Background: Cowden syndrome (CS) is dominantly inherited and predisposes patients to tumors in multiple organs. We characterized CS-associated malignant and benign thyroid disease. Methods: Of data from 3,477 prospectively recruited CS patients with known genetic analysis, we analyzed 225 PTEN mutation+ patients whose treatment occurred at our center (n = 25) or other hospitals nationwide (n = 200). Results: A total of 32 of 225 PTEN mutation+ patients (14%) had thyroid cancer: 52% papillary, 28% follicular-variant papillary, 14% follicular, and 6% anaplastic. Median age at diagnosis was 35 years compared with 49 years for Surveillance Epidemiology and End Results population data. Initial thyroid ultrasonography in 16 of 25 patients revealed thyroiditis/goiters in all >13 years age, leading to FNA in 7 (64%), thyroidectomy in 3 (27%), and new cancer diagnosis in 2 (18%). Three with severe autism required intraoperative sedation for ultrasonography. A total of 9 of 25 patients were monitored after multiple partial thyroidectomies for goiters by age 42 (n = 5), thyroiditis, or cancer detected by age 36 (n = 3). Conclusion: PTEN mutation+ patients with CS have an enormous prevalence of thyroid disease. Earlier screening may be advisable because thyroiditis and nodules are seen by the time patients reach adolescence, and cancer diagnosis occurs on average 14 years earlier than expected. Furthermore, the risks observed may justify prophylactic total thyroidectomy in select, if not all, patients, particularly those with developmental disorders.
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