Administration Of Propylthiouracil Research Articles

258 Post-ischemic cardiac remodeling is accelerated in diabetic rats: similarities to clinical and tissue hypothyroidism

We investigated whether postischemic cardiac remodeling (REM) is accelerated in diabetic rats with possible involvement of thyroid hormone (TH) signaling in this response. Changes in TH signaling occur during REM after acute myocardial infarction (MI) and contribute to cardiac dysfunction. Diabetes was induced in Wistar rats by streptozotocin injection (35mg/Kg i.p.). After 30 days diabetic rats (DM-AMI, n=9) were subjected to MI, while control rats were either sham-operated (SHAM, n=10) or subjected to MI (AMI(1), n=10). After 2 weeks, TRα1 and TRα1 expression and TH levels were measured. Hypothyroid rats by propyl-thiouracil administration (0.05%) in water for 3 weeks were subjected to MI (HYPO-AMI, n=6) while untreated MI rats served as controls (AMI(2), n=6). LV dimensions (LVEDD and LVEDS) and ejection fraction (EF%) were used to assess contractility and REM 2 weeks after MI using echocardiography. Cardiac function was markedly decreased in DM –AMI. Scar (mm 2 ) LVEDD (mm) LVEDS (mm) EF% SHAM ----- 6.5 (0.1) 3.8 (0.2) 76 (2.6) AMI(1) 79 (4.0) 7.7 (0.2) * 5.7 (0.2) * 52 (1.5) * DM-AMI 83 (4.9) 8.5 (0.2) ** 7.0 (0.3) ** 39 (2.1) ** * p<0.05 vs SHAM, ** p<0.05 vs SHAM and AMI(1) In AMI(1), TRα1 and TRβ1 protein expression were not changed significantly as compared to SHAM while in DM-AMI, both TRα1 and TRβ1 were decreased 1.7 and 1.9 fold respectively as compared to SHAM, p<0.05. T3 and T4 levels were not different between groups. HYPO-AMI hearts, with scar areas comparable to AMI(2) hearts [97(4.7) vs 105 (10.3), p>0.05], showed a similar unfavorable functional response : EF% was found to be markedly reduced [24 (0.9) in HYPO-AMI vs 36.2 (1.0) in AMI(2), p<0.05], while LVEDS was 8.3 (0.2) for HYPO-AMI and 7.5(0.1) for AMI(2), p<0.05. LVEDD equally increased in the 2 groups. Postischemic cardiac remodeling is accelerated both in hypothyroid and diabetic hearts. Tissue hypothyroidism which occurs in DM after myocardial infarction, may at least in part, account for this response.

Unusual location of purpura fulminans associated with acquired protein C deficiency and administration of propylthiouracil

Unusual location of purpura fulminans associated with acquired protein C deficiency and administration of propylthiouracil

Biomechanical performance of diaphyseal shafts and bone tissue of femurs from hypothyroid rats

The bone changes in hypothyroidism are characterized by a low bone turnover with a reduced osteoid apposition and bone mineralization rate, and a decreased osteoclastic resorption in cortical bone. These changes could affect the mechanical performance of bone. The evaluation of such changes was the object of the present investigation. Hypothyroidism was induced in female rats aged 21 days through administration of propylthiouracil in the drinking water for 70 days (HT group). Controls were untreated rats (C group). Right femur mechanical properties were tested in 3-point bending. Structural (load bearing capacity and stiffness), geometric (cross-sectional area and moment of inertia) and material (modulus of elasticity) properties were evaluated. The left femur was ashed for calcium content determination. Plasma T(4) concentration was significantly decreased in HT rats. Body and femur weight and length in HT rats were also reduced. Femoral calcium concentration in ash was higher in HT than in C rats. However, the femoral calcium mass was significantly lower in HT than in C rats because of the reduced femoral size seen in the former. The stiffness of bone material was higher in HT than in C rats, while the bone geometric properties were significantly lower. The "load capacity" was between 30 and 50% reduced in the HT group, although, the differences disappeared when the values were normalized per 100-g body weight. The lowered biomechanical ability observed in the femoral shafts of HT rats seems to be the expression of a diminished rate of growth. Qualitative alterations in the intrinsic mechanical properties of bone tissue were observed in HT rats, probably because the mineral content and the modulus of elasticity were positively affected. The cortical bone of the HT rat thus appears as a bone with a higher than normal strength and stiffness relative to body weight, probably due to improvement of bone material quality due to an increased matrix calcification.

