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PubMed1972

Propylthiouracil inhibits the conversion of L-thyroxine to L-triiodothyronine. An explanation of the antithyroxine effect of propylthiouracil and evidence supporting the concept that triiodothyronine is the active thyroid hormone.

6-n-propylthiouracil (PTU) administered to male Sprague-Dawley rats maintained on 2 and 5 mug L-thyroxine (T(4))/100 g body weight resulted in a marked reduction in the rate of conversion of L-thyroxine to L-triiodothyronine (T(3)). These effects could not be ascribed to induced hypothyroidism since the group maintained on 5 mug T(4)/day had normal levels of liver mitochondrial alpha glycerophosphate dehydrogenase. In confirmation of previous studies, PTU also reduced the fractional rate of deiodination of T(3). These observations provide a possible explanation of the many published observations indicating that PTU antagonizes the tissue effects of T(4) but not of T(3). The data suggest that monodeiodination of T(4) but not of T(3) is essential before hormonal effects can be manifested at the cellular level.

Administration, Oral↗
PubMed1987

Long-term treatment of alcoholic liver disease with propylthiouracil.

Propylthiouracil has been shown experimentally to protect against alcohol-induced hepatocellular necrosis in hypoxic conditions. An earlier, short-term study of patients with alcoholism and liver disease indicated clinical improvement with propylthiouracil, but the effect on mortality could not be assessed. In the present study, we investigated the effect of propylthiouracil on mortality in patients with alcoholic liver disease in a long-term, double-blind, randomized clinical trial involving 310 compliant patients who received propylthiouracil (n = 157) or placebo (n = 153) for a maximum of two years. There were no differences between the two groups in demographic and clinical characteristics and biopsy-confirmed diagnoses at randomization, or in daily urinary alcohol levels during the study. The cumulative dropout rate over two years was not significantly different (propylthiouracil group, 0.68; placebo group, 0.60). The group receiving propylthiouracil (300 mg per day) had a cumulative mortality rate half that in the group receiving placebo (0.13 vs. 0.25 [P less than 0.05] in the total sample, and 0.25 vs. 0.55 [P less than 0.03] in a subgroup of severely ill patients [propylthiouracil group, n = 56; placebo group, n = 41]). Proportional-hazards stepwise regression analyses indicated that only propylthiouracil treatment, prothrombin time, hemoglobin levels, and mean daily urinary alcohol levels significantly affected mortality. The hazards ratio for the complete group indicated that mortality in the propylthiouracil group was 0.38 (95 percent confidence interval, 0.20 to 0.83) that of the placebo group. Protection by propylthiouracil was not observed in patients with high morning urinary alcohol levels. No clinically important side effects of propylthiouracil were observed at the dose used. We conclude that the administration of propylthiouracil can reduce mortality due to alcoholic liver disease.

Alcohol Drinking↗
PubMed1989

Effects of propylthiouracil and methimazole on splanchnic hemodynamics in awake and unrestrained rats.

The treatment of alcoholic liver disease with propylthiouracil is based on its effect of suppressing the ethanol-induced increase in hepatic oxygen consumption. It has been postulated that liver necrosis ensues when the increase in oxygen demand by the liver exceeds oxygen delivery to this organ. Data are now presented which show that propylthiouracil also increases portal blood flow in awake, unrestrained rats. Liver blood flow was determined using the labeled microsphere technique in rats at various intervals (0.25, 0.5, 1.0, 3.0, 6.0 and 24 hr) after oral propylthiouracil (50 mg per kg). Administration of propylthiouracil (dose range: 6.25 to 100.0 mg per kg) produced a dose-dependent increase in portal blood flow when given either orally or intraarterially. Maximal flows were obtained with 50 mg per kg (controls = 37.8 +/- 1.5, oral propylthiouracil = 50.7 +/- 2.2 ml.kg-1.min-1). This increase in portal blood flow was accompanied by a decrease in preportal vascular resistance (controls = 2.61 +/- 0.16; propylthiouracil, 50 mg per kg = 1.79 +/- 0.09 mmHg per ml.kg-1.min-1). These effects were correlated with the plasma concentrations of propylthiouracil (r = 0.67, n = 68, p less than or equal to 0.001). The effect of oral propylthiouracil (50 mg per kg) on portal blood flow started at 0.5 hr and lasted for 6 hr after administration, whereas total liver blood flow was increased for 3 hr. Oral propylthiouracil (50 mg per kg) for 5 days resulted in a 53% increase in thyroid weight, an 85% reduction in 125I thyroid uptake and a 74% decrease in serum thyroxine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Vasodilatory effects of propylthiouracil in patients with alcoholic cirrhosis.

