Showing papers on "Propylthiouracil published in 2017"
TL;DR: A quantitative adverse outcome pathway where serum thyroxin (T4) reduction following inhibition of thyroperoxidase in the thyroid gland are described and related to deficits in fetal brain TH and the development of a brain malformation, cortical heterotopia is developed.
48 citations
TL;DR: For pregnant women with hyperthyroidism, exposure to MMI/CMZ significantly increased the incidence of neonatal congenital malformations compared to exposure to PTU and no antithyroid drug exposure; however, no differences were observed between PTU exposure and no anticancer drug exposure.
Abstract: Objective The aim of this study was to determine the effect of exposure to different antithyroid drugs during pregnancy on the incidence of neonatal congenital malformations. Methods A meta-analysis was performed to compare the incidence of neonatal congenital malformations after exposure to different antithyroid drugs during pregnancy. Twelve studies that met the inclusion criteria were included in this meta-analysis. PubMed, Embase, and CENTRAL databases were searched from inception until January 2017. Study designs included case-control studies, prospective cohort studies, and retrospective cohort studies. Results Twelve studies involving 8028 participants with exposure to different antithyroid drugs during pregnancy were included in this study; however, only 10 studies involving 5059 participants involved exposure to different antithyroid drugs exactly during pregnancy. Our results indicated that exposure to methimazole (MMI)/carbimazole (CMZ) only during pregnancy significantly increased the risk of neonatal congenital malformations compared to no antithyroid drug exposure (OR 1.88; 95%CI 1.33 to 2.65; P = 0.0004). No differences were observed between propylthiouracil (PTU) exposure and no antithyroid drug exposure only during pregnancy (OR 0.81; 95%CI 0.58 to 1.15; P = 0.24). Exposure to MMI/CMZ only during pregnancy significantly increased the risk of neonatal congenital malformations compared to that associated with exposure to PTU (OR 1.90; 95%CI 1.30 to 2.78; P = 0.001). Conclusion For pregnant women with hyperthyroidism, exposure to MMI/CMZ significantly increased the incidence of neonatal congenital malformations compared to exposure to PTU and no antithyroid drug exposure; however, no differences were observed between PTU exposure and no antithyroid drug exposure.
35 citations
TL;DR: Thyroid dysfunction in pregnancy has consequences for mother and baby and potential problems include pre-eclampsia, prematurity and congenital abnormality.
Abstract: Thyroid dysfunction in pregnancy has consequences for mother and baby. Potential problems include pre-eclampsia, prematurity and congenital abnormality.
For women known to have hypothyroidism, an increase in thyroxine dose by 20–40% when pregnancy is confirmed usually ensures they remain euthyroid. Treatment of subclinical hypothyroidism is recommended if the woman has antithyroid antibodies.
Treatment of hyperthyroidism, unless it is related to human chorionic gonadotrophin, involves propylthiouracil in the first trimester. Carbimazole may be used in the second trimester. Thyroid function tests are checked every month and every two weeks following a change in dose.
Women with a current or a past history of Graves’ disease who have thyrotropin receptor antibodies require early specialist referral as there is a 1–5% risk of fetal hyperthyroidism.
Women with thyroid disorders in pregnancy should be followed up by their GP in the postpartum period. Postpartum thyroiditis may present months after delivery.
23 citations
TL;DR: In this paper, the effect of PTU on hepatocytes mitochondria in different experimental models was evaluated in mice and showed that PTU-induced hepatotoxicity was biochemically evident in mice by increased serum biomarkers.
Abstract: Background: Propylthiouracil
(PTU) administration is associated with several cases of hepatotoxicity, especially in children. The
mechanism(s) of PTU-induced hepatotoxicity is obscure. In the current study, we
aimed to assess the effect of PTU on hepatocytes mitochondria in different
experimental models.
Methods: Mice
were treated with PTU (10, 20, 40, 80, and 100 mg/kg, i.p) then, the liver
mitochondria were isolated and evaluated. Moreover, liver mitochondria were
isolated from normal mice and incubated with increasing concentrations of PTU
(10 µM-1 mM). Mitochondrial dehydrogenases activity, mitochondrial membrane
potential, mitochondrial swelling, and mitochondrial adenosine triphosphate
(ATP) content were monitored.
