Increased Urinary Excretion of Sulfated 3,3′,5-Triiodothyronine in Patients with Nodular Goiters Receiving Suppressive Thyroxine Therapy

Increased serum 3,3′,5-triiodothyronine sulfate (T₃S) levels have been detected in various pathophysiologic states. However, little is known about T₃S concentrations in other biological fluids. By employing a highly sensitive, specific, and reproducible radioimmunoassay (RIA), we measured T₃S in the serum and urine of 20 premenopausal women with benign nodular goiters before and after administration of thyroxine for 6 months (T₄; 3.2 μg/kg/day). Serum T₃ concentrations did not change significantly after treatment (2.0 vs. 1.7 nmol/L; p > 0.05). However, the mean serum T₄ and free T₄ concentrations were significantly higher after treatment (138 vs. 88 nmol/L and 28 vs. 17 pmol/L; _p < 0.01, respectively). Serum thyroid stimulating hormone (TSH) levels were significantly reduced after T₄ treatment (0.13 vs. 0.66 mU/L, p < 0.01) and the serum levels of T₃S were significantly increased after treatment (82 vs. 45 pmol/L; p < 0.01). A good correlation was observed between increased serum T₃S and T₄ concentrations (r = 0.66; p < 0.001). The sulfoconjugate of T₃ was significantly increased in creatinine-corrected urine after treatment (606 vs. 253 pmol/umol Cr.; p < 0.01). There was a significant correlation between increased creatinine-corrected urine T₃S and increased serum free T₄ (r = 0.65: p < 0.001). In summary, significant increases in serum and urine T₃S levels were noted in T₄-treated patients with subnormal serum TSH and borderline elevated T₄. We thus conclude that the sulfation pathway may play a role in the homeostasis of thyroid hormone metabolism in T₄-treated subjects with relative hyperthyroxinemia. In addition, the creatinine-corrected urine concentrations of T₃S may serve as an index for the evaluation of T₄-treated patients with elevated levels of T₄.