Factors related to clinical hypothyroid severity in thyroid cancer patients after thyroid hormone withdrawal.

Background: Thyroid hormone withdrawal (THW) to stimulate thyrotropin (TSH) secretion produces acute thyroid hormone deficiency in patients who have undergone thyroidectomy for differentiated thyroid cancer (DTC), but not all patients developed clinically overt features of hypothyroidism. This prospective study was performed to test the hypothesis that selected factors, including serum thyroid hormone levels and insulin resistance, are associated with the development of overt features of hypothyroidism.

Methods: Thirty-two patients (27 women, aged 51.1 +/- 12.3 years) with DTC who had undergone total or subtotal thyroidectomy were studied while on thyroid hormone suppressive therapy (THST) and 5 weeks after THW. Thyroid function and other tests as well as anthropometric parameters and the Zulewski score for clinical hypothyroidism were assessed. Overt clinical hypothyroidism was defined as having a Zulewski score of > or = 3 after THW. Clinical euthyroidism was defined as having a Zulewski score of <3.

Results: Fifteen patients (46.9%) developed overt clinical hypothyroidism after THW. Patients with overt clinical hypothyroidism were older (p = 0.005), had lower baseline serum free thyroxine (p = 0.040) and free triiodothyronine (fT3) (p = 0.006), and higher body mass index (p = 0.038), fasting plasma glucose (p = 0.005), and homeostasis model assessment for insulin resistance (p = 0.043) than those with clinical euthyroidism. The independent factors related to overt clinical hypothyroidism after THW were higher HOMA-IR (odds ratio [OR], 1.098; confidence interval [CI], 1.007-1.198; p = 0.034), lower fT3 (OR, 0.069; CI, 0.006-0.733; p = 0.027), and higher Zulewski score (OR, 3.633; CI, 1.144-11.536; p = 0.029) before THW.

Conclusions: Nearly half of DTC patients suffer from overt clinical hypothyroidism after 5 weeks of THW, as assessed by Zulewski score. Patients with higher HOMA-IR, lower fT3 level, and higher initial Zulewski score are at greatest risk of overt clinical hypothyroidism after THW. Insulin resistance is closely related to post-THW hypothyroidism in patients of DTC.