Keywords
gonadotropin-independent
McCune-Albright
syndrome
ovarian cysts
aromatase inhibitors
How to Cite
Abstract
Peripheral precocious puberty (PPP), also known as gonadotropin-independent precocious puberty, refers to the premature development of secondary sexual characteristics caused by steroid hormone production, independent of hypothalamicpituitary-gonadal activation. Although rarer than the central form, early recognition is essential to prevent growth and psychosocial complications. This review summarizes current knowledge on the pathophysiology, classification, diagnosis and treatment of PPP, emphasizing recent evidence and therapeutic advances; taking into account that this is a condition with significant clinical and etiological heterogeneity that poses a diagnostic challenge. Accurate identification of the cause allows for specific treatment and prevention of complications.
References
Laufer D, Davrieux M, García L. Desarrollo puberal en la niña y adolescente. Arch Pediatr Urug, 2023 Jun;94(s1):e403. [Disponible en: http://www.scielo.edu.uy/pdf/adp/v94nnspe1/1688-1249-adp-94-nspe1-e403.pdf][Último acceso: 5/12/2025]
Soriano Guillén L, Argente J. Pubertad precoz periférica: fundamentos clínicos y diagnóstico-terapéuticos. An Pediatr (Barc). 2012 Apr;76(4):229.e1-10. doi: 10.1016/j.anpedi.2011.09.014. Epub 2011 Nov 25. PMID: 22119235.
Kang E, Cho JH, Choi JH, Yoo HW. Etiology and therapeutic outcomes of children with gonadotropin-independent precocious puberty. Ann Pediatr Endocrinol Metab. 2016 Sep;21(3):136-142. doi: 10.6065/apem.2016.21.3.136. Epub 2016 Sep 30. PMID: 27777905; PMCID: PMC5073159.
Eugster EA. Peripheral precocious puberty: causes and current management. Horm Res. 2009 Jan;71 Suppl 1:64-7. doi: 10.1159/000178041. Epub 2009 Jan 21. PMID: 19153509.
M Pombo Arias, J Argemí. Tratado de endocrinología pediátrica. Madrid: Díaz De Santos; 1997.
Albright F, Butler AM, Hampton AO, Smith P. Syndrome characterized by osteitis fibrosa disseminata, areas of pigmentation and endocrine dysfunction, with precocious puberty in females. N Engl J Med. 1937;216:727-46.[Disponible en:https://www.nejm.org/doi/full/10.1056/NEJM193704292161701] [Último acceso: 5/12/2025]
Spencer T, Pan KS, Collins MT, Boyce AM. The Clinical Spectrum of McCune-Albright Syndrome and Its Management. Horm Res Paediatr. 2019;92(6):347-356. doi: 10.1159/000504802. Epub 2019 Dec 19. PMID: 31865341; PMCID: PMC7302983.
Phornphutkul C, Okubo T, Wu K, Harel Z, Tracy TF Jr, Pinar H, Chen S, Gruppuso PA, Goodwin G. Aromatase p450 expression in a feminizing adrenal adenoma presenting as isosexual precocious puberty. J Clin Endocrinol Metab. 2001 Feb;86(2):649-52. doi: 10.1210/jcem.86.2.7201. PMID: 11158024.
Papanikolaou A, Michala L. Autonomous Ovarian Cysts in Prepubertal Girls. How Aggressive Should We Be? A Review of the Literature. J Pediatr Adolesc Gynecol. 2015 Oct;28(5):292-6. doi: 10.1016/j.jpag.2015.05.004. Epub 2015 May 16. PMID: 26228588.
Mieszczak J, Eugster EA. Treatment of precocious puberty in McCune-Albright syndrome. Pediatr Endocrinol Rev. 2007 Aug;4 Suppl 4(0 4):419-22. PMID: 17982389; PMCID: PMC4118734.