BACKGROUND/AIMS: An experimental study has shown that propylthiouracil increases portal blood flow in normal rats. Whether propylthiouracil has a similar effect in patients with alcoholic cirrhosis remains to be demonstrated. The aim of this study was to evaluate the effects of oral propylthiouracil (300 mg) on systemic and portal hemodynamics in patients with alcoholic cirrhosis. METHODS: Plasma propylthiouracil levels were also measured by high performance liquid chromatography in five patients with alcoholic cirrhosis. In eight patients with cirrhosis, mean arterial pressure, cardiac output and portal blood flow were evaluated before and after placebo and propylthiouracil administration. Hemodynamic measurements were performed by the Doppler technique. The plasma peak level of propylthiouracil was achieved at 1.4 +/- 0.1 h in patients with alcoholic cirrhosis. This time was chosen to express hemodynamic changes. RESULTS: Propylthiouracil administration caused a significant increase in portal blood flow (+16.5%, p < 0.05) in patients with alcoholic cirrhosis. This effect was associated with a mild and significant rise in cardiac output (from 5.8 +/- 0.2 to 6.1 +/- 0.3 l/min, p < 0.05) and a decrease in peripheral vascular resistance (from 1171 +/- 69 to 1070 +/- 67 dyn . s-1 . cm-5, p < 0.01). A significant correlation was observed between changes in portal blood flow and peripheral vascular resistance (r = 0.79, p < 0.05). No significant changes were observed after placebo. CONCLUSIONS: Our findings show that propylthiouracil has a vasodilatory effect in patients with alcoholic cirrhosis. We postulate that this effect could be the mechanism by which propylthiouracil decreases hypermetabolic state, and increases oxygen delivery to the liver, in patients with alcoholic liver diseases.

Female↗
PubMed2002

Propylthiouracil for alcoholic liver disease.

BACKGROUND: Alcohol is the most common cause of liver disease in the Western world today. Randomised clinical trials have addressed the question whether propylthiouracil has any efficacy in patients with alcoholic liver disease. OBJECTIVES: The objectives were to assess the efficacy of propylthiouracil on mortality, clinical symptoms and complications, liver biochemistry, and liver histology in patients with alcoholic liver disease. Adverse events were also analysed. SEARCH STRATEGY: The Cochrane Hepato-Biliary Group Controlled Trials Register (searched July 2001), The Cochrane Controlled Trials Register (Cochrane Library Issue 3, 2001), MEDLINE (January 1966 to July 2001), EMBASE (January 1985 to July 2001) were searched. These electronic searches were combined with full text searches. Manufacturers and researchers in the field were also contacted. SELECTION CRITERIA: Randomised clinical trials studying patients with alcoholic steatosis, alcoholic fibrosis, alcoholic hepatitis, and/or alcoholic cirrhosis were included. Interventions encompassed propylthiouracil at any dose versus placebo or no intervention. The trials could be double-blind, single-blind, or unblinded. The trials could be unpublished or published as an article, an abstract, or a letter and no language limitations were applied. DATA COLLECTION AND ANALYSIS: All analyses were performed according to the intention-to-treat method. The statistical package (RevMan and MetaView) provided by the Cochrane Collaboration was used. The methodological quality of the randomised clinical trials was evaluated by components of quality and the Jadad-scale. MAIN RESULTS: Combining the results of six randomised clinical trials including 710 patients demonstrated no significant effects of propylthiouracil versus placebo on mortality (Peto odds ratio (OR) 0.91, 95% confidence interval (CI) 0.59 to 1.40), liver related mortality (OR 0.78, 95% CI 0.45 to 1.33), complications of the liver disease (OR 1.14, 95% CI 0.58 to 2.24), or liver histology. Propylthiouracil was associated with a non significant trend towards an increased risk of non-serious adverse events (OR 1.49, 95% CI 0.74 to 2.99) and with the seldom occurrence of serious adverse events (leukopenia). REVIEWER'S CONCLUSIONS: This systematic review could not demonstrate any significant efficacy of propylthiouracil on any clinically important outcomes (mortality, liver related mortality, liver complications, and liver histology) of patients with alcoholic liver disease and propylthiouracil was associated with adverse events. Accordingly, there is no evidence for using propylthiouracil for alcoholic liver disease outside randomised clinical trials.

