The Impact of Hashimoto Thyroiditis on Thyroid Nodule Cytology and Risk of Thyroid Cancer

Nathalie Silva de Morais; Jessica Stuart; Haixia Guan; Zhihong Wang; Edmund S. Cibas; Mary C. Frates; Carol B. Benson; Nancy L. Cho; Mathew A. Nehs; Caroline A. Alexander; Ellen Marqusee; Mathew I. Kim; Jochen H. Lorch; Justine A. Barletta; Trevor E. Angell; Erik K. Alexander


J Endo Soc. 2019;3(4):791-800. 

In This Article


Our final study population included 9851 patients with 21,397 relevant nodules. As expected, the population was predominantly female (83.9%) and had a mean age of 52.2 years. Within the evaluable cohort, 14,063 (66%) nodules were aspirated. The remaining nonaspirated nodules were generally cystic, small, had sonographically benign characteristics, or were resected in conjunction with a separate index nodule prompting concern in the same gland. Baseline patient and nodules characteristics are summarized in Table 1.

Evidence (i.e., serological, sonographic or histologic) of HT was confirmed in 2651 patients (27%). A total of 3895 nodules were evaluated in patients with HT; the remaining 10,168 nodules were evaluated in patients without evidence of HT.

The influence of HT on the diagnostic evaluation and cytology classification is described by the data in Table 2. The proportion of nodules with indeterminate and malignant cytology was higher in the HT group than in the non-HT group. Indeterminate cytology was obtained in 20.6% of patients with nodules in the setting of HT, compared with 17.1% of patients with nodules in a gland not affected by HT (indeterminate cytology: RR, 1.3, 95% CI, 1.17 to 1.44, P < 0.01). An increase in malignant cytology was similarly identified in patients with HT (RR, 1.7; 95% CI, 1.44 to 1.99; P < 0.01; Figure 1).

Figure 1.

Relative risk of indeterminate or malignant cytology vs benign cytology, given HT. Indeterminate cytology includes TBSRTC categories 3, 4, and 5. Malignant cytology includes TBSRTC category 6.

Finally, we evaluated the association between HT and the risk of malignancy in the setting of clinically relevant thyroid nodular disease. The frequency of a nodule proving cancerous was higher in patients with coexistent HT compared with those without (23.3% vs 15.9%; RR, 1.6; 95% CI, 1.44 to 1.79; P < 0.01; Figure 2). This increased cancer prevalence was maintained when patients with solitary or multiple nodules were analyzed separately, suggesting a field effect of HT itself (HT vs non-HT groups: 24.5% vs 16.3% in solitary nodules; 22.1% vs 15.4% in multinodular glands; P< 0.01). The types and proportions of thyroid cancer in both groups are listed in Table 3. The frequency of malignancy was also higher in the setting of HT when we evaluated only patients with a final indeterminate cytology (HT vs non-HT: 43.1% vs 38.7%; P = 0.05). The association between HT and thyroid cancer according to the final cytological diagnosis is reported in Table 4.

Figure 2.

Relative risk of having one or more malignant nodules vs no malignant nodules given HT.

Given the increased risk of thyroid cancer in the setting of HT, we also investigated if such malignancy showed signs of increased aggressivity. We investigated the proportion of cancers in both groups showing signs of invasion, local or distant metastasis, or tumor size. Importantly, no significant differences in malignant pathologic characteristics or markers of aggressiveness were identified among patients with or without HT (Table 5).

Though 13 cases of thyroid lymphoma were documented in the entire study cohort, lymphoma alone was not responsible for the increased prevalence of malignant disease in patients with HT. Of the 13 total cases, nine cases of thyroid lymphoma were documented in the 7200 patients without HT. Four cases of thyroid lymphoma were detected in the 2651 patients with HT.