Showing papers on "Propylthiouracil published in 2016"

Antithyroid Drug Side Effects in the Population and in Pregnancy

Abstract: Objective: Methimazole (MMI) and propylthiouracil (PTU) are both associated with birth defects and may also rarely be associated with agranulocytosis and liver failure. The frequency of these side effects when antithyroid drugs (ATDs) are used in the population in general or in pregnancy remains to be elucidated. Design: All individuals registered as the parent of a live-born child in Denmark, 1973–2008, were identified (n = 2 299 952) and studied from 1995 through 2010 for the use of ATDs. Outcomes were agranulocytosis, liver failure, and birth defects in their offspring. To evaluate the frequency of these side effects associated with the use of ATDs in pregnancy, all live-born pregnancies (n = 830 680), 1996–2008, were identified in a subanalysis. Results: In the population studied, 28 998 individuals redeemed prescriptions of ATDs (exposure in 2115 pregnancies), which was associated with 45 cases of agranulocytosis (one in pregnancy) and 10 cases of liver failure (one in pregnancy). This corresponded t...

HLA-B*38:02:01 predicts carbimazole/methimazole-induced agranulocytosis.

Abstract: Thioamides antithyroid-drugs (ATDs) are important in hyperthyroid disease management. Identification of the susceptibility locus of ATD-induced agranulocytosis is important for clinical management. We performed a genome-wide association study (GWAS) involving 20 patients with ATD-induced agranulocytosis and 775 healthy controls. The top finding was further replicated. A single-nucleotide polymorphism (SNP), rs185386680, showed the strongest association with ATD-induced agranulocytosis in GWAS (odds ratio (OR) = 36.4; 95% confidence interval (CI) = 12.8-103.7; P = 1.3 × 10(-24)) and replication (OR = 37; 95% CI = 3.7-367.4; P = 9.6 × 10(-7)). HLA-B*38:02:01 was in complete linkage disequilibrium with rs185386680. High-resolution HLA typing confirmed that HLA-B*38:02:01 was associated with carbimazole (CMZ)/methimazole (MMI)-induced agranulocytosis (OR = 265.5; 95% CI = 27.9-2528.0; P = 2.5 × 10(-14)), but not associated with propylthiouracil (PTU). The positive and negative predictive values of HLA-B*38:02:01 in predicting CMZ/MMI-induced agranulocytosis were 0.07 and 0.999. Approximately 211 cases need to be screened to prevent one case. Screening for the risk allele will be useful in preventing agranulocytosis in populations in which the frequency of the risk allele is high.

Hyperthyroidism: Diagnosis and Treatment

Abstract: Hyperthyroidism is an excessive concentration of thyroid hormones in tissues caused by increased synthesis of thyroid hormones, excessive release of preformed thyroid hormones, or an endogenous or exogenous extrathyroidal source. The most common causes of an excessive production of thyroid hormones are Graves disease, toxic multinodular goiter, and toxic adenoma. The most common cause of an excessive passive release of thyroid hormones is painless (silent) thyroiditis, although its clinical presentation is the same as with other causes. Hyperthyroidism caused by overproduction of thyroid hormones can be treated with antithyroid medications (methimazole and propylthiouracil), radioactive iodine ablation of the thyroid gland, or surgical thyroidectomy. Radioactive iodine ablation is the most widely used treatment in the United States. The choice of treatment depends on the underlying diagnosis, the presence of contraindications to a particular treatment modality, the severity of hyperthyroidism, and the patient's preference.

Characteristics of Antithyroid Drug–Induced Agranulocytosis in Patients with Hyperthyroidism: A Retrospective Analysis of 114 Cases in a Single Institution in China Involving 9690 Patients Referred for Radioiodine Treatment Over 15 Years

Abstract: Background: Antithyroid drug (ATD)–induced agranulocytosis is a rare but life-threatening disease. Clinical features of ATD-induced agranulocytosis and outcomes remain incompletely understood. Method: Patients with clinically diagnosed ATD-induced agranulocytosis were retrospectively studied, involving 9690 patients who were referred for radioiodine treatment during a 15-year period (2000–2015) in China. There were 114 cases of agranulocytosis attributable to ATD included, and their clinical characteristics and therapy outcomes were analyzed. Results: The female-to-male ratio of ATD-induced agranulocytosis was 10.4:1. The mean age (±standard deviation) of the patients with ATD-induced agranulocytosis was 41.7 ± 12.3 years. The methimazole and propylthiouracil doses given at the onset were 22.9 ± 8.0 mg/day and 253.6 ± 177.5 mg/day, respectively. ATD-induced agranulocytosis occurred in 45.1%, 74.3%, and 88.5% of patients within 4, 8, and 12 weeks of the onset of ATD therapy, respectively. Fever (78.9%) and...

