Showing papers on "Propylthiouracil published in 1992"
TL;DR: It is suggested that sublethal complement attack in autoimmune thyroid diseases exacerbates tissue injury by causing thyroid cells to release potent phlogistic mediators, although some degree of protection may be afforded in vivo by cytokine-mediated upregulation of CD59.
87 citations
TL;DR: Results demonstrate that, in Graves' retroocular fibroblasts, H2O2-induced HSP 72 expression is diminished both by classical ORS and by the antithyroid agents PTU and MT, and the beneficial effect of MT and PTU on the clinical course and immune status of patients with GD may be related to their OFR-scavanging properties.
Abstract: Reactive oxygen species are generated in tissues by activated mononuclear cells and macrophages. These cells infiltrate the thyroid gland in Graves' disease (GD), as well as the retroocular and pretibial space in Graves' ophthalmopathy and pretibial myxedema (PTM). Because a 72 kilodalton heat shock protein (HSP 72) is associated with autoimmune thyroid disease and is selectively expressed in fibroblasts derived from involved sites of patients with Graves' ophthalmopathy and pretibial myxedema, we studied the influence of oxygen free radicals (OFR), oxygen radical scavangers (ORS), and antithyroid drugs on HSP 72 expression in Graves' retroocular fibroblasts. Fibroblast monolayers were exposed to hydrogen peroxide (H2O2) or heat stress with simultaneous treatment, or pretreatment, with the ORS diaminobenzidine, nicotinamide, glutathione, propylthiouracil (PTU), or methimazole (MT). HSP 72 expression was determined by sodium dodecylsulfate polyacrylamide-gel electrophoresis, followed by immunoblotting with...
85 citations
TL;DR: A 72-year-old woman presenting with respiratory failure and hemoptysis following initiation of propylthiouracil therapy for Graves' disease has cutaneous stigmata of hypersensitivity vasculitis and diffuse pulmonary infiltrates.
83 citations
TL;DR: After the pregnancy is terminated, persistent or recurrent hyperthyroidism should be treated definitively to prevent another episode of pregnancy complicated by hyperthyoidism.
Abstract: Most of the hyperthyroidism seen in association with pregnancy is Graves' disease. The best treatment is prevention. For most patients there is an opportunity to treat the hyperthyroidism decisively with radioiodine or surgery before the patient becomes pregnant. Pregnancy complicated by hyperthyroidism is often a consequence of the conscious decision to treat hyperthyroidism in women in the childbearing years with antithyroid drugs. Propylthiouracil (PTU) is the preferred treatment for hyperthyroidism in pregnancy, but it does cross the placenta and can induce fetal goiter, with mental and physical retardation. Hence, the lowest possible PTU dose should be used. One should aim for high normal or slightly elevated thyroid function in the mother. Patients should be followed at 3-week intervals if progress is satisfactory, more often otherwise. Thyroid function should be monitored by the free T4 assay. PTU dosage should be reduced progressively in anticipation of the customary steady amelioration in the hyperthyroidism that occurs in later stages of pregnancy. Since pregnant hyperthyroid patients are sometimes irresponsible and continue PTU without supervision, PTU prescriptions should be limited to the amount required for the time until the next scheduled visit. For about one third of patients, PTU can be discontinued in the second half of the pregnancy. After the pregnancy is terminated, persistent or recurrent hyperthyroidism should be treated definitively to prevent another episode of pregnancy complicated by hyperthyroidism.
74 citations
TL;DR: It is concluded that exposure to methimazole or propylthiouracil during pregnancy in doses sufficient to control maternal hyperthyroidism does not pose any threat to intellectual capacity of the offspring.
Abstract: Antithyroid drugs, considered the treatment of choice for hyperthyroidism during pregnancy, may have an adverse effect on intellectual development of the offspring. We examined the intellectual capacity of 31 subjects aged 4–23 years, born to women with Graves disease who received antithyroid drugs throughout pregnancy. Methimazole 40–140 mg/week (n=15) or propylthiouracil 250–1400 mg/week (n=16) was given. I.Q. was assessed using the Wechsler test appropriate for age. Twenty-five unexposed siblings served as controls. The exposed and unexposed groups did not differ with respect to the total I.Q. Both groups scored equally in verbal and performance skills and in each of six main subcategories of the tests. There was no difference between exposure to methimazole and propylthiouracil or between the higher (>40 mg/week and >600 mg/week, respectively) and lower dosages. All children were euthyroid at birth and none had goitre. We conclude that exposure to methimazole or propylthiouracil during pregnancy in doses sufficient to control maternal hyperthyroidism does not pose any threat to intellectual capacity of the offspring.
72 citations
TL;DR: The findings indicate that, depending on severity and duration, experimental hypothyroidism may cause a significant increase in hypothalamic TRH release in rats.
