Showing papers on "Propylthiouracil published in 1991"

Effect of thyroid hormone on the expression of mRNA encoding sarcoplasmic reticulum proteins.

Abstract: The purpose of this study was to determine the expression of genes encoding various sarcoplasmic reticulum components that are functionally coupled with calcium release, uptake, and storage function during cardiac hypertrophy induced by thyroid hormone. Hyperthyroidism was induced in two groups of rabbits by the injection of 200 micrograms/kg L-thyroxine (T4) daily for 4 days (T4-4-day group) and 8 days (T4-8-day group). Hypothyroidism was induced in another group of rabbits by adding 0.8 mg/ml propylthiouracil to the drinking water for 4 weeks. The relative expression level of mRNA encoding different sarcoplasmic reticulum proteins was determined by RNA slot blot and Northern blot analysis. In hyperthyroid hearts, the steady-state level of cardiac ryanodine receptor mRNA and sarcoplasmic reticulum cardiac/slow-twitch Ca(2+)-ATPase mRNA were both increased to 147% (T4-4-day group) and 186% (T4-8-day group) of control, respectively, but decreased to 71% and 75%, respectively, in hypothyroid ventricles. The mRNA level for phospholamban was decreased in both hyperthyroidism (T4-8-day group, 72%) and hypothyroidism (77%) in these hearts. On the other hand, calsequestrin mRNA levels did not change in hyperthyroid and hypothyroid ventricles. In accord with the changes in Ca(2+)-ATPase mRNA levels, the Ca(2+)-ATPase protein was increased to 199% (T4-8-day group) in hyperthyroid ventricles and decreased to 86% of control in hypothyroid ventricles. The expression levels of ryanodine receptor, Ca(2+)-ATPase, phospholamban, and calsequestrin mRNAs were similarly altered in skeletal muscle tissues from hyperthyroid and hypothyroid rabbits. These results indicate that the mRNA levels of sarcoplasmic reticulum proteins responsible for calcium release and calcium uptake are coordinately regulated in response to changes in thyroid hormone level in both heart and skeletal muscle. These changes in mRNA level should lead to changes in protein levels and thus to altered calcium release and uptake in the chronic stages of hyperthyroidism and hypothyroidism.

Oxidation of propylthiouracil to reactive metabolites by activated neutrophils. Implications for agranulocytosis.

Abstract: Propylthiouracil (PTU) is associated with idiosyncratic agranulocytosis that may be due to reactive metabolites generated from oxidative metabolism by neutrophils. Therefore, the metabolism of PTU was investigated in activated neutrophils. Three oxidized metabolites were observed on HPLC: PTU-disulfide, propyluracil-2-sulfinate, and propyluracil-2-sulfonate (PTU-SO3-). No metabolism was detected in cells that had not been activated. Metabolism was inhibited by sodium azide and by catalase. The same products were produced by myeloperoxidase (MPO) in an MPO/H2O2/Cl- system. PTU inhibited its own metabolism; however, complete conversion to PTU-SO3- could be achieved with optimal PTU concentrations. MPO/H2O2 without Cl- produced only slight metabolism. The PTU-sulfenyl chloride is a postulated intermediate. In the absence of chloride, oxidation might proceed through propyluracil-2-sulfenic acid. The sulfenyl chloride and PTU-SO3- are both chemically reactive with sulfhydryl compounds such as N-acetylcysteine. Such reactive metabolites, generated by activated neutrophils, may be involved in hypersensitivity reactions associated with PTU, such as agranulocytosis.

Recovery of spleen cell natural killer activity by thyroid hormone treatment in old mice.

Abstract: The age-dependent changes in thyroid-hormone blood levels and the effects of in vivo and in vitro thyroid-hormone administration on both basal and lymphokine-induced spleen cell natural killer (NK) activities have been investigated in young and old Balb/c mice Both thyroxine (T4) and triiodothyronine (T3) plasma levels decline progressively with increasing age of the mice, displaying in 25-month-old mice only 50 and 60% of the T4 and T3 blood levels, respectively, found in young mice In vivo T4 administration to old mice causes a significant increment in endogenous NK activity (22-fold increase), which approaches the values observed in young animals, while it does not modify NK activity in young mice The T4 injection in old mice does not induce changes in the lymphocyte sub-populations When T4 is administered in vitro alone or in combination with interferon (IFN) and/or interleukin 2 (IL-2), no effect is observed either on basal activity or IL-2-induced cytotoxicity, whereas the IFN sensitivity of spleen cells from old mice is significantly recovered (4-fold increase) T4 is able to increase IFN-induced cytotoxicity even when administered in vitro simultaneously with IFN to the cytotoxic assay (15- and 27-fold increases in young and old mice, respectively) Under these conditions, IFN alone is not able to exert any boosting effect even at a young age In vivo propylthiouracil (PTU) administration completely abrogates the IFN responsiveness of spleen cells in young mice The interruption of the PTU treatment results in a recovery of IFN-inducible NK cytotoxicity Taken together, our findings point out the important role of thyroid hormones in the modulation of NK cell activity and provide a new insight into the mechanisms by which the endocrine system is able to influence the expression of natural immunity

