A B S T R A C T Propylthiouracil (PTU) inhibits peripheral deiodination of thyroxine (T4) and triiodothyronine (T3) and decreases the metabolic effectiveness of T4 in animals. To assess the effect of PTU on extrathyroidal conversion of T4 to Ta in man, 15 studies were performed in 7 athyreotic patients treated with 100 or 200 Ag of L-T4 daily for 1 mo before the addition of PTU, 250 mg every 6 h for 8 days. Serum T3, T4, and thyrotropin (TSH) were measured daily by radioimmunoassay; serum TSH response to 500-ig thyrotropin-releasing hormone (TRH) was measured before and on the last day of giving PTU.On the 100-Ag L-T4 dose, serum T3 fell from 120±5 The data suggest that PTU blocks extrathyroidal conversion of To to Ts, thus increasing pituitary TSH secretion and augmenting the TSH response to TRH.

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Ten patients with hyperthyroidism due to Graves' disease were treated with sodium ipodate (1 g daily) in addition to propranolol (P) plus propylthiouracil (PTU; 100 mg every 8 h) and were compared with a control group of 8 patients treated with P and PTU. Patients on P and PTU had a mean (+/- SEM) basal free T3 index of 387 +/- 59 (normal, 70--160) compared with that of 409 +/- 47 (P greater than 0.05) in the sodium ipodate group. The respective basal free T4 index values (normal, 4.5-10.9) were 21.3 +/- 2.8 for the controls and 25.9 +/- 2.8 for the ipodate group (P greater than 0.5), and the basal rT3 values were 192 +/- 49 and 210 +/- 41 (normal, 16--50 ng/dl; P greater than 0.05). The average percent changes in each thyroid index and rT3 were calculated. The first 3 days on P and PTU served as the basal period for the control group, and comparisons were made to the following 9 days. The ipodate group received P and PTU for 2.7 +/- 3.0 days, and comparisons were made with the interval on ipodate, P, and PTU (mean, 9.1 +/- 0.9 days). For the free T3 index, the control group showed a mean decrement of 20.5 +/- 4.4% compared with 50.2 +/- 3.1% for the ipodate group (P less than 0.001). The respective free T4 index decrements were 14.5 +/- 4.4% and 18.5 +/- 2.7% (P greater than 0.05). The respective changes in rT3 were -13.4 +/- 7.6% and +140 +/- 26.9% (P less than 0.001). In patients with hyperthyroidism, short term daily therapy with sodium ipodate plus P and PTU produces a greater reduction of free T3 index values than that caused by P and PTU alone.

To determine the patterns of recovery of the hypothalamic-pituitary-thyroid axis following long-term thyroid hormone therapy, TRH tests were performed on 8 euthyroid nongoitrous patients, 5 euthyroid goitrous patients, and 5 hypothyroid patients while they were taking full doses of thyroid hormone and 3, 7, 10, 14, 17, 21, 28, 35, 42, 49, and 56 days after stopping it. Serum TSH, T3, and T4 were measured before and at multiple intervals over a 4-h period after giving 500 mug TRH iv. In euthyroid non-goitrous patients, the mean duration of suppressed TSH response to TRH (maximum deltaTSH less than 8 muU/ml) was 12 +/- 4 (SE) days after stopping thyroid hormone and the mean time to recovery of normal TSH response to TRH (maximum deltaTSH greater than 8 muU/ml) was 16 +/- 5 days. None of the euthyroid nongoitrous patients ever hyperresponded to TRH; their average maximal deltaTSH was 24.5 +/- 2.2 muU/ml. Serum T4 fell below normal in 4 euthyroid non-goitrous patients, reaching lowest values at 4 to 28 days. While serum T4 was low, deltaTSH was subnormal. Normal increments of T4 and T3 after TRH occurred at 19 +/- 5 and 22 +/- 6 days, respectively. In the 5 goitrous patients, patterns of recovery of pituitary and thyroid function assessed by the same parameters were much less consistent. In the 5 hypothyroid patients, the mean duration of suppressed basal TSH and suppressed deltaTSH was 13 +/- 3 days; mean time to attain a supranormal basal TSH (greater than 8 muU/ml) was 16 +/- 4 days and to reach a supranormal deltaTSH (greater than 38 muU/ml) after TRH was 29 +/- 8 days. Following prolonged thyroid therapy in euthyroid patients, recovery of normal TSH responsiveness to TRH preceded recovery of the normal T3 and T4 response to TRH by 3 to 6 days. Basal serum TSH may be used to differentiate euthyroid from hypothyroid patients 35 days after withdrawal of thyroid therapy; the response to TRH does not improve this differentiation.