Results: PTU
hepatotoxicity was biochemically evident in mice by increased serum biomarkers
of liver injury. PTU also caused a decrease
in mitochondrial dehydrogenases activity, increased mitochondrial swelling,
depleted mitochondrial ATP, and caused
mitochondrial depolarization both in vitro and in vivo.
Conclusion: Our
data suggest mitochondrial dysfunction as a mechanism for PTU-induced
hepatotoxicity.
21 citations
TL;DR: This is the first study to reveal that C. pictus extract has therapeutic potential to restore thyroid hormone levels and prevent the biochemical complications due to thyroid hormone insufficiency in the animal model of experimental hypothyroidism.
Abstract: Background: The aim of the present study was to investigate the preventive effect of Costus pictus leaf extract in experimental hypothyroidism. Materials and Methods: Forty male Wistar rats were randomly divided into four groups with ten rats in each group: Control (C), hypothyroid (H), control+extract (C+E), and hypothyroid+extract (H+E). Rats in C group did not receive any intervention throughout the experimental period. The rats in the C+E and H+E groups received pretreatment with C. pictus leaf extract for 4 weeks. Subsequently, for the next 6 weeks, rats in the H group received 0.05% propylthiouracil in drinking water while C+E group received C. pictus leaf extract and H+E group received propyl thiouracil and C. pictus leaf extract. Results: Hypothyroid group rats exhibited dramatic increase in thyroid-stimulating hormone (TSH) levels with concomitant depletion in the levels of thyroid hormones. Treatment with the extract resulted in remarkable improvement in thyroid profile. Extract produced 10.59-fold increase in plasma free T3, 8.65-fold increase in free T4, and 3.59-fold decrease in TSH levels in H+E group in comparison with H group. Treatment with the extract ameliorated hypercholesterolemia, decreased levels of plasma C-reactive protein and tumor necrosis factor alpha, suppressed tissue oxidative stress and prevented hepatic and renal damage caused due to thyroid hormone depletion in the H+E group. Pentacyclic triterpenes alpha and beta amyrins were identified and quantified in the extract. Conclusions: This is the first study to reveal that C. pictus extract has therapeutic potential to restore thyroid hormone levels and prevent the biochemical complications due to thyroid hormone insufficiency in the animal model of experimental hypothyroidism.
14 citations
TL;DR: This work presents an unusual case of severe hyperthyroidism-associated hepatotoxicity, in which adjuvant therapies, including glucocorticoids, saturated solution of potassium iodide, and cholestyramine, were used as a bridge to definitive therapy with thyroidectomy.
Abstract: Graves thyrotoxicosis rarely presents with painless jaundice resulting from hyperthyroidism-associated hepatotoxicity, without preexisting liver disease. Management in patients with this presentation is challenging, given that the thionamides, methimazole and propylthiouracil, have both been associated with drug-induced liver injury. Radioactive iodine ablation and thyroidectomy are well-established alternatives, but each have their associated risks and contraindications. We present an unusual case of severe hyperthyroidism-associated hepatotoxicity, in which adjuvant therapies, including glucocorticoids, saturated solution of potassium iodide, and cholestyramine, were used as a bridge to definitive therapy with thyroidectomy.
12 citations
TL;DR: Thyroid hormones deficiency suppresses the anticontractile effect of NO and potentiates the procontractile Rho-kinase effects in mesenteric arteries of 2-week-old pups, which disturb perinatal cardiovascular homeostasis and might lead to cardiovascular pathologies in adulthood.
