Showing papers on "Propylthiouracil published in 2015"

Pregnancy outcome in women treated with methimazole or propylthiouracil during pregnancy.

Abstract: Control of thyroid function in hyperthyroid women during pregnancy is based on antithyroid drugs (ATD) [propylthiouracil (PTU) and methimazole (MMI)]. While a teratogenic effect has been suggested for MMI and, more recently, for PTU, a clear demonstration is still lacking. Aim of this study was to assess the safety of ATD during pregnancy. A total of 379 pregnancies were retrospectively recruited in eight Italian Departments of Endocrinology and divided in five groups: (1) MMI-treated and euthyroid throughout pregnancy (n = 89); (2) MMI-treated and hyperthyroid on at least two occasions (n = 35); (3) PTU-treated women and euthyroid throughout pregnancy (n = 32); (4) PTU-treated women and hyperthyroid on at least two occasions (n = 20); and (5) non-ATD-treated (n = 203). Data on maternal thyroid function, miscarriages, type of delivery, neonatal weight, length and TSH, perinatal complications and congenital malformation were analyzed. The gestational age at delivery, the rate of vaginal delivery, neonatal weight, length and neonatal TSH did not significantly differ among groups. In all groups, the rates of spontaneous miscarriage and of major congenital malformations were not higher than in the general population. No newborns were born with a phenotype similar to those described in the “MMI embryopathy”. While a clear demonstration of a teratogenic effect of MMI is currently lacking, it seems reasonable to follow the current guidelines and advice for PTU treatment in hyperthyroid women during the first trimester of pregnancy. Further, large and prospective worldwide studies will be needed to fully clarify the issue of ATD safety during pregnancy.

Therapeutic Potential of Date Palm Pollen for Testicular Dysfunction Induced by Thyroid Disorders in Male Rats.

Abstract: Hyper- or hypothyroidism can impair testicular function leading to infertility. The present study was designed to examine the protective effect of date palm pollen (DPP) extract on thyroid disorder-induced testicular dysfunction. Rats were divided into six groups. Group I was normal control. Group II received oral DPP extract (150 mg kg-1), group III (hyperthyroid group) received intraperitoneal injection of L-thyroxine (L-T4, 300μg kg-1; i.p.), group IV received L-T4 plus DPP extract, group V (hypothyroid group) received propylthiouracil (PTU, 10 mg kg-1; i.p.) and group VI received PTU plus DPP extract. All treatments were given every day for 56 days. L-T4 or PTU lowered genital sex organs weight, sperm count and motility, serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone (T), testicular function markers and activities of testicular 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD). Moreover, L-T4 or PTU increased estradiol (E2) serum level, testicular oxidative stress, DNA damage and apoptotic markers. Morphometric and histopathologic studies backed these observations. Treatment with DPP extract prevented LT4- or PTU induced changes. In addition, supplementation of DPP extract to normal rats augmented sperm count and motility, serum levels of LH, T and E2 paralleled with increased activities of 3β-HSD and 17β-HSD as well as testicular antioxidant status. These results provide evidence that DPP extract may have potential protective effects on testicular dysfunction induced by altered thyroid hormones.

Substituting potassium iodide for methimazole as the treatment for graves' disease during the first trimester may reduce the incidence of congenital anomalies: A retrospective study at a single medical institution in Japan

Abstract: Background: To control hyperthyroidism due to Graves' disease, antithyroid drugs should be administered. Several studies have shown that exposure to methimazole (MMI) during the first trimester of pregnancy increases the incidence of specific congenital anomalies that are collectively referred to as MMI embryopathy. Congenital anomalies associated with exposure to propylthiouracil (PTU) have also recently been reported. Methods: This study investigated whether substituting potassium iodide (KI) for MMI in the first trimester would result in a lower incidence of major congenital anomalies than continuing treatment with MMI alone. The cases of 283 women with Graves' disease (GD) were reviewed whose treatment was switched from MMI to KI in the first trimester (iodine group), as well as the cases of 1333 patients treated with MMI alone (MMI group) for comparison. Another major outcome of interest was the incidence of neonatal thyroid dysfunction. The subjects of the analysis of major congenital anomalies and ...

