Gonadotropin-dependent Pubertal Disorders Are Common in Patients with Virilizing Adrenocortical Tumors in Childhood

Overview

Journal Endocr Connect

Specialty Endocrinology

Date 2019 Apr 9

PMID 30959478

Citations 3

Authors

Monica F Stecchini

Zilda Braid

Candy B More

Davi C Aragon

Margaret Castro

Ayrton C Moreira

Sonir R Antonini

Affiliations

Soon will be listed here.

Abstract

Objective: To investigate the impact of early exposure to androgen excess on gonadotropin-dependent puberty (GDP) and final height (FH) of patients with androgen-secreting adrenocortical tumors (ACT) in childhood.

Methods: Retrospective cohort study. Occurrence of GDP and achievement of FH were evaluated. Central precocious puberty (CPP) and early fast puberty (EFP) were considered pubertal disorders. Patients with normal puberty and pubertal disorders were compared.

Results: The study included 63 patients (44F), followed in a single institution from 1975 until 2017. At diagnosis of ACT, median age was 25.8 months; duration of signs, 6 months; stature SDS, 0.5 (-3.6 to 3.9) and bone age advancement, 14.7 months (-27.9 to 85.4). To date, 37 patients developed GDP: 26 had normal puberty; one, precocious thelarche; seven, CPP and three, EFP. GnRHa effectively treated CPP/EFP. Tall stature and older age at diagnosis of ACT were associated with risk of CPP alone (RR 4.17 (95% CI 1.17-14.80)) and CPP/EFP (RR 3.0 (95% CI 1.04-8.65)). Recurrence/metastasis during follow-up were associated with risk of CPP alone (RR 4.17 (95% CI 1.17-14.80)) and CPP/EFP (RR 3.0 (95% CI 1.12-8.02)). Among the 19 patients that reached FH, stature SDS dropped from 1.4 to -0.02 since diagnosis of ACT (P = 0.01). Seventeen achieved normal FH. There was no difference in FH SDS between patients with normal puberty and pubertal disorders (P = 0.75).

Conclusions: Gonadotropin-dependent pubertal disorders are common in patients with androgen-secreting ACT in childhood. FH is usually not impaired. The study reinforces the importance of close follow-up after surgery to identify and treat consequences of early exposure to androgen excess.

Citing Articles

Central precocious puberty secondary to peripheral precocious puberty due to a pineal germ cell tumor: a case and review of literature.

Chen H, Mo C, Zhong L BMC Endocr Disord. 2023; 23(1):237.

PMID: 37884982 PMC: 10601200. DOI: 10.1186/s12902-023-01494-0.

Peripheral precocious puberty in Li-Fraumeni syndrome: a case report and literature review of pure androgen-secreting adrenocortical tumors.

Ryckx S, De Schepper J, Giron P, Maes K, Vaeyens F, Wilgenhof K J Med Case Rep. 2023; 17(1):195.

PMID: 37179382 PMC: 10183130. DOI: 10.1186/s13256-023-03889-y.

Central precocious puberty after resection of a virilising adrenocortical oncocytic tumour.

Madi L, Shvalb N, Sade Zaltz C, Levy-Shraga Y BMJ Case Rep. 2021; 14(5).

PMID: 34045190 PMC: 8162081. DOI: 10.1136/bcr-2020-239562.

References

Valerio G, Spagnuolo M, Muzzi G, Buono P, Lombardi F, Palmieri R . Adrenocortical tumor in a boy: final height is not impaired despite a severe advancement of bone age. J Pediatr Endocrinol Metab. 2003; 16(7):1061-3. DOI: 10.1515/jpem.2003.16.7.1061. View

Marshall W, Tanner J . Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969; 44(235):291-303. PMC: 2020314. DOI: 10.1136/adc.44.235.291. View

Lee P, Winter R, GREEN O . Virilizing adrenocortical tumors in childhood: eight cases and a review of the literature. Pediatrics. 1985; 76(3):437-44. View

Barstow C, Rerucha C . Evaluation of Short and Tall Stature in Children. Am Fam Physician. 2015; 92(1):43-50. View

Flor-Cisneros A, Leschek E, Merke D, Barnes K, Coco M, Cutler Jr G . In boys with abnormal developmental tempo, maturation of the skeleton and the hypothalamic-pituitary-gonadal axis remains synchronous. J Clin Endocrinol Metab. 2004; 89(1):236-41. DOI: 10.1210/jc.2002-021954. View