Abstract: The mechanisms of vascular alterations resulting from early thyroid hormones deficiency are poorly understood. We tested the hypothesis that antenatal/early postnatal hypothyroidism would alter the activity of endothelial NO pathway and Rho-kinase pathway, which are specific for developing vasculature. Dams were treated with propylthiouracil (PTU, 7 ppm) in drinking water during gestation and 2 weeks after delivery, and their progeny had normal body weight but markedly reduced blood levels of thyroid hormones (ELISA). Small arteries from 2-week-old male pups were studied using wire myography, qPCR and Western blotting. Mesenteric arteries of PTU pups, compared to controls, demonstrated smaller maximum response to α1-adrenergic agonist methoxamine and reduced mRNA contents of smooth muscle differentiation markers α-actin and SERCA2A. Inhibition of basal NO synthesis by l-NNA led to tonic contraction of mesenteric arteries and augmented their contractile responses to methoxamine; both l-NNA effects were impaired in PTU pups. PTU pups demonstrated lower blood level of NO metabolites compared to control group (Griess reaction). Rho-kinase inhibitor Y27632 strongly reduced mesenteric arteries responses to methoxamine in PTU pups, that was accompanied by elevated Rho-kinase content in their arteries in comparison to control ones. Unlike mesenteric, saphenous arteries of PTU pups, compared to controls, had no changes in α-actin and SERCA2A contents and in responses to l-NNA and Y27632. In conclusion, thyroid hormones deficiency suppresses the anticontractile effect of NO and potentiates the procontractile Rho-kinase effects in mesenteric arteries of 2-week-old pups. Such alterations disturb perinatal cardiovascular homeostasis and might lead to cardiovascular pathologies in adulthood.
11 citations
TL;DR: It is revealed that recovery following experimental hyperthyroidism could potentially ameliorate cardiac function and decrease the risk for additional cardiac complications, yet, this appears to be model-dependent and should be cautiously construed.
Abstract: Persistent cardiovascular pathology has been described in hyperthyroid patients even with effective antithyroid treatment. Here, we studied the effect of a well-known antithyroid drug, propylthiouracil (PTU; 20 mg/kg/day), on thyroxine (T4; 500 µg/kg/day)-induced increase in blood pressure (BP), cardiac hypertrophy, and altered responses of the contractile myocardium both in vivo and ex vivo after 2 weeks of treatment. Furthermore, the potential recovery through 2 weeks of T4 treatment discontinuation was also investigated. PTU and T4 recovery partially reduced the T4-prompted increase in BP. Alternatively, PTU significantly improved the in vivo left ventricular (LV) function with no considerable effects on cardiac hypertrophy or ex vivo right ventricular (RV) contractile alterations subsequent to T4 treatment. Conversely, T4 recovery considerably enhanced the T4-provoked cardiac changes both in vivo and ex vivo. Altogether, our data is in agreement with the proposal that hyperthyroidism-induced cardiovascular pathology could persevere even with antithyroid treatments, such as PTU. However, this cannot be generalized and further investigation with different antithyroid treatments should be executed. Moreover, we reveal that recovery following experimental hyperthyroidism could potentially ameliorate cardiac function and decrease the risk for additional cardiac complications, yet, this appears to be model-dependent and should be cautiously construed.
9 citations
TL;DR: The temporal relationship between methimazole intake and the development of pleural effusion combined with the extensive exclusion of alternative causes, namely infectious, neoplastic and primary auto-immune diseases, led to the diagnosis of hypersensitivity reaction to methimzole.
Abstract: Adverse reactions associated to anti-thyroid drugs include fever, rash, arthralgia, agranulocytosis and hepatitis that are thought to be hypersensitivity reactions. Five cases of pleural effusion associated to thionamides have also been reported, two with propylthiouracil and three with carbimazole. We report here a case of a 75-year-old man admitted because of unilateral pleural effusion. The patient had a recent diagnosis of hyperthyroidism and 6 days after starting methimazole complained of pleuritic chest pain. He had elevated C-reactive protein and erythrocyte sedimentation rate and normal white blood cell count and liver enzymes. Chest radiography showed a moderate right pleural effusion and the ultrasound revealed a loculated effusion that was shown to be an eosinophilic exudate. The temporal relationship between methimazole intake and the development of pleural effusion combined with the extensive exclusion of alternative causes, namely infectious, neoplastic and primary auto-immune diseases, led to the diagnosis of hypersensitivity reaction to methimazole. The thionamide was stopped and corticosteroid was started with complete resolution of the pleural effusion in 3 months. Awareness of this rare adverse reaction of anti-thyroid drugs is important and methimazole can be added to the list of possible etiologies of drug-induced eosinophilic pleural effusion.