Uptake and metabolism of iodine is crucial for the development of thyroiditis in obese strain chickens.

Abstract: To assess the importance of the role of thyroidal iodine in the pathogenesis of thyroiditis in the obese strain (OS) chicken, a model of spontaneous and severe disease, we studied the effect of antithyroid drugs that reduce thyroidal iodine or prevent its metabolism. Reduction of thyroidal iodine was achieved with KClO4, an inhibitor of iodine transport and mononitrotyrosine (MNT), a drug that promotes loss of thyroidal iodine as iodotyrosines. A regimen consisting of KClO4 and MNT administration beginning in ovo and continuing after hatching reduced thyroidal infiltration to 2% of control values and decreased thyroglobulin antibody (TgAb) production for as long as 9 wk. Untreated birds had severe disease by 5 wk of age. The suppression of disease was independent of TSH, not mediated by generalized immunosuppression and reversed by excess dietary iodine. Two drugs that inhibit the metabolism of iodine, propylthiouracil (PTU) and aminotriazole, reduced thyroidal infiltration and TgAb levels, although to a lesser extent. When splenocytes from OS chickens with thyroiditis were transferred to Cornell strain (CS) chickens, a related strain that develops late onset mild disease, only the recipients that were iodine supplemented developed thyroiditis. In conclusion, autoimmune thyroiditis in an animal model can be prevented by reducing thyroidal iodine or its metabolism and optimal effects require intervention at the embryonic stage.

Mania secondary to thyrotoxicosis.

Abstract: A case of severe mania due to thyrotoxicosis responded to propranolol and propylthiouracil.

Pharmacokinetics of intravenous and oral methimazole following single- and multiple-dose administration in normal cats.

Abstract: The pharmacokinetics of methimazole (MMI) administered intravenously and orally were determined in six adult domestic shorthaired cats. There was no significant difference between mean serum MMI concentrations after oral and i.v. administration by 30 min post-MMI administration, indicating relatively rapid and complete absorption of the drug. The bioavailability of MMI ranged from 27% to 100% (mean = 81.1 +/- 11.4%). The mean serum elimination half-life was 6.6 +/- 2.0 h, with a wide range of values (1.9 h to 15.1 h). After repeat i.v. administration of MMI following 2 weeks of oral administration of the drug, no significant difference was found between mean serum concentrations after single-dose and multiple-dose administration. No significant change in serum elimination half-life or total body clearance was found after multiple-dose administration of MMI. Two cats with the longest half-lives (9.9 h and 15.1 h), however, did exhibit markedly shorter t1/2 values (3.5 h and 3.3 h, respectively) after multiple-dose administration. Values for central and steady state volumes of distribution also decreased after multiple-dose administration, possibly indicating saturation of thyroid uptake of MMI with chronic administration. These results indicate that MMI has good oral bioavailability and has a longer mean serum elimination half-life than propylthiouracil, the other anti-thyroid drug that has been evaluated in cats. Although no significant change in mean values occurred after multiple-dose administration of MMI, drug-induced acceleration of metabolism may occur in some cats after long-term MMI administration.

Thyroid hormones and glucocorticoids act synergistically in the regulation of the low affinity glucocorticoid binding sites in the male rat liver.

Abstract: The low affinity glucocorticoid binding sites (LAGS) have been described and partially characterized in both the nuclei and microsomes of rat liver. The LAGS concentration is under endocrine regulation, as proved by their decrease after adrenalectomy and their almost complete disappearance after hypophysectomy. This article describes new data that also implicate the thyroid hormones in the endocrine regulation of LAGS. The LAGS were measured by [3H]dexamethasone exchange assay in crude microsome suspensions of rat liver. Propylthiouracil- induced hypothyroidism (TX) provoked a 90% reduction in the LAGS levels with respect to the control value. The administration of T3 to TX rats was able to completely restore the LAGS level. On the other hand, adrenalectomy (ADX) provoked a 50% decrease in LAGS levels, and this effect could be reverted by treatment with corticosterone acetate. TX rats that were also adrenalectomized (TX-ADX) showed a LAGS level similar to that of the TX rats. However, treatment of these r...