Abstract: The aim of this study was to investigate whether the severity and duration of primary hypothyroidism influence hypothalamic TRH release. Hypothyroidism was induced in male Wistar rats by treatment with different thyrostatic drugs or by thyroidectomy. Serum TSH in rats treated for up to 3 weeks with methimazole (MMI; 0.05% in drinking water) increased 20-fold, but TRH release into hypophyseal portal blood (HPB) did not change. Treatment with propylthiouracil (PTU; 0.1% in drinking water), which inhibits thyroidal T4 production and peripheral conversion of T4 to T3, resulted in a more rapid reduction in serum T3 levels and increase in serum TSH than those in rats treated with 0.1% MMI. Although these differences were no longer observed after 3 weeks of treatment, TRH release into HPB of rats treated with PTU was 34-49% higher than that in MMI-treated rats. Combined treatment with MMI (0.05-0.1% in drinking water) and iopanoic acid (IOP; 4 mg/100 g BW.day, ip), an inhibitor of both peripheral and central T4 to T3 conversion, also tended to produce a more rapid decrease in serum T3 and increase in serum TSH. After 3 weeks of treatment, serum T4, T3, and TSH were not different in the two groups, but TRH release into HPB was 48-65% increased by MMI plus IOP vs. MMI alone. Three to 10 weeks after thyroidectomy, TRH release into HPB was 58-72% higher than that in untreated controls. In vitro incubation of hypothalami isolated from rats treated for 3 weeks with MMI, MMI plus IOP, or PTU, as described above, showed that basal and 56 mM K(+)-induced TRH release were not influenced by the different drugs. Also, the total hypothalamic TRH content was not changed by any of these treatments. However, in rats treated for 1 or 2 weeks with MMI or PTU, the TRH content of the median eminence was decreased by 17-25%. These findings indicate that, depending on severity and duration, experimental hypothyroidism may cause a significant increase in hypothalamic TRH release in rats. The magnitude of these changes compared with the much larger increases in serum TSH suggests that the feedback of thyroid hormone on TSH secretion is mainly exerted at the pituitary level.
44 citations
TL;DR: The data obtained raise the possibility that GH may modify the effect of thyroid hormones on the pituitary by a feed-back mechanism through changing the level of a sex-dominant phenol sulfotransferase(s) in rat livers.
Abstract: The regulatory mechanism of cytosolic sulfation of T3 has been studied in rat liver. Sulfation of T3 is sexually differentiated in adult rats of Sprague-Dawley (SD), Fisher 344, and ACI strains. In SD strain, the male animals showed 4 times higher sulfating activity than did the females. The specific activity was decreased by hypophysectomy of male adult rats, but was not affected in the females. Thus, the sex-difference was abolished in the hypophysectomized condition. Supplement of human GH intermittently twice daily for 7 days, to mimic the male secretory pattern, increased T3 sulfating activity in both sexes of hypophysectomized rats, whereas continuous infusion to mimic a female secretory pattern had no appreciable effect. Cytosolic sulfation of T3 was decreased by 25 to 30% by thyroidectomy or propylthiouracil treatment of male adult rats, and was restored by the supplementation of T3 (50 micrograms/kg daily for 7 days) to thyroidectomized rats. Administration of T3 in hypophysectomized rats almost completely restored the sulfating activity in the males and increased the activity in the females. Cytosolic T3 sulfation was inhibited by the addition of known inhibitors of phenol sulfotransferase, pentachlorophenol or 2,6-dichloro-4-nitrophenol. These results indicate a role of pituitary GH in hepatic sulfation of thyroid hormones in rats. The data obtained also raise the possibility that GH may modify the effect of thyroid hormones on the pituitary by a feed-back mechanism through changing the level of a sex-dominant phenol sulfotransferase(s) in rat livers. T3 was also sulfated in hepatic cytosols of mouse, hamster, rabbit, dog, monkey, and human.(ABSTRACT TRUNCATED AT 250 WORDS)
42 citations
Journal Article•
TL;DR: The results suggest that a critical period exists in which regulation of pituitary-thyroid axis function is programmed, so that early hypothyroidism results in reduced T4 and T3 levels in adulthood, despite normal levels of TSH.
Abstract: To evaluate the role of perinatal thyroid status in the development of pituitary-thyroid axis regulation, we administered triiodothyronine to newborn rats for the first five days postpartum to achieve hyperthyroidism, or propylthiouracil perinatally to rat dams and pups from gestational day 17 through postnatal day 5 to achieve hypothyroidism. Plasma T4, T3, and TSH levels were determined from birth through 50 days postpartum. Administration of exogenous T3 produced the expected immediate suppression of plasma T4 and TSH, with recovery toward normal values beginning within days of discontinuing the T3 regimen. Plasma T3 values were markedly elevated during the period in which T3 was being given, but subsequently became subnormal, with deficits persisting into young adulthood. With the PTU regimen, plasma T4 and T3 levels were markedly suppressed through postnatal day 10, rose over the ensuing two weeks, but nevertheless showed significant deficits into adulthood. TSH levels in the immediate neonatal period were subnormal in the PTU group, despite the marked lowering of circulating thyroid hormones; TSH then rose dramatically to levels four times normal, subsiding to control values by the end of the first month. These results suggest that a critical period exists in which regulation of pituitary-thyroid axis function is programmed. During this phase, TSH secretion can be suppressed by excess thyroid hormones, but cannot be increased by hormone deficiencies. Perhaps more importantly, perinatal thyroid status "programs" its own future reactivity, so that early hypothyroidism results in reduced T4 and T3 levels in adulthood, despite normal levels of TSH.