8 citations
17 Nov 2017
TL;DR: Treating patients with agranulocytosis from PTU with a modified total thyroidectomy using ligation of the vascular supply as the initial surgical step limits release of thyroid hormone into the blood stream during thyroidectomy and decreases the possibility of intra operative thyroid storm.
Abstract: Thyroid storm is a rare, potentially lethal condition involving collapse of the hypothalamic-pituitary-thyroid feedback loop. Thyroid storm carries a significant mortality rate, thus requiring prom...
7 citations
TL;DR: Ulastructural changes in zebrafish thyrocytes appear specific for different chemicals, most likely depending on their specific modes of action.
Abstract: Histopathology is a widely used approach to evaluate effects of endocrine-active chemicals in the thyroid. However, effects at an ultrastructural level have hardly been examined in fish thyroids. In the present study, zebrafish was exposed to sublethal concentrations of propylthiouracil (PTU; 0-50 mg/L) and perchlorate (PER; 0-5,000 µg/L) for 5 weeks in a modified early life-stage test. None of the treatments caused significant mortality (no observed effect concentrations for survival ≥50 mg/L [PTU] and ≥5,000 µg/L [PER]). PTU induced dose-dependent alterations in the rough endoplasmic reticulum (rER) in all exposure groups, whereas only the 2 highest PER exposure groups (500 and 5,000 µg/L) resulted in alterations of the rER. Both substances caused an increase in the numbers of lysosomes and mitochondria, with mitochondria displaying distorted cristae. Increased mitochondrial diameters were only observed in the PTU treatment. PER-exposed samples displayed an increase in apical microvilli. The highest PTU concentration (50 mg/L) showed first signs of cellular degeneration. Ultrastructural changes in zebrafish thyrocytes thus appear specific for different chemicals, most likely depending on their specific modes of action. Additional knowledge of subcellular changes in thyrocytes can help to better understand and interpret existing histological data in the future.
TL;DR: A case of an 80-year-old woman who developed agranulocytosis and pneumonia approximately 4 weeks after starting low dose methimazole therapy, and died despite aggressive treatment with broad-spectrum antibiotics and granulocyte colony stimulating factor.
Abstract: Thionamides, such as methimazole and propylthiouracil, are used for the management of hyperthyroidism. Agranulocytosis is a rare adverse effect of thionamides and elderly patients are especially vulnerable. Here we discuss a case of an 80-year-old woman who developed agranulocytosis and pneumonia approximately 4 weeks after starting low dose methimazole therapy. Despite aggressive treatment with broad-spectrum antibiotics and granulocyte colony stimulating factor, she developed multiorgan failure and died. Our goals are to identify risk factors common to elderly patients and hopefully improve outcomes in this population when prescribed thionamides.
TL;DR: The binding free energy calculation done using Molecular Mechanics Poisson–Boltzmann (MM-PBSA) and generalized Born and surface area continuum solvation (GBSA) results indicated that both drugs bind strongly to TPO201-500, with Propylthiouracil having slightly higher binding energy than Methimazole.
Abstract: Graves’ disease (GD), an autoimmune disorder, scars majority of women worldwide, causing hyperthyroidism, Graves’s ophthalmopathy and goitre. Thyroid Peroxidase (TPO) is an active target of anti-thyroid drugs, Methimazole and Propylthiouracil, which inhibit the enzyme function of catalysing the thyroid hormones synthesis. Most of the protein-drug interaction studies so far have been focussed mainly at in vivo level, or by using Myeloperoxidase and Lactose peroxidases as TPO surrogates for the same. This makes the molecular interaction of TPO with the drugs crucial to understand. In this study, we used the molecular dynamics (MD) to study the molecular interaction differences between TPO201-500 and both drugs. The binding free energy calculation done using Molecular Mechanics Poisson–Boltzmann (MM-PBSA) and generalized Born and surface area continuum solvation (GBSA) results indicated that both drugs bind strongly to TPO201-500, with Propylthiouracil having slightly higher binding energy than Methimazole. We found that both drugs interacted with the residues- Asp238, His239, Phe243, Thr487 and His494 through hydrophobic interactions and formed stable hydrogen bonds with residue Arg491 of TPO201-500. Since both drugs engage residues- Asp238, His239 and His494 which falls within the proximal heme binding site and catalytic site of TPO201-500, we can conclude that these drugs may be conducive in inhibiting the enzymatic activity of TPO201-500.
