Triiodothyronine and Thyroxine in Hyperthyroidism COMPARISON OF THE ACUTE CHANGES DURING THERAPY WITH ANTITHYROID AGENTS

J. Abuid; P. R. Larsen

doi:10.1172/JCI107744

In 66 untreated patients with hyperthyroidism, serum triiodothyronine (T₃) and thyroxine (T₄) concentrations were measured by immunoassay. The mean T₃ level was 478±28 ng/100 ml (all values mean±SEM) and the T₄ was 20.6±0.6 μg/100 ml. The serum T₄/T₃ ratio by weight was 48±2 as opposed to a value of 71±3 in euthyroid adults. There was a significant inverse correlation of the T₄/T₃ ratios with serum T₃ (r=0.77; P<0.01) but not with serum T₄(r=0.21). These results suggested that relative overproduction of T₃ is consistently present in patients with hyperthyroidism.

To examine the acute effects of various antithyroid agents on serum T₃ and T₄ concentrations, iodide, propylthiouracil (PTU), and methylmercaptoimidazole (MMI) were given alone to mine patients, and serial T₃ and T₄ measurements were made. There was an acute decrease in serum T₃ over the first 5 days in the three iodide and three PTU-treated patients which was greater than that seen in the MMI group. This suggested that PTU and MMI had different effects on T₃ production.

To compare the effects of PTU and MMI under conditions in which thyroidal hormone release was minimized, these drugs were given in combination with iodide. The mean daily dosage of PTU was 827 (n=11) and of MMI was 88 (n=8). In the PTU+iodide group, the initial serum T₃ concentration was 586±61 ng/100 ml and decreased significantly to 326±41 on day 1 and to 248±21 on days 2 and 3, respectively, and did not change further on days 4 and 5. In the MMI + iodide group, basal serum T₃ was 645±90 ng/100 ml and decreased to 568±81, 452±73, and 344±51 on days 1, 2, and 3, respectively, and did not change thereafter. While the initial T₃ concentrations in serum were not different in the PTU and MMI groups, the T₃ concentrations in the PTU patients were significantly lower on days 1 and 2 and during the apparent plateau period on days 3-5. Serum T₄ concentrations decreased gradually in both groups, from 23.9±2.0 μg/100 ml, initially, to 17.5±1.6 on day 5 in the PTU group and from 22.0±2.6 to 14.6±2.0 in the MMI-treated patients. The T₄ values were not significantly different at any time. These changes resulted in increases in the serum T₄/T₃ ratios in both groups, but these ratios were substantially higher in the patients treated with PTU + iodide. The initial serum T₄/T₃ ratio was 43±3 and increased to 74±7 and 88±7 on days 1 and 2 in the PTU group, reaching a plateau value of 91±7 during days 3-5. Comparable values for MMI-treated patients were 35±2, 42±3, 52±6, and 54±3 during the plateau period.

Previous investigations have shown that PTU inhibits T₄ deiodination in hyperthyroid patients and decreases T₃ production from T₄ in animals. The greater acute decrease in serum T₃ and the higher serum T₄/T₃ ratios in the PTU-treated patients seems best explained by an inhibition of peripheral T₃ production by this agent. This conclusion is further supported by a direct relationship between the T₄/T₃ ratio on days 3-5 and the dose of PTU administered. These results further suggest that both thyroidal and extrathyroidal pathways contribute substantially to the apparent overproduction of T₃ in hyperthyroidism.