Methimazole Regulation of Thyroglobulin Biosynthesis and Gene Transcription in Rat FRTL-5 Thyroid Cells*

Abstract: Methimazole (MMI) increases thyroglobulin (Tg) mRNA levels in FRTL-5 rat thyroid cells. The increase reflects a transcriptional action of the antithyroid agent and is inhibited by cycloheximide, as is the transcriptional action of TSH. It takes several hours to be apparent, is maximal between 24-48 h, and is specific, in that thyroid peroxidase and beta-actin mRNA levels are not increased simultaneously. The increased mRNA levels are associated with increased recovery of immunoprecipitable Tg in the medium of cells exposed to [35S]methionine. The MMI effect appears to be independent of the action of TSH or its cAMP signal, since the MMI-induced increase in Tg mRNA levels is evident in cells treated with TSH or maintained in its absence and is associated not with increases in cAMP levels but, rather, under some circumstances with a decrease. The effect is evident under conditions in which the ability of insulin or insulin-like growth factor-I to increase Tg mRNA levels is already maximal. The MMI-induced increase is inhibited by concentrations of iodide associated with autoregulation of FRTL-5 rat thyroid cells, is inhibited but not mimicked by propylthiouracil, and is not altered by T3. The increase in Tg mRNA levels does not correlate with increased DNA synthesis as a function of MMI concentration either in cells treated with TSH or in those maintained in its absence. A concentration of MMI (5 mM) that increases Tg mRNA levels can also inhibit 8-bromo-cAMP- or phorbol ester-induced increases in [3H]thymidine incorporation into DNA.

Hypothalamic-pituitary somatotropic function in prepubertal hypothyroid rats: effect of growth hormone replacement therapy.

Abstract: The effect of thyroid hormone deficiency and growth hormone (GH) treatment on hypothalamic GH-releasing hormone (GHRH)/somatostatin (SS) concentrations, GHRH/SS mRNA levels, and plasma GH and somatomedin-C (IGF-I) concentrations were studied in 28- and 35-day-old rats made hypothyroid by giving dams propylthiouracil in the drinking water since the day of parturition. Hypothyroid rats, at both 28 and 35 days of life, had decreased hypothalamic GHRH content and increased GHRH mRNA levels, unaltered SS content and SS mRNA levels, and reduced plasma GH and IGF-I concentrations. Treatment of hypothyroid rats with GH for 14 days completely restored hypothalamic GHRH content and reversed the increase in GHRH mRNA, but did not alter plasma IGF-I concentrations. These data indicate that, in hypothyroid rats, the changes in hypothalamic GHRH content and gene expression are due to the GH deficiency ensuing from the hypothyroid state. Failure of the GH treatment to increase plasma IGF-I indicates that the feedback regulation on GHRH neurons is operated by circulating GH and/or perhaps tissue but not plasma IGF-I concentrations. Presence of low plasma IGF-I concentrations would be directly related to thyroid hormone deficiency.

Propylthiouracil Hypersensitivity with Circumstantial Evidence for Drug-Induced Reversible Sensorineural Deafness: A Case Report

Abstract: Severe adverse reactions to propylthiouracil occur in 1–5% of patients. Three major side effects, namely agranulocytosis, hepatotoxicity and drug-induced hypersensitivity, have been described though t

Agranulocytosis associated with anti-thyroid drug in patients with Graves' thyrotoxicosis--report of 11 cases.

Abstract: Retrospective analysis of 11 Chinese patients with Graves' thyrotoxicosis developing agranulocytosis during anti-thyroid treatment was done. Seven of them received methimazole and 4 received carbimazole. None of the 11 patients had taken propylthiouracil. The major chief complaints were high fever (100%), chillness (91%), and sore throat (73%). The duration of drug treatment prior to the detection of agranulocytosis ranged from 13 to 63 days (mean +/- 1SE: 33.1 +/- 16.1). At the time of agranulocytosis detected, the peripheral leukocyte counts were 0.5 to 2.1 X 1000/mm3 (mean +/- 1SE: 1.05 +/- 0.47 X 1000/mm3), absolute neutrophil counts 0 to 450/mm3 (mean +/- 1SE: 54.27 +/- 132.12/mm3), and hemoglobin 8.2 to 15.9 g/dl (mean +/- 1SE: 11.85 +/- 2.24 gm/dl). Three of the 11 patients had positive bacterial blood cultures. The recovery time of absolute neutrophil counts above 500/mm3 ranged from 3 to 25 days (mean +/- 1SE: 10.5 +/- 6.6) after discontinuation of antithyroid drugs. Mortality was found in 2 of them (18%).