Hyperthyroidism in Children

Abstract: On the basis of strong research evidence, hyperthyroidism is a rare but potentially serious disorder in childhood that, if uncontrolled, can lead to a wide range of complications, including effects on growth and development. • On the basis of strong research evidence, Graves' disease is the most common cause of hyperthyroidism in children, accounting for greater than 95% of cases. It is caused by stimulating antibodies to the thyroid-stimulating hormone receptor. • On the basis of some research evidence and consensus, history, physical examination, and thyroid function tests help diagnose hyperthyroidism. The condition is characterized by suppressed serum thyrotropin and elevated serum triiodothyronine and thyroxine. Radioactive iodine (or technetium-99) uptake and serum thyroid antibody measurements help determine the cause of hyperthyroidism. • On the basis of some research evidence and consensus, treatment options for Graves' disease in children include antithyroid medications, radioactive iodine, and surgery. Antithyroid medications are commonly used as the first-line therapy in children. However, because of the low rates of spontaneous remission, most children eventually require permanent treatment with radioactive iodine or surgery. Of the available antithyroid medications, current guidelines recommend use of methimazole and not propylthiouracil because of the unacceptable risk of hepatotoxicity associated with propylthiouracil. • On the basis of strong research evidence, thyroid storm is a rare life-threatening endocrine emergency that should be suspected in children with hyperthyroidism who demonstrate evidence of systemic decompensation. • On the basis of strong research evidence, neonatal hyperthyroidism can occur in infants born to mothers with a history of Graves' disease due to transplacental passage of TSH receptor stimulating antibodies.

Antithyroid Drug Use in Pregnancy and Birth Defects: Why Some Studies Find Clear Associations, and Some Studies Report None

Abstract: Background: Rare cases of birth defects after the use of methimazole (MMI) or carbimazole to treat hyperthyroidism in early pregnancy have been reported since 1972, whereas propylthiouracil (PTU) has not been considered teratogenic. Recently, two studies reported birth defects after the use of MMI in early pregnancy to affect 2–4% of exposed children, and one study also found birth defects after the use of PTU. On the other hand, some published studies did not find associations between the use of thionamides and birth defects. Summary: The methods used in the two positive and the four negative reports are reviewed. The two positive studies included a sufficient number of children exposed to MMI (n = 1231 and 1097) to evaluate the studied outcomes, whereas the four negative studies included a much lower number of exposed children (n = 73, 108, 30, and 124). Considering PTU, the birth defects observed in one study were in general milder and tended to be diagnosed and registered only when they resulted in co...

Effects of thyroxine and donepezil on hippocampal acetylcholine content, acetylcholinesterase activity, synaptotagmin-1 and SNAP-25 expression in hypothyroid adult rats

Abstract: A growing number of studies have revealed that neurocognitive impairment, induced by adult-onset hypothyroidism, may not be fully restored by traditional hormone substitution therapies, including thyroxine (T4). The present study has investigated the effect of T4 and donepezil (DON; an acetylcholinesterase (AChE) inhibitor) treatment on the hypothyroidism-induced alterations of acetylcholine (ACh) content and AChE activity. Furthermore, we examined synaptotagmin-1 (syt-1) and SNAP-25 expression in the hippocampus of adult rats. Adding 0.05% propylthiouracil to their drinking water for five weeks induced hypothyroidism in the rat models. From the fourth week, the rats were treated with T4, DON or a combination of both. Concentration of ACh and the activity of AChE was determined colorimetrically. The results demonstrated that hypothyroidism induced a significant decrease of Ach content and AChE activity (by 17 and 34%, respectively), which were restored to control values by T4 administration. DON treatment also restored Ach to the normal level. Protein levels of syt-1 and SNAP-25 were determined by immunohistochemistry. The results demonstrated that syt-1 was expressed at significantly lower levels in hypothyroid rats, while SNAP-25 levels were notably higher compared with the controls. Two-week treatment with T4 alone failed to normalize the expression levels of these two proteins, while co-administration of T4 and DON was able to induce this effect. These data suggested that the thyroid hormone, T4, may have a direct effect on the metabolism of hippocampal ACh in adult rats, and that the DON treatment may facilitate the recovery of synaptic protein impairments induced by hypothyroidism.

