Gonadotropin-dependent pubertal disorders are common in patients with virilizing adrenocortical tumors in childhood

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.

Abnormal linear growth in paediatric adrenal diseases: Pathogenesis, prevalence and management

“…Growth patterns after surgical removal of virilizing ACT in 9 girls, showed that 5 continued to grow rapidly for up to 18 months after surgery and subsequently had normal growth velocities. 45 Central precocious puberty is recognized as a potential complication after surgical removal of androgen-secreting ACTs 46 and in a retrospective analysis of 63 paediatric patients with virilizing ACTs, 58.7% developed early gonadotropin-dependent puberty, which was effectively treated by GnRH analogues, leading to normal adult height. 46 A clear message is that close clinical follow-up after removal of a virilizing ACT is crucial for early detection of activation of the hypothalamic-pituitary-gonadal axis and initiation of GnRH analogue therapy when clinically indicated.…”

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

“…Transition from peripheral PP to central PP is rare, which means activating GnRH or inhibiting gonadotropin inhibitory hormone after a period of overexposure to steroids. This transition has been reported in patients with Leydig cell tumors [ 17 – 24 ], adrenal tumors [ 25 – 31 ], congenital adrenal hyperplasia [ 32 – 35 ], overy granulosa cell tumors [ 36 – 38 ], familial male-limited PP [ 39 , 40 ], McCune-Albright syndrome [ 41 ] and pineal mature teratoma [ 42 ], probably due to the circulating sex steroid hormones’ suddenly reduced feedback inhibition on gonadotropin releasing hormone and gonadotropins. In addition to primary gonadal diseases, only one case of central PP secondary to extragonadal hCG-secreting iGCT has been reported, and this patient has long-term exposure to endogenous testosterone [ 42 ].…”

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

“…Thus, intensive tumor surveillance with annual total body and brain MRI is needed in these patients, and exposure to ionizing radiation should be avoided. Furthermore, long-term endocrine follow-up is indicated as gonadotropin-dependent pubertal disorders are common in children with a history of virilizing ACT [ 35 ].…”