Propylthiouracil-associated hepatitis.

Abstract: The case of a 43-year-old female with propylthiouracil-induced hepatitis is reported. The case is unique because the patient's liver function deteriorated 2 weeks after medication was discontinued.

Thyroid vascular conductance: differential effects of elevated plasma thyrotropin (TSH) induced by treatment with thioamides or TSH-releasing hormone.

Abstract: We have reported previously that thyroid gland blood flow, expressed as vascular conductance (C) per mass, is decreased at very low and increased at very high chronic plasma TSH concentrations, but is apparently unchanged over a broad range of plasma TSH concentrations encompassing normal levels. The aim of the present study was to examine the apparently very steep dose-response relationship between elevated plasma TSH and thyroid vascular C/mass. In the first series of experiments, endogenous plasma TSH concentrations were manipulated by treating male Sprague-Dawley rats (250–280 g) for 6 days as follows: 1) controls (0.5 ml saline/day, ip), 2) propylthiouracil injections (2.0 mg PTU/day, ip), 3) PTU plus partial thyroid hormone replacement (2.0 mg PTU/day and 0.3–0.9 μg T4 plus 0.075–0.225 μg T3/100 g ⋅ day via continuous sc infusion), or 4) TRH (9–1200 μg TRH/100 g ⋅ day via continuous iv infusion). The vascular C values of the thyroid gland, salivary gland, kidney, and pancreas were determined using t...

Propylthiouracil-Induced Agranulocytosis in Four Patients Previously Treated With the Drug

Abstract: To the Editor. —Agranulocytosis is a well-known major complication of antithyroid drug treatment. Most studies emphasize the initial period of drug treatment (1 to 3 months), as that in which agranulocytosis is most likely to happen.1-3We found only one case report of agranulocytosis in the second course of propylthiouracil (PTU) treatment,4and a few more cases on methimazole.3,5We report here four cases of agranulocytosis on second exposure to PTU. We think it is important to draw attention to the possibility of agranulocytosis in patients who were previously treated successfully with PTU. Study. —The records of all our patients who were treated with PTU for thyrotoxicosis in the years 1985 through 1990 were reviewed. The diagnosis of thyrotoxicosis was made on the basis of symptoms, physical findings, elevated thyroid function tests (total thyroxine [T4], triiodothyronine uptake [T3U], and free thyroxin index), and suppressed

Urinary N-acetyl-beta-D-glucosaminidase (NAG) activity in patients with Graves' disease, subacute thyroiditis, and silent thyroiditis: a longitudinal study.

Abstract: Urinary N-acetyl-beta-D-glucosaminidase (NAG) activity was measured longitudinally in 12 patients with Graves' disease, 5 patients with subacute thyroiditis, and 1 patient with silent thyroiditis, and compared with that of 36 normal controls. The patients with Graves' disease and subacute thyroiditis were treated with anti-thyroid drug (methimazole or propylthiouracil) and prednisolone, respectively. On the other hand, no treatment was given to the patient with silent thyroiditis. Since two patients with Graves' disease clearly showed transient deterioration of the thyroid function during the treatment period, data from these two patients were separately investigated. Urinary levels of NAG in the remaining ten patients with Graves' disease before, 1, 3, 6 and 12 months after the treatment were 15.59 +/- 7.93 (SD), 8.96 +/- 6.82, 4.39 +/- 2.33, 3.46 +/- 2.24, and 3.63 +/- 2.38 U/g.creatinine (g.Cr.), respectively. Those obtained before, 1 and 3 months after the treatment were significantly higher than those of the controls (2.85 +/- 1.12 U/g.Cr.). Free thyroid hormone levels became normal or low 3 months after the treatment. The two Graves' patients mentioned above showed a transient increase in urinary NAG with concomitant changes in free thyroid hormone levels. Urinary NAG levels in the patients with subacute thyroiditis before, 2, 4, and 6 weeks after the treatment were 16.56 +/- 10.97, 6.76 +/- 2.79, 3.14 +/- 0.48 and 3.70 +/- 1.44 U/g.Cr., respectively. Those obtained before and 2 weeks after the treatment were significantly higher than those of the controls. Free thyroid hormones were normal 2 weeks after therapy. Urinary NAG in the patient with silent thyroiditis was 9.60 U/g.Cr. on the first visit and gradually decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of thyroid state alterations in ovo on the plasma levels of thyroid hormones and on the populations of fibers in the plantaris muscle of male and female chickens.