40 citations
TL;DR: It appears T3SO4 has no intrinsic biological activity, but, under certain circumstances, may be reactivated by desulfation.
Abstract: Hepatic microsomes and isolated hepatocytes in short term culture desulfate T3 sulfate (T3SO4). We, therefore, wished to determine whether T3SO4 could mimic the action of thyroid hormone in vitro. T3SO4 had no thyromimetic effect on the activity of Ca(2+)-ATPase in human erythrocyte membranes at doses up to 10,000 times the maximally effective dose of T3 (10(-10) mol/L). In GH4C1 pituitary cells, T3SO4 failed to displace [125I]T3 from nuclear receptors in intact cells or soluble preparations. Thus, T3SO4 was not directly thyromimetic in either an isolated human membrane system or a pituitary cell system in which nuclear receptor occupancy correlates with GH synthesis. Thyroid hormones inhibit [3H]glycosaminoglycan synthesis by cultured human dermal fibroblasts, and T3SO4 displayed about 0.5% the activity of T3 at 72 h. Human fibroblasts contained roughly the same level of microsomal p-nitrophenyl sulfatase activity as that previously observed in hepatic microsomes. Propylthiouracil (50 mumol/L) did not af...
37 citations
Journal Article•
TL;DR: The predominance of propylthiouracil effects on isoproterenol-stimulated adenylate cyclase but not on enzymatic responses to forskolin suggests that thyroid hormones may be controlling the development of regulatory G-proteins.
Abstract: In mature animals, thyroid hormone is permissive for beta adrenergic receptor expression and adrenergic control of adenylate cyclase. To determine if endogenous thyroid hormones play a similar role in the development of receptors and transduction mechanisms, we administered propylthiouracil perinatally to rat dams and pups from gestational day 17 through postnatal day 5. Circulating thyroid hormones were completely suppressed through postnatal day 10 and then rose to only slightly subnormal values by the 3rd to 4th postnatal week. In the heart, hypothyroidism completely suppressed the initial development of beta adrenergic receptor binding sites, with recovery paralleling the return of thyroid hormone levels. In contrast, development of basal and isoproterenol-stimulated adenylate cyclase activity showed more lasting deficiencies with a delayed onset corresponding to general growth impairment; however, forskolin-stimulated adenylate cyclase developed in a nearly normal pattern. Effects on development of renal beta receptors and adenylate cyclase were of smaller magnitude and comprised only the delayed onset phase; receptor deficiencies appeared after 10 days and adverse effects on adenylate cyclase were limited to the isoproterenol-sensitive component, consisting of a shift of the ontogenetic peak to later ages. Endogenous thyroid hormones thus contribute two distinct factors to beta receptor/adenylate cyclase development: they are obligatory for cardiac beta receptor development, but also, in parallel with general effects on growth and development, serve to program the ontogeny of transduction factors linking the receptors to adenylate cyclase. The predominance of propylthiouracil effects on isoproterenol-stimulated adenylate cyclase but not on enzymatic responses to forskolin suggests that thyroid hormones may be controlling the development of regulatory G-proteins.
29 citations
TL;DR: The role of thyroid hormone in the control of cardiac and renal cell development was examined in neonatal rats made hyperthyroid by administration of triiodothyronine and propylthiouracil, and the cardiac hyperplasia is unique to the developing animal, as post-replicative heart cells in adult animals show only hypertrophy in response to thyroid hormone.
Abstract: The role of thyroid hormone in the control of cardiac and renal cell development was examined in neonatal rats made hyperthyroid by administration of triiodothyronine (T3, 0.1 mg/kg s.c. on postnatal days 1-5) or hypothyroid by administration of propylthiouracil (PTU, 20 mg/kg s.c. given to dams on gestational day 17 through postnatal day 5 and to pups on postnatal days 1-5). Indices of total cell number (total DNA per tissue), cell packing density (DNA per g tissue), and relative cell size (protein/DNA ratio) were evaluated from birth through young adulthood. PTU administration led to primary shortfalls in cell number that were of similar magnitude in both tissues, but persisted somewhat longer in the kidney than in the heart. Deficits in cell packing density and cell size in the hypothyroid animals were secondary to the effect on cell number, displaying smaller magnitudes of effect and a lag in appearance and disappearance of the deficits compared to that for total DNA; indeed, the phase in which tissues were restoring their cell numbers was accompanied by increased cell packing density, reflecting a more rapid restitution of cell numbers than tissue weight or cell size. In contrast to the relatively similar effects of PTU on developing cardiac and renal cells, the effects of T3 were selective for the heart. Although T3 caused general growth impairment, it evoked marked cardiac overgrowth that was accompanied by a striking increase in cell number and a small increase in cell size. The cardiac hyperplasia is unique to the developing animal, as post-replicative heart cells in adult animals show only hypertrophy in response to thyroid hormone.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: The data suggest that mild changes in thyroid status associated with PTU affects regulation of T3, T4 and TSH more than GH or IGF-I in steers.
