Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter March 8, 2019

Idiopathic gonadotropin-independent precocious puberty – is regular surveillance required?

  • Ved Bhushan Arya ORCID logo and Justin H. Davies EMAIL logo

Abstract

Context

Germ cell tumours (GCTs) secreting β-human chorionic gonadotropin (β-HCG) are a rare cause of gonadotropin-independent precocious puberty (GIPP).

Case description

A 5.7-year-old boy presented with GIPP. Investigations to elucidate the underlying cause revealed elevated serum β-HCG. Ultrasound of the abdomen and testes, urine steroid profile, bone isotope scan, and sequencing of the luteinizing hormone receptor gene (LHCGR) were normal. Despite paired serum and cerebrospinal fluid β-HCG measurement suggesting local (brain) β-HCG production, repeated magnetic resonance imaging (MRI) of the brain as well as MRI of the mediastinum did not identify a tumour source of persistently elevated serum β-HCG. Treatment with cyproterone acetate and spironolactone was unsuccessful. Increase in testicular volumes prompted the addition of a gonadotropin releasing hormone (GnRH) analogue. Due to progressing virilisation and skeletal maturation, treatment was changed to a combination of anastrozole and bicalutamide at the age of 7 years. One year later, serum β-HCG and testosterone concentrations spontaneously normalised followed by reductions in the height velocity, skeletal maturation and virilisation. The proband achieved his genetic height potential. No medication side effects were observed. The patient subsequently presented with non-secreting pineal GCT at 14 years, 8½ years after his initial presentation with GIPP.

Conclusions

Our case highlights that GIPP with no definite underlying aetiology at diagnosis should be considered as a prodrome for GCTs, and regular radiological surveillance for earlier tumour identification is warranted. To the best of our knowledge, our case is the first reported case of the use of anastrozole and bicalutamide in the setting of idiopathic GIPP. The good height outcome in our case warrants the trial of anastrozole and bicalutamide in similar cases.


Corresponding author: Dr. Justin H. Davies, Consultant Paediatric Endocrinologist, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK; and Department of Paediatric Endocrinology, Southampton Children’s Hospital, University Hospital Southampton NHS Trust, Southampton SO16 6YD, UK, Phone: +44 (0) 2381 206985

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission. VBA collected the data and wrote the manuscript. JHD critically appraised the manuscript and conceptualised the idea of manuscript. JHD is guarantor of this work.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Echevarria ME, Fangusaro J, Goldman S. Pediatric central nervous system germ cell tumors: a review. Oncologist 2008;13:690–9.10.1634/theoncologist.2008-0037Search in Google Scholar PubMed

2. Atay Z, Yesilkaya E, Erdeve SS, Turan S, Akin L, et al. The etiology and clinical features of non-CAH gonadotropin-independent precocious puberty: a multicenter study. J Clin Endocrinol Metab 2016;101:1980–8.10.1210/jc.2015-3500Search in Google Scholar PubMed

3. Winston K, Stein R. Mixed germ cell tumour after testotoxicosis. Clin Endocrinol (Oxf) 2014;81:786–7.10.1111/cen.12416Search in Google Scholar PubMed

4. Choi KH, Chung SJ, Kang MJ, Yoon JY, Lee JE, 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 2013;18:183–90.10.6065/apem.2013.18.4.183Search in Google Scholar PubMed PubMed Central

5. Di Iorgi N, Allegri AE, Napoli F, Calcagno A, Calandra E, et al. Central diabetes insipidus in children and young adults: etiological diagnosis and long-term outcome of idiopathic cases. J Clin Endocrinol Metab 2014;99:1264–72.10.1210/jc.2013-3724Search in Google Scholar PubMed

6. Crawford JR, Santi MR, Vezina G, Myseros JS, Keating RF, et al. CNS germ cell tumor (CNSGCT) of childhood: presentation and delayed diagnosis. Neurology 2007;68:1668–73.10.1212/01.wnl.0000261908.36803.acSearch in Google Scholar PubMed

7. Okochi Y, Nihashi T, Fujii M, Kato K, Okada Y, et al. Clinical use of (11)C-methionine and (18)F-FDG-PET for germinoma in central nervous system. Ann Nucl Med 2014;28:94–102.10.1007/s12149-013-0787-4Search in Google Scholar PubMed PubMed Central

8. Nogueira K, Liberman B, Pimentel-Filho FR, Goldman J, Silva ME, et al. hCG-secreting pineal teratoma causing precocious puberty: report of two patients and review of the literature. J Pediatr Endocrinol Metab 2002;15:1195–201.10.1515/JPEM.2002.15.8.1195Search in Google Scholar PubMed

9. Winder AD, Mora AS, Berry E, Lurain JR. The “hook effect” causing a negative pregnancy test in a patient with an advanced molar pregnancy. Gynecol Oncol Rep 2017;21:34–6.10.1016/j.gore.2017.06.008Search in Google Scholar PubMed PubMed Central

10. Kreher NC, Pescovitz OH, Delameter P, Tiulpakov A, HochbergZ. Treatment of familial male-limited precocious puberty with bicalutamide and anastrozole. J Pediatr 2006;149:416–20.10.1016/j.jpeds.2006.04.027Search in Google Scholar PubMed

11. Wit JM, Hero M, Nunez SB. Aromatase inhibitors in pediatrics. Nat Rev Endocrinol 2011;8:135–47.10.1038/nrendo.2011.161Search in Google Scholar PubMed

12. Reiter EO, Mauras N, McCormick K, Kulshreshtha B, AmrheinJ, et al. Bicalutamide plus anastrozole for the treatment of gonadotropin-independent precocious puberty in boys with testotoxicosis: a phase II, open-label pilot study (BATT). J Pediatr Endocrinol Metab 2010;23:999–1009.10.1515/jpem.2010.161Search in Google Scholar PubMed

Received: 2018-09-27
Accepted: 2019-01-14
Published Online: 2019-03-08
Published in Print: 2019-04-24

©2019 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 30.3.2024 from https://www.degruyter.com/document/doi/10.1515/jpem-2018-0419/html
Scroll to top button