MiR-124 effect in neurons apoptosis in newborn rat with thyroid hypofunction.

Abstract: Congenital thyroid hypofunction can cause a variety of developmental disorders. Hippocampus is an important structure participating in the cognitive activities. Neural function damage is able to induce hippocampal neuron apoptosis. As a miRNA expressed specifically and abundantly in brain tissue, miR-124 has protective effect to neuron apoptosis caused by cerebral apoplexy. However, its role in neuron apoptosis caused by thyroid hypofunction is still unclear. The rats were divided into four groups including normal group, thyroid hypofunction group, miR-124 negative control group, and miR-124 mimics group. Propylthiouracil (50 mg/d) was injected to the stomach to the rats with 15 d pregnancy till the newborn rats were born. Inducing the thyroid hypofunction rat model and then injecting miR-124 mimics to ventricle. Serum TSH, FT3 and FT4 were detected to confirm the model. Immunohistochemistry was carried out to calculate neuron number. Tunel assay was used to detect neuron apoptosis. Western blot was applied to detect apoptosis related protein Caspase-3, Bcl-2 and Bax expression. After brain injection miR-124 mimics, hippocampal neuron number and morphology both improved in 15 d newborn mice compared with thyroid hypofunction group. Tunel staining found positive neurons reduced, which indicated that miR-124 can inhibit hippocampal neuron apoptosis in thyroid hypofunction rats. Further Western blot results revealed that apoptosis inhibition might be related to down-regulating activated Caspase-3 and Bax levels, and up-regulating tumor-suppressor gene Bcl-2 expression. MiR-124 can protect neuron apoptosis in thyroid hypofunction rat.

Anti-thyroid drugs in pediatric Graves' disease.

Abstract: Graves' disease is the most common cause of hyperthyroidism in children. Most children and adolescents are treated with anti-thyroid drugs as the initial modality. Studies have used Methimazole, Carbimazole and Propylthiouracil (PTU) either as titration regimes or as block and replacement regimes. The various studies of anti-thyroid drug (ATD) treatment of Graves' disease in pediatric patients differ in terms of the regimes, remission rate, duration of therapy for adequate remission, follow up and adverse effects of ATD. Various studies show that lower thyroid hormone levels, prolonged duration of treatment, lower levels of TSH receptor antibodies, smaller goiter and increased age of child predicted higher chance of remission after ATD. A variable number of patients experience minor and major adverse effects limiting initial and long term treatment with ATD. The adverse effects of various ATD seem to more in children compared to that of adults. In view of liver injury including hepatocellular failure need of liver transplantation associated with PTU, the use has been restricted in children. The rate of persistent remission with ATD following discontinuation is about 30%. Radioactive iodine therapy is gaining more acceptance in older children with Graves's disease in view of the limitations of ATD. For individual patients, risk-benefit ratio of ATD should be weighed against benefits of radioactive iodine therapy and patient preferences.

Propylthiouracil-Induced Liver Injury in Mice and the Protective Role

Abstract: A B S T R A C T Background: Propylthiouracil (PTU) is a thionamide drug used in the management of hyperthyroidism in human. On the other hands, several cases of hepatotoxicity, hepatic failure and even death have been reported after PTU administration. No specific protective agent has been developed against this complication yet. Taurine is a sulfur containing amino acid which its beneficial effects in liver tissue has been reported in previous studies. This study was designed to investigate the effect of taurine on PTU-induced liver injury. Methods: Mice received PTU (100 mg/kg, oral) and different doses of taurine (250, 500 and 1000 mg/kg, i.p, administered 2 hours after PTU) and markers of liver injury were monitored. Results: Acute exposure to PTU caused hepatotoxicity in mice as evidenced by increase in plasmatic alanine aminotransferase (ALT), occurrence of significant lipid peroxidation, and hepatic glutathione depletion. The mentioned changes were endorsed by histopathological lesions of liver which were mainly manifested as pre-portal inflammation. Taurine administration (500 and 1000 mg/kg, i.p) resulted in reduction of lipid peroxidation, showed rebalancing effect on liver GSH level, and normalized plasma ALT. Taurine administration didn't affect PTU-induced inflammatory cell aggregation in liver. Conclusion: In view of these results, taurine seems to exert some beneficial effects against PTU-induced liver injury. A r t i c l e i n f o