Antimetabolites↗
PubMed1981

Correlation between antithyroid effect and serum concentrations of propylthiouracil in patients with hyperthyroidism.

1 Correlation between the kinetics of propylthiouracil and its antithyroid effect was studied in 17 hyperthyroid patients. The serum concentration of propylthiouracil 1 h after an oral dose of 400 mg of hyperthyroid patients. The serum concentration of propylthiouracil 1 h after an oral dose of 400 mg of the drug was used as kinetic parameter as this concentration from the previous study was found to correlate significantly (r = 0.84, P less than 0.01) with the area under the serum concentration-time curve. 2 After 3 weeks of treatment with 200 mg propylthiouracil three times daily the serum concentration of propylthiouracil was correlated to the decrease in various thyroid parameters such as total and free indexes of serum thyroxine, triiodothyronine and reverse triiodothyronine. 3 Significant correlations were found between the serum concentration of propylthiouracil and all the measured thyroid variables except reverse triiodothyronine. The highest degree of correlation was obtained between serum propylthiouracil and the percentage decrease in total and free indexes of triiodothyronine (r = 0.63 and 0.70, respectively, P less than 0.01). 4 It is suggested that a serum concentration of propylthiouracil above 4 to 5 micrograms/ml 1 h after an oral dose of 400 mg of the drug will secure a sufficient and rapid antithyroid effect during continuous therapy.

Adult↗
PubMed1987

Effects of propylthiouracil and methylthiouracil on cyclic AMP and ion movements in rat pancreatic islets.

Propylthiouracil and methylthiouracil have been shown to potentiate glucose-induced insulin secretion from rat pancreatic islets: the effect of methylthiouracil being less pronounced than that of propylthiouracil. In this study the effects of these substances on cAMP levels, 86Rb+ efflux, 45Ca2+ net uptake, and 45Ca2+ efflux were tested in isolated rat islets in order to obtain information on their possible mechanism of action. Propylthiouracil and to a lesser extent methylthiouracil increased islet cyclic AMP in a concentration-related manner. Maximum increases at the highest concentrations tested were 261% and 190% respectively. In the presence of 3 mM glucose propylthiouracil and methylthiouracil led to a decrease in the 86Rb efflux rate. With 5.6 mM glucose, both thiourea derivatives produced an increase in the 86Rb+ efflux rate which was independent of the presence or absence of calcium in the medium. Propylthiouracil and methylthiouracil augmented the 45Ca2+ efflux rate in the presence as well as in the absence of external calcium at various glucose concentrations. Propylthiouracil did not change, and methylthiouracil only slightly augmented, 45Ca2+ net uptake into the isolated islets. It is suggested that the synergistic effect of propylthiouracil and methylthiouracil on glucose-induced insulin release is at least in part due to an increase in islet cAMP levels. Whether the two substances have additional direct effects on ionic fluxes which contribute to their insulinotropic action or whether the observed changes in ion movements are secondary to the elevation of cAMP levels remains to be unclear and needs further investigation.

Animals↗
PubMedDate not supplied

Inhibition of rat hepatic thyroxine 5'-monodeiodinase by propylthiouracil: relation to site of interaction of thyroxine and glutathione.

