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Effect of Various Doses of Recombinant Human Thyrotropin on the Thyroid Radioactive Iodine Uptake and Serum Levels of Thyroid Hormones and Thyroglobulin in Normal Subjects

Department of Medicine, Division of Endocrinology and Metabolism and Department of Radiology, Division of Nuclear Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01655

Address all correspondence and requests for reprints to: Charles H. Emerson, M.D., Division of Endocrinology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655.

Recombinant human TSH (rhTSH), usually given as 0.9-mg doses im on 2 successive days, increases serum thyroglobulin (Tg) and radioactive iodine uptake (RAIU) in residual thyroid tissue in patients with thyroid cancer. We previously reported that a single, relatively low dose of rhTSH (0.1 mg im) is a potent stimulator of T₄, T₃, and Tg secretion in normal subjects. The present study describes the effects of higher doses of rhTSH on thyroid hormone and Tg secretion. Six normal subjects for each dose group, having no evidence of thyroid disease, received either 0.3 or 0.9 mg rhTSH by im injection. Serum TSH, T₄, T₃, and Tg concentrations were measured at 2, 4, and 8 h and 1, 2, 3, 4, and 7 days after rhTSH administration. The peak serum TSH concentrations were 82 ± 18 and 277 ± 89 mU/L, respectively, for the 0.3- and 0.9-mg doses of rhTSH. Serum T₄, T₃, and Tg concentrations increased significantly in subjects receiving 0.3 and 0.9 mg rhTSH, with significant increases in T₄ and T₃ being observed before significant increases in serum Tg. Peak concentrations of serum T₄, T₃, and Tg, after 0.3 mg rhTSH administration, were 100 ± 19, 131 ± 14, and 1035 ± 724% above individual baselines, respectively. Similarly, peak concentrations of serum T₄, T₃, and Tg, after 0.9 mg rhTSH administration, were 102 ± 16, 134 ± 7, and 1890 ± 768% above individual baselines, respectively. These data, compared with previously reported data for the responses to 0.1 mg rhTSH, indicated that 0.1, 0.3, and 0.9 mg rhTSH had similar quantitative stimulatory effects on thyroid hormone and Tg secretion, except that the T₄ response was greater in groups receiving 0.3 and 0.9 mg rhTSH than in the group receiving 0.1 mg rhTSH. We also studied the effect of rhTSH on the thyroid RAIU in the group that received 0.9 mg rhTSH. The 6- and 24-h RAIU values were significantly higher after rhTSH (pre-rhTSH, 6-h value = 12.5 ± 1.8%; 24 h value = 23 ± 2.7%; post-rhTSH, 6 h value = 27 ± 4.8%; 24-h value = 41 ± 4.2%). The stimulating effects of 0.9 mg rhTSH on the 6- and 24-h RAIUs were similar. rhTSH is a potent stimulator of T₄, T₃, and Tg secretion and the RAIU in normal subjects. Single doses greater than 0.1–0.3 mg do not seem to further enhance thyroid hormone or Tg secretion.

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