TL;DR: Nesfatin-1 and adiponectin levels were modified considerably in hypo- and hyperthyroidism, whereas with the restoration of the thyroid function, modified hormone levels went back to normal.
Abstract: Background Changes in thyroid hormone concentrations may affect adiponectin concentrations through various mechanisms. A molecule released primarily from the fat cells adiposities; adiponectin has important effects on the regulation of body weight. Aim The present study aimed to explore the effects of experimental thyroid dysfunction and its treatment on nesfatin-1 and adiponectin levels in rats. Methods The study included 40 adult male Sprague-Dawley rats which were grouped as follows: (1) control; (2) hypothyroidism [hypothyroidism was induced by intraperitoneal injection of 10 mg/kg/day propylthiouracil (PTU) for 3 weeks]; (3) hypothyroidism + thyroxine group [after hypothyroidism was induced by 2-week PTU injection, they were treated with high-dose L-thyroxine (1.5 mg/kg/day) for 1 week]; (4) hyperthyroidism [hyperthyroidism was induced by 3-weeks' thyroxine injection (0.3 mg/kg/day)]; (5) hyperthyroidism + PTU (after hyperthyroidism was induced by 2-weeks' thyroxine injection, the animals were given 10 mg/kg/day PTU for 1 week). Blood samples taken at the end of the study were analyzed to measure nesfatin-1 and adiponectin levels. Results It was found that nesfatin-1 levels increased in hypothyroidism, while adiponectin levels decreased (p < 0.001). In experimental hyperthyroidism, on the other hand, both nesfatin-1 and adiponectin levels were found significantly elevated (p < 0.001). Conclusion The results of the study indicate that nesfatin-1 and adiponectin levels were modified considerably in hypo- and hyperthyroidism, whereas with the restoration of the thyroid function, modified hormone levels went back to normal.
29 Aug 2017
TL;DR: The results suggest that HT induced by PTU significantly reduces myocardial SIRT1 content, and decreases TT3 concentrations, both in the control group and HT group.
Abstract: Background: In this study, the changes in sirtuin1 (SIRT1) levels in the heart of rats with hypothyroidism (HT) were evaluated. Methods: A total of 20 Wistar male rats were randomly divided into control groups (n=10) and HT groups (n=10). In the HT groups, we used 0.05% propylthiouracil (PTU) saline solution to prepare the HT model, while 0.9% sodium chloride solution was used as a placebo in the control groups. During the intervention period, the body weight of rats was measured weekly, and serum triiodothyronine (TT 3 ), tetraiodothyronine (TT 4 ), thyroid-stimulating hormone (TSH), body weight, heart weight, and SIRT1 content in the heart were measured after intervention. We compared the differences in SIRT1 content between the two groups and analyzed the correlation between SIRT1 and thyroid hormone concentrations. Results: After 8 weeks of intervention, the HT rat model was successfully produced. The body weight of the HT group rats increased more slowly than that of the control groups. The heart weight of the HT groups was significantly lower than that of the control groups, and SIRT1 content decreased significantly compared to in control group rats. However, there were no significant differences between the two groups in heart weight index. The relative content of SIRT1 was significantly correlated with TT3 concentrations, both in the control group and HT group. Conclusions: Our results suggest that HT induced by PTU significantly reduces myocardial SIRT1 content. Decreased TT3 was significantly associated with decreased SIRT1 content.
TL;DR: Current guidelines highlight the need for clinical attention on the use of ATDs in early pregnancy, but if the risk of relapse or worsening of hyperthyroidism is considered low, it is suggested that ATD treatment can be withdrawn followed by frequent monitoring of thyroid function.