TL;DR: It is confirmed that the predominant effect of food deprivation on the thyroid axis is at the hypothalamic or suprahypothalamic level and that it can, at least in part, overcome the increase in TRH mRNA due to diminished T3 feedback.
Abstract: Propylthiouracil (PTU) was administered to rats for different lengths of time with or without food deprivation on the last 2 days. Within 4 days of PTU treatment peripheral 3,5,3'-tri-iodothyronine (T3) fell to low levels and beta-subunit of thyroid-stimulating hormone (beta-TSH) mRNA increased significantly in the anterior pituitary. Pro-thyrotrophin-releasing hormone (pro-TRH) mRNA in the hypothalamic paraventricular nucleus (PVN) increased significantly in the control group of animals by 8 days and in the food-deprived group by day 12; the increment of pro-TRH mRNA in the food-deprived group on day 12 was significantly less than that in the control group. In a second study, animals were treated with intraperitoneal injections of T3 with or without the food deprivation. After 4 days of T3 treatment, peripheral T3 levels were markedly increased and pro-TRH mRNA in the PVN and beta-TSH mRNA in the anterior pituitary were significantly reduced. Food deprivation had no additional suppressive effect. These studies confirm that the predominant effect of food deprivation on the thyroid axis is at the hypothalamic or suprahypothalamic level and that it can, at least in part, overcome the increase in TRH mRNA due to diminished T3 feedback.
TL;DR: The data suggest that p27 may be a type I 5'-D itself or at least the substrate-binding subunit of this enzyme in human thyroid, and that both Graves' and follicular adenoma thyroids contain larger amounts of it, and papillary adenocarcinoma Thyroids smaller than normal amounts.
Abstract: N-Bromoacetyl-[125I]T4(BrAc[125I]T4) was used as affinity label to identify type I 5'-deiodinase (5'-D) in human thyroid glands. Affinity labeled proteins were analyzed by autoradiography after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Human thyroid microsomes labeled with BrAc[125I]T4 showed the most prominent radiolabeled band of protein at a mol wt of approximately 27,000 (p27). BrAc[125I]T4 incorporations into p27 were significantly higher in both Graves' and follicular adenomas than in normal thyroids. On the other hand, four cases out of five carcinomas were lower than the least value of normal thyroids. Furthermore, an excellent correlation was observed between 5'-D activities and quantities of p27 in all cases (r = 0.96; P less than 0.001). Labeling of p27 was strongly inhibited by preferred type I 5'-D substrate rT3, but to a lesser extent by poor substrate T4 or T3, and the type I 5'-D inhibitor, propylthiouracil and iopanoic acid, also inhibited the p27 labeling in normal and v...
TL;DR: Two patients with hemiagenesis of the thyroid gland experienced thyrotoxicosis and went into remission after PTU treatment, and TSI levels returned to normal.
Abstract: Two patients with hemiagenesis of the thyroid gland experienced thyrotoxicosis. They constituted 1.1% of our clinic's total population of 178 thyrotoxic patients treated in the years 1986–1990 and 1.7% of 120 patients with thyrotoxic Graves' disease encountered during that period. The diagnosis was made on the basis of unilateral homogeneous 99mTcO4 uptake on thyroid scan, no change in the scan after both cessation of propylthiouracil (PTU) treatment for 4 days and TSH stimulation test, and high thyroid-stimulating immunoglobulin (TSI) levels. Both patients went into remission after PTU treatment, and TSI levels returned to normal. The diagnosis of toxic Graves' disease with thyroid hemiagenesis was, therefore, made. This combination is rare but important to recognize because treatment as well as prognosis might be different from that of toxic adenoma.
TL;DR: The rates of BrdU incorporation in thyroid follicles indicated higher proliferation activity in the area of adenoma and carcinoma rather than in the hyperplastic area, which suggested that E2 treatment increases the ER levels in MNU and LID/PTU-induced thyroid tumors.
