Topic
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.
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TL;DR: It is demonstrated that propylthiouracil and methimazole are equally effective and safe in the treatment of hyperthyroidism in pregnancy.
190 citations
TL;DR: The mechanism of the antithyroid effect appears to be inhibition of peroxidase activity, and it is recommended that all patients treated with sunitinib be monitored for hypothyroidism.
Abstract: Objective: Sunitinib is a novel tyrosine kinase inhibitor with antitumor and antiangiogenic effects. An observed higher than expected rate of hypothyroidism in sunitinib-treated patients prompted assessment of the incidence of hypothyroidism. Design: Patients taking sunitinib had their thyroid function tests (TFTs) assessed via chart review. To explore potential effects on the thyroid, we examined the antiperoxidase activity of sunitinib by in vitro testing its effect on guaiacol oxidation and protein iodination by lactoperoxidase. Main outcome: Of the 89 patients who took sunitinib, 49 patients were excluded from analysis for several reasons. Of the remaining 40 patients, 21 (53%, 24% of the original 89) developed elevated thyrotropin (TSH) after a median of 5 months (range 1–36 months). Median TSH was 21.4 mU/L (range 4.6–174 mU/L). In vitro, sunitinib had antiperoxidase activity that was about one-fourth the potency of propylthiouracil. Conclusions: Of the 40 patients who had TFTs assessed after starti...
186 citations
TL;DR: A pregnant woman with Graves’ disease and an intact thyroid should receive the minimal dose of antithyroid drugs which keeps her thyroid function near the upper end of normality, and especially when she is receiving thyroxine substitution therapy.
Abstract: Hyperthyroidism due to Graves’ disease is induced by autoantibodies stimulating the thyroid-stimulating hormone (TSH) receptor. In most patients these antibodies can be measured in serum. Graves’ disease is common in women of reproductive age, with a prevalence rate of past or present disease of 0.5‐1% (1). Classically, three therapeutic approaches are used: (i) Antithyroid drugs given for a long period, which is commonly 1‐2 years. During therapy most patients enter remission, but relapses are frequent (around 50%) after withdrawal of medication; (ii) Radioiodine therapy. This may initially aggravate the autoimmune reaction, but most patients become euthyroid or hypothyroid, due to the reduction in thyroid follicular cell mass; (iii) Subtotal or near total thyroidectomy. Pregnancy is commonly accompanied bya fall in thyroid autoimmune activity, and women with Graves’ disease may spontaneously enter remission during pregnancy. However, disease activity persists in some pregnant patients, and occasionally onset of Graves’ disease is seen. The recommended therapy for Graves’ disease during pregnancy is monotherapy with antithyroid drugs (propylthiouracil, methimazol or carbimazol). While thyroid hormones produced by or given to the mother cross the placenta in only limited amounts, both TSH-receptor stimulating antibodies and antithyroid drugs readily cross the placenta and affect fetal thyroid function. Ideally, a balance between stimulating antibodies and drugs which keeps the mother euthyroid will also maintain euthyroidism in the fetus. Fortunately this is close to reality; during therapy with antithyroid drugs the thyroid state of the fetus parallels that of the mother, but with a tendency to be slightly lower (2). Hence, a pregnant woman with Graves’ disease and an intact thyroid should receive the minimal dose of antithyroid drugs which keeps her thyroid function near the upper end of normality. After delivery, antithyroid drugs are cleared from the neonatal circulation within the first days, whereas TSH-receptor antibodies disappear much more slowly and may stimulate the thyroid during the first weeks or even months of life. Delayed neonatal hyperthyroidism may therefore develop, constituting a potentially life-threatening medical condition. The situation is different when a pregnant woman has previously been treated for Graves’ hyperthyroidism with radioiodine or surgery, and especially when she is receiving thyroxine substitution therapy. In this situation, the thyroid function of the mother does not reflect thyroid function in the fetus. If the mother still produces large amounts of TSH-receptor stimulating antibodies, fetal hyperthyroidism may develop. Also, neonatal hyperthyroidism may be present at birth and last for months if left untreated. Occasionally antibodies against the TSH receptor will bind to the receptor without stimulation, but rather will block the normal effect of TSH. This may cause hypothyroidism in the mother and the fetus, and transiently in the newborn. This rare variant, which has been detected in 1 in 180 000 newborns in North America (3), is not discussed in detail.