Bercaw-Pratt JL, Moorjani TP, Santos XM, Karaviti L, Dietrich JE. Diagnosis and Management of Precocious Puberty in Atypical Presentations of McCune-Albright Syndrome: A Case Series Review. Journal of Pediatric and Adolescent Gynecology [Internet]. 2011 Nov 3;25(1):e9–13. [Disponible en: https://www.sciencedirect.com/science/article/abs/pii/S1083318811003779][Último acceso: 5/12/2025]
Dhivyalakshmi J, Bhattacharyya S, Reddy R, Arulselvi KI. Precocious pseudopuberty due to ovarian causes. Indian Pediatr. 2014 Oct;51(10):831-3. PMID: 25362018.
de Sousa G, Wunsch R, Andler W. Precocious pseudopuberty due to autonomous ovarian cysts: a report of ten cases and long-term follow-up. Hormones (Athens). 2008 Apr- Jun;7(2):170-4. doi: 10.1007/BF03401509. PMID: 18477555.
Koukourakis GV, Kouloulias VE, Koukourakis MJ, Zacharias GA, Papadimitriou C, Mystakidou K, et al. Granulosa cell tumor of the ovary: tumor review. Integr Cancer Ther. 2008 Sep;7(3):204-15. doi: 10.1177/1534735408322845. PMID: 18815151.
Tobia González SG, Urresti A, Varea S, Braschi JC. Gonadoblastoma in an anatomical normal man. Case report and bibliography review. RevArg de Urol.2000; 65(1):23. [Disponible en: https://www.revistasau.org/index.php/revista/article/viewFile/2981/2930][Último acceso: 5/12/2025]
Roth LM, Cheng L. Gonadoblastoma: origin and outcome. Hum Pathol. 2020 Jun;100:47-53. doi: 10.1016/j.humpath.2019.11.005. Epub 2019 Dec 2. PMID: 31805291.
Grand T, Hermann AL, Gérard M, Arama E, Ouerd L, Garrouche N, et al. Precocious puberty related to Leydig cell testicular tumor: the diagnostic imaging keys. Eur J Med Res. 2022 May 12;27(1):67. doi: 10.1186/s40001-022-00692-1. PMID: 35550623; PMCID: PMC9097322.
Haddad NG, Eugster EA. Peripheral precocious puberty including congenital adrenal hyperplasia: causes, consequences, management and outcomes. Best Pract Res Clin
Endocrinol Metab. 2019 Jun;33(3):101273. doi: 10.1016/j.beem.2019.04.007. Epub 2019 Apr 13. PMID: 31027974.
Ferrito L, Cobellis G, Giobbi D, Pannunzi CP, Iannilli A, Cherubini V. Peripheral Precocious Puberty due to Functioning Adrenocortical Tumor: Description of Two Cases. J Pediatr Adolesc Gynecol. 2017 Feb;30(1):e1-e4. doi: 10.1016/j.jpag.2016.09.006. Epub 2016 Sep 22. PMID: 27666809.
Young J, Bulun SE, Agarwal V, Couzinet B, Mendelson CR, Simpson ER, et al. Aromatase expression in a feminizing adrenocortical tumor. J Clin Endocrinol Metab. 1996 Sep;81(9):3173-6. doi: 10.1210/jcem.81.9.8784064. PMID: 8784064.
Shibata N, Nyuzuki H, Sasaki S, Ogawa Y, Okada M, Nagasaki K. Peripheral precocious puberty in a girl with an intracranial hCG-producing tumor: case report and literature review. Endocr J. 2021 Dec 28;68(12):1463-1467. doi: 10.1507/endocrj.EJ21-0117. Epub 2021 Jul 17. PMID: 34275973.
Nella AA, Kaplowitz PB, Ramnitz MS, Nandagopal R. Benign vaginal bleeding in 24 prepubertal patients: clinical, biochemical and imaging features. J Pediatr Endocrinol Metab. 2014 Sep;27(9-10):821-5. doi: 10.1515/jpem-2013-0415. PMID: 24756050.
Baranowski E, Högler W. An unusual presentation of acquired hypothyroidism: the Van Wyk-Grumbach syndrome. Eur J Endocrinol. 2012 Mar;166(3):537-42. doi: 10.1530/EJE-11-0494. Epub 2011 Dec 14. PMID: 22170796.
Cabrera SM, DiMeglio LA, Eugster EA. Incidence and characteristics of pseudoprecocious puberty because of severe primary hypothyroidism. J Pediatr. 2013 Mar;162(3):637-9. https://pubmed.ncbi.nlm.nih.gov/23196132/
Martinez-Pajares JD, Diaz-Morales O, Ramos-Diaz JC, Gomez- Fernandez E. Peripheral precocious puberty due to inadvertent exposure to testosterone: case report and review of the literature. J Pediatr Endocrinol Metab. 2012;25(9- 10):1007-12. doi: 10.1515/jpem-2012-0124. PMID: 23426834.