When rat liver cytosol, dialyzed free of glutathione, was chromatographed on Sephadex G-100 after incubation with 35S-propylthiouracil, 2 peaks of bound radioactivity were observed, 1 of which contained nearly all the thyroxine 5'-monodeiodinase activity in rat liver cytosol. Binding of propylthiouracil to this peak was inhibited by glutathione but not by thyroxine. Approximately 25% of 35S-propylthiouracil initially bound to the thyroxine 5'-monodeiodinating activity peak remained bound after dialysis, precipitation with trichloroacetic acid, and multipe extractions with ethanol, methanol, and chloroform, suggesting that binding was at least in part covalent. Dialysis studies showed that the presumed covalent binding of 35S-propylthiouracil to the thyroxine 5'-monodeiodinase peak could be inhibited by glutathione, dithioerythritol, and unlabelled propylthiouracil but not by oxidized glutathione or thyroxine. Conversely, thyroxine binding was unaffected by thiol compounds. We studied the kinetics of thyroxine 5'-monodeiodination by radioimmunoassay techniques using rat liver homogenates as source of enzyme and observed the dependence of enzymic reaction upon glutathione (Km = 2.4 mM). Propylthiouracil inhibited the reaction and this inhibition could be overcome with increasing glutathione concentrations. We conclude that the thiol-dependent thyroxine 5'-monodeiodinase is inhibited by propylthiouracil through its covalent binding, probably as mixed disulfide, to s site on the enzyme at which glutathione interacts either as a cosubstrate or reducing agent. This binding site is separate from the site at which thyroxine binds.

Animals↗
PubMed1993

Hepatic injury during propylthiouracil therapy in patients with hyperthyroidism. A cohort study.

OBJECTIVE: To evaluate the incidence, severity, and course of propylthiouracil-induced hepatic injury in patients with hyperthyroidism. DESIGN: Cohort study. SETTING: Outpatient clinic of a university-based hospital. PATIENTS: Fifty-four patients with normal aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values and a definite diagnosis of hyperthyroidism. INTERVENTION: Treatment with propylthiouracil, 300 mg/d for 2 months followed by 100 to 150 mg/d for 3 months and a subsequent maintenance dose of 100 mg/d. MEASUREMENTS: Liver biochemical tests were studied before therapy and 2 months and 5 months after starting propylthiouracil therapy. The patients were monitored with clinical evaluation and weekly liver biochemical tests after AST or ALT levels became abnormal. Serologic markers of hepatitis A, B, C, and delta virus infection were also studied when appropriate. RESULTS: Fifteen (28%; 95% CI, 16% to 42%) of the 54 patients showed ALT elevations 2 months after propylthiouracil therapy. The mean peak ALT level for these patients was 1.35 mu kat/L (range, 0.65 3.85 mu kat/L). None of these patients had symptoms or hyperbilirubinemia. Liver biopsy in three patients showed mild perivenular focal necrosis or ill-defined granuloma composed of foamy histiocytes with ceroid pigment and mild fatty metamorphosis. Despite continued propylthiouracil therapy at a reduced dose, ALT levels returned to normal in 13 of 15 patients in the following 3 months. None of these ALT elevations resulted from hepatitis A, B, C, or delta virus infection. No statistical difference was seen in the pretreatment characteristics between patients with and those without ALT elevation, except that the former had a higher pretreatment T4 level (270 +/- 12.9 compared with 237 +/- 7.72 nmol/L, P = 0.027) and T3 level (7.22 +/- 0.72 compared with 5.85 +/- 0.39 nmol/L, P = 0.048). CONCLUSIONS: Propylthiouracil-induced subclinical liver injury is common and is usually transient and asymptomatic. Therapy with propylthiouracil may be continued with caution in the absence of symptoms and hyperbilirubinemia.

Adult↗
PubMed1993

Effect of propylthiouracil on the ethanol-induced increase in liver oxygen consumption in awake rats.

It has been postulated that the beneficial effects of the antithyroid drug propylthiouracil in the treatment of alcoholic liver disease depend primarily on the action of propylthiouracil in suppressing the increase in hepatic oxygen consumption induced by ethanol. The evidence for this effect of propylthiouracil is derived from studies in which liver oxygen consumption has been determined in in vitro preparations. In our study the effects of ethanol and propylthiouracil on liver oxygen consumption were assessed in vivo in an unrestrained and unanesthetized rat model, where liver blood flow and hepatic vein and portal vein oxygen content can be measured. Data show that the liver oxygen consumption increased in rats treated with ethanol-containing liquid diets for 4 to 6 wk, both on withdrawal of alcohol (30%, p < 0.01), and after readministration of ethanol (50%, p < 0.01). Single-dose ethanol administration increased portal tributary blood flow without affecting hepatic arterial blood flow in both controls and rats withdrawn from long-term ethanol treatment. Long-term ethanol administration per se had no effect on portal tributary blood flow; however, hepatic arterial blood flow was increased by 38% (p < 0.01). Treatment with propylthiouracil for 5 days resulted in complete suppression of the increase in liver oxygen consumption induced by long-term ethanol administration. Propylthiouracil treatment also attenuated the increase in portal tributary blood flow after the administration of a single dose of ethanol. These determinations were made 24 hr after the last dose of propylthiouracil.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Propylthiouracil-induced hepatic damage.