Endocrinology in Pregnancy: Pregnancy and the incidence, diagnosing and therapy of Graves' disease

Abstract: Thyroid hormones are essential developmental factors, and Graves' disease (GD) may severely complicate a pregnancy. This review describes how pregnancy changes the risk of developing GD, how early pregnancy by several mechanisms leads to considerable changes in the results of the thyroid function tests used to diagnose hyperthyroidism, and how these changes may complicate the diagnosing of GD. Standard therapy of GD in pregnancy is anti-thyroid drugs. However, new studies have shown considerable risk of birth defects if these drugs are used in specific weeks of early pregnancy, and this should be taken into consideration when planning therapy and control of women who may in the future become pregnant. Early pregnancy is a period of major focus in GD, where pregnancy should be diagnosed as soon as possible, and where important and instant change in therapy may be warranted. Such change may be an immediate stop of anti-thyroid drug therapy in patients with a low risk of rapid relapse of hyperthyroidism, or it may be an immediate shift from methimazole/carbimazole (with risk of severe birth defects) to propylthiouracil (with less risk), or maybe to other types of therapy where no risk of birth defects have been observed. In the second half of pregnancy, an important concern is that not only the mother with GD but also her foetus should have normal thyroid function.

Effect of Hypothyroidism and Hyperthyroidism on Tissue Thyroid Hormone Concentrations in Rat

Abstract: Background and Objective: The present study was aimed at determining the effects of experimental hypothyroidism and hyperthyroidism on tissue thyroid hormones by a mass spectrometry-based technique. Methods: Rats were subjected to propylthiouracil treatment or administration of exogenous triiodothyronine (T3) or thyroxine (T4). Tissue T3 and T4 were measured by liquid chromatography tandem mass spectrometry in the heart, liver, kidney, visceral and subcutaneous adipose tissue, and brain. Results: Baseline tissue T3 and T4 concentrations ranged from 0.2 to 20 pmol ∙ g-1 and from 3 to 125 pmol ∙ g-1, respectively, with the highest values in the liver and kidney, and the lowest values in the adipose tissue. The T3/T4 ratio (expressed as a percentage) was in the 7-20% range in all tissues except the brain, where it averaged 75%. In hypothyroidism, tissue T3 was more severely reduced than serum free T3, averaging 1-6% of the baseline versus 30% of the baseline. The extent of tissue T3 reduction, expressed as percentage of the baseline, was not homogeneous (p brain > heart > adipose tissue. The tissue T3/T4 ratio significantly increased in all organs except the kidney, averaging 330% in the brain and 50-90% in the other tissues. By contrast, exogenous T3 and T4 administration produced similar increases in serum free T3 and in tissue T3, and the relative changes were not significantly different between different tissues. Conclusions: While the response to increased thyroid hormones availability was similar in all tissues, decreased thyroid hormone availability induced compensatory responses, leading to a significant mismatch between changes in serum and in specific tissues.

Therapeutic Effects of Blue Honeysuckle on Lesions of Hyperthyroidism in Rats

Abstract: Hyperthyroidism is a hypermetabolic syndrome characterized by an overproduction of thyroid hormones, which enhances the hormone-induced oxidative stress responsible for some complications in the liver, heart and muscle Blue honeysuckle (BH) is an edible berry, rich in polyphenols, especially flavonoids or anthocyanins, known as strong antioxidants The chemo-protective activities of the berry have been connected to the improvement of symptoms in cancer, diabetes mellitus, tumor or cardiovascular diseases Therefore, the therapeutic effects of BH were examined in hyperthyroidism rat model The hyperthyroidism was induced by injection with levothyroxine (LT4), and the model was treated with distilled water (LT4 control), propylthiouracil (PTU) or BH at 3 dosages of 500, 250 and 125[Formula: see text]mg/kg The treatment was performed once a day for 15 days Compared to LT4 control, the oral administration of BH dose-dependently ameliorated the hyperthyroidism, reducing thyroid hormones and increasing thyroid stimulating hormones These effects were accompanied by improvement of body weight loss and atrophy in the thyroid gland, liver and epididymal fat pads BH treatments also reduced the levels of hepatic enzymes (AST and ALT), which suggests BH exerts protective effects on hepatocytes BH might also be involved in the augmentation of the anti-oxidant activities, supported by increased endogenous antioxidant (glutathione) In addition, the histopathological analyses revealed the beneficial effects of BH on the atrophic changes and cellular injuries in the thyroid gland, liver and epididymal fat pads The therapeutic potentials of BH were either similar or more effective than PTU These results provide valuable information that will guide more detailed studies to use the BH as a complementary and alternative medicine

The Effect of Experimental Thyroid Dysfunction on Markers of Oxidative Stress in Rat Pancreas.

