Propylthiouracil

About: Propylthiouracil is a research topic. Over the lifetime, 2181 publications have been published within this topic receiving 46996 citations. The topic is also known as: Thyreostat® & 2,3-dihydro-6-propyl-2-thioxo-4(1H)-pyrimidinone.

Thyroid hormone regulation of alpha-adrenergic receptors: studies in rat myocardium.

Abstract: The effects of alterations in thyroid state on cardiac alpha-adrenergic receptors were investigated by the binding of [3H]dihydroergocryptine (DHE), a potent alpha-adrenergic antagonist. In seven experiments, cardiac membranes from euthyroid rats bound 47 +/- 9 fmoles DHE/mg protein (mean +/- SE) at saturation and demonstrated a dissociation constant (KD) of 2.5 +/- 0.4 nM. Hyperthyroidism, produced by parenteral injection of triiodothyronine, significantly reduced the binding of DHE at all concentrations studied. Scatchard analysis showed this reduction of binding to be due largely to a decreased affinity (KD = 4.0 +/- 0.8 nM, p less than 0.05), although possibly due to a decreased number of binding sites as well (29 +/- 7 fmoles/mg protein, p less than 0.10). Hypothyroidism, produced either by oral propylthiouracil or by surgical thyroidectomy, did not produce a significant change in either the number of binding sites for DHE (56 +/- 8 fmoles/mg protein, p less than 0.40) or in binding affinity (KD = 3.1 +/- 0.5 nM, p less than 0.40). Thus, in addition to the regulation of cardiac beta-receptors by thyroid hormone that has been described previously, thyroid hormone exerts a regulatory effect on the characteristics of cardiac alpha-receptors as well. These changes provide a possible molecular mechanism for the thyroid hormone-induced alterations in cardiac responsiveness to alpha-adrenergic stimulation that have been reported previously.

Increased Lipid Peroxidation in Hyperthyroid Patients: Suppression by Propylthiouracil Treatment

Abstract: Plasma and urinary levels of thiobarbituric acid reactive substances (TBAR) were determined in 24 hyperthyroid patients, 19 hypothyroid subjects, 35 controls, and 17 hyperthyroid patients before and after propylthiouracil (PTU) treatment (400 mg/day for 2-3 months), as indexes of lipid peroxidation. These measurements were carried out together with t-butyl hydroperoxide (t-BHP)-induced oxygen uptake and visible chemiluminescence in erythrocytes as functional tests related to the antioxigenic capacity of cells. Hyperthyroid patients exhibited increased levels of plasma and urinary TBAR compared to controls. Erythrocyte suspensions from hyperthyroid patients showed, compared to controls, higher rates of oxygen consumption with shorter induction periods upon addition of t-BHP, together with 142% and 75% increases in basal and t-BHP-induced chemiluminescence, respectively. Levels of TBAR in untreated hyperthyroid patients in plasma (16.2 +/- 1.3 pmol/mg of protein) and urine (15.9 +/- 1.5 nmol/mg of creatinine) were decreased after PTU treatment (Plasma, 9.5 +/- 0.7, p less than 10(-4); urine, 7.8 +/- 0.9, P less than 10(-5) to values not significantly different from those of the control group (plasma, 10.3 +/- 0.6; urine, 7.9 +/- 0.7). Compared to control, elevated rates of oxygen uptake induced by t-BHP, basal and t-BHP-induced chemiluminescence in erythrocyte suspensions from untreated hyperthyroid patients were reverted to normal by PTU, while decreased induction period (T0) values were enhanced. Determination of these lipid peroxidative parameters in hypothyroid patients revealed no significant changes over control values, excepted t-BHP-induced chemiluminescence in erythrocytes that was diminished. These data indicate that hyperthyroidism is associated with a pro-oxidant condition characterized by an enhancement in circulating and urinary lipid peroxidative indexes, which is suppressed by PTU treatment. It is suggested that this condition might reflect an oxidative stress at cellular level in tissues which are target for thyroid hormone action with a calorigenic response.

Propylthiouracil reduces the effectiveness of radioiodine treatment in hyperthyroid patients with Graves' disease.

Abstract: In order to assess the effect of propylthiouracil (PTU) or methimazole (MMI) pretreatment on patient outcome after radioiodine therapy, we examined 100 patients with Graves' disease 3, 6, 9, and 12 months after administration of a 10-mCi standard single dose of 131I. They were assigned to one of three groups: no drug (ND) treatment (30 cases); MMI (45 cases); and PTU (25 cases). Antithyroid drugs (ATD) were withdrawn 15 days before radioiodine administration. The groups were similar concerning age, gender, ATD pretreatment duration, goiter size, and initial serum triiodothyronine (T3), thyroxine (T4), free thyroxine (FT4), antithyroid autoantibody levels, 24-hour radioiodine uptake and 131I dose administered per gram of thyroid tissue. ND and MMI groups presented a similar rate of cure of 73.3% and 77.8% respectively (p = NS). In contrast, the PTU group showed a rate of cure of only 32% (p < 0.05). Logistic regression analysis indicated that PTU administration (p = 0.003) and thyroid size (p = 0.02) were the variables related to radioiodine therapy failure. Our data demonstrate that the chance of 131I treatment failure is higher in individuals using PTU than in patients using MMI or not using any ATD before radioiodine (odds ratio [OR] 5.84; 95% confidence interval [CI] 1.82-18.76) suggesting that PTU should be avoided in the treatment of patients with Graves' disease.

Reevaluation of the effects of methylmercaptoimidazole and propylthiouracil in patients with Graves' hyperthyroidism.

Abstract: The effects of methylmercaptoimidazole (MMI) and propylthiouracil (PTU) were compared in patients with Graves' hyperthyroidism. Firstly, the duration of action of the drugs was studied by the perchlorate discharge test, which was performed 2, 12, or 24 h after administering a single dose of 15 mg MMI or 300 mg PTU. After 2 h, the 9 MMI-treated patients who were tested had marked discharge (mean +/- SD, 65.0 +/- 15.8%), as did the 6 patients treated with PTU (57.6 +/- 26.6%). The mean values for the percent discharge 12 and 24 h after drug administration were 34.9 +/- 31.9% (4 patients) and 36.5 +/- 26.9% (69 patients), respectively, in the MMI group and 19.1 +/- 11.7% (11 patients) and 8.6 +/- 10.5% (7 patients) in the PTU group, indicating that the effect of MMI lasted longer. Secondly, the clinical effects of long term administration of the drugs were compared in a different group of patients with Graves' hyperthyroidism. Within 5 weeks after the onset of treatment, 34 (52%) of 66 patients treated with MMI (10 mg, 3 times daily) were euthyroid, while only 1 of 17 patients treated with PTU (100 mg, 3 times daily) was euthyroid. The average time required to achieve euthyroidism, namely normal serum T3 and T4 levels, was significantly shorter in the MMI group [6.7 +/- 4.6 (+/-SD) weeks] than in the PTU group (16.8 +/- 13.7). In spite of the well known effect of PTU on the extrathyroidal conversion of iodothyronines, the serum T3 level normalized much faster with MMI than with PTU. These results indicate that in our patient population 15 mg MMI had a longer inhibitory effect on the organification of iodide than did 300 mg PTU, and that MMI was more rapidly effective in the treatment of Graves' hyperthyroidism.