Precocious puberty in children with tumours of the suprasellar and pineal areas: Organic central precocious puberty

Abstract

During the past 11 y, 115 children younger than 8/9 y of age (female/male) with tumours of the suprasellar or pineal areas were followed in our clinic to study the incidence of precocious puberty. In addition, type of central lesion, clinical characteristics and gonadotropic secretion were studied in order to elucidate the different mechanisms of gonadal activation. A control group of 21 patients with idiopathic precocious puberty and a control group of 10 age‐matched patients with suprasellar tumours without precocious puberty were also studied. Precocious puberty associated with organic central lesions was found at diagnosis in 30 patients (26%), in 9 out of 48 patients with glial cell tumours (18.7%), 6 out of 9 patients with gem cell tumours (66.6%), 11 out of 11 patients with hypothalamic hamartomas (100%) and in 4 out of 4 patients with subarachnoid cysts or arachnoidocele (100%). Precocious puberty was not found in any of 36 patients with craniopharyngioma. With the exception of one patient with pineal germinoma, all lesions were localized to the suprasellar area. In all patients with hypothalamic hamartoma, precocious puberty was diagnosed before 4 y of age, while in most patients with the other lesions, it was diagnosed after this age. Height SDS, weight increase and advancement of bone age were similar in both idiopathic and organic central precocious puberty. Maximal LH responses to GnRH in idiopathic and organic central precocious puberty were similar except for germ cell tumours. Patients with suprasellar tumours without precocious puberty had lower maximal LH (but not FSH) responses to GnRH, with the exception of germ cell tumours. In the latter, elevation of serum β‐hCG indicates that this gonadotropin was responsible for gonadal stimulation. In hypothalamic hamartomas, the prepubertal hiatus in the activity of the GnRH pulse generator was absent. The mechanism of this failure in the inactivation of GnRH is unknown. Data suggest that in glial cell tumours and in subarachnoid cysts, an unknown factor, probably secreted by the tumours, advances the tempo of GnRH maturation. Therefore, the aetiology of organic central precocious puberty is multiple and is directly related to location and type of lesion. Conclusion: This clinical information suggests that the onset of puberty is not the result of the disruption of a putative pulse generator inhibitory influence but the consequence of secretion of stimulatory substances by the lesions.

Elevated Serum β-Human Chorionic Gonadotropin in Nonpregnant Conditions

“…The types of tumor associated with precocious puberty are usually genital or nongenital germ cell tumors. Rivarola et al reported precocious puberty in 9 of 48 children with glial cell tumors, 6 of 9 patients with supracellar germ cell tumors, and all 11 patients with hypothalamic hamartomas (6). hCG-producing primary CNS tumors are rarely encountered (7).…”

Hamartomas hipotalámicos: distintas formas de debut. Casos clínicos

“…Este trastorno endócrino se describe en varias series de pacientes con HH entre 40%-60% a lo largo de la evolución, que inicialmente son asintomáticos. 3,5,11,12 Paciente TSH T4 Estradiol LH LH FSH FSH Prolactina ACTH Cortisol IGF-1 17 OH S-DHEA AFP PL (mUI/ libre (pg/ basal pico basal pico (ng/ (ng/ (mcg/ (ng/ml)/ Progesterona (mcg/ (ng/ml)/ ml) (ng/ ml) (mUI/ (mUI/ (mUI/ (mUI/ ml) ml) dl) IGF-BP3 (ng/ ml) B -HCG dl) ml) ml) ml) ml) (mcg/ml) ml) (mUI7mL) …”

“…[1][2][3][4] Su prevalencia en niños y adolescentes se estima en torno a 1-2 casos/100 000 habitantes. 5 Pueden ser sésiles (intrahipotalámicos) o pedunculados (parahipotalámicos); estos últimos son los que con mayor frecuencia se asocian con PPC.…”

Pseudopubertas praecox

“…Angaben zum Vorkommen einer Pseudopubertas praecox bei ZNS-Erkrankungen sind rar. In einer Gruppe von 115 Kindern mit unterschiedlichen ZNSTumoren der Hypophyse/Pinealisregion fand sich in 26% der Fälle eine Pseudopubertas praecox [7]. Das Vorkommen als isoliertes Symptom eines Pinealistumors ist nur in Einzelfällen beschrieben [7], jedoch bei Keimzelltumoren durch die Pathophysiologie (s. unten) erklärbar.…”

“…Die 2 Polypeptidketten des β-hCG besitzen Strukturähnlichkeit zu LH [8] und stimulieren die Leydig-Zellen des Hodens über den LH-/β-hCG-Rezeptor zur Testosteronproduktion. Eine Pseudopubertas praecox durch β-hCG tritt nur bei Jungen auf, da Mädchen nicht LH, sondern FSH zur Stimulation der Östrogenbildung am Ovar benötigen [7].…”