Skip to main content

Advertisement

SpringerLink
Log in

Central precocious puberty may be a manifestation of endocrine dysfunction in pediatric patients with mitochondrial disease

  • Original Article
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

We retrospectively reviewed the data of 140 female pediatric patients with rare mitochondrial diseases (MDs) confirmed using muscle biopsy. We evaluated patients who were diagnosed with central precocious puberty (PP) with early pubertal development to determine whether PP is a clinical manifestation of MDs. We also examined the clinical, auxiological, laboratory, and radiological parameters after 1 year of gonadotropin-releasing hormone treatment for central PP. Among the 140 girls with MDs, 29 had early pubertal development and underwent endocrine evaluation. Ten (7.1%) patients were diagnosed with central PP; the prevalence of central PP was higher than was that previously thought. Patients with central PP exhibited bone age advancement over 1 year and increased sex hormone levels despite their young age at diagnosis. Serum estradiol levels were significantly higher in younger patients than in older patients (P = 0.004). Patients with central PP treated with gonadotropin-releasing hormone had favorable outcomes, and their pubertal development was suppressed for 1 year.

Conclusion: Central PP may be a manifestation of endocrine dysfunction in young girls with MDs.

What is Known:

• The general characteristics of mitochondrial diseases include developmental delays and retarded growth.

• Precocious puberty has rarely been suggested as a clinical manifestation of mitochondrial diseases.

What is New:

• Among the 140 girls with mitochondrial diseases, 10 (7.1%) were diagnosed with central precocious puberty.

• Serum estradiol levels were significantly higher in younger patients than in older patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

E2:

Estradiol

FSH:

Follicular-stimulating hormone

GnRH:

Gonadotropin-releasing hormone

LH:

Luteinizing hormone

MD:

Mitochondrial disease

PP:

Precocious puberty

References

  1. Lee YM (2012) Mitochondrial diseases. J Epilepsy Res 2(1):1–4. https://doi.org/10.14581/jer.12001

    Article  PubMed  PubMed Central  Google Scholar 

  2. Ardissone A, Lamantea E, Invernizzi F, Zeviani M, Genitrini S, Moroni I, Uziel G (2014) Mitochondrial diseases in childhood. Curr Mol Med 14(8):1069–1078. https://doi.org/10.2174/1566524014666141010155317

    Article  CAS  PubMed  Google Scholar 

  3. Gropman AL (2004) The neurological presentations of childhood and adult mitochondrial disease: established syndromes and phenotypic variations. Mitochondrion 4(5–6):503–520. https://doi.org/10.1016/j.mito.2004.07.009

    Article  CAS  PubMed  Google Scholar 

  4. Kim SH, Huh K, Won S, Lee KW, Park MJ (2015) A significant increase in the incidence of central precocious puberty among Korean girls from 2004 to 2010. PLoS One 10(11):e0141844. https://doi.org/10.1371/journal.pone.0141844

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kim YJ, Kwon A, Jung MK, Kim KE, Suh J, Chae HW, Kim DH, Ha S, Seo GH, Kim HS (2019) Incidence and prevalence of central precocious puberty in Korea: an epidemiologic study based on a national database. J Pediatr 208:221–228. https://doi.org/10.1016/j.jpeds.2018.12.022

    Article  PubMed  Google Scholar 

  6. Berberoglu M (2009) Precocious puberty and normal variant puberty: definition, etiology, diagnosis and current management. J Clin Res Pediatr Endocrinol 1(4):164–174. https://doi.org/10.4274/jcrpe.v1i4.3

    Article  PubMed  Google Scholar 

  7. Nissenkorn A, Zeharia A, Lev D, Fatal-Valevski A, Barash V, Gutman A, Harel S, Lerman-Sagie T (1999) Multiple presentation of mitochondrial disorders. Arch Dis Child 81(3):209–214. https://doi.org/10.1136/adc.81.3.209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Al-Gadi IS, Haas RH, Falk MJ, Goldstein A, McCormack SE (2018) Endocrine disorders in primary mitochondrial disease. J Endocr Soc 2(4):361–373. https://doi.org/10.1210/js.2017-00434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bernier FP, Boneh A, Dennett X, Chow CW, Cleary MA, Thorburn DR (2002) Diagnostic criteria for respiratory chain disorders in adults and children. Neurology 59(9):1406–1411

    Article  CAS  Google Scholar 

  10. Lee PA (1999) Central precocious puberty. An overview of diagnosis, treatment, and outcome. Endocrinol Metab Clin N Am 28(4):901–918 xi