Comparison of potential protective effects of melatonin and propylthiouracil against lipid peroxidation caused by nitrobenzene in the thyroid gland.

Abstract: Background:Nitrobenzene is a carcinogen, which induces—among others—thyroid tumors. Melatonin is an effective antioxidant, whereas some antioxidative effects of propylthiouracil (PTU; an antithyroi...

Propylthiouracil-Induced Liver Injury in Mice and the Protective Role of Taurine

Abstract: Propylthiouracil (PTU) is a thionamide drug used in the management of hyperthyroidism in human. On the other hands, several cases of hepatotoxicity, hepatic failure and even death have been reported after PTU administration. No specific protective agent has been developed against this complication yet. Taurine is a sulfur containing amino acid which its beneficial effects in liver tissue has been reported in previous studies. This study was designed to investigate the effect of taurine on PTU‑induced liver injury. Methods: Mice received PTU (100 mg/kg, oral) and different doses of taurine (250, 500 and 1000 mg/kg, i.p, administered 2 hours after PTU) and markers of liver injury were monitored. Results: Acute exposure to PTU caused hepatotoxicity in mice as evidenced by increase in plasmatic alanine aminotransferase (ALT), occurrence of significant lipid peroxidation, and hepatic glutathione depletion. The mentioned changes were endorsed by histopathological lesions of liver which were mainly manifested as pre-portal inflammation. Taurine administration (500 and 1000 mg/kg, i.p) resulted in reduction of lipid peroxidation, showed rebalancing effect on liver GSH level, and normalized plasma ALT. Taurine administration didn’t affect PTU-induced inflammatory cell aggregation in liver. Conclusion: In view of these results, taurine seems to exert some beneficial effects against PTU‑induced liver injury.

Sickness behavior is delayed in hypothyroid mice.

Abstract: Sickness behavior is an expression of a motivational state triggered by activation of the peripheral innate immune system, whereby an organism reprioritizes its functions to fight infection. The relationship between thyroid hormone and immune cells is complex, and additional insights are needed about the involvement of the cross-talk between thyroid hormone, the central nervous system and immune function, as demonstrated by the consequences to sickness behavior. The aim of this work was to evaluate sickness behavior in hypothyroid mice. Control mice and mice treated with propylthiouracil (PTU) for 30 days (0.05%; added to drinking water) received a single dose of LPS (200 μg/kg; i.p.) or saline, and the behavioral response was assessed for 24 h. We provide evidence that thyroid status acts a modulator for the development of depressive-like and exploratory behaviors in mice that are subjected to an immunological challenge because the PTU pretreatment delayed the LPS-induced behavioral changes observed in an open field test and in a forced swimming test. This response was observed concomitantly with a lower thermal index until 4 h after the LPS administration. This result demonstrates that thyroid status modifies behavioral responses to immune challenge and suggests that thyroid hormones are essential for the manifestation of sickness behavior during endotoxemia.

Antineutrophilic Cytoplasmic Antibody Positive Vasculitis Associated with Methimazole Use.

Abstract: ANCA-associated vasculitis (AAV) is a rare and potentially life threatening complication associated with antithyroid drug use. It is more commonly reported with propylthiouracil, with fewer cases reported with methimazole use. We present the case of a 55-year-old man with toxic multinodular goiter which was treated with methimazole for 6 months. He developed ANCA positive leukocytoclastic vasculitis with hemorrhagic and necrotic bullous lesions of lower extremities. The vasculitis was initially thought to be secondary to recent cephalosporin use; however, the skin lesions progressed despite stopping the cephalosporin and treatment with steroids, and he developed osteomyelitis. His vasculitis resolved after cessation of methimazole use. This case highlights the importance of careful monitoring for variable manifestations of AAV in patients treated with methimazole.