Abstract: Propylthiouracil (PTU), thyroxine (T4) or thyreoliberin (TRH) were injected in ovo to modify the thyroid state of chicken embryos. Significant sexual differences were observed in the effects of these treatments on the plasma concentrations of thyroid hormones and on plantaris muscle characteristics (DNA, RNA, populations of muscle fibers) in 3- and 35-day old male and female chickens. The T4 plasma concentration is lower in control males; it is decreased in PTU treated females and in the T4 treated females at 35 days. The T3 plasma concentration is lowered at 3 days in all treated chickens and also at 35 days in the TRH treated animals. The slow (STnO) and the fast (FTOG) fibers of the plantaris are always more numerous in males. In controls, the number of FTOG fibers remains steady between 3 and 35 days; at the same time, the number of STnO fibers rises in males only. Both PTU and T4 treatments increase the number of the FTOG and the STnO fibers respectively before and after the 3rd day. TRH treatment increases the number of STnO fibers at 3 and 35 days in males, but reduces it at 3 days in females. Thus changes in the number of FTOG fibers can be induced during in ovo myogenesis, whereas the number of STnO fibers may increase after hatching.

In vivo effect of thyrotropin on intracellular translocation of thyroid peroxidase in rat thyroid cells by an indirect immunofluorescence method.

Abstract: The in vivo effect of thyrotropin (TSH) on the intracellular localization of thyroid peroxidase (TPO) in rat thyroid epithelial cells was examined by an indirect immunofluorescence method. The staining for TPO in the epithelial cells of normal rats appeared all over the cytoplasm, especially in the apical region. The injection of propylthiouracil for 3-10 days increased the staining in the apical region. The administration of L-thyroxine for 7-10 days to normal rats abolished the relatively high localization of TPO in the apical region, and resulted in TPO staining all over the cytoplasm. Six hours after TSH was injected into the thyroxine-treated rats, localization of TPO staining in the apical region was observed. These results suggest that TSH may play a role in the translocation of preexisting TPO to the apical region before TSH-induced biosynthesis becomes evident.

Effects of amiodarone on serum T3 and T4 concentrations in hyperthyroid patients treated with propylthiouracil.

Abstract: Amiodarone (Cordarone) has been proven to be useful in the management of atrial fibrillation. However, because of a large iodine content, this drug is not used in this complication of thyrotoxicosis. We previously have observed a greater fall in serum T3 and T4 concentrations in hyperthyroid patients treated with amiodarone and methimazole than with methimazole alone. In the present study, we determined whether the addition of amiodarone to propylthiouracil (PTU) could improve the levels of circulating thyroid hormones in hyperthyroid patients, and we assessed the release of iodide from amiodarone by measuring the 24 h urinary iodine excretion. Twelve hyperthyroid patients were treated either with PTU, 600 mg daily for 10 days (group PTU), or with amiodarone (A), 1200 mg daily for 3 days in addition to PTU (group A-PTU). Basal serum T4, T3, and rT3 concentrations (mean +/- SEM) were respectively 206 +/- 13 nmol/L, 5.13 +/- 0.8 nmol/L, and 81 +/- 7 ng/dL for group PTU and 238 +/- 39 nmol/L, 4.73 +/- 1.06 nmol/L, and 84 +/- 12 ng/dL for group A-PTU (NS). In group A-PTU, plasma amiodarone peaked on day 3 (mean +/- SEM: 0.48 +/- 0.11 mg/L), and urinary iodine reached 5.27 +/- 1.28 mg/day on day 5. The fall in serum T3 and the increase in serum rT3 concentrations were significantly greater in group A-PTU than in group PTU (ANOVA, p less than 0.05). In group A-PTU, the minimal serum T3 concentration was observed on day 5 of treatment (28 +/- 6% of the pretreatment values).(ABSTRACT TRUNCATED AT 250 WORDS)

Role of thyroid hormone in the development of beta adrenergic control of ornithine decarboxylase in rat heart and kidney.