Abstract: Purpose of reviewHyperthyroidism in pregnant women should be adequately treated to prevent maternal and fetal complications. The treatment of choice in pregnancy is antithyroidal medications (ATDs). The risk of embryopathies associated with the use of Methimazole (MMI) and Propylthiouracil (PTU) in
TL;DR: Women with a pre-conception thyroid-stimulating hormone level of < 1.2 mIU/L usually do not require an increase in levothyroxine once they are pregnant.
Abstract: Increasing levothyroxine by two extra dosages per week after pregnancy is confirmed prevents development of overt hypothyroidism among most women.[1][1] Women with a pre-conception thyroid-stimulating hormone (TSH) level of < 1.2 mIU/L usually do not require an increase in levothyroxine once they
TL;DR: The case of a 27-year-old woman who is 3 months post-partum, breastfeeding, and suffering with Graves’ disease hyperthyroidism, who received 6 therapeutic plasma exchange procedures to clear thyroid hormones and anti-TSH receptor antibodies from blood, resulting in a pre-surgical euthyroid state without antithyroid drug therapy.
Abstract: Antithyroid drugs can be a rare cause of agranulocytosis (0.5% of treated patients). Suspension of these drugs is mandatory in these patients and may result in worsening hyperthyroidism. We report the case of a 27-year-old woman who is 3 months post-partum, breastfeeding, and suffering from Graves’ disease hyperthyroidism treated first with methimazole and then with propylthiouracil due to a methimazole allergy. She was admitted for urosepsis and agranulocytosis. The patient was diagnosed with propylthiouracil related agranulocytosis, diffuse toxic goiter, and thyro-gastric syndrome. Antithyroid drug therapy was stopped resulting in a worsening of thyrotoxicosis. Agranulocytosis was treated with 8 doses of G-CSF with full recovery. To rapidly restore euthyroidism and to perform a thyroidectomy, the patient received 6 plasmapheresis procedures, to clear thyroid hormones and anti-TSH receptor antibodies from the blood, resulting in a pre-surgical euthyroid state without antithyroid drugs. One year after thyroidectomy, the patient is well on thyroid hormone replacement therapy. Key Words: Plasmapheresis; Hyperthyroidism, Agranulocytosis; Propylthiouracil.
01 Apr 2017
TL;DR: Results indicates that T3 supplementation can augment hypothyroid induced alterations of central cholinergic neurotransmission vis-à-vis peripheral thyroid morphology.
Abstract: The role of thyroid hormone (TH) in adult mammalian brain function including cholinergic neurotransmission is illusive, and its clinical application in recovery of mood disorder during altered thyroidal conditions appears to be dispersed. In this study, we explored whether TH supplementation helps in recovery of adult brain status during thyroid dysfunction. We observed a dose-dependent stimulation of acetylcholinesterase (AChE) activities by triiodothyronine (T3) in the synaptosomes prepared from adult rat cerebral cortex. The AChE activation in both propylthiouracil (PTU)-treated and T3-treated animals remained elevated indicating the presence of an autoregulatory mechanism for thyroid hormone levels in altered thyroidal conditions. Additive effects were also found with gradual decreases in the enzyme activities at 24, 48 and 72 h after single injection of T3 to the PTU-treated rats. It appears that T3 exhibit a stimulatory effect on cholinergic neurotransmission in adult mammalian brain. Moreover, the histomorphological observation of thyroid gland revealed the disappearance of colloids and changes of follicular structures in 14-day PTU-treated condition. But the colloids reappeared and follicular structures normalized after a single injection of T3 to PTU-treated animals gradually at 24, 48 and 72 h. The results therefore, indicates that T3 supplementation can augment hypothyroid induced alterations of central cholinergic neurotransmission vis-à-vis peripheral thyroid morphology.
TL;DR: The case of a female patient with hypothyroidism who spontaneously developed Graves hyperthyroidism during pregnancy and then reverted back to hypothyroxine in a subsequent pregnancy is reported.