    Article  CAS  Google Scholar 

  11. Latronico AC, Brito VN, Carel JC (2016) Causes, diagnosis, and treatment of central precocious puberty. Lancet Diabetes Endocrinol 4(3):265–274. https://doi.org/10.1016/S2213-8587(15)00380-0

    Article  PubMed  Google Scholar 

  12. Ahn Y, Choi S, Sohn M (2013) Adiposity of Korean school-age children measured by national and international growth charts. Res Nurs Health 36(1):16–25. https://doi.org/10.1002/nur.21510

    Article  PubMed  Google Scholar 

  13. Yim CH, Kim GH, Eun BL (2017) Usefulness of the Korean Developmental Screening Test for infants and children for the evaluation of developmental delay in Korean infants and children: a single-center study. Korean J Pediatr 60(10):312–319. https://doi.org/10.3345/kjp.2017.60.10.312

    Article  PubMed  PubMed Central  Google Scholar 

  14. van den Ouweland JM, Lemkes HH, Ruitenbeek W, Sandkuijl LA, de Vijlder MF, Struyvenberg PA, van de Kamp JJ, Maassen JA (1992) Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness. Nat Genet 1(5):368–371. https://doi.org/10.1038/ng0892-368

    Article  PubMed  Google Scholar 

  15. Luoma P, Melberg A, Rinne JO, Kaukonen JA, Nupponen NN, Chalmers RM, Oldfors A, Rautakorpi I, Peltonen L, Majamaa K, Somer H, Suomalainen A (2004) Parkinsonism, premature menopause, and mitochondrial DNA polymerase gamma mutations: clinical and molecular genetic study. Lancet 364(9437):875–882. https://doi.org/10.1016/S0140-6736(04)16983-3

    Article  CAS  PubMed  Google Scholar 

  16. Lamperti C, Diodato D, Lamantea E, Carrara F, Ghezzi D, Mereghetti P, Rizzi R, Zeviani M (2012) MELAS-like encephalomyopathy caused by a new pathogenic mutation in the mitochondrial DNA encoded cytochrome c oxidase subunit I. Neuromuscul Disord 22(11):990–994. https://doi.org/10.1016/j.nmd.2012.06.003

    Article  PubMed  Google Scholar 

  17. Le Moal J, Rigou A, Le Tertre A, De Crouy-Channel P, Leger J, Carel JC (2018) Marked geographic patterns in the incidence of idiopathic central precocious puberty: a nationwide study in France. Eur J Endocrinol 178(1):33–41. https://doi.org/10.1530/EJE-17-0379

    Article  PubMed  Google Scholar 

  18. Papadimitriou A, Nicolaidou P, Fretzayas A, Chrousos GP (2010) Clinical review: constitutional advancement of growth, a.k.a. early growth acceleration, predicts early puberty and childhood obesity. J Clin Endocrinol Metab 95(10):4535–4541. https://doi.org/10.1210/jc.2010-0895

    Article  CAS  PubMed  Google Scholar 

  19. Lucaccioni L, Trevisani V, Marrozzini L, Bertoncelli N, Predieri B, Lugli L, Berardi A, Iughetti L (2020) Endocrine-disrupting chemicals and their effects during female puberty: a review of current evidence. Int J Mol Sci 21(6). https://doi.org/10.3390/ijms21062078

  20. Bulus AD, Asci A, Erkekoglu P, Balci A, Andiran N, Kocer-Gumusel B (2016) The evaluation of possible role of endocrine disruptors in central and peripheral precocious puberty. Toxicol Mech Methods 26(7):493–500. https://doi.org/10.3109/15376516.2016.1158894

    Article  CAS  PubMed  Google Scholar 

  21. Brix N, Ernst A, Lauridsen LLB, Parner ET, Arah OA, Olsen J, Henriksen TB, Ramlau-Hansena CH (2020) Childhood overweight and obesity and timing of puberty in boys and girls: cohort and sibling-matched analyses. Int J Epidemiol 49:834–844. https://doi.org/10.1093/ije/dyaa056

    Article  PubMed  PubMed Central  Google Scholar 

  22. Schaefer AM, Walker M, Turnbull DM, Taylor RW (2013) Endocrine disorders in mitochondrial disease. Mol Cell Endocrinol 379(1–2):2–11. https://doi.org/10.1016/j.mce.2013.06.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wolny S, McFarland R, Chinnery P, Cheetham T (2009) Abnormal growth in mitochondrial disease. Acta Paediatr 98(3):553–554. https://doi.org/10.1111/j.1651-2227.2008.01148.x