Immediate and dose-response related increase of biliary excretion of reverse triiodothyronine after propylthiouracil administration.

In a group of rats infused with L-thyroxine (0.13 micrograms T4 in 0.6 ml alkaline saline per hour) for 6 h to which an infusion of propylthiouracil (PTU) was added beginning from the 3rd hour (2 mg PTU in 0.6 ml saline per hour) a significant increase of biliary excretion of reverse triiodothyronine (rT3) was found. In another experiment a dose-response related rT3 excretion by bile was observed in groups of rats infused with 0.05, 0.10, 0.20 or 0.40 mg PTU in 1.2 ml alkaline saline per 2 h, all animals receiving a pulse dose of 1 micrograms rT3 at the beginning of PTU infusion. It was concluded that the increase of rT3 excretion results from the inhibition of 5'-deiodinase type I activity in the liver caused by PTU. It thus appears that such phenomenon may be used as in vivo marker of that enzyme activity.

Perinatal exposure to PTU decreases expression of Arc, Homer 1, Egr 1 and Kcna 1 in the rat cerebral cortex and hippocampus

Environmental chemicals have a potential impact on neuronal development and children's health. The current developmental neurotoxicity (DNT) guideline studies to assess their underlying risk are costly and time-consuming; therefore the more efficient protocol for DNT test is needed. Hypothyroidism in rats induced by perinatal exposure to propylthiouracil (PTU), a thyroid hormone synthesis inhibitor, offers an advantageous model of developmental neurotoxicity (DNT). Understanding the associated alterations in gene expression in brain is a key to elucidate mechanisms and find appropriate molecular markers. The purpose of the present study was to identify PTU treatment-affected transcriptomes in the rat cerebral cortex and the hippocampus using DNA microarrays, and to specify candidate genes linked to DNT. We used an approximately 9000 probe microarray to examine differentially expressed genes between PTU-dosed and vehicle-dosed rats at postnatal days 4, 14, 22 and 70. Expression of immediate early genes (IEGs) such as activity-regulated cytoskeleton-associated protein ( Arc), Homer 1, early growth response 1 ( Egr 1), myelin-associated genes such as myelin-associated oligodendrocytic basic protein (MOBP), myelin basic protein (MBP) and proteolipid protein (PLP) and Kcna1 was apparently affected by perinatal administration of PTU. The results suggest that the alterations may be responsible for the detrimental effects caused by PTU treatment on the nervous system.

A Genomic Analysis of Subclinical Hypothyroidism in Hippocampus and Neocortex of the Developing Rat Brain

Hypothyroidism during pregnancy and the early postnatal period has severe neurological consequences for the developing offspring. The impact of milder degrees of perturbation of the thyroid axis as encompassed in conditions of subclinical hypothyroidism and hypothyroxinemia, however, has not been established. The present investigation examined the effects of graded levels of hypothyroidism, from subclinical to severe, on global gene expression in the developing rodent brain. Thyroid hormone insufficiency was induced by administration of propylthiouracil (PTU) to pregnant rats via drinking water from gestational day 6 until sacrifice of pups prior to weaning. In the first study a specialised microarray, the Affymetrix Rat Neurobiology array RN_U34, was used to contrast gene expression in the hippocampus of animals exposed to 0 or 10 ppm (10 mg/l) PTU, a treatment producing severe hypothyroidism. In the second study, a more complete genome array (Affymetrix Rat 230A) was used to compare gene expression in the neocortex and hippocampus of postnatal day (PN) 14 animals experiencing graded degrees of thyroid hormone insufficiency induced by delivery of 0, 1, 2 or 3 ppm PTU to the dam. Dose-dependent up- and down-regulation were observed for gene transcripts known to play critical roles in brain development and brain function. Expression levels of a subset of approximately 25 genes in each brain region were altered at a dose of PTU (1 ppm) that induced mild hypothyroxinemia in dams and pups. These data indicate that genes driving important developmental processes are sensitive to relatively modest perturbations of the thyroid axis, and that the level of gene expression is related to the degree of hormone reduction. Altered patterns of gene expression during critical windows of brain development indicate that thyroid disease must be viewed as a continuum and that conditions typically considered 'subclinical' may induce structural and functional abnormalities in the developing central nervous system.

