Neoplastic causes of abnormal puberty

Abstract

Background: Neoplasm-related precocious puberty (PP) is a rare presenting feature of childhood cancer. Moreover, evaluation of suspected PP in a child is complex, and cancer is often not considered. We characterized the clinicopathologic features of patients presenting with PP at a large pediatric cancer center, reviewed the relevant literature, and developed an algorithm for the diagnostic work-up of these patients.

Methods: We examined the records of all patients with a neoplasm and concomitant PP treated at St. Jude Children's Research Hospital from January 1975 through October 2011, reviewed the available literature, and analyzed the demographic, clinical, endocrine, and neoplasm-related features.

Results: Twenty-four of 13,615 children and adolescents (0.18%) were diagnosed with PP within 60 days of presentation. Primary diagnoses included brain tumor (12), adrenocortical carcinoma (5), hepatoblastoma (4), and others (3). PP was observed 0-48 months before diagnosis of neoplasm; 17 patients had peripheral PP and 7 had central PP.

Conclusions: Neoplasm-related PP is rare and takes the form of a paraneoplastic syndrome caused by tumor production of hormones or by alteration of physiologic gonadotropin production. PP can precede diagnosis of malignancy by months or years, and neoplastic causes should be considered early to avoid delayed cancer diagnosis. Treatment of the primary malignancy resolved or diminished PP in surviving patients with an intact hypothalamic-pituitary-gonadal axis.

Keywords: adrenocortical carcinoma; brain tumor; gonadal tumor; hepatoblastoma; paraneoplastic endocrinopathy; paraneoplastic precocious puberty.

Fig. 1

Months between onset of precocious puberty and cancer diagnosis in the 24 study patients. ACC, adrenocortical carcinoma; GCT, germ cell tumor; JGCT, juvenile granulosa cell tumor; JPA, juvenile pilocytic astrocytoma; NG GCT, non-germinomatous germ cell tumor; PNET, primitive neuroectodermal tumor.

Fig. 2

Diagnostic algorithm for precocious puberty, including malignancy as an underlying cause. AFP, alpha-fetoprotein; BHCG, beta-human chorionic gonadotropin; CAH, congenital adrenal hyperplasia; CNS, central nervous system; CPP, central precocious puberty; DHEA-S, dehydroepiandrosterone; E&M, evaluation and management; GnRH, gonadotropin–releasing hormone; H&P, history and physical examination; LH/FSH, luteinizing hormone and follicle stimulating hormone; MAS, McCune Albright syndrome; PP, precocious puberty.