Influence of hypothyroidism on oxidative stress, c-Fos expression, cell cycle, and apoptosis in rats testes

Abstract: The molecular basis of male reproduction for cross-regulation between androgen and thyroid hormone axes is still rudimentary. This study aims to define a possible mechanism of hypothyroidism-induced reproductive influence with respect to sex hormone, mineral, sperm motility, oxidative stress, c-Fos expression, cell cycle, and apoptosis in rat testes. The Wistar rats were randomly divided into control group (NS) and hypothyroidism group [1 ml/100g BW/day, 0.1% propylthiouracil (PTU)] by intragastric gavage for 60 days. Blood samples were collected to measure the serum levels. The epididymis was excised to measure sperm motility and testes were excised to measure mineral, oxidative stress, c-Fos expression, cell cycle, and apoptosis. After 60 days, body weight, relative testes weight, triiodothyronine, and total thyroxine were all significantly decreased, whereas thyroid stimulating hormone was increased in the hypothyroidism group. A significant increase in sex hormone level of estradiol (E2) and significa...

Liver dysfunction and anti-thyroid therapy.

Abstract: Thioamides have been used in the management of hyperthyroidism for over 50 years. Liver dysfunction is a rare but important side effect associated with their use. Recently, cases of liver failure associated with propylthiouracil have prompted the Federal Drug Administration to issue a Boxed Warning to the label of propylthiouracil regarding its risk of potentially fatal liver injury and acute liver failure in adults and children. Herein, we present a case to underline the importance of recognising the similar potential for severe hepatic dysfunction with the use of other thioamides.

Thyroid Hormone and Estrogen Regulate Exercise-Induced Growth Hormone Release

Abstract: Growth hormone (GH) regulates whole body metabolism, and physical exercise is the most potent stimulus to induce its secretion in humans. The mechanisms underlying GH secretion after exercise remain to be defined. The aim of this study was to elucidate the role of estrogen and pituitary type 1 deiodinase (D1) activation on exercise-induced GH secretion. Ten days after bilateral ovariectomy, animals were submitted to 20 min of treadmill exercise at 75% of maximum aerobic capacity and tissues were harvested immediately or 30 min after exercise. Non-exercised animals were used as controls. A significant increase in D1 activity occurred immediately after exercise (~60%) in sham-operated animals and GH was higher (~6-fold) 30 min after exercise. Estrogen deficient rats exhibited basal levels of GH and D1 activity comparable to those found in control rats. However, after exercise both D1 activity and serum GH levels were blunted compared to sedentary rats. To understand the potential cause-effect of D1 activation in exercise-induced GH release, we pharmacologically blocked D1 activity by propylthiouracil (PTU) injection into intact rats and submitted them to the acute exercise session. D1 inhibition blocked exercise-induced GH secretion, although basal levels were unaltered. In conclusion, estrogen deficiency impairs the induction of thyroid hormone activating enzyme D1 in the pituitary, and GH release by acute exercise. Also, acute D1 activation is essential for exercise-induced GH response.

Graves'-Basedow disease in pregnancy. New trends in the management and guidance to reduce the risk of birth defects caused by antithyroid drugs.

Abstract: Thyroid hormones are essential development factors and maternal thyroid dysfunction may cause pregnancy complications and diseases in the fetus/child. In the present review we discuss new data on the incidence of Graves’-Basedow disease (GBD) in and around pregnancy, and how hyperthyroidism may affect the risk of spontaneous abortion and stillbirth. A special concern in pregnant women is the potential side effects from the use of antithyroid drugs (ATDs). One type of side effects is the allergic/toxic reactions to the drugs, which seem to be similar in and outside pregnancy, and another is that ATDs tend to over treat the fetus when the mother with GBD is made euthyroid. To avoid fetal hypothyroidism, the lowest possible ATD dose should be used to keep maternal thyroid function at the upper limit of normality with low serum TSH. Birth defects after the use of methimazole (MMI) (or its prodrug carbimazole) have been considered to be very rare, and no risk has previously been associated with the use of propylthiouracil (PTU). However, a recent Danish national study found that 1/30 of children exposed to MMI in early pregnancy had birth defects associated with this, and many defects were severe. PTU exposure was associated with defects in 1/40, and these defects were less severe. Proposals are given on how to reduce the risk of ATD associated birth defects.