Abstract: Objective: To report the case of a female patient with hypothyroidism who spontaneously developed Graves hyperthyroidism during pregnancy and then reverted back to hypothyroidism in a subsequent pregnancy. Methods: The pertinent clinical features, laboratory data, and clinical course of the case are reported, along with a brief literature review. Results: A 30-year-old female with hypothyroidism diagnosed at age 20 years unexpectedly required decreased levothyroxine dosing during her second pregnancy. She was taking levothyroxine 12.5 μg daily when she became pregnant a third time. In the first trimester, levothyroxine was discontinued, and she presented in the third trimester with clinical and biochemical hyperthyroidism and a diffusely enlarged goiter. Propylthiouracil (PTU) was initiated. Thyroid-stimulating hormone–receptor antibodies (TRAbs) were positive. After delivery, her baby developed transient neonatal Graves disease. She was continued on a stable dose of PTU for 10 months postpartum ...
07 Oct 2017
TL;DR: It was concluded that PTU treatment cannot alter absorption, distribution and elimination half time Na131I, but the accumulation in thyroid was decrease in A group to control.
Abstract: IN VIVO INTERACTION OF PROPYLTHIOURACIL WITH SODIUM IODIDE (Na 131 I) RADIOPHARMACEUTICAL IN RATS ( Rattus norvegicus ) . . The aim of this research is to determine the effect of propylthiouracil (PTU) treatment to pharmacokinetics interaction and biodistribution profile of Na 131 I radiopharmaceuticals. Three groups of animal model were used in this experiment, i.e. experimental animals which given PTU for 1 time (onset or A groups), PTU for six days (B Groups) and without treatment (control or C Groups). Pharmacokinetics and biodistribution test were conducted by giving PTU per oral and after 24 hours, continued by giving Na 131 I solution per oral. In pharmacokinetics test, percentage of injection dose/gram of blood (%ID/g) was calculated to determine the absorption, distribution and elimination half time. In biodistribution test, percentage of injection dose/gram of organs was calculated to determine the accumulation of Na 131 I in spesific organs. The results showed that the absorption half time of A, B and C groups were 3.14 ± 1.42, 2.49 ± 0.49 and 2.52 ± 0.7 hours, respectively. The distribution half time of A, B and C groups were 10.58 + 5.85, 12.92 + 3.75 and 11.42 + 3.15 hours, respectively. The elimination half time of A, B and C groups were 113.03 + 46.03, 96.57 + 47.76 and 196.71 + 145.21 hours, respectively. Biodistribution test results showed that the accumulation of Na 131 I in thyroid of A, B and C groups were 1.31 + 0.45, 5.03 + 0.55 and 4.45 + 2.24 % respectively. This research was concluded that PTU treatment cannot alter absorption, distribution and elimination half time Na 131 I, but the accumulation in thyroid was decrease in A group to control.
TL;DR: Both serum irisin and CK levels may be considered as parameters for diagnosis of both hypo-and hyperthyroidism in rats.
Abstract: Background: Thyroid dysfunction is one of the most common metabolic disorders that has not been dependent yet in its diagnosis on evaluation of serum levels of thyroid stimulating hormone (TSH), tri-iodothyronine (T3), thyroxine (T4). Other markers like serum irisin which is an adipo-myokine secreted by muscles during exercise, and serum creatine kinase (CK) which is a marker of muscle damage, show changes in their levels with hypo and hyperthyroidism in different species.
Objective: To evaluate the levels of both serum irisin and serum creatine kinase in hypo- and hyperthyroid rats, and to illustrate the relationship between their levels and thyroid function tests.
Methods: This study was performed on 30 adult healthy male local strain albino rats that were divided into three equal groups: Group I (Control " Euthyroid" group): Fed on commercial rat laboratory chow, Group II (Hypothyroid group): Hypothyroidism was induced by administration of propylthiouracil, and Group III ( Hyperthyroid group): Hyperthyroidism was induced by administration of T4. BMI in each group was calculated at the end of the experiment. Hormonal assay was performed to measure serum levels of TSH, FT3, FT4, insulin, glucose, irisin and CK.
Results: Serum irisin was negatively correlated with TSH levels, and positively correlated with FT3 and FT4 levels in both hypo-and hyperthyroid groups. However, serum CK was positively correlated with TSH levels and negatively correlated with FT3 and FT4 levels in both hypo-and hyperthyroid groups. Also, a negative correlation between serum irisin and serum CK was recorded in both cases of thyroid dysfunction.