Abstract: Estrogen receptor (ER) levels were evaluated in thyroid tumors induced by N-methyl-N-nitrosourea (MNU) and low iodine diet (LID) or propylthiouracil (PTU) in intact and estrogen (E2) loaded Long-Evans (LE) rats. MNU at 40 mg/kg body wt was injected in 50 day-old LE rats of both sexes. The animals were killed 17-22 weeks later and the thyroid tissues were subjected to ER assay. In LID-treated groups, cytosolic ER (cER) levels were 6.7 +/- 5.8 (fmol/mg protein, mean +/- SE) in females and 0.7 +/- 1.4 in males, E2 increased the ER levels. In E2-loaded LID groups, cER levels were 12.9 +/- 3.7 in females and 1.7 +/- 1.7 in males. PTU treatment produced almost comparable ER levels as LID treatment. PTU treatment as well as LID treatment increased the serum TSH levels with E2 treatment producing additional elevation. In evaluating ER levels by histological type of thyroid tumors, the level in cER plus nER showed the lowest value of 6 +/- 6.4 (fmol/mg DNA, mean +/- SE) in hyperplasia, followed by 129 +/- 52.3 in adenoma and 289 +/- 51.7 in carcinoma. The rates of BrdU incorporation in thyroid follicles indicated higher proliferation activity in the area of adenoma and carcinoma rather than in the hyperplastic area. These data suggested that E2 treatment increases the ER levels in MNU and LID/PTU-induced thyroid tumors. The level of ER was correlated to the histological type of thyroid tumors.
TL;DR: There was a quite close correlation between the effects of thyroid status on PRL-R mRNA levels and specific lactogenic binding to membranes prepared from the same tissue samples, suggesting a novel and complex tissue- and sex-dependent regulation by thyroid hormone.
Abstract: The nature and tissue distribution of prolactin receptor (PRL-R) mRNA in both male and female rats was studied. A single mRNA species of 2.2 kb was identified in the liver, kidney, adrenal, prostate, lactating mammary gland and ovary but not in the male lung, heart, skeletal muscle, thymus, adipose tissue or brain. There were distinct and contrasting sex differences in abundance of PRL-R mRNA in some tissues: liver (female much greater than male), kidney and adrenal (male much greater than female). A mRNA species of 4 kb was occasionally detected in the male adrenal and female liver. Given previous reports on the effects of thyroid status on PRL binding, the effects of thyroxine (T4), propylthiouracil (PTU) or combined treatment on PRL-R mRNA were assessed. In the male rat, PTU treatment markedly increased (three- to fourfold) PRL-R mRNA in the liver but decreased it (approximately 50%) in the kidney. These changes were reflected in similar changes in lactogenic binding activity. T4 or PTU treatment increased PRL-R mRNA in the prostate, with no obvious changes in binding. No major changes were seen in adrenal glands. In the female rat, PTU had little effect on PRL-R mRNA in any tissue, although binding of 125I-labelled lactogen was decreased in both the liver and kidney. There was an unexpected threefold rise in PRL-R mRNA in the female kidney following combined T4 and PTU treatment. Overall, there was a quite close correlation between the effects of thyroid status on PRL-R mRNA levels and specific lactogenic binding to membranes prepared from the same tissue samples. These studies provide data on the tissue distribution and size of PRL-R mRNA in rats and suggest a novel and complex tissue- and sex-dependent regulation by thyroid hormone.
TL;DR: The results presented here support the previous findings that thyroid hormone plays a significant role in the development of the olfactory system in Xenopus, and PTU significantly reduced the normal increase in o aroma axon number compared to stage 58 control larvae, whose thyroid hormone levels are high.
Abstract: Quantitative and morphological data were obtained on developing olfactory axons in normal and hypothyroid larvae of the African clawed frog Xenopus laevis. Hypothyroid larvae were produced by rearing the animals, beginning at stage 48, in a 0.01% solution of propylthiouracil (PTU), a treatment that blocks synthesis of thyroid hormone. These PTU-treated larvae were compared to their age-matched siblings when these siblings reached stage 52 (premetamorphic larvae; prior to synthesis of thyroid hormone), stage 57 (late premetamorphic larvae; after the onset of thyroid hormone synthesis), or stage 58 (larvae at the onset of metamorphic climax; thyroid hormone levels continue to rise). The number of olfactory axons did not differ between stage 52 control animals and the age-matched, PTU-treated animals, but there were only about half the number of axons in the PTU-treated animals that were age-matched to the stage 57 or 58 controls. Thus, PTU had no effect on olfactory axon number prior to the normal rise in thyroid hormone levels. But PTU significantly reduced the normal increase in olfactory axon number compared to stage 58 control larvae, whose thyroid hormone levels are high. While PTU also produced some changes in several other body measurements, the effect on the olfactory axons was the most consistent and prominent. The results presented here support our previous findings that thyroid hormone plays a significant role in the development of the olfactory system in Xenopus.
TL;DR: It took 24 mo after initiation of antithyroid drugs for OC to normalize, suggesting not only thyroid hormone per se but also some unknown factor(s) participates in serum OC secretion, suggesting that osteoblastic activity is enhanced in hyperthyroidism and suppressed in hypothyroidism.
