Gonadotropin-Dependent Precocious Puberty: Neoplastic Causes and Endocrine Considerations

The onset of isosexual puberty is typically heralded by breast development in girls and testicular enlargement in boys, usually followed by pubarche/adrenarche, the pubertal growth spurt, and completion of secondary sexual development. Traditionally, normal pubertal onset is considered to occur between 8 and 13 years in girls and between 9 years 6 months and 13 years 6 months in boys [1, 2]. Recent data suggests that pubertal onset is occurring at earlier ages in girls, especially among ethnic minorities and those with higher body mass indices [3–10]. Therefore, it has been suggested to redefine the age of precocious puberty in non-Hispanic black girls to <6 years of age and to <7 years in all other girls [8]. It remains generally accepted that pubertal onset at less than 9 years remains precocious in boys. Significant controversy has risen from these recommendations, given the possible risk of delaying or missing the diagnosis of a pathologic cause of precocious puberty [11, 12]. Importantly, sexual development that occurs at a very young age or puberty that progresses asynchronously or at an accelerated tempo may indicate underlying pathology.The prevalence of precocious puberty has been estimated to be at least 10–20-fold higher in girls compared with boys [13]. However, the likelihood of finding an organic cause of precocious puberty is much higher in boys than girls [13–16]. Neoplastic causes of precocious puberty are uncommon but nonetheless important etiologies of precocious sexual development, and prompt recognition of these rare presentations is paramount.The intent of the current manuscript is to review the neoplastic and developmental causes of gonadotropin-dependent precocious puberty and to share some of our clinical experience at the Children's Cancer Hospital of the University of Texas M D Anderson Cancer Center. We will not review gonadotropin-independent sexual precocity, such as seen with sex steroid production by primary adrenal or gonadal neoplas