Triiodothyronine and thyroxine in hyperthyroidism. Comparison of the acute changes during therapy with antithyroid agents.
Triiodothyronine and thyroxine in hyperthyroidism. Comparison of the acute changes during therapy with antithyroid agents.
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甲状腺功能亢进症中的三碘甲状腺原氨酸和甲状腺素。
DOI：
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发表时间：
1974
影响因子：
15.9
通讯作者：
P. Larsen
中科院分区：
文献类型：
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作者：
J. Abuid;P. Larsen
用免疫分析法测定了66例未经治疗的甲亢患者血清三碘甲状腺原氨酸（T（3））和甲状腺素（T（4））浓度。平均T（3）水平为478+/-28 ng/100 ml（所有值均为+/-SEM），T（4）为20.6+/-0.6 mug/100 ml。按体重计算的血清T（4）/T（3）比值为48+/-2，而甲状腺功能正常成人的值为71+/-3。T（4）/T（3）比值与血清T（3）呈显著负相关（r=0.77; P<0.01），与血清T（4）无相关性（r=0.21）。这些结果表明，甲状腺功能亢进症患者体内T（3）的相对过量产生是一贯存在的。为研究各种抗甲状腺药物对血清T（3）和T（4）浓度的急性效应，对我的病人单独给予碘化物、丙基硫氧嘧啶（PTU）和甲巯基咪唑（MMI），并进行了系列T（3）和T（4）测定。在前5天，三个碘化物和三个PTU治疗的患者的血清T3急剧下降，这比MMI组更大。这表明PTU和MMI对T（3）产生的影响不同。为了比较PTU和MMI在甲状腺激素释放最小化的条件下的作用，这些药物与碘化物联合给药。PTU的平均日剂量为827（n=11），MMI的平均日剂量为88（n=8）。在PTU+碘化物组中，初始血清T3浓度为586+/-61 ng/100 ml，第1天显著下降至326+/-41，第2天和第3天分别下降至248+/-21，第4天和第5天没有进一步变化。在MMI +碘化物组中，基础血清T3为645+/-90 ng/100 ml，在第1、2和3天分别降至568+/-81，452+/-73和344+/-51，此后无变化。虽然PTU组和MMI组的初始血清T3浓度没有差异，但PTU患者的T3浓度在第1天和第2天以及第3-5天的明显平台期显著较低。两组患者的血清T（4）浓度逐渐降低，PTU组从最初的23.9 ± 2.0 μ g/100 ml降至第5天的17.5 ± 1.6，MMI组从22.0 ± 2.6降至14.6 ± 2.0。T（4）值在任何时间均无显著差异。这些变化导致两组患者血清T（4）/T（3）比值升高，但PTU +碘化物治疗组患者的这些比值明显更高。PTU组的初始血清T（4）/T（3）比值为43+/-3，在第1天和第2天分别增加至74+/-7和88+/-7，在第3-5天达到91+/-7的平台值。在平台期，MMI治疗患者的可比值分别为35+/-2，42+/-3，52+/-6和54+/-3。以前的研究表明，PTU抑制甲状腺功能亢进患者的T（4）脱碘，并减少动物T（3）从T（4）的生产。PTU治疗患者血清T（3）的急性下降幅度更大，血清T（4）/T（3）比值更高，这似乎最好地解释为该药物抑制外周T（3）的产生。第3-5天的T（4）/T（3）比值与PTU给药剂量之间的直接关系进一步支持了这一结论。这些结果进一步表明，甲状腺和甲状腺外途径都对甲状腺功能亢进症中明显的T（3）过量产生有重要作用。
In 66 untreated patients with hyperthyroidism, serum triiodothyronine (T(3)) and thyroxine (T(4)) concentrations were measured by immunoassay. The mean T(3) level was 478+/-28 ng/100 ml (all values mean+/-SEM) and the T(4) was 20.6+/-0.6 mug/100 ml. The serum T(4)/T(3) 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 T(4)/T(3) ratios with serum T(3) (r=0.77; P<0.01) but not with serum T(4)(r=0.21). These results suggested that relative overproduction of T(3) is consistently present in patients with hyperthyroidism. To examine the acute effects of various antithyroid agents on serum T(3) and T(4) concentrations, iodide, propylthiouracil (PTU), and methylmercaptoimidazole (MMI) were given alone to mine patients, and serial T(3) and T(4) measurements were made. There was an acute decrease in serum T(3) 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 T(3) 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 T(3) 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 T(3) 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 T(3) concentrations in serum were not different in the PTU and MMI groups, the T(3) concentrations in the PTU patients were significantly lower on days 1 and 2 and during the apparent plateau period on days 3-5. Serum T(4) concentrations decreased gradually in both groups, from 23.9+/-2.0 mug/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 T(4) values were not significantly different at any time. These changes resulted in increases in the serum T(4)/T(3) ratios in both groups, but these ratios were substantially higher in the patients treated with PTU + iodide. The initial serum T(4)/T(3) 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 T(4) deiodination in hyperthyroid patients and decreases T(3) production from T(4) in animals. The greater acute decrease in serum T(3) and the higher serum T(4)/T(3) ratios in the PTU-treated patients seems best explained by an inhibition of peripheral T(3) production by this agent. This conclusion is further supported by a direct relationship between the T(4)/T(3) 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 T(3) in hyperthyroidism.