\u201cThyroid nodular disease and PTEN mutation in a multicentre series of children with PTEN hamartoma tumor syndrome (PHTS)\u201d

Gerdi Tuli,Alessandro Mussa,Paola Borgia,Maria Cristina Vigone,Marco Abbate,Jessica Munarin,Diana Carli,Giovanni Battista Ferrero,Roberto Gastaldi,Luisa De Sanctis

doi:10.1007/s12020-021-02805-y

Abstract

PurposeTo report the incidence of 4–12% of differentiated thyroid cancer (DTC) and up to 50% of benign thyroid nodular disease and to describe nodular thyroid disease in a multicentre pediatric population with PTEN mutations. Methods: Retrospective data of pediatric patients with PTEN mutations collected from tertiary Departments of Pediatric Endocrinology of Turin, Milan and Genua, Italy, in the period 2010–2020.ResultsSeventeen children with PTEN mutations were recruited in the study. Thyroid involvement was present in 12/17 (70.6%) subjects, showing a multinodular struma in 6/17 (35.3%), nodules with benign ultrasound features in 5/17 (29.4%) and a follicular adenoma in 1/17 (6%). No correlation was found between thyroid disease and gender, puberty, vascular manifestations, delayed development, or brain MRI abnormalities, while multiple lipomas were associated with thyroid disease (p = 0.03), as was macrocephaly. Standard Deviation (SD) score head circumference was 4.35 ± 1.35 cm in subjects with thyroid disease, 3 ± 0.43 cm (p = 0.02) in the group without thyroid disease. Thyroid involvement was present in all subjects with mutations in exon 6 (4/4) and exon 8 (3/3) of the PTEN gene (p = 0.02).ConclusionIn the presented cohort, benign thyroid disorders were prevalent, with no evidence of DTC. A correlation was found between thyroid lesions and head circumference and the occurrence of multiple lipomas. Future studies in larger cohorts should assess whether risk stratification is needed when recommending surveillance strategies in children or young adolescents with PTEN hamartoma syndrome.

Highlights

The phosphatase and tensin homolog (PTEN) gene, located on 10q23 chromosome band, is a tumor suppressor gene with a fundamental role in the molecular pathways that mediate cell proliferation, migration, and apoptosis
Differentiated thyroid cancer (DTC) is one of the Endocrine most common types of cancer, with a lifetime risk of 3538% [6]; the increased risk is present in pediatric age
Several authors report an incidence of 4–12% of DTC in the pediatric population affected by PTEN mutations, mainly follicular, and up to 50% of benign nodular thyroid disease [6]

Summary

Introduction

The phosphatase and tensin homolog (PTEN) gene, located on 10q23 chromosome band, is a tumor suppressor gene with a fundamental role in the molecular pathways that mediate cell proliferation, migration, and apoptosis. Other phenotypic features of BRRS disorder include prenatal or postnatal onset of high-arched palate overgrowth, macrosomia, hypotonia, joint hyperextensibility, downward slanting palpebral fissures, frontal bossing, hypoglycemia, seizures, and café au lait spots. These phenotypic features are highly variable, they seem to cluster within the same family [1,2,3,4,5]. We describe nodular thyroid disease in a multicentre cohort of 17 patients with PTEN mutation and discuss the DTC surveillance program in childhood

Materials and methods

Discussion

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Compliance with ethical standards