Abstract: The role of thyroid status in the ontogeny of beta adrenergic receptor control of ornithine decarboxylase (ODC) activity was assessed in hearts and kidneys of neonatal rats. Hyperthyroidism induced by administration of tri-iodothyronine on postnatal days 1 to 5 caused a reduction in the ability of isoproterenol to stimulate cardiac ODC but subsequently accelerated the onset of the postweaning peak of the response; the latter effect was even more prominent when tri-iodothyronine administration was given on postnatal days 14 to 18. Hypothyroidism induced by propylthiouracil administration led to persistent subsensitivity of the cardiac ODC response to beta receptor stimulation. Kidney ODC, which does not become subject to beta receptor regulation until after weaning, was resistant to hyperthyroid-induced changes in reactivity, but hypothyroidism still resulted in long-term response deficits. These results suggest that thyroid hormone is permissive for normal development of the beta receptor-ODC link, and that the euthyroid state provides the optimal conditions for maturation of this signal transduction mechanism. The relative resistance of kidney ODC responses to alterations by hyperthyroidism further indicates that the effects of excess hormone can only be expressed when the receptor-enzyme link is already competent. Finally, thyroid status had equivalent effects on the abilities of vasopressin or angiotensin to stimulate ODC, suggesting that the site of thyroid hormone action is at a transduction locus common to several different receptor types.

Treatment of supraventricular tachyarrhythmias associated with hyperthyroidism by radioiodine, amiodarone and propylthiouracil.

Abstract: Beta-blockers and calcium antagonists have been advocated for thyrotoxicosis induced tachyarrhythmias. Amiodarone is generally considered as contraindicated because of its high iodine content. Since amiodarone combined with propylthiouracil induced a greater fall in serum thyroid hormone concentrations than propylthiouracil alone, we treated 2 hyperthyroid patients with supraventricular arrhythmias by radioiodine (day 0) followed after 24 h by amiodarone and propylthiouracil. Serum T3 was normalized on day 2 (patient 1) and 3 (patient 2). Effective t1/2 of intrathyroidal 131I were 6.6 and 4.3 days (versus 5.9 days for 131I given alone). In patient 1, atrial fibrillation, reverted to sinus rhythm after verapamil and digoxin, and did not recur. In patient 2, conversion of atrial fibrillation to sinus rhythm occurred on day 11; from day 0 to day 11, ventricular rate decreased and was significantly correlated to T3 (r = 0.82; p < 0.05). In conclusion, amiodarone may be beneficial in thyrotoxicosis associated tachyarrhythmias, given with propylthiouracil 24 h after radioiodine, it did not decrease thyroid irradiation and rapidly decreased serum T3.

Recurrence of 131I-induced thyroid storm after discontinuing glucocorticoid therapy.

Abstract: A 19-year-old woman with Graves' disease developed thyroid storm 8 days after radioactive iodine therapy The clinical manifestations of thyroid storm promptly improved after treatment with large doses of propylthiouracil, potassium iodide, propranolol hydrochloride, and dexamethasone Four days after discontinuing dexamethasone, the syndrome recurred and was corrected by reinstitution of the glucocorticoid We conclude that dexamethasone was an important adjunct for treating thyroid storm and was effective mainly by reducing peripheral triiodothyronine production

Critical analysis of the histomorphometry of rat thyroid after treatment with thyroxin and propylthiouracil.

Abstract: The morphological variations of rat thyroid follicles after treatment with either thyroxin or propylthiouracil were evaluated by histomorphometry. A silver impregnation technique allowed a precise visualization of thyroid follicles on histological sections. The histomorphometric values (cell height, follicular diameter, percentage of epithelial cells) were obtained using a semi-automatic image analyser. The statistical tests used were analysis of variance (Fisher's test) and the Newman-Keuls tests. The results obtained showed that thyroxin treatment did not lead to any modification in histomorphometric values. Propylthiouracil, on the contrary, caused profound alterations in the morphology of thyroid follicles and in particular an increase in the height of the follicular epithelium. These changes were induced by a deficiency in thyroid hormones leading to an increase in thyroid-stimulating hormone (TSH) release. This study shows that with rigorous methodology, histomorphometry is adaptable to the requirements of a simple and reproducible evaluation of substances capable of causing functional perturbations and their effects on the thyroid gland.