Pasquino AM, Balducci R, Manca Bitti ML, Spadoni GL, Boccherini B. Transient pseudo-precocious puberty by probable oestrogen intake in 3 girls. Arch Dis Child. 1982 Dec;57(12):954-6. doi: 10.1136/adc.57.12.954. PMID: 6758707; PMCID: PMC1628083.
Gurnurkar S, DiLillo E, Carakushansky M. A Case of Familial Male-limited Precocious Puberty with a Novel Mutation. J Clin Res Pediatr Endocrinol. 2021 Jun 2;13(2):239-244. doi: 10.4274/jcrpe.galenos.2020.2020.0067. Epub 2020 Aug 6. PMID: 32757547; PMCID: PMC8186329.
Qudsiya Z, Gupta V. Precocious Pseudopuberty [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2021. [Disponible en: https://www.ncbi.nlm.nih.gov/books/NBK560588/][Último acceso: 9/12/2025]
Pasternak Y, Friger M, Loewenthal N, Haim A, Hershkovitz E. The utility of basal serum LH in prediction of central precocious puberty in girls. Eur J Endocrinol. 2012 Feb;166(2):295- 9. doi: 10.1530/EJE-11-0720. Epub 2011 Nov 14. PMID: 22084156.
Lee DS, Ryoo NY, Lee SH, Kim S, Kim JH. Basal luteinizing hormone and follicular stimulating hormone: is it sufficient for the diagnosis of precocious puberty in girls? Ann Pediatr Endocrinol Metab. 2013 Dec;18(4):196-201. doi: 10.6065/apem.2013.18.4.196. Epub 2013 Dec 31. PMID: 24904877;
PMCID: PMC4027088.
Cantas-Orsdemir S, Eugster EA. Update on central precocious puberty: from etiologies to outcomes. Expert Rev Endocrinol Metab. 2019 Mar;14(2):123-130. doi: 10.1080/17446651.2019.1575726. Epub 2019 Feb 12. PMID: 30763521.
Talarico V, Rodio MB, Viscomi A, Galea E, Galati MC, Raiola G. The role of pelvic ultrasound for the diagnosis and management of central precocious puberty: An update. Acta Biomed. 2021 Nov 4;92(5):e2021480. doi: 10.23750/abm.v92i5.12295. PMID: 34738554; PMCID: PMC8689311.
Outwater EK, Siegelman ES, Hunt JL. Ovarian teratomas:tumor types and imaging characteristics. Radiographics. 2001;21(2):475-90. [Disponible en: https://pubs.rsna.org/doi/10.1148/radiographics.21.2.g01mr09475?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed][Último acceso: 9/12/2025]
Dunnick NR, Korobkin M, Francis I. Adrenal radiology: distinguishing benign from malignant adrenal masses. AJR Am J Roentgenol. 1996;167(4):861-7 [Disponible en: https://www.ajronline.org/doi/10.2214/ajr.167.4.8819372][Último acceso: 9/12/2025]
Estrada A, Boyce AM, Brillante BA, Guthrie LC, Gafni RI, Collins MT. Long-term outcomes of letrozole treatment for precocious puberty in girls with McCune-Albright syndrome. Eur J Endocrinol. 2016 Nov;175(5):477-483. doi: 10.1530/EJE-16-0526. Epub 2016 Aug 25. PMID: 27562402; PMCID:PMC5066167.
Neyman A, Eugster EA. Treatment of Girls and Boys with McCune-Albright Syndrome with Precocious Puberty - Update 2017. Pediatr Endocrinol Rev. 2017 Dec;15(2):136-141. doi: 10.17458/per.vol15.2017.nau.treatmentgirlsboys. PMID: 29292624; PMCID: PMC5808444.
Ng SM, Apperley LJ, Upradrasta S, Natarajan A. Vaginal Bleeding in Pre-pubertal Females. J Pediatr Adolesc Gynecol. 2020 Aug;33(4):339-342. doi: 10.1016/j.jpag.2020.01.152. Epub 2020 Feb 6. PMID: 32035994.
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