A case of thyroid storm complicated by acute hepatitis due to propylthiouracil treatment

Abstract: A 57-year-old female presented 17 days after treatment with radioactive iodine (RAI) for difficult-to-control hyperthyroidism. She was febrile, had a sinus tachycardia, and was clinically thyrotoxic. Her thyroid function tests showed a suppressed TSH 75 pmol/l and total triiodothyronine (TT3) 6.0 nmol/l. She was diagnosed with thyroid storm and was managed with i.v. fluids, propylthiouracil (PTU) 200 mg four times a day, prednisolone 30 mg once daily and propanolol 10 mg three times a day. She gradually improved over 2 weeks and was discharged home on PTU with β blockade. On clinic review 10 days later, it was noted that, although she was starting to feel better, she had grossly abnormal liver function (alanine transaminase (ALT) 852 U/l, bilirubin 46 μmol/l, alkaline phosphatase (ALP) 303 U/l, international normalized ratio (INR) 0.9, platelets 195×109/l). She was still mildly thyrotoxic (TSH <0.02 mU/l, FT4 31 pmol/l, TT3 1.3 nmol/l). She was diagnosed with acute hepatitis secondary to treatment with PTU. Ultrasound showed mild hepatic steatosis. PTU was stopped and she was managed with fluids and prednisolone 60 mg once daily and continued β blockade. Her liver function gradually improved over 10 days (bilirubin 9 μmol/l, ALT 164 U/l, ALP 195 U/l, INR 0.9, platelets 323×109/l) with conservative management and had normalised by clinic review 3 weeks later. This case highlights the potentially fatal, but rare, complications associated with both RAI and PTU, namely, thyroid storm and acute hepatitis respectively. Learning points Thyroid storm is an important, albeit rare, endocrinological emergency. Thyroid storm following RAI treatment is extremely rare. Management is with i.v. fluids, β blockade, anti-thyroid drugs and steroids. High dose glucocorticoid steroids can block the peripheral conversion of T4 to active T3. Liver dysfunction, acute hepatitis and potential hepatic failure are significant adverse drug reactions known to occur with PTU treatment. Supervising clinicians should be vigilant for evidence of this developing and intervene accordingly. Clinicians need to be aware of possible interactions between regular paracetamol use and PTU in predisposing to liver impairment.

Rapid Preoperative Preparation for Thyroidectomy of a Severely Hyperthyroid Patient with Graves’ Disease who Developed Agranulocytosis

Abstract: Preoperative preparation of the hyperthyroid patient for thyroidectomy is imperative to avoid perioperative complications due to severe thyrotoxicosis. The mainstay of preparation is the administration of anti-thyroid drugs (ATD). When ATDs cause adverse reactions, an alternative regimen to prepare the patient for definitive management is crucial. We present the case of a 35-year-old Filipino female with Graves’ disease who developed methimazole-induced agranulocytosis. She refused to undergo radioactive iodine (RAI) therapy. She was admitted for thyroidectomy with elevated thyroid hormone levels. She was rapidly prepared for thyroidectomy using high-dose steroid, beta-adrenergic blocker, propylthiouracil (PTU) and Lugol’s solution. The patient’s free thyroxine level decreased after 8 days of treatment, without complications. She then underwent an uneventful subtotal thyroidectomy. In conditions with very limited options, although contraindicated, administration of another ATD may be the last alternative for patients who developed agranulocytosis.