OBJECTIVE: To report a case of propylthiouracil-induced hepatic damage. CASE SUMMARY: A 64-year-old white woman with hyperthyroidism received propylthiouracil 250 mg/d for 1 year. She developed hepatitis after 1 year of therapy. Alcohol and drug abuse were ruled out and all serologic tests for hepatitis A, B, and C were negative. Cytomegalovirus and Epstein-Barr virus infection were also ruled out. Antinuclear antibody, antimitochondrial antibody, and antismooth muscle antibody were negative. The clinical picture was similar to that of viral hepatitis characterized by nausea, vomiting, and jaundice. Histologic examination of a liver biopsy specimen showed chronic active hepatitis. The patient developed cirrhosis during follow-up. DISCUSSION: Propylthiouracil is widely used in the treatment of hyperthyroidism. Despite its widespread use, there have been only a few reported cases of propylthiouracil-induced hepatotoxicity. The precise mechanism of the injury is unknown, although immunologic factors are suggested. CONCLUSIONS: Hepatic damage induced by propylthiouracil is a rare complication. However, the danger of permanent hepatic damage should be kept in mind. The best way of preventing propylthiouracil hepatotoxicity is careful screening of patients considered for treatment.

Antithyroid Agents↗
PubMed1985

Propylthiouracil levels in hyperthyroid patients unresponsive to large doses. Evidence of poor patient compliance.

Nine patients with hyperthyroidism due to Graves' disease did not respond to therapy with very large doses (800 to 2000 mg/d) of propylthiouracil. In eight patients, studies showed propylthiouracil was absorbed and metabolized normally. Five patients had no detectable propylthiouracil in their serum 2 to 3 hours after supposedly taking their medication at home, and three patients had markedly abnormal results of perchlorate discharge tests after receiving propylthiouracil under supervision. After evaluation, noncompliance was thought to be the reason for treatment failure in six of the nine patients; one patient was possibly resistant. In two patients, data were insufficient, although intermittent noncompliance could not be ruled out. Among patients who respond poorly to propylthiouracil therapy, noncompliance is the most likely reason. In such patients, methimazole should be substituted for continued massive doses of propylthiouracil.

Adolescent↗
PubMed1987

Pharmacology of propylthiouracil in thyrotoxicosis and chronic renal failure.

The simultaneous occurrence of thyrotoxicosis and renal failure has rarely been reported in the literature, and data concerning appropriate antithyroid drug management in this circumstance are limited. We studied propylthiouracil pharmacokinetics in one such patient basally and while the patient was receiving hemodialysis. On a day when the patient was not receiving hemodialysis, propylthiouracil serum levels were high, but serum propylthiouracil half-life was not prolonged. During hemodialysis, serum propylthiouracil levels were normal, and the time to peak serum levels was delayed; the disappearance of the drug from the serum was normal after hemodialysis was completed. The amount of propylthiouracil that appeared in the dialysate was approximately 5% of the administered dose. These data suggest that propylthiouracil can be administered in standard dosages to patients with thyrotoxicosis and renal failure.

Adult↗
PubMed1994

A comparison of propylthiouracil versus methimazole in the treatment of hyperthyroidism in pregnancy.

OBJECTIVE: Our purpose was to demonstrate that propylthiouracil and methimazole are equally effective and safe in the treatment of hyperthyroidism during pregnancy. STUDY DESIGN: Between 1974 and 1990 records were available on 185 pregnant patients with a history or diagnosis of hyperthyroidism. Ninety-nine patients were treated with propylthiouracil and 36 with methimazole. The response to therapy was compared with respect to the time to normalization of the free thyroxine index and the incidences of congenital anomalies and hypothyroidism. RESULTS: The time to normalization of the free thyroxine index was compared in the two groups by means of survival analysis. The median time to normalization of the free thyroxine index on propylthiouracil and methimazole was 7 and 8 weeks, respectively (p = 0.34, log-rank test). The incidence of major congenital malformations in mothers treated with propylthiouracil and methimazole was 3.0% and 2.7%, respectively. No neonatal scalp defects were seen. One infant was overtly hypothyroid at delivery. CONCLUSION: Propylthiouracil and methimazole are equally effective and safe in the treatment of hyperthyroidism in pregnancy.

