Hashimoto's thyroiditis pathology and risk for thyroid cancer

Abstract

Background: Hashimoto's thyroiditis (HT) has been found to coexist with differentiated thyroid cancer (DTC) in surgical specimens, but an association between the two conditions has been discounted by the medical literature. Therefore, we performed this study to determine any potential relationship between HT and the risk of developing DTC.

Methods: We collected data for thyrotropin (TSH), thyroxine (T4), thyroid peroxidase antibody (TPO-Ab) titers, surgical pathology, and weight-based levothyroxine (LT4) replacement dose for patients who were referred for thyroid surgery. Patients with HT at final pathology were studied further. To estimate thyroid function, patients with preoperative hypothyroid HT (Hypo-HT) were divided into three equal groups based on their LT4 replacement: LT4-Low (<0.90 μg/kg), LT4-Mid (0.90-1.43 μg/kg), and LT4-High (>1.43 μg/kg). A group of preoperatively euthyroid (Euth-HT) patients but with HT by pathology was also studied. All subjects were also grouped based on their TPO-Ab titer in TPO-high (titer >1:1000) or TPO-low/negative (titer <1:1000 or undetectable) groups. The relationship of HT and DTC was studied extensively.

Results: Of 2811 subjects, 582 had HT on surgical pathology, 365 of whom were Euth-HT preoperatively. DTC was present in 47.9% of the Euth-HT, in 59.7% of LT4-Low, 29.8% of LT4-Mid, and 27.9% of LT4-High groups. The relative risk (RR) for DTC was significantly elevated for the Euth-HT and LT4-Low groups (p<0.001), but not for the LT4-Mid or LT4-High replacement dose groups. TPO-low/negative status conferred an increased RR in the Euth-HT and LT4-Low replacement dose groups (p<0.001 both), while TPO-high status decreased it in Euth-HT group (p<0.05) and made it nonsignificant in the LT4-Low group.

Conclusions: HT pathology increases the risk for DTC only in euthyroid subjects and those with partially functional thyroid glands (LT4-Low) but not in fully hypothyroid HT (LT4-Mid and LT4-High). High TPO-Ab titers appear to protect against DTC in patients with HT.

FIG. 1.

Study flowchart. Non-HT, subjects without Hashimoto's thyroiditis; Euth-HT, euthyroid patients with Hashimoto's thyroiditis; Hypo-HT, hypothyroid patients with Hashimoto's thyroiditis; DTC, differentiated thyroid cancer (see text for details).

FIG. 2.

Comparison of the odds ratios for differentiated thyroid cancer (DTC) among the different subgroups of patients affected by Hashimoto's thyroiditis (HT) and the Non-HT population. Euth-HT and LT₄-Low subgroups have a significantly increased odds ratio (OR) for DTC, while the LT₄-Mid and LT₄-High subgroups do not confer such a risk. Non-HT, subjects without Hashimoto's thyroiditis; Euth-HT, euthyroid patients with Hashimoto's thyroiditis; LT_4, hypothyroid patients on levothyroxine replacement; Low/Mid/High, tertiles of levothyroxine replacement dose (see text for details).

FIG. 3.

Frequency of differentiated thyroid cancer (DTC) in the different patient groups. The highest risk for DTC is found in the Euth-HT and the LT₄-Low groups. Non-HT, subjects without Hashimoto's thyroiditis; Euth-HT, euthyroid patients with Hashimoto's thyroiditis; LT₄, hypothyroid patients on levothyroxine replacement; Low/Mid/High, tertiles of levothyroxine replacement dose (see text for details). *Relative risk compared to the Non-HT group. Fisher's exact test p<0.001.

FIG. 4.

Comparison of odds ratios for DTC among the different subgroups of patients affected by Hashimoto's thyroiditis (HT) and the Non-HT population based on TPO antibody status. Patients affected by HT were split by the TPO-Ab status (see Methods for details) into TPO-High (A) and TPO-Low/Negative (B). We found that the TPO-Low/Negative status conferred an increased risk for DTC in all groups except for the LT₄-Mid and LT₄-High. On the other hand, the TPO-High group was not significantly different compared to the Non-HT. Non-HT, patients unaffected by Hashimoto's thyroiditis on surgical pathology. TPO-AB, thyroid peroxidase antibodies; TPO-High, TPO-Ab titer>1:1000; TPO-Low/Negative, TPO-Ab titer<1:1000 or undetectable (negative); Euth-HT, euthyroid patients with Hashimoto's thyroiditis; LT₄, hypothyroid patients on levothyroxine replacement; Low/Mid/High, tertiles of levothyroxine replacement dose (see text for details).