Graves-Basedow-Krankheit in der Schwangerschaft

Abstract: Thyroid hormones are essential development factors and maternal thyroid dysfunction may cause pregnancy complications and diseases in the fetus/child. In the present review we discuss new data on the incidence of Graves’-Basedow disease (GBD) in and around pregnancy, and how hyperthyroidism may affect the risk of spontaneous abortion and stillbirth. A special concern in pregnant women is the potential side effects from the use of antithyroid drugs (ATDs). One type of side effects is the allergic/toxic reactions to the drugs, which seem to be similar in and outside pregnancy, and another is that ATDs tend to over treat the fetus when the mother with GBD is made euthyroid. To avoid fetal hypothyroidism, the lowest possible ATD dose should be used to keep maternal thyroid function at the upper limit of normality with low serum TSH. Birth defects after the use of methimazole (MMI) (or its prodrug carbimazole) have been considered to be very rare, and no risk has previously been associated with the use of propylthiouracil (PTU). However, a recent Danish national study found that 1/30 of children exposed to MMI in early pregnancy had birth defects associated with this, and many defects were severe. PTU exposure was associated with defects in 1/40, and these defects were less severe. Proposals are given on how to reduce the risk of ATD associated birth defects.

Effects of propylthiouracil-induced hypothyroidism on nonalcoholic fatty liver disease in rats fed a high-fat and high-cholesterol diet.

Abstract: Received: Revised: Accepted: February 27, 2014 April 21, 2014 May 09, 2014 Nonalcoholic fatty liver disease (NAFLD) is a common liver disease that manifests as a wide range of pathological conditions ranging from fat accumulation to inflammation, fibrosis and finally cirrhosis. Recently, it suggested that hypothyroidism is closely associated with NAFLD. In addition, 11.7% of hepatocellular carcinoma (HCC) patients were shown to have hypothyroidism. In this study, Wistar rats were fed different high-fat diets (with or without propylthiouracil) and allowed to develop NAFLD. At the end of the experiments, the serum and liver were collected for the analysis of lipid and cholesterol metabolism parameters. Our results showed that the hypothyroid rats had a fleshless body, significantly higher concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) in the serum and an increased serum alanine transaminase (ALT) level. In addition, the concentration of serum triglycerides and the expression of ApoB100, MTP, SREBP-2 and ABCA1 in the hypothyroid rats showed fluctuating patterns similar to that of liver triglycerides. This finding suggested that propylthiouracil-induced hypothyroidism plays an important role in progressive NAFLD. ©2014 PVJ. All rights reserved

Hypothyroidism Exacerbates Thrombophilia in Female Rats Fed with a High Fat Diet

Abstract: Clotting abnormalities are discussed both in the context with thyroid dysfunctions and obesity caused by a high fat diet. This study aimed to investigate the impact of hypo-, or hyperthyroidism on the endogenous thrombin potential (ETP), a master indicator of clotting activation, on Sprague Dawley rats fed a normal or high fat diet. Female Sprague Dawley rats (n = 66) were grouped into normal diet (ND; n = 30) and high-fat diet (HFD; n = 36) groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3) treatment, respectively. After 12 weeks of treatment ETP, body weight and food intake were analyzed. Successfully induced thyroid dysfunction was shown by T3 levels, both under normal and high fat diet. Thyroid dysfunction was accompanied by changes in calorie intake and body weight. In detail, compared to euthyroid controls, hypothyroid rats showed significantly increased—and hyperthyroid animals significantly decreased—ETP levels. High fat diet potentiated these effects in both directions. In summary, we are the first to show that hypothyroidism and high fat diet potentiate the thrombotic capacity of the clotting system in Sprague Dawley rats. This effect may be relevant for cardiovascular disease where thyroid function is poorly understood as a pathological contributor in the context of clotting activity and obesogenic nutrition.