Salt A, Savage M, Grant D . Growth patterns after surgery for virilising adrenocortical adenoma. Arch Dis Child. 1992; 67(2):234-6. PMC: 1793400. DOI: 10.1136/adc.67.2.234. View

Soliman A, AlLamki M, alSalmi I, Asfour M . Congenital adrenal hyperplasia complicated by central precocious puberty: linear growth during infancy and treatment with gonadotropin-releasing hormone analog. Metabolism. 1997; 46(5):513-7. DOI: 10.1016/s0026-0495(97)90186-4. View

Brachet C, Heinrichs C . Central precocious puberty after interpersonal transfer of testosterone gel: just a coincidence?. J Pediatr Endocrinol Metab. 2012; 25(7-8):757-60. DOI: 10.1515/jpem-2012-0067. View

Antonini S, Leal L, Cavalcanti M . Pediatric adrenocortical tumors: diagnosis, management and advancements in the understanding of the genetic basis and therapeutic implications. Expert Rev Endocrinol Metab. 2019; 9(5):445-464. DOI: 10.1586/17446651.2014.941813. View

10.

Speiser P . Transient central precocious puberty in non-classic 21-hydroxylase deficiency. J Pediatr Endocrinol Metab. 1995; 8(4):287-9. DOI: 10.1515/jpem.1995.8.4.287. View

11.

Criscuolo T, Sinisi A, Perrone L, Graziani M, Bellastella A, Faggiano M . Isosexual precocious pseudopuberty secondary to a testosterone-secreting Leydig cell testicular tumour: true isosexual development early after surgery. Andrologia. 1986; 18(2):175-83. DOI: 10.1111/j.1439-0272.1986.tb01757.x. View

12.

Sandrini R, Ribeiro R, DeLacerda L . Childhood adrenocortical tumors. J Clin Endocrinol Metab. 1997; 82(7):2027-31. DOI: 10.1210/jcem.82.7.4057. View

13.

Moreira A, VERISSIMO J, Foss M, Iazigi N, Maciel L, Pimenta W . Pubertal maturation of the lh stimulatory response to clomiphene citrate in congenital virilizing adrenal hyperplasia. Clin Endocrinol (Oxf). 1982; 17(5):441-47. DOI: 10.1111/j.1365-2265.1982.tb01611.x. View

14.

Lazar L, KAULI R, Pertzelan A, Phillip M . Gonadotropin-suppressive therapy in girls with early and fast puberty affects the pace of puberty but not total pubertal growth or final height. J Clin Endocrinol Metab. 2002; 87(5):2090-4. DOI: 10.1210/jcem.87.5.8481. View

15.

Wolthers O, Cameron F, Scheimberg I, Honour J, Hindmarsh P, Savage M . Androgen secreting adrenocortical tumours. Arch Dis Child. 1999; 80(1):46-50. PMC: 1717797. DOI: 10.1136/adc.80.1.46. View

16.

Breidbart E, Cameo T, Garvin J, Hibshoosh H, Oberfield S . Pubertal outcome in a female with virilizing adrenocortical carcinoma. J Pediatr Endocrinol Metab. 2016; 29(4):503-9. PMC: 4836965. DOI: 10.1515/jpem-2015-0123. View

17.

Ribeiro R, Pinto E, Zambetti G, Rodriguez-Galindo C . The International Pediatric Adrenocortical Tumor Registry initiative: contributions to clinical, biological, and treatment advances in pediatric adrenocortical tumors. Mol Cell Endocrinol. 2011; 351(1):37-43. DOI: 10.1016/j.mce.2011.10.015. View

18.

Dacou-Voutetakis C, Karidis N . Congenital adrenal hyperplasia complicated by central precocious puberty: treatment with LHRH-agonist analogue. Ann N Y Acad Sci. 1993; 687:250-4. DOI: 10.1111/j.1749-6632.1993.tb43873.x. View

19.

Almeida M, Brito V, Lins T, Guerra-Junior G, de Castro M, Antonini S . Long-term treatment of familial male-limited precocious puberty (testotoxicosis) with cyproterone acetate or ketoconazole. Clin Endocrinol (Oxf). 2007; 69(1):93-8. DOI: 10.1111/j.1365-2265.2007.03160.x. View

20.

Ribeiro R, Sandrini Neto R, Schell M, Lacerda L, Sambaio G, CAT I . Adrenocortical carcinoma in children: a study of 40 cases. J Clin Oncol. 1990; 8(1):67-74. DOI: 10.1200/JCO.1990.8.1.67. View