Abstract: Serum concentration of osteocalcin (OC) was measured in sera from untreated patients with Graves' disease, hypothyroidism due to Hashimoto's thyroiditis, and subacute thyroiditis. Serum concentration of OC in Graves' disease and hypothyroidism were 14.1 +/- 5.6 micrograms/L and 3.8 +/- 2.7 micrograms/L, respectively which were significantly different from that of healthy subjects (Graves' disease, p less than 0.001, hypothyroidism, p less than 0.01). Serum concentration of OC in patients with subacute thyroiditis was 8.0 +/- 3.5 micrograms/L which was not statistically different from age-matched normal controls. Serial measurement of serum OC for 24 mo in 15 patients with Graves' disease after initiation of antithyroid drugs disclosed that the decline of serum OC was obtained only 24 mo after antithyroid drug therapy. On the other hand, in hypothyroid patients, increased serum OC was observed after 1-2 months treatment of L-T4. Correlation coefficients between serum concentrations of OC and T3, T4, FT3 or FT4 in all the patients with thyroid disorders were 0.66, 0.51, 0.50 and 0.54, respectively, which were statistically significant (all, p less than 0.001). These results suggest that osteoblastic activity is enhanced in hyperthyroidism and suppressed in hypothyroidism. In hyperthyroid patients, despite of normalization of FT4 concentration in relatively short period (within 3-4 mo), it took 24 mo after initiation of antithyroid drugs for OC to normalize, suggesting not only thyroid hormone per se but also some unknown factor(s) participates in serum OC secretion. In contrast to thyrotoxic patients, rapid increase in serum OC after initiation of supplemental L-T4 treatment in hypothyroidism was observed, suggesting a direct effect of thyroid hormone on the osteoblasts in patients with hypothyroidism.
Journal Article•
TL;DR: The experiments demonstrated that the effect of propylthiouracil on DNA synthesis in the liver is mediated primarily by way of its direct effect on the liver.
Abstract: The effect of propylthiouracil (PTU) on the growth activity of intact liver and liver regenerating after partial (65-70%) hepatectomy (PH) was studied in rats. PTU (Propycil, Kali-Chemie, FRG) was dissolved in drinking water (1 g PTU per litre) and this was given to the rats, as their sole source of fluids, three days before PH and then up to the end of the experiment. In rats given PTU, marked inhibition of liver DNA synthesis and the mitotic activity of hepatocytes was found after PH. This effect was potentiated to some extent by partial inanition of the experimental animals given PTU, as demonstrated in a paired feeding test in control rats. PTU inhibition of DNA synthesis in intact and regenerating liver also took effect in thyroidectomized rats, even with substitution (thyroid hormone) therapy. The experiments demonstrated that the effect of propylthiouracil on DNA synthesis in the liver is mediated primarily by way of its direct effect on the liver.
TL;DR: A 49-year-old woman was diagnosed as having autoimmune thyroid disease and her serum IgA, IgM and IgG were revealed to be 4.1, 154, 1930 and 1930 mg/dl, respectively.
Abstract: Selective immunoglobulin (Ig) A deficiency is reported to occur in 1 in 16,000 in Japan and has been reported to be complicated with various autoimmune diseases. A 49-year-old woman was diagnosed as having autoimmune thyroid disease. Her serum IgA, IgM and IgG were revealed to be 4.1, 154 and 1930 mg/dl, respectively. Severe skin eruption which occurred with 30 mg/day of methimazole (MMI) or 300 mg/day of propylthiouracil (PTU), was relieved by reducing MMI to 15 mg/day and administering anti-allergic drugs. Although the influence of IgA deficiency on autoimmunity and allergy still remains unclear, this is a report of IgA deficiency associated with autoimmune thyroid disease.
TL;DR: The results suggest that a higher liver concentration of N-acetylglutamate and ornithine in the hypothyroid (6-propyl-2-thiouracil only) rats is likely to stimulate urea synthesis.
Abstract: The purpose of this study was to elucidate the mechanism by which thyroid hormone alters urea synthesis. A set of three experiments was investigated in three groups of rats given 6-propyl-2-thiouracil (a thyroid inhibitor) without triiodothyronine treatment, treated with 6-propyl-2-thiouracil plus triiodothyronine or neither 6-propyl-2-thiouracil nor triiodothyronine (control). We attempted to determine whether the concentration of ornithine and N-acetylglutamate regulated urea synthesis and whether activities of two ornithine-catabolizing enzymes accounted for changes in ornithine concentration. Urinary excretion of urea and the liver concentration of N-acetylglutamate and ornithine in rats given 6-propyl-2-thiouracil plus triiodothyronine were significantly lower than in rats given 6-propyl-2-thiouracil alone. The liver concentration of N-acetylglutamate was correlated to urea excretion (r = 0.911, P less than 0.001). The activities of carbamylphosphate, synthetase, ornithine aminotransferase and ornithine decarboxylase in liver of the group treated with 6-propyl-2-thiouracil alone were significantly lower than those of the 6-propyl-2-thiouracil plus triiodothyronine-treated group. The results suggest that a higher liver concentration of N-acetylglutamate and ornithine in the hypothyroid (6-propyl-2-thiouracil only) rats is likely to stimulate urea synthesis. The thyroid hormone-induced increase in activities of ornithine catabolizing enzymes may be primarily responsible for changes in ornithine concentration.