Propylthiouracil, independent of its antithyroid effect, decreases VSMC collagen expression

Propylthiouracil (PTU), in addition to its antithyroid effect, is recently found to have a potent antiatherosclerotic effect. Because collagen accumulation is the major contributor to the growth of atherosclerotic lesions and the neointimal formation after arterial injury, the aim of this study is to investigate the impact of PTU on collagen regulation. In the rat carotid injury model, PTU administration reversed the up-regulation of collagen in the neointima induced by balloon injury. In vitro, vascular smooth muscle cells (VSMCs), the main origin of arterial collagen, were treated with PTU. Propylthiouracil caused a concentration-dependent decrease in collagen I and III steady-state protein and mRNA levels, as determined by immuno-cytochemistry, Western, and/or Northern blot analyses. Transient transfection experiments using rat type I collagen promoter construct showed that PTU failed to affect collagen gene transcription in VSMCs. Actinomycin D studies demonstrated that the half-life of collagens mRNA decreased with PTU treatment, suggesting that PTU down-regulates collagen expression predominantly at the post-transcriptional level. Taken together, these data suggest that PTU inhibits VSMC collagen production via destabilization of collagen mRNA that contributes to its beneficial effect on atherogenesis and neointimal formation after arterial injury. However, whether the destabilization of collagen may induce plaque rupture in PTU-treated arteries merits further investigation.

Apoptose, proliferação e histomorfometria do baço de ratas adultas com hipofunção tireoidiana e ovariana

Apoptosis, proliferation and histomorphometry of spleen were investigated in ovariectomized and non-ovariectomized adult Wistar rats maintained in hypothyroidism induced by daily administration of propylthiouracil (PTU) during 120 days. Two groups ovariectomized euthyroid and non-ovariectomized euthyroid were used as controls. Plasma was collected for free T4 dosage and the spleen for histomorphometry analysis, apoptosis index and the immunohistochemistry expression of caspase 3 and CDC47. Values of free T4 were lower in rats treated with PTU (p<0.05). In the hypothyroid groups there was some decrease in the spleen weight as well as the number and size of lymphoid follicles and there was some increase in the apoptotic index and the caspase 3 expression (p<0.05). However, the increase in the apoptosis index and the expression of caspase 3 in ovariectomized hypothyroid rats spleen was less accentuated than non-ovariectomized hypothyroid ones (p<0.05). The ovariectomized euthyroid group presented white pulp hyperplasia in comparison to the non-ovariectomized euthyroid group. There was no difference in the CDC47 expression between groups. It was concluded that the thyroid and ovarian hypofunction have distinct effects on the spleen and that in the hypothyroidism-hypogonadism association, the increase in the apoptosis index and in the expression of splenic caspase 3 is not as much as in isolated hypothyroidism.

The effect of mildronate and related substances on levels of thyroid hormones and some intermediates of lipid and carbohydrate metabolism in hyperthyroid and hypothyroid rats

We have investigated effects of Mildronate, gamma-butyrobetaine (GBB) and their combination ("Neomildronate") on the plasma levels of thyroid gland hormones and some intermediates of basal metabolism (free fatty acids, triglycerides, glucose) in rats with different dysfunctions of thyroid gland, including idiopathic hyperfunction and hypofunction induced by propylthiouracil or L-carnitin administration. Histological investigation of the thyroid gland was also performed. Intraperitoneal injections of Mildronate (150 mg/kg) during 20 days to Wistar male rats with elevated level of thyroid hormones and basal metabolism normalized thyroxine level and parameters of lipid metabolism. Mildronate, GBB and their combination did not affect the natural resurgence of rats with experimental hypofunction induced by propylthiouracil or L-carnitin administration. The possible biochemical role of given treatment in regulation of thyroid gland function is discussed.