Abstract: Preclinical Research The aim of the present study was to evaluate the effects of thyroid dysfunction on markers of oxidative stress in rat pancreas. Hypothyroidism and hyperthyroidism were, respectively, induced in rats via administration of propylthiouracil (PTU) and L-thyroxine sodium salt in drinking water for 45 days. The activities of superoxide dismutase (SOD), catalase (CAT), glutathioen peroxidase (GPx), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD), xanthine oxidase (XO), and nonenzymatic markers of oxidative stress including malondialdehyde (MDA), protein carbonyl (PC), reduced glutathione (GSH), and total thiols (T-SH) were determined in the rat pancreas. In hyperthyroid rats, pancreatic CAT, SOD, GPx, GR, XO, G6PD activities were increased compared with those in hypothyroid and control groups. There were no differences in activities of antioxidant enzymes between hypothyroid and control rats. Pancreatic MDA and PC in hyperthyroid rats increased compared with hypothyroid and the control animals. Whereas, hyperthyroid rats had decreased levels of tissue GSH and T-SH compared with hypothyroid and the control groups. The findings showed that only GSH level has decreased significantly in the hypothyroid group compared with control groups. In conclusion, our results showed that experimental hyperthyroidism induces oxidative stress in pancreas of rats, but hypothyroidism has no major impact on oxidative stress markers. Drug Dev Res 77 : 199-205, 2016. © 2016 Wiley Periodicals, Inc.

Sequential Amniotic Fluid Thyroid Hormone Changes Correlate with Goiter Shrinkage following in utero Thyroxine Therapy.

Abstract: Several isolated reports of fetal goiter treatment have shown limited generalizability of approaches and provide no real guidance for optimal timing, dosages, and treatment strategies. Graves' disease accounts for >60% of these cases. Maternal treatments of hyperthyroidism include antithyroid medications such as methimazole and more commonly propylthiouracil (PTU). Here, our management of a patient with a fetal thyroid goiter from maternal exposure to PTU diagnosed at 23.6 weeks' gestation and the management of other cases allow us propose a general strategy for treatment. Intrauterine therapy with 200 and then 400 μg of levothyroxine (3 weeks apart) showed an 85% reduction in fetal thyroid goiter volume. We collected amniotic fluid samples at the time of treatments and assayed thyroid hormones and associated antibodies which closely reflected the changes in thyroid goiter mass volume. Our observations suggest a weekly or biweekly therapeutic intervention schedule. Utilizing both goiter size as well as a novel approach in using amniotic fluid hormone levels to monitor therapy efficacy might improve the quality of treatments. Only with a standardized approach and collection of amniotic fluid thyroid panels do we have the opportunity to develop the database required to determine the number and timing of treatments needed.

Agranulocytoses aux antithyroïdiens de synthèse : revue de la littérature

Abstract: The antithyroid agents (carbimazole, methimazole, thiamazole, propylthiouracil and benzylthiouracile) are the drug class that is associated with a high risk of agranulocytosis Acute and profound (<05×10(9)/L) isolated neutropenia occurring in a subject treated with antithyroid agents should be considered as a drug-induced agranulocytosis, until proven otherwise The clinical spectrum ranges from discovery of acute severe but asymptomatic neutropenia, to isolated fever, localized infections (especially ear, nose and throat, or pulmonary) or septicemia With an optimal management (discontinuation of antithyroid agents, antibiotics in the presence of fever or a documented infection, or use of hematopoietic growth factor) the current mortality is close to 2%

Thymoquinone protects against hypothyroidism-induced cardiac histopathological changes in rats through a nitric oxide/antioxidant mechanism.