Conclusions: Serum irisin level decreased in hypothyroid and increased in hyperthyroid rats. At the same time, serum CK level increased in hypothyroid and decreased in hyperthyroid rats. Both serum irisin and CK levels may be considered as parameters for diagnosis of both hypo-and hyperthyroidism in rats.
01 Feb 2017
01 Jan 2017
TL;DR: In hyperthyroidism patients, propylthiouracil and methimazole are the drugs of choice depending on fetal gestational age and more than half of patients with hypothyroidism will need to increase the dose of their replacement during pregnancy.
Abstract: Pregnancy results in increased thyroxine-binding globulin and increased thyroid-stimulating hormone receptor activation due to human chorionic gonadotropin. This results in increased secretion of thyroid hormones. In hyperthyroidism patients, propylthiouracil and methimazole are the drugs of choice depending on fetal gestational age. More than half of patients with hypothyroidism will need to increase the dose of their replacement during pregnancy. Thyroid storm is rare but life-threatening and should be managed in an intensive care unit [1].
TL;DR: Pregnant women with autoimmune hypothyroidism should ideally have their TSH concentrations measured before empirically increasing their levothyroxine dose, according to Thyroid guidelines.
Abstract: Background: Pregnancy strongly influences the thyroid gland and its function. Thyroid guidelines recommend a 30 to 50% increase of the preconceptional levothyroxine dose in women with hypothyroidism, when pregnancy is diagnosed.Case: A 33 year-old, 8-week pregnant woman with hypothyroidism, presents with a 2-week history of palpitations, sweating, nervousness and fatigue. Physical examination shows tachycardia (108 bpm), distal tremors and diffuse goiter. After biochemical confirmation of hyperthyroidism, her levothyroxine dose is reduced and finally interrupted. Propylthiouracil is started and maintained until after the delivery of a healthy baby at week 40. Two weeks postpartum, hyperthyroidism worsens and propylthiouracil is replaced by methimazole. Eighteen months after delivery 7.5 mCi 131Iodine was given. Two months later, hypothyroidism developed and levothyroxine was initiated.Conclusion: Although conversion of Hashimoto's hypothyroidism into Graves' disease is exceptional in pregnancy, pr...
DOI•
01 Jan 2017TL;DR: The case of a 62-year-old man with long-standing hyperthyroidism unresponsive to carbimazole, developing acute polymorphic psychotic disorder without symptoms of schizophrenia, after seven months of treatment with propylthiouracil is reported.
Abstract: Precipitation of acute psychosis following normalisation of thyroid status has been reported previously. Here, we report the case of a 62-year-old man with long-standing hyperthyroidism unresponsive to carbimazole, developing acute polymorphic psychotic disorder without symptoms of schizophrenia, along with normalization of thyroid status, after seven months of treatment with propylthiouracil.
TL;DR: I-131 therapy showed both appropriate effectiveness and safety in this case and may be considered as a suitable treatment alternative to thyroidectomy when antithyroid drugs are unsuccessful.
Abstract: Although radioiodine (131-I) can be used as treatment of hyperthyroidism for patients in hemodialysis, its use is limited and the experience is mainly related to differentiated thyroid carcinoma. We report a 58 years old female on hemodialysis with recurrent hyperthyroidism after propylthiouracil treatment. She was successfully treated with 131-I and four months after the intervention her euthyroid state was confirmed. We measured 131-I activity in blood, dialysate liquid and other waste products, as well as patient radiation exposure rates. We found that 131-I elimination was prolonged through time with no major dependence on hemodialysis, as opposed to the elimination of 131-I in patients with thyroid carcinoma. This was probably due to high radiotracer uptake in hyper functioning thyroid tissue. Conversely, radiation content in dialysate wastes or equipment was minimal. Furthermore, the rate of both environmental exposure and exposure of nursing staff in charge of hemodialysis sessions, was minimal and met international security standards. In conclusion, I-131 therapy showed both appropriate effectiveness and safety in this case and may be considered as a suitable treatment alternative to thyroidectomy when antithyroid drugs are unsuccessful.