Possible implications of leptin, adiponectin and ghrelin in the regulation of energy homeostasis by thyroid hormone

Thyroid hormone plays a critical role in energy homeostasis through mechanisms, which are not fully understood. In the present study, we investigated possible alterations of important energy regulators such as leptin, adiponectin, and ghrelin in relation to changes in thyroid hormones. Thyroid hormone (250 microg/kg) was administered in male Wistar rats for 2 weeks (THYR), while hypothyroidism (HYPO) was induced by propylthiouracil administration (0.05% in drinking water) for 3 weeks. Untreated animals served as controls (NORM). Leptin and adiponectin were measured in plasma by ELISA, while total ghrelin was measured with RIA. Body weight was significantly reduced both in THYR and HYPO rats, while food intake was significantly increased in THYR and decreased in HYPO. This response was associated with various changes in leptin, adiponectin, and ghrelin in plasma. In fact, in THYR rats, leptin levels (mean +/- SEM) were 240 +/- 55 pg/ml as compared to 819 +/- 70 pg/ml in untreated rats (P < 0.05), while no changes were observed in ghrelin and adiponectin. In HYPO rats, leptin levels were 1400 +/- 200 pg/ml vs. 819 +/- 70 pg/ml in untreated rats (P < 0.05), while ghrelin and adiponectin were significantly increased in HYPO rats as compared to untreated rats (P < 0.05). Furthermore, T(3) and T(4) levels were inversely correlated to leptin (P = 0.014), while ghrelin and adiponectin were inversely correlated to weight changes (P = 0.05 and P = 0.03, respectively). In conclusion, leptin seems mainly to be involved in the thyroid hormone effects on energy homeostasis. Ghrelin and adiponectin may serve a compensatory physiological role in hypothyroidism.

Lichenoid drug eruption of nails induced by propylthiouracil

We present the case of a patient who developed deformities of the fingernails and reddish nodules on the nail beds after administration of propylthiouracil (PTU) for 6 months to treat Grave's disease. Histological examination of the lesion revealed a lichenoid tissue reaction. After withdrawal of PTU, she noticed an improvement in the eruption and the growth of the nails. No recurrence of the eruption was detected after the withdrawal of PTU. Thus, we strongly suggest that this was a rare case of PTU-induced lichenoid drug eruption of nail.

Effects of developmental hypothyroidism induced by maternal administration of methimazole or propylthiouracil on the immune system of rats

Methimazole (MMI) and propylthiouracil (PTU) are popularly used antithyroid drugs (ATDs) for the treatment of Graves' hyperthyroidism. The aim of the present study was to determine the effects of ATDs on the developing immune system of the rats.Maternal Sprague–Dawley rats were given drinking water containing 200 ppm of MMI, 12 ppm of PTU (high-dose PTU), or 3 ppm of PTU (low-dose PTU) between gestational day (GD) 10 and postnatal week (PNW) 3. Exposure to the ATDs was ceased upon weaning at PNW3, and the male offspring were sampled at PNWs 3 or 11. The serum thyroid-related hormone levels and the hematological components in the offspring were then determined. The expressions of surface markers in the spleen, thymus and peripheral blood were determined using flowcytometry. The weights of the body, spleen and thymus and the splenic and thymic cell numbers were decreased in the MMI-treated and the high-dose PTU-treated animals at PNWs 3 and 11. The serum levels of thyroid-related hormones were depressed in the MMI and high-dose PTU groups. FACS analysis revealed that the ATDs caused proportional changes in the lymphoid cell subpopulations. The proportion of B cells among the total lymphocytes was significantly decreased at PNW3, whereas that of T cells, especially of inactive T cells, was dramatically increased. Moreover, the proportion of CD4+CD25+ regulatory T cells was significantly increased in the spleen and peripheral blood at PNW3. Most of the above-described changes had recovered to normal levels at PNW11. These results suggest that ATDs might have temporal immunomodulatory effects on the developing immune system.

Effects of Thyroid Hormones on Memory and on Na+, K+-ATPase Activity in Rat Brain

Thyroid hormones (THs), including triiodothyronine (T3) and tetraiodothyronine (T4), are recognized as key metabolic hormones of the body. THs are essential for normal maturation and function of the mammalian central nervous system (CNS) and its deficiency, during a critical period of development, profoundly affects cognitive function. Sodium-potassium adenosine 5'-triphosphatase (Na(+), K(+)-ATPase) is a crucial enzyme responsible for the active transport of sodium and potassium ions in the CNS necessary to maintain the ionic gradient for neuronal excitability. Studies suggest that Na(+), K(+)-ATPase might play a role on memory formation. Moreover, THs were proposed to stimulate Na(+), K(+)-ATPase activity in the heart of some species. In this work we investigated the effect of a chronic administration of L-thyroxine (L-T4) or propylthiouracil (PTU), an antithyroid drug, on some behavioral paradigms: inhibitory avoidance task, open field task, plus maze and Y-maze, and on the activity of Na(+), K(+)-ATPase in the rat parietal cortex and hippocampus. By using treatments which have shown to induce alterations in THs levels similar to those found in hyperthyroid and hypothyroid patients, we aimed to understand the effect of an altered hyperthyroid and hypothyroid state on learning and memory and on the activity of Na(+), K(+)-ATPase. Our results showed that a hyper and hypothyroid state can alter animal behavior and they also might indicate an effect of THs on learning and memory.