TL;DR: In most patients the transition from hyperthyroidism to euthyroidism induced by antithyroid drug therapy is associated with the improvement of the Graves’ ophthalmopathy, and no marked difference can be drawn between the two treatment regimens.
Abstract: We analyzed the evolution of the ophthalmopathy associated with Graves' hyperthyroidism in 45 patients treated with two different antithyroid drug regimens. Group A patients (n = 31) received either methimazole (40-100 mg daily) or propylthiouracil (400-900 mg daily) combined with T3 daily throughout treatment. Group B patients (n = 14) were treated with conventional regimen with lower doses of either methimazole (5-25 mg daily) or propylthiouracil (50-300 mg daily) and no T3 addition. Eye signs and proptosis measurement were evaluated just before the beginning of the treatment and compared with the results after antithyroid drug withdrawal. Improvement of the eye signs considered on grounds of the NOSPECS classification was greater in group A than group B (p less than 0.01). Also, the decrease in proptosis measurement was greater (p less than 0.01) in patients treated with combined regimen (21.5 +/- 2.4 mm to 20.4 +/- 2.3 mm) than in patients receiving conventional therapy (20.4 +/- 1.6 mm to 20.0 +/- 1.7 mm). Serum thyroglobulin concentrations did not correlate with either the severity or the evolution of the ophthalmopathy. Negative serum antithyroglobulin antibody (TgAb) was associated with the improvement of the ophthalmopathy that was noted in 24 out of 27 patients (Chi-Square = 5.84; p less than 0.001). Thus, serum TgAb levels might have some connection with progression of eye signs but serum Tg concentration does not. Our study suggests that in most patients the transition from hyperthyroidism to euthyroidism induced by antithyroid drug therapy is associated with the improvement of the Graves' ophthalmopathy. However, no marked difference can be drawn between the two treatment regimens.
Journal Article•
TL;DR: It appears from the present data that ferritin metabolism is influenced by thyroid hormone as well as by iron, and the raised serum ferrit in hyperthyroid patients may be partially attributed to increased ferritIn synthesis in the liver and its possible leakage into circulation.
Abstract: Rats were made hypo and 'hyperthyroid' with propylthiouracil (PTU) and L-Thyroxine (L-T) respectively. The hypo and hyperthyroid status in these rats were confirmed by serum level of T4 and T3. Liver iron was significantly increased in both the hypo and hyperthyroid animals. However, liver ferritin synthesis rate was reduced by 36% in hypothyroid rats, and elevated by 38% in hyperthyroid ones. A similar trend was seen in liver ferritin concentration. Further, serum transaminases were elevated only in animals of the hyperthyroid group. It appears from the present data that ferritin metabolism is influenced by thyroid hormone as well as by iron. Thus, the raised serum ferritin in hyperthyroid patients may be partially attributed to increased ferritin synthesis in the liver and its possible leakage into circulation.
TL;DR: It is concluded that Mn-transport into the thyroid is controlled by the thyroid state.
Abstract: The present study deals with a possible mechanism controlling the transport of manganese (Mn), an essential trace element, from the circulation to the thyroid. Mice were pretreated with propylthiouracil (PTU) or triiodothyronine (T3), and a measurement of the thyroid:serum concentration ratio (T/S) of radioactive manganese (54Mn) was carried out. The T/S of 54Mn was greatly enhanced by PTU, but reduced by T3. Several methods were used to demonstrate that the T/S of 54Mn depends upon the level of thyroid-stimulating hormone (TSH) in the serum. First, bovine TSH was injected into mice; an increase in the T/S resulted. Secondly, serum thyroxine and T3 levels measured by radioimmunoassay (RIA) suggested that PTU produced an increase in serum TSH and T3 a decrease. However, direct measurement of mouse TSH by RIA for rat TSH failed to produce proof of any changes in TSH level, owing to poor cross-reactivity. Taking all the information into account, it is concluded that Mn-transport into the thyroid is controlled by the thyroid state.
TL;DR: Vasoactive intestinal peptide significantly increased iodide uptake in rats fed an iodine deficient diet but not in those fed a normal iodine diet, while neuropeptide Y did not alter iodide absorption in rats on either the low or the high iodine diet; regardless of the presence or absence of propylthiouracil.
Abstract: The presence of vasoactive intestinal peptide and neuropeptide Y in thyroid nerves and their effects on thyroid blood flow are well known. However, the effects of these two neuropeptides on the various processes involved in thyroid hormone biosynthesis and release have not been fully explored. We have now tested these two peptides for effects on an early step in thyroid hormone biosynthesis, namely iodide uptake, a process which is comprised of trapping and organification. In these experiments, we have used anesthetized adult male rats pretreated with thyroxine or fed a low iodine diet to increase thyroidal sensitivity. Vasoactive intestinal peptide significantly increased iodide uptake in rats fed an iodine deficient diet but not in those fed a normal iodine diet. This effect disappeared if animals were pretreated with propylthiouracil. Neuropeptide Y did not alter iodide uptake in rats on either the low or the high iodine diet, regardless of the presence or absence of propylthiouracil. The effect of vas...