Oxidized LDL Is Strictly Limited to Hyperthyroidism Irrespective of Fat Feeding in Female Sprague Dawley Rats

Abstract: Metabolic dysfunctions might play a crucial role in the pathophysiology of thyroid dysfunctions. This study aimed to investigate the impact of a controlled diet (normal versus high fat feeding) on hypothyroid and hyperthyroid Sprague Dawley rats. Female Sprague Dawley rats (n = 66) were grouped into normal diet (n = 30) and high-fat diet (n = 36) groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3) treatment, respectively. After 12 weeks of treatment metabolic parameters, such as oxidized LDL (oxLDL), malondialdehyde (MDA), 4-hydroxynonenal (HNE), the lipid profile, body weight and food intake parameters were analyzed. Successfully induced thyroid dysfunctions were shown by T3 levels, both under normal and high fat diet. Thyroid dysfunctions were accompanied by changes in calorie intake and body weight as well as in the lipid profile. In detail, hypothyroid rats showed significantly decreased oxLDL levels, whereas hyperthyroid rats showed significantly increased oxLDL levels. These effects were seen under high fat diet and were less pronounced with normal feeding. Taken together, we showed for the first time in female SD rats that only hyper-, but not hypothyroidism, is associated with high atherogenic oxidized LDL irrespective of normal or high-fat diet in Sprague Dawley rats.

Effect of Different Conditions of Thyroid Function on Serum Adiponectin, Visfatin and Vaspin Levels in Rats

Abstract: Adipocytokines are a variety of active biological substances secreted by adipose tissue. These substances have a pivotal role in control of metabolism, appetite, thermogenesis, thyroid and reproductive functions. Endocrine disorders were reported to affect their secretion and function. Abnormal levels of adipocytokines in hypo- and hyperthyroidism have been reported with controversial results. Therefore, this study was designed to demonstrate the effect of experimental hypo and hyperthyroidism on adiponectin, visfatin and vaspin levels in rats. Design: This study was performed on 45 adult male albino rats divided into 3 equal groups: Control (Group I), Hypothyroid (Group II) and Hyperthyroid (Group III) groups. Hypothyroidism was induced by propylthiouracil administration (0.05% in drinking water) for 3 weeks. Hyperthyroidism was inducted by L-thyroxine administration (250 µg/kg) subcutaneously for 2 weeks, while untreated animals served as controls. Results: The mean values for visfatin and vaspin were found to be significantly increased (P< 0.001) while Adiponectin was non-significantly changed in group II (Hypothyroid Group) when compared with group I (Euthyroid Group). In-group III (Hyperthyroid group), the mean values of adiponctin were found to be significantly increased (P< 0.001). While visfatin and vaspin were significantly decreased (P< 0.001) when compared with their respective values of group I and group II. Serum levels of adiponectin and visfatin were found to have significant positive correlation with serum levels of T3 and T4 and significant negative correlation with serum levels of TSH in all groups. However, serum levels of vaspin were found to have significant negative correlation with serum levels of T3 and T4 and significant positive correlation with serum levels of TSH in all groups. Conclusion: The results of this study suggest that adipokines can be affected by thyroid hormone disorders, so changes in the production of adipokines that accompany thyroid dysfunction may represent adaptive mechanisms to the changes in basal energy expenditure and in energy substrate requirements in thyroid disorders.

Pancytopenia in the first trimester: An indicator of hidden hyperthyroidism.

Abstract: Pancytopenia in the first trimester is very rare. A 33-year-old multiparous woman presented with nausea, loss of appetite, and bodyweight loss of 7.4 kg at 9(1/7) weeks of gestation due to hyperemesis gravidarum. Her laboratory data demonstrated pancytopenia involving white blood cell count of 3500/μL, a hemoglobin level of 9.8 g/dL, and a platelet count of 10.5 × 10(4)/μL. An extensive investigation into the causes of the pancytopenia detected true hyperthyroidism: thyroid-stimulating hormone, <0.02 μU/mL; free triiodothyronine, 11.25 pg/mL; free thyroxine, 4.74 ng/dL; and anti-thyroid-stimulating hormone receptor antibodies, 12.2 IU/L. Propylthiouracil was started at a dose of 300 mg/day at 10(5/7) weeks of gestation, which resulted in the normalization of her blood parameters and concomitant improvements in her free triiodothyronine and free thyroxine levels at 12(0/7) weeks of gestation. Pancytopenia in the first trimester might be indicative of hidden hyperthyroidism.