Changes in acetylcholinesterase, Na +,K +-ATPase, and Mg 2+-ATPase activities in the frontal cortex and the hippocampus of hyper- and hypothyroid adult rats

The thyroid hormones (THs) are crucial determinants of normal development and metabolism, especially in the central nervous system. The metabolic rate is known to increase in hyperthyroidism and decrease in hypothyroidism. The aim of this work was to investigate how changes in metabolism induced by THs could affect the activities of acetylcholinesterase (AChE), (Na +,K +)− and Mg 2+-adenosinetriphosphatase (ATPase) in the frontal cortex and the hippocampus of adult rats. Hyperthyroidism was induced by subcutaneous administration of thyroxine (25 μg/100 g body weight) once daily for 14 days, and hypothyroidism was induced by oral administration of propylthiouracil (0.05%) for 21 days. All enzyme activities were evaluated spectrophotometrically in the homogenated brain regions of 10 three-animal pools. A region-specific behavior was observed concerning the examined enzyme activities in hyper- and hypothyroidism. In hyperthyroidism, AChE activity was significantly increased only in the hippocampus (+22%), whereas Na +,K +-ATPase activity was significantly decreased in the hyperthyroid rat hippocampus (−47%) and remained unchanged in the frontal cortex. In hypothyroidism, AChE activity was significantly decreased in the frontal cortex (−23%) and increased in the hippocampus (+21%). Na +,K +-ATPase activity was significantly decreased in both the frontal cortex (−35%) and the hippocampus (−43%) of hypothyroid rats. Mg 2+-ATPase remained unchanged in the regions of both hyper- and hypothyroid rat brains. Our data revealed that THs affect the examined adult rat brain parameters in a region- and state-specific way. The TH-reduced Na +,K +-ATPase activity may increase the synaptic acetylcholine release and, thus, modulate AChE activity. Moreover, the above TH-induced changes may affect the monoamine neurotransmitter systems in the examined brain regions.

Clinical and Pathological Features of Renal Involvement in Propylthiouracil-Associated ANCA-Positive Vasculitis

The kidney is one of the organs affected in patients with propylthiouracil (PTU)-associated antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis. We present a series of Chinese patients with renal involvement in PTU-associated ANCA-positive vasculitis and describe their clinical and pathological characteristics. Clinical and pathological data from patients with PTU-associated ANCA-positive vasculitis with renal involvement, diagnosed in Peking University First Hospital, were collected and analyzed retrospectively. Nineteen patients with PTU-associated ANCA-positive vasculitis were treated at Peking University First Hospital between December 1999 and December 2005, and 15 of them had renal involvement. Of the 15 patients, 13 were female and 2 were male, with an average age of 26.3 +/- 11.8 years. All 15 patients were perinuclear ANCA positive with specificities to myeloperoxidase (15 of 15), cathepsin G (9 of 15), human leukocyte elastase (8 of 15), lactoferrin (7 of 15), azurocidin (5 of 15), and proteinase 3 (4 of 15). Duration of PTU administration was 43.0 +/- 31.2 months. All 15 patients had clinical markers of renal involvement, including hematuria (100%), proteinuria (100%), and renal function abnormality (47%). All 15 patients underwent percutaneous renal biopsy. Ten patients had necrotizing crescentic glomerulonephritis, and 7 of these 10 patients had immune complex deposition. Three patients had minimal involvement, 2 patients had immunoglobulin A nephropathy, and 2 patients had membranous nephropathy. PTU treatment was discontinued in all 15 patients. All except 2 patients with minimal renal involvement received immunosuppressive treatment. Eleven of 15 patients achieved complete clinical remission. Renal involvement in our case series of patients with PTU-associated ANCA-positive vasculitis was heterogeneous, and nearly half our patients had renal immune complex deposition.