Chi-Square Distribution↗
PubMed2001

Meta-analysis of propylthiouracil for alcoholic liver disease--a Cochrane Hepato-Biliary Group Review.

AIMS/BACKGROUND: The aim of this review was to determine the benefits and adverse effects of propylthiouracil for patients with alcoholic liver disease. METHODS: Systematic Cochrane Review of randomised clinical trials. The Cochrane Hepato-Biliary Controlled Clinical Trials Register, The Cochrane Library, MEDLINE, and full text searches were combined. All analyses were performed according to the intention-to-treat method. Only randomised clinical trials studying patients with alcoholic steatosis, alcoholic fibrosis, alcoholic hepatitis and/or alcoholic cirrhosis were included. Interventions encompassed propylthiouracil at any dose versus placebo or no intervention. The trials could be double-blind, single-blind or unblinded. RESULTS: Six randomised clinical trials randomising 710 patients demonstrated no significant effects of propylthiouracil versus placebo on mortality (Peto odds ratio (OR) 0.91, 95% confidence interval (CI) 0.59 to 1.40), liver-related mortality (OR 0.78, CI 0.45 to 1.33), complications to the liver disease (OR 1.14, CI 0.58 to 2.24), and liver histology. Propylthiouracil was associated with a nonsignificant trend toward an increased risk of nonserious adverse events (OR 1.49, CI 0.74 to 2.99) and with the rare occurrence of serious adverse events (leukopenia). CONCLUSIONS: This systematic review could not demonstrate any significant effect of propylthiouracil on any clinically important outcomes (mortality, liver-related mortality, liver complications and liver histology) of patients with alcoholic liver disease.

Antithyroid Agents↗
PubMed1997

The effect of propylthiouracil on subsequent radioactive iodine therapy in Graves' disease.

OBJECTIVE: Antithyroidal drugs (ATD) are used in the management of Graves' disease either as primary therapy for several months while awaiting remission of the disease or as pretreatment for several weeks prior to definitive radioactive iodine therapy (RAI). We have reported previously that pretreatment with propylthiouracil (PTU) before definitive RAI therapy is associated with a higher RAI treatment failure rate than RAI therapy alone. The objectives of the current study were 2-fold. First, to verify the results of our prior study regarding the effect of PTU used as pretreatment before RAI in a cohort of patients from a different institution and, secondly, to better define the relationship between the number of days off PTU before RAI therapy and therapeutic efficacy of RAI dosing. DESIGN: A retrospective review of Graves' disease patients treated from 1980 to 1994. PATIENTS: Study patients had to meet the following inclusion criteria: radionuclide studies and thyroid hormone values consistent with Graves' disease, at least 1 year of follow-up data available and discontinuation of the ATD at least 4 days before RAI administration. Exclusion criteria included therapy with any ATD other than PTU or ATD therapy during or following RAI dosing. MEASUREMENTS: Effectiveness of RAI therapy, days on PTU, days off PTU and calculated RAI dose to the thyroid were recorded for each subject. We compared the efficacy of RAI therapy in patients treated with PTU (used either as pretreatment in preparation for RAI therapy or as primary long-term therapy) before RAI administrations to those treated with RAI alone with special attention to the number of days on and off PTU before RAI dosing. Patients were considered RAI treatment failures if a second dose of RAI was required to achieve a euthyroid or hypothyroid state. RESULTS: One hundred and sixteen patients met our study criteria. Forty patients received PTU therapy for a mean of 221 +/- 59 days. The PTU was discontinued for a mean of 60 +/- 25 days before RAI dosing. Persistent hyperthyroidism was seen in 9% (7/76) of patients treated with RAI alone. The failure rate of a single dose of radioactive iodine was significantly increased when PTU was discontinued between 4 and 7 days before the administration of RAI (29% vs 9% for RAI alone, P = 0.039). PTU discontinued for at least 1 week before RAI dosing was associated with a nearly 2-fold increase in failure rate, but this difference did not achieve significance (17% vs 9% for RAI alone, P = 0.24). Examining only those patients receiving PTU, patients who had successful single dose RAI therapy tended to receive a higher dose of RAI than patients failing RAI therapy (480 +/- 30 vs 410 +/- 40 MBq administered dose, P = 0.18; and 8.0 +/- 0.9 vs 5.5 +/- 1.1 MBq/g thyroid tissue calculated dose, P = 0.21). Furthermore, total serum thyroxine at diagnosis was significantly higher in patients failing RAI therapy after PTU administration than in patients successfully treated with RAI after receiving PTU (316 +/- 40 vs 225 +/- 13 nmol/L, P = 0.03). CONCLUSIONS: Propylthiouracil discontinued 4-7 days before radioiodine dosing is associated with a significant increase in the failure rate of a single dose of radioiodine. Discontinuation of the propylthiouracil for at least a week before radioiodine administration is associated with a higher, although not statistically significant, radioiodine failure rate. In patients that require treatment with propylthiouracil before radioiodine therapy, a higher total serum thyroxine level at diagnosis is associated with an increased rate of radioiodine failure. Consideration should be given to increasing empirically the dose of radioiodine administered to Graves' disease patients that have received propylthiouracil within a week of radioiodine administration in an effort to decrease the radioiodine failure rate to an acceptable level.

