Adrenocortical tumors associated with the TP53 p.R337H germline mutation can be identified during child-care consultations

Mastellaro, Maria José; Ribeiro, Raul C.; Seidinger, Ana Luíza; Cardinalli, Izilda Aparecida; Miranda, Eliana Cristina Martins; Aguiar, Simone S.; Brandalise, Sílvia Regina; Yunes, José Andrés; Barros-Filho, Antônio A.

doi:10.1016/j.jped.2017.06.009

Cited by 10 publications

(10 citation statements)

References 24 publications

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“…This predominance may explain why the majority of patients in this cohort had normal (79.3%) or tall stature (17.5%) and advanced BA (63.5%) at diagnosis of ACT, although most had M-ACT. This finding is in accordance with previous reports (18, 19, 24, 30, 31, 32, 34, 42, 43, 47). In addition, the combination of androgen and glucocorticoid effects may have accounted for the lack of difference in initial stature SDS, BMI SDS and Δ BA between V-ACT and M-ACT.…”

Section: Discussionsupporting

confidence: 94%

“…The general features of the patients from this cohort were similar to previously published series (19, 24, 34, 42, 43). The majority were female (44/63), had the diagnosis of ACT before the age of 4 years (44/63), with clinical presentation of a virilizing syndrome (54/63) and harbored the P53 p.R337H mutation (48/52).…”

Section: Discussionsupporting

confidence: 81%

“…There are only scarce studies reporting gonadotropin-dependent pubertal disorders after treatment of ACT. These studies are either small series (18, 31, 33, 34) or larger series in which the number of patients that reached pubertal age is not stated; therefore, the proportion of pubertal disorders cannot not be accurately calculated (19, 24). In the present study, this issue was addressed in a straight line.…”

Section: Discussionmentioning

confidence: 99%

“…However, their incidence is 10–15 times higher in Southern and Southeastern Brazil (19), where 75–97% of the patients harbor a specific TP53 mutation. The P53 p.R337H is the most significant and well-characterized genetic risk for ACT in these regions; it is widespread due to a founder effect (20, 21, 22, 23, 24). This mutation was initially described in association with ACTs in Brazilian children (21), but it has been shown to be associated with the development of other types of cancer in adulthood, in the context of Li-Fraumeni syndrome (25, 26).…”

Section: Introductionmentioning

confidence: 99%

“…Although morbidity (metastasis, recurrence and complications of ACT treatment) and mortality in patients with ACTs are well documented (17, 19, 23, 24), the late effects of early exposure to androgen excess on gonadotropin-dependent puberty and on growth have been scarcely presented in case reports (30, 31, 32, 33), in small series of patients (18, 34) or in studies with other purposes (19, 24).…”

Section: Introductionmentioning

confidence: 99%

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

Stecchini

Braid

Marrero-Gutiérrez

et al. 2019

Endocrine Connections

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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.

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