Effects of hyper- and hypothyroidism on acetylcholinesterase, (Na+, K+)- and Mg 2+ -ATPase activities of adult rat hypothalamus and cerebellum

Thyroid hormones (THs) are recognized as key metabolic hormones, and the metabolic rate increases in hyperthyroidism, while it decreases in hypothyroidism. The aim of this work was to investigate how changes in metabolism induced by THs could affect the activities of acetylcholinesterase (AChE), (Na(+), K(+))- and Mg(2+)-ATPase in the hypothalamus and the cerebellum of adult rats. Hyperthyroidism was induced by subcutaneous administration of thyroxine (25 microg/100 g body weight) once daily for 14 days, while hypothyroidism was induced by oral administration of propylthiouracil (0.05%) for 21 days. All enzyme activities were evaluated spectrophotometrically in the homogenated brain regions of 10 three-animal pools. Neither hyper-, nor hypothyroidism had any effect on the examined hypothalamic enzyme activities. In the cerebellum, hyperthyroidism provoked a significant decrease in both the AChE (-23%, p < 0.001) and the Na(+), K(+)-ATPase activities (-26%, p < 0.001). Moreover, hypothyroidism had a similar effect on the examined enzyme activities: AChE (-17%, p < 0.001) and Na(+), K(+)-ATPase (-27%, p < 0.001). Mg(2+)-ATPase activity was found unaltered in both the hyper- and the hypothyroid brain regions. neither hyper-, nor hypothyroidism had any effect on the examined hypothalamic enzyme activities. In the cerebellum, hyperthyroidism provoked a significant decrease in both the AChE and the Na(+), K(+)-ATPase activities. The decreased (by the THs) Na(+), K(+)-ATPase activities may increase the synaptic acetylcholine release, and thus, could result in a decrease in the cerebellar AChE activity. Moreover, the above TH-induced changes may affect the monoamine neurotransmitter systems.

Responses of simultaneously recorded intraperitoneal and subcutaneous temperatures of Black Bedouin goats to transient thyrosuppression during cold stress

Unlike poikilotherms, homeotherms resist wide amplitudes of core body temperature (Tcore) fluctuation when exposed to reasonably variant ambient temperature (Ta) extremes. The degree of cold/heat thermotolerance varies tremendously amongst mammalian species. Thermotolerance can be partially inferred by the extent of resistance in body temperature displacement from normothermia when subjected to thermal stress. Regulation of thyroid calorigenic hormones is primarily contingent upon thermal homeostasis. Thyrosuppression generally exacerbates cold stress and hence may be a useful tool to examine the extent of cold-tolerance. An experiment was conducted to examine the extent of cold-tolerance on artificially goitrous Black Bedouin goats. Ten goat kids (initial Avg. BW = 30.6 ± 0.4 kg) were fitted with two miniature temperature data loggers, intraperitoneally and subcutaneously to identify core (Tcore) and subcutaneous (Tsq) temperature responses, respectively, to chronically (47 days) cold (< 10 °C) environment along with or without oral administration of the thyreostat propylthiouracil (PTU 20 mg/kg BW/day). Five animals served as controls (CON) whereas the remaining five were treated with PTU for 31 out of the overall 47-day observation period. Despite its 74.5%-evoked transient depression of circulating free thyroxine (FT4), PTU-treatment failed (P > 0.10) to cause significant displacements in Tcore or Tsq as compared to CON values throughout the 52-day trial period. As a function of Ta, Tcore − Tsq thermal gradient revealed a significantly (P < 0.01) linear regression (r2 = 0.41), to indirectly infer a graded blood redistribution from peripheral to splanchnic vascular beds with the fall in Ta. In the light of the current findings, it can be deduced that– in addition to the fact that it is superior in terms of heat-tolerance– the Black Bedouin goat is also profoundly cold-tolerant. Furthermore, our recently developed technique in concurrently recording Tcore and Tsq proves efficient and feasible to simultaneously record temperatures of different body sites in free-roaming animals, thereby overcoming potentially erroneous artifacts caused by frequent experimenter intrusion.

