Natural History of Thyroid Disease in Children with PTEN Hamartoma Tumor Syndrome

• Published in: The journal of clinical endocrinology and metabolism 2021-03, Vol.106 (3), p.e1121-e1130
• Main Authors: Smith, Jessica R, Liu, Enju, Church, Alanna J, Asch, Elizabeth, Cherella, Christine E, Srivastava, Siddharth, Kamihara, Junne, Wassner, Ari J
• Format: Article
• Language: English
• Subjects: Analysis; Biopsy; Children; Children's hospitals; Diseases; Evidence-based medicine; Hamartoma; Lymph nodes; Malignancy; Medical research; Medicine, Experimental; Multivariate analysis; Natural history; Neoplasia; Nodules; Pediatrics; Prevalence studies (Epidemiology); PTEN protein; Risk factors; Sex differences; Sex ratio; Thyroid diseases; Tumors; Ultrasonic imaging; Ultrasound
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgaa944

Abstract Context Thyroid ultrasound screening is recommended in children with PTEN hamartoma tumor syndrome (PHTS) due to increased risk of thyroid neoplasia, but the natural history of thyroid disease in children with PHTS is unclear. Objective Determine the prevalence and natural history of thyroid disease in children with PHTS. Methods Retrospective cohort study (1998-2019) in an academic pediatric hospital of individuals with genetically confirmed PHTS diagnosed before age 19 years. Clinical, thyroid ultrasound, and laboratory characteristics are described. Primary outcomes were the prevalence of thyroid nodules ≥10 mm diameter and time course and risk factors for nodule development assessed by Cox regression analysis. Secondary outcomes included thyroid nodule requiring biopsy, other ultrasound findings, and prevalence of autoimmune thyroid disease. Results Among 64 subjects with PHTS, 50 underwent thyroid ultrasound. A thyroid nodule ≥10 mm was diagnosed in 22/50 (44%) subjects at median (range) age 13.3 (7.0-22.9) years. Nodules were diagnosed earlier in females than in males (10.8 [7.0-17.9] vs 14.2 [9.9-22.9] years, P = .009). In multivariate analysis, risk of thyroid nodules was significantly associated with female sex (hazard ratio 2.90, 95% CI 1.16-7.27, P = .02) and inversely associated with the presence of neurologic findings of PHTS (HR 0.27, 95% CI 0.10-0.69, P = .007). Abnormal-appearing lymph nodes with echogenic foci were observed by ultrasound in 20% of subjects, but these were not associated with malignancy. Autoimmune thyroid disease was present in 10/33 (30.3%) of subjects in whom it was assessed. Conclusion Thyroid disease is common in children with PHTS. This study supports current consensus recommendations for ultrasound screening.