174 citations
TL;DR: Little relationship was observed between maternal doses and fetal thyroid status; in fact, when low doses of both PTU and MMI were administered, high TSH levels in the fetus were observed in 7 of the 34 fetuses and in 6 of the 43 fetuses, respectively.
Abstract: Thionamide therapy is a mainstay of the treatment of hyperthyroidism complicated by pregnancy, but it can expose the fetus to hypothyroidism. In terms of fetal thyroid status, propylthiouracil (PTU) has been preferred over methimazole (MMI) based on experimental data on limited transplacental passage, and lower doses have been recommended. However, neither of these practices is supported by convincing clinical evidence. We compared the effect of maternal ingestion of PTU with that of MMI on fetal thyroid status using cord sera at delivery in 77 mothers with Graves' hyperthyroidism who were receiving thionamides and whose free T4 (FT4) levels were within the normal range. We also examined the dose effects on fetal thyroid status in these women. Thirty-four women were taking PTU (group P), and 43 were taking MMI (group M). Neither the mean fetal FT4 nor the mean fetal TSH level was significantly different between the two groups. No significant difference in the occurrence of low FT4 levels or high fetal TSH levels was found between group P and group M (low FT4, 6% vs. 7%; high TSH, 21% vs. 14%). Little relationship was observed between maternal doses and fetal thyroid status; in fact, when low doses of both PTU (100 mg daily or less) and MMI (10 mg daily or less) were administered, high TSH levels in the fetus were observed in 7 of the 34 fetuses (21%) and in 6 of the 43 fetuses (14%), respectively. Higher doses were associated with normal or low fetal TSH levels. These findings demonstrate that in terms of fetal hypothyroidism-inducing potential, there is little reason to choose PTU over MMI. Individualized, not uniformly low, doses of these drugs may prevent fetal hypothyroidism.
172 citations
TL;DR: The rat liver system provides a suitable model for the study of factors that influence the conversion of T(4) to T(3) in man, and the findings strongly indicate that this process, at least in the liver, is closely linked to the utilization of carbohydrate.
Abstract: As judged from both paper and column chromatography, slices or homogenates of liver from rats fasted for 48 h displayed a lesser rate of generation of (125)I-labeled 3,5,3'-triiodothyronine (T(3)) from (125)I-labeled thyroxine (T(4)) added to incubation media than did preparations from normal chow-fed animals. A similar defect in the conversion of T(4) to T(3) in the livers of fasted animals was observed when preparations were incubated with substrate concentrations of T(4) so that T(3) generation could be assessed by radioimmunoassay. The effect of fasting could be prevented, wholly or in part, by administration of glucose in the drinking water to otherwise fasted animals, and the degree of prevention appeared to be proportional to the concentration of glucose employed. Diminished generation of T(3) from T(4) was similarly evident in the livers of animals with streptozotocin-induced diabetes mellitus, and this defect was overcome by the provision of insulin in vivo, but not in vitro. Decreased formation of T(3) from T(4) was also observed in preparations of liver from animals given dexamethasone, amiodarone, and propylthiouracil. In no case could these effects on the net formation of T(3) from T(4) be explained by effects of the experimental conditions on the degradation of the T(3) generated, as judged from the rate of degradation of exogenous (125)I-T(3) measured in parallel incubates. An analysis of the rate of disappearance of (125)I-T(4) from reaction mixtures in relation to the rate of appearance of (125)I-T(3) and (125)I-iodide was employed to estimate the activity of the 5-monodeiodinating pathway of T(4) metabolism that leads to the formation of 3,3',5'-triiodothyronine (reverse T(3)). Such estimates indicated that reverse T(3) formation was actively proceeding in the preparations studied, was slightly enhanced by fasting, was unaffected by dexamethasone and amiodarone, and was markedly inhibited by propylthiouracil. In view of the similarities between the effect of these experimental manipulations on the generation of T(3) from T(4) by rat liver in vitro to their effects on the production rates and serum concentrations of T(3) in man, it is concluded that the rat liver system provides a suitable model for the study of factors that influence the conversion of T(4) to T(3) in man. In addition, the findings strongly indicate that this process, at least in the liver, is closely linked to the utilization of carbohydrate.
171 citations