Adult↗
PubMed1975

Stimulation by propylthiouracil of the hexose monophosphate shunt in human polymorphonuclear leucocytes during phagocytosis.

The effect of propylthiouracil on glucose metabolism in human polymorphonuclear leucocytes was studied. At a therapeutically achievable concentration (0.1 mM), propylthiouracil stimulated hexose monophosphate shunt activity in normal leucocytes during phagocytosis but not in resting cells. However, in the presence of hydrogen peroxide it stimulated hexose monophosphate shunt activity in resting cells, and in the soluble fraction when reduced glutathione and reduced nictotinamide adenine dinucleotide phosphate (NADPH) were also present. Propylthiouracil had nor effect on glucose-1-C oxidation in either phagocytosing or resting leucocytes obtained from two male patients with chronic granulomatous disease. Stimulation of the hexose monophosphate shunt activity in normal leucocytes during phagocytosis also was demonstrated with methimazole, thiouracil and thiourea, but not with adenine, uracil or urea. There was an apparent minimal common structure requirement in thriourea. Propylthiouracil had no effect on phagocytosis, formate oxidation, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase or catalase activities. Thus, the stimulation of the hexose monophosphate shunt activity by propylthiouracil is dependent on hydrogen peroxide and is best explained by its stimulation or participation in the glutathione cycle.

Blood Glucose↗
PubMed2003

CD1a expression in psoriatic skin following treatment with propylthiouracil, an antithyroid thioureylene.

BACKGROUND: The antithyroid thioureylenes, propylthiouracil (PTU) and methimazole (MMI), are effective in the treatment of patients with plaque psoriasis. The mechanism of action of the drugs in psoriasis is unknown. Since the drugs reduce circulating IL-12 levels in patients with Graves' hyperthyroidism, the effect of propylthiouracil on CD1a expression in psoriatic lesions was examined in biopsy samples of patients with plaque psoriasis. CD1a is a marker of differentiated skin antigen presenting cells (APC, Langerhans cells). Langerhans cells and skin monocyte/macrophages are the source of IL-12, a key cytokine involved in the events that lead to formation of the psoriatic plaque. METHODS: Biopsy specimens were obtained from six patients with plaque psoriasis who were treated with 300 mg propylthiouracil (PTU) daily for three months. Clinical response to PTU as assessed by PASI scores, histological changes after treatment, and CD1a expression in lesional skin before and after treatment were studied. RESULTS: Despite significant improvement in clinical and histological parameters the expression of CD1a staining cells in the epidermis did not decline with propylthiouracil treatment. CONCLUSIONS: It appears that the beneficial effect of propylthiouracil in psoriasis is mediated by mechanisms other than by depletion of skin antigen-presenting cells.

Adult↗