormalities. Pediatrics 109, 61–67 (2002).

    Article  Google Scholar 

  23. Bridges, N. A., Christopher, J. A., Hindmarsh, P. C. & Brook, C. G. D. Sexual precocity: Sex incidence and aetiology. Arch. Dis. Child. 70, 116–118 (1994).

    CAS  Article  Google Scholar 

  24. Kornreich, L. et al. Central precocious puberty: Evaluation by neuroimaging. Pediatr. Radiol. 25, 7–11 (1995).

    CAS  Article  Google Scholar 

  25. Cisternino, M. et al. Etiology and age incidence of precocious puberty in girls: A multicentric study. J. Pediatr. Endocrinol. Metab. 13, 695–701 (2000).

    Article  Google Scholar 

  26. Taher, B. M. et al. Precocious puberty at an endocrine centre in Jordan. Eur. J. Clin. Investig. 34, 599–604 (2004).

    CAS  Article  Google Scholar 

  27. Choi, K. H. et al. 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 (2013).

    Article  Google Scholar 

  28. Soriano-Guillén, L. et al. Central precocious puberty in children living in Spain: Incidence, prevalence, and influence of adoption and immigration. J. Clin. Endocrinol. Metab. 95, 4305–4313 (2010).

    Article  Google Scholar 

  29. Bizzarri, C. et al. 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. 99, 433–439 (2014).

    CAS  Article  Google Scholar 

  30. Chiu, C. F., Wang, C. J., Chen, Y. P. & Lo, F. S. Pathological and Incidental Findings in 403 Taiwanese Girls With Central Precocious Puberty at Initial Diagnosis. Front. Endocrinol. 11, 256 (2020). https://www.frontiersin.org/article/10.3389/fendo.2020.00256.

    Article  Google Scholar 

  31. Chen, Y. & Liu, J. Do most 7- to 8-year-old girls with early puberty require extensive investigation and treatment? J. Pediatr. Adolesc. Gynecol. 34, 124–129 (2021).

    Article  Google Scholar 

  32. Helvacıoğlu, D. et al. Cranial MRI abnormalities and long-term follow-up of the lesions in 770 girls with central precocious puberty. J. Clin. Endocrinol. Metab. 106, e2557–e2566 (2021).

    Article  Google Scholar 

  33. Kim, S. H. et al. Findings of brain magnetic resonance imaging in girls with central precocious puberty compared with girls with chronic or recurrent headache. J. Clin. Med. 10, 2206 (2021).

    Article  Google Scholar 

  34. Bajpai, A., Sharma, J., Kabra, M., Gupta, A. K. & Menon, P. S. N. Precocious puberty: Clinical and endocrine profile and factors indicating neurogenic precocity in Indian children. J. Pediatr. Endocrinol. Metab. 15, 1173–1181 (2002).

    PubMed  Google Scholar 

  35. Listernick, R., Charrow, J. & Gutmann, D. H. Intracranial gliomas in neurofibromatosis type 1. Am. J. Med. Genet. - Semin. Med. Genet. 89, 38–44 (1999).

    CAS  Article  Google Scholar 

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Authors and Affiliations

  1. Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

    Anna B. Hansen, Christoffer H. Renault, Ditte Wøjdemann, Anders Juul & Rikke Beck Jensen

  2. Department of Diagnostic Radiology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

    Peter Gideon

  3. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

    Anders Juul & Rikke Beck Jensen

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  1. Anna B. Hansen
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Contributions

Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data: A.B.H., C.H.R., D.W., P.G., A.J., R.B.J Drafting the article or revising it critically for important intellectual content: A.B.H., A.J., R.B.J. Approval of the version to be published: A.B.H., C.H.R., D.W., P.G., A.J., R.B.J.

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Correspondence to Rikke Beck Jensen.

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The authors declare no competing interests.

Consent Statement

This study was approved by the Danish Health Authorities no. 31-1521-50 and has been processes in concordance with the General Data Protection Regulation (GDPR) and Danish Health Law.

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Hansen, A.B., Renault, C.H., Wøjdemann, D. et al. Neuroimaging in 205 consecutive Children Diagnosed with Central Precocious Puberty in Denmark. Pediatr Res (2022). https://doi.org/10.1038/s41390-022-02047-2

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