Abstract: Background: The heart is one of the organs which is affected by the thyroid hormones and hence the alterations in the thyroid status influences its function and structure. Objectives: This study aimed to reassess hypothyroidism-induced histopathological cardiac changes and to evaluate the proposed protective role of thymoquinone (TQ) against these changes. In addition, the mechanism of TQ-induced protection is studied regarding the oxidative stress and nitric oxide (NO) pathway. Materials and Methods: A model of propylthiouracil (PTU)-induced hypothyroidism in Wister rats is used in this study. Four groups of rats were used; control, TQ, PTU (hypothyroidism) and PTU+TQ groups. Thyroid hormones, cardiac enzymes, NO and antioxidants were assessed in the blood. Hearts were histopathologically and immunohistochemically examined. Results: A significant increase in plasma cardiac enzymes activity was recorded in hypothyroid rats, which is accompanied by significant histopathological changes in the left ventricle. Treatment of rats with TQ significantly protected the heart muscle against hypothyroidism- induced histopathological and immunohistochemical changes. It also significantly decreased plasma cardiac enzymes activity. TQ caused a reduction in malondialdehyde (MDA) formation, and increased, reduced glutathione (GSH), NO and superoxide dismutase (SOD) production. It also, increased the expression of constitutive nitric oxide synthase (eNOS) activity. Conclusion: hypothyroidism may induce cardiac pathological changes, which is prevented by TQ as it restores thyroid hormones, increases NO formation and eNOS expression, and decreases reactive oxygen species (ROS) production.

Assessment of synergistic thyroid disrupting effects of a mixture of EDCs in ovariectomized rats using factorial analysis and dose addition.

Abstract: Endocrine disrupting chemicals (EDCs) have been implicated in a broad spectrum of health problems related to reproduction, thyroid function, neurodevelopment, and metabolism. In many cases, EDCs in the environment are at extremely low concentrations which rarely induce health problems alone, however, a mixture of these EDCs may interact and induce potential additive and synergistic effects. Many mixture studies on EDCs were conducted in terms of high doses with the direct effect addition method, which didn't comply with the dose-response relationship of toxicants in the "S" or "U" shaped curves. In the present study, the thyroid disrupting effects of a mixture of three EDCs, propylthiouracil (PTU), polychlorinated biphenyls (PCBs), and ammonium perchlorate (AP), were measured in an ovariectomized rat model. Sixty female SD rats were ovariectomized bilaterally and randomly assigned to ovariectomization (OVX) control, PTU + PCBs, PTU + AP, PCBs + AP and PTU + PCBs + AP groups treated with doses at lowest observed adverse effect levels (LOAELs) or benchmark dose lower limits (BMDLs) obtained from our previous dose-response relationship studies. OVX control animals were treated with vehicle control while all other animals were treated with different combinations of EDCs by gavage for 8 days. The body weight change, serum total thyroxine (tT4), triiodothyroxine (tT3), the thyroid/body weight ratio, and thyroid histopathological endpoints were measured and analyzed using factorial analysis and dose addition. All EDC treated groups showed a marked change compared to vehicle control in serum tT4, the thyroid/body weight ratio, and the thyroid epithelium/colloid ratio. Both factorial analysis and dose addition analysis showed a synergistic effect on thyroid function by PTU, PCBs and AP together, but the modes of interaction varied when either two were mixed at LOAELs. To conclude, a mixture of PTU, PCBs, and AP mainly acted synergistically on thyroid function and induced a significant health effect.

Management of Hyperthyroidism during the Preconception Phase, Pregnancy, and the Postpartum Period.

Abstract: Hyperthyroidism can occur during pregnancy and the postpartum period, and the treatment of hyperthyroidism should be considered in the preconception phase. Pregnancy has multiple normal physiologic effects on thyroid hormone, which is a separate process distinct from syndromes such as transient hyperthyroidism of hyperemesis gravidarum. The rationale regarding antithyroid drug use during different stages of pregnancy is reviewed, including the literature regarding adverse neonatal outcomes such as aplasia cutis and methimazole embryopathy in the setting of first trimester maternal methimazole use. The use of treatment modalities for hyperthyroidism during pregnancy such as surgery is also discussed. Studies of maternal, fetal, and neonatal complications of hyperthyroidism are examined in this article. Moreover, the evidence regarding antithyroid drugs, specifically methimazole and propylthiouracil, during lactation is considered. Other disease conditions that can take place during pregnancy and the postpartum period such as hyperemesis gravidarum, subclinical hyperthyroidism, gestational trophoblastic disease, and postpartum thyroiditis and their treatments are also presented.

