Thyroid nodules in xeroderma pigmentosum patients: a feature of premature aging

Abstract

Purpose: Xeroderma pigmentosum (XP) is an autosomal recessive disease with defective DNA repair, a markedly increased risk of skin cancer, and premature aging. Reports from North Africa have described thyroid nodules in XP patients, but thyroid nodule prevalence has never been determined in XP patients enrolled in our natural history study at the National Institutes of Health (NIH).

Methods: We performed thyroid ultrasound examinations on all 29 XP patients examined from 2011 to 2019 and assessed nodule malignancy using the Thyroid Imaging Reporting and Data System. Thyroid nodule prevalence was also obtained from comparison cohorts. DNA sequencing was performed on thyroid tissue from XP patients who had surgery for thyroid cancer.

Results: Thyroid nodules were identified in 18/29 XP patients (62%). The median age of patients with thyroid nodules in our XP cohort (20 years) was younger than that of three comparison groups: 36 years (California study-208 subjects), 48 years (Korean study-24,757 subjects), and 52 years (NIH-682 research subjects). Multiple (2-4) thyroid nodules were found in 12/18 (67%) of the patients with nodules. Autopsy examination revealed follicular adenomas in 4/8 (50%) additional XP patients. DNA sequencing revealed rare mutations in two other XP patients with papillary thyroid cancer.

Conclusions: XP patients have an increased incidence of thyroid nodules at an early age in comparison to the general population. These finding confirm another premature aging feature of XP.

Keywords: DNA repair; DNA sequencing; Thyroid cancer; Thyroid nodules; Thyroid ultrasound; Xeroderma pigmentosum.

Figure 1.. Summary of ultrasound findings for XP patients with detectable thyroid nodules.

A total of 18/29 patients examined by ultrasound scan had nodules. Nodule multiplicity and Thyroid Imaging Reporting and Data System (TI-RADS) score are reported for each patient, which are separated according to XP group and age. XP-C, mutations in XPC; XP-V, XP variant with mutations in pol eta; ND, not determined.

Figure 2.. Cumulative incidence of thyroid nodules across age categories in XP and comparison cohorts.

XP patients, this study (n=18), filled squares; Comparison, NIH - BTRIS, NIH Biomedical Translational Research Information Systems, this study (n=682), open triangles; Comparison, Korea - Moon et al. (22) cohort from South Korea (n=24,757), filled diamonds; Comparison, California - Smith-Bindman et al. (21) cohort from University of California, San Francisco study (n=369), filled circles.