Serum thyroid hormones and performance of offspring in ewes receiving propylthiouracil with or without melatonin

Two experiments were conducted during mid-gestation to examine effects in ewes of propylthiouracil (PTU) treatment alone or with melatonin on serum thyroid hormones, postpartum reproduction, and lamb performance. In the first experiment, beginning on day 0 (first day of treatment when all animals were 72.2 ± 0.9 days of gestation), ewes received daily treatments (gavage) consisting of either 0 mg ( n = 6) or 40 mg ( n = 6) PTU/kg body weight/day for 15 days. After 15 days, the 40 mg dosage was decreased to 20 mg/kg body weight for an additional 20 days (35 days of PTU). Serum thyroxine (T4) did not differ ( P > 0.10) between groups through day 4; but on day 5, control females had a serum value of 67 ng/ml compared with 46 (±5) ng/ml for PTU-treated ewes ( P = 0.02). On the last day that 40 mg of PTU was administered, serum T4 averaged 67 and 7 (±5) ng/ml ( P < 0.001) in the two respective groups. Serum T4 remained low and was 80 and 1 ng/ml ( P < 0.001) in control and treated ewes on day 34. Serum T4 rose gradually after PTU but remained different from that observed in control ewes through day 48. Lambs from control and treated ewes had similar ( P = 0.46) T4 values at birth but lambs from PTU-treated ewes had lower ( P = 0.03) birth weights than did those from control ewes. Serum progesterone (P4) after parturition indicated a lack of cyclicity in all ewes. In the second experiment, beginning on day 0 (76.8 ± 4.7 days of gestation), ewes received PTU as in Experiment 1. In addition, after 15 days of PTU, melatonin was given (i.m. injections at 5 mg/day) for 30 days. Propylthiouracil decreased ( P ≤ 0.05) serum T4 on days 25 through 41 of the treatment period. Serum T3 was lower ( P < 0.05) in PTU-treated ewes from day 8 through the end of PTU administration. Postpartum P4 was below 1 ng/ml on all days indicating acyclicity. Lamb body weight and serum IGF-I were similar ( P > 0.60) for lambs born to control and treated ewes. Female offspring of PTU + melatonin-treated dams reached puberty, became anestrus, and returned to cyclicity at similar ( P > 0.10) times to contemporary ewe lambs. Results indicate that 40/20 mg PTU alone or with melatonin does not induce cyclicity after lambing in spring lambing ewes and has little effect on offspring performance.

Thyrotoxicosis-induced Prinzmetal Variant Angina

We describe a postmenopausal women with new onset of variant angina caused by thyrotoxicosis due to Graves' disease. During exercise bicycle ergometry at 50 Watts, the patient developed typical angina with ST segment elevation in the precordial leads. A coronary angiogram revealed normal coronary arteries. Graves' disease with overt hyperthyroidism was diagnosed. After achieving an euthyroid state with administration of propylthiouracil, the symptoms resolved completely and the patient had a normal exercise capacity without electrocardiographic changes. Thus, we conclude that in patients with thyrotoxicosis, variant angina and normal coronary arteries, restoration of normal thyroid function may be curative.

Measurement of Free Thyroxine Concentration in Horses by Equilibrium Dialysis

The purpose of the study reported here was to validate measurement of free thyroxine (fT4) concentration in equine serum by equilibrium dialysis (fT4D), and to compare values with fT4 concentration measured directly and with total T4 (TT4) concentration. The fT4D, fT4, and TT4 concentrations were measured over a range of values in euthyroid horses and horses made hypothyroid by administration of propylthiouracil (PTU). Concentrations of fT4D (<1.8-83 pmol/L) were consistently higher than those of fT4 (<1-40 pmol/L). There was a significant (P < .001) regression of fT4D on fT4 in 503 samples from normal horses (y = 2.086x - 0.430). In baseline samples from 71 healthy euthyroid horses, fT4 concentration ranged from 6-21 pmol/L (median, 11 pmol/L; 95% confidence interval [CI]10.5-11.8 pmol/L), and fT4D concentration ranged from 7-47 pmol/L (median, 22 pmol/L; 95% CI 20.9-25.1 pmol/L). Free T4D, fT4, and TT4 concentrations were also measured in 34 ill horses. Horses consuming PTU and ill horses had significantly (P < .05) lower serum concentration of TT4, fT4, and fT4D than did clinically normal, healthy horses. If serum samples from ill horses were further subdivided into samples from horses that lived and samples from horses that died, fT4D concentration was not significantly different in ill horses that lived, compared with that in healthy horses, whereas fT4 concentration was still significantly decreased in ill horses that died (P < 0.001). We conclude that measurement of fT4 concentration by equilibrium dialysis is a valid technique in the horse, and its use may provide improved ability to distinguish nonthyroidal illness syndrome from hypothyroidism in that species.