    Article  CAS  PubMed  Google Scholar 

  24. Wheeler MD, Styne DM (1990) Diagnosis and management of precocious puberty. Pediatr Clin N Am 37(6):1255–1271

    Article  CAS  Google Scholar 

  25. Chen M, Eugster EA (2015) Central precocious puberty: update on diagnosis and treatment. Paediatr Drugs 17(4):273–281. https://doi.org/10.1007/s40272-015-0130-8

    Article  PubMed  PubMed Central  Google Scholar 

  26. Brauner R, Couto-Silva AC, Chemaitilly W, Adan L, Trivin C (2005) Central precocious puberty in girls: prediction of the etiology. Arch Pediatr 12(11):1661–1664. https://doi.org/10.1016/j.arcped.2005.09.003

    Article  CAS  PubMed  Google Scholar 

  27. Chow J, Rahman J, Achermann JC, Dattani MT, Rahman S (2017) Mitochondrial disease and endocrine dysfunction. Nat Rev Endocrinol 13(2):92–104. https://doi.org/10.1038/nrendo.2016.151

    Article  CAS  PubMed  Google Scholar 

  28. Selin AA, Lobysheva NV, Nesterov SV, Skorobogatova YA, Byvshev IM, Pavlik LL, Mikheeva IB, Moshkov DA, Yaguzhinsky LS, Nartsissov YR (2016) On the regulative role of the glutamate receptor in mitochondria. Biol Chem 397(5):445–458. https://doi.org/10.1515/hsz-2015-0289

    Article  CAS  PubMed  Google Scholar 

  29. Jackson JG, O’Donnell JC, Takano H, Coulter DA, Robinson MB (2014) Neuronal activity and glutamate uptake decrease mitochondrial mobility in astrocytes and position mitochondria near glutamate transporters. J Neurosci 34(5):1613–1624. https://doi.org/10.1523/JNEUROSCI.3510-13.2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Brook CG (1999) Mechanism of puberty. Horm Res 51(Suppl 3):52–54. https://doi.org/10.1159/000053162

    Article  CAS  PubMed  Google Scholar 

  31. Stojilkovic SS, Krsmanovic LZ, Spergel DJ, Catt KJ (1994) Gonadotropin-releasing hormone neurons: intrinsic pulsatility and receptor-mediated regulation. Trends Endocrinol Metab 5(5):201–209

    Article  CAS  Google Scholar 

  32. Chiu CF, Wang CJ, Chen YP, Lo FS (2020) Pathological and incidental findings in 403 Taiwanese girls with central precocious puberty at initial diagnosis. Front Endocrinol (Lausanne) 11:256. https://doi.org/10.3389/fendo.2020.00256

    Article  Google Scholar 

  33. Roth C, Schmidberger H, Lakomek M, Witt O, Wuttke W, Jarry H (2001) Reduction of gamma-aminobutyric acid-ergic neurotransmission as a putative mechanism of radiation induced activation of the gonadotropin releasing-hormone-pulse generator leading to precocious puberty in female rats. Neurosci Lett 297(1):45–48

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, Gangnam Severance Hospital, Severance Children’s Hospital, Yonsei University College of Medicine, 211 Eonjuro, Seodaemun-gu, Seoul, South Korea

    Hyun-Wook Chae, Ji-Hoon Na, Ahreum Kwon, Ho-Seong Kim & Young-Mock Lee

Authors
  1. Hyun-Wook Chae
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ji-Hoon Na
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ahreum Kwon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ho-Seong Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Young-Mock Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HWC researched, wrote, and reviewed the manuscript. JHN conceptualized the study and collected data. AK prepared the tables and figure. HSK contributed to the discussion and reviewed the manuscript. YML researched and reviewed/edited the manuscript. YML is guarantor of this work and, as such, had complete access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors have reviewed the manuscript and have approved the submitted and published versions.

Corresponding author

Correspondence to Young-Mock Lee.

Ethics declarations

All procedures were approved by the Institutional Review Board (IRB) of Gangnam Severance Hospital, Seoul, South Korea (IRB number 3-2015-0135). Informed consent was obtained from the parent/legal guardian of all patients, and all methods were performed in accordance with the relevant guidelines and regulations of the IRB.

Conflict of interest

The authors declare that there are no conflicts of interest.

Additional information

Communicated by Peter de Winter

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chae, HW., Na, JH., Kwon, A. et al. Central precocious puberty may be a manifestation of endocrine dysfunction in pediatric patients with mitochondrial disease. Eur J Pediatr 180, 425–432 (2021). https://doi.org/10.1007/s00431-020-03804-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-020-03804-3

Keywords

Search

Navigation