01 Jan 1992
TL;DR: In this article, a measurement of thyroid :serum concentration ratio (T/S) of radioactive manganese (54Mn) was carried out and it was concluded that Mn-transport into the thyroid is controlled by the thyroid state.
Abstract: The present study deals with a possible mechanism controlling the transport of manganese (Mn), an essential trace element, from the circulation to the thyroid. Mice were pretreated with propylthiouracil (PTU) or triiodothyronine (T3), and a measurement of the thyroid :serum concentration ratio (T/S) of radioactive manganese (54Mn) was carried out. The T/S of 54Mn was greatly enhanced by PTU, but reduced by T 3 . Several methods were used to demonstrate that the T/S of 54Mn depends upon the level of thyroid-stimulating hormone (TSH) in the serum. First, bovine TSH was injected into mice; an increase in the T/S resulted. Secondly, serum thyroxine and T 3 levels measured by radioimmunoassay (RIA) suggested that PTU produced an increase in serum TSH and T 3 a decrease. However, direct measurement of mouse TSH by RIA for rat TSH failed to produce proof of any changes in TSH level, owing to poor cross-reactivity. Taking all the information into account, it is concluded that Mn-transport into the thyroid is controlled by the thyroid state. Manganese (Mn) is distributed ubiquitously throughout the body. It is an essential trace element which plays an important role in a variety of physiological functions 1. Substantial amounts of Mn have been found in some endocrine glands 2' 3, but the function of Mn in these glands is not well understood. The thyroid is one of the glands which tend to accumulate Mn 2, 3, but the signifi- cance of this accumulated Mn is unknown. The authors have demonstrated that excess Mn induced goiter in the thyroid of female mice 4, and that some pathological con- ditions altered the distribution of Mn in the thyroid of experimental animals 5 and in the human thyroid 6. These observations indicate that Mn-transport might be con- trolled by the state of the thyroid. Further study is neces- sary to investigate what conditions are required for Mn- transport into the thyroid.
TL;DR: Results indicate that changes within the thyroid axis in response to these hypo- and hyperthyroid conditions do not include alterations in steady-state prepro NPY or precursor VIP mRNA concentrations in the major ganglia which supply nerves to the thyroid gland, however, intrathyroidal preproNPY mRNA levels are increased as a consequence of the thyroidal adaptation to a PTU challenge.
TL;DR: Doctors are suggested to be aware of the presence of AAb in pregnant women with Graves’ disease, in order to avoid inappropriate treatment which could lead to fetal and neonatal hypothyroidism.
Abstract: At birth, a clinically euthyroid male neonate was found to have unexpectedly high levels of free T3 and T4 concurrent with a high TSH level. The mother was treated with propylthiouracil for Graves' disease during and after pregnancy. The neonate also had an extremely high titer of TSH receptor antibodies. He soon became clinically thyrotoxic as TSH levels were suppressed and thyroid hormone levels rose. After instituting antithyroid therapy, TSH levels became elevated again, while thyroid hormone levels decreased but were still above normal. Around 3 months after birth, both TSH receptor antibodies and discordance, between the levels of thyroid hormones and TSH, disappeared. Because of high maternal TSH levels in conjunction with an elevated free T3 level at 7 months postpartum, we suspected the presence of autoantibodies against thyroid hormones (AAb). Maternal and infant blood samples were then examined retrospectively for AAb and were detected in all the samples except those of the infant taken more than 3 months after birth. The authors, therefore, suggest that physicians be aware of the presence of AAb in pregnant women with Graves' disease, in order to avoid inappropriate treatment which could lead to fetal and neonatal hypothyroidism.
TL;DR: It is shown that mEGF levels in the thyroid could be depleted by hypothyroidism and may also be androgen responsive.
Abstract: The effects of testosterone (TP) and thyroxine (T4) on the level of epidermal growth factor (mEGF) in the thyroid were compared in a hypothyroid mouse model. Groups of five adult female BALB/c mice were given a “severe” hypothyroid regimen consisting of an iodine deficient diet together with oral and s.c propylthiouracil (PTU). Sialoadenectomy or sham operation was performed after 18 days on the hypothyroid regimen. The mice convalesced on normal diet for 5 days and beginning from day 23 received either T4, 1ug/g or 2ug/g, s.c daily or TP, 0.3mg or 0.75mg, i.m. every third day until day 33, while continuing the hypothyroid regimen. Control mice received normal diet and vehicles for the various injections. The mice were killed on day 33 and thyroidal EGF levels determined by radioimmunoassay. The mean + S.E. levels of mEGF in the thyroid were 10.12 ± 1.75 ng/mg protein (control), 3.82 ± 0.67 ng/mg (hypothyroid; p< 0.01), 3.07 ± 1.52 (T4, 1ug/g; p< 0.02), 2.59 ± 0.46 ng/mg (T4, 2ug/g; p<0.01), 8.58 ± 2.48 (...