Propylthiouracil, Perchlorate, and Thyroid-Stimulating Hormone Modulate High Concentrations of Iodide Instigated Mitochondrial Superoxide Production in the Thyroids of Metallothionein I/II Knockout Mice

Abstract: Background: Increased oxidative stress has been suggested as one of the underlying mechanisms in iodide excess-induced thyroid disease. Metallothioneins (MTs) are regarded as scavengers of reactive oxygen species (ROS) in oxidative stress. Our aim is to investigate the effects of propylthiouracil (PTU), a thyroid peroxidase inhibitor, perchlorate (KClO4), a competitive inhibitor of iodide transport, and thyroid stimulating hormone (TSH) on mitochondrial superoxide production instigated by high concentrations of iodide in the thyroids of MT-I/II knockout (MT-I/II KO) mice. Methods: Eight-week-old 129S7/SvEvBrd-Mt1 tm1Bri Mt2 tm1Bri /J (MT-I/II KO) mice and background-matched wild type (WT) mice were used. Results: By using a mitochondrial superoxide indicator (MitoSOX Red), lactate dehydrogenase (LDH) release, and methyl thiazolyl tetrazolium (MTT) assay, we demonstrated that the decreased relative viability and increased LDH release and mitochondrial superoxide production induced by potassium iodide (100 μM) can be relieved by 300 μM PTU, 30 μM KClO4, or 10 U/L TSH in the thyroid cell suspensions of both MT-I/II KO and WT mice (P<0.05). Compared to the WT mice, a significant decrease in the relative viability along with a significant increase in LDH release and mitochondrial superoxide production were detected in MT-I/II KO mice (P<0.05). Conclusion: We concluded that PTU, KClO4, or TSH relieved the mitochondrial oxidative stress induced by high concentrations of iodide in the thyroids of both MT-I/II KO and WT mice. MT-I/II showed antioxidant effects against high concentrations of iodide-induced mitochondrial superoxide production in the thyroid.

Placental Iodothyronine Deiodinases Expression in Pregnant Cows Exposed to Propylthiouracil (Ptu) and Thyroid Axis Activity of their Calves

Abstract: Abstract The aim of our study was to investigate if the thyroid axis of newborn calves is affected by prenatal application of propylthyouracil (PTU). The study included 20 late pregnant Holstein cows. One group (n=10) was treated with PTU (4 mg/kg of BW daily) from day 20 before expected calving until the day of calving. The other group (n=10) was non-treated. Placental samples of dams were obtained for measuring mRNA expression of iodothyronine deiodinases type I (D1), type II (D2) and type III (D3). After parturition calves were separated from the dams and included in the study. Blood samples were taken daily from each calf starting on the day of birth until day 7 of age. Blood T3, T4 and TSH concentrations were measured. PCR analysis of the placental tissue revealed an abundance of all three types of placental deiodinases in non-treated cows, and a significant elevation of mRNA levels for all three types of deiodinases after PTU treatment. Calves that originated from dams treated with PTU had significantly lower T3 and T4 and significantly higher TSH concentrations compared to non-treated calves during the first 2 days of life. Starting from day 4 until day 6 of life the opposite effect was observed meaning that calves prenatally exposed to PTU had significantly higher T3 and T4 and slightly lower TSH. Our study, for the first time, provides information related to iodothyronine deiodinases mRNA expression in bovine placenta, and confirm that PTU treatment of pregnant dams provokes depression of thyroid function in newborns during the first days of life.

Lateralized exanthem mimicking figurate inflammatory dermatosis of infancy after methimazole therapy.

Abstract: We reported a case of an 11-year-old girl admitted to our hospital for goiter, tachycardia, sweating, and visible and palpable thyroid. Thyroid function tests revealed a low thyrotropin level (<0.004 mIU/L) and elevated free thyroxine level (3.4 ng/ dL) diagnosed with Graves' disease and treated with methimazole. This anti-thyroid drug is recommended as first-line treatment in children with Graves' disease because it produces minor adverse effects with respect to propylthiouracil. She developed a lateralized exanthem mimicking figurate inflammatory dermatosis of infancy after methimazole therapy. The symptoms resolved after discontinuation of methimazole and treatment with an antihistamine and a corticosteroid. Furthermore, the treatment was changed to propylthiouracil without any adverse effects. According to current literature this is the first case of cutaneous figurate erythema related to methimazole, different from other well-known reactions such as skin eruption or urticaria.

Protective Effects of Blue Honeysuckle on Rat Hypothyroidism Induced by Propylthiouracil

Abstract: The objective of the present study is to determine whether blue honeysuckle lyophilized concentrated powder (BH) has favorable effects on hypothyroidism and related reproductive organ damage. Hypothyroidism was induced by 9 subcutaneous administration of propylthiouracil (PTU) for 28 days. Levothyroxine (LT4)-treated group was intraperitoneally injected with LT4 for the same period, while for BH (125, 250, and 500 mg/kg) or Flos Lonicerae lyophilized aqueous extract (LF, 250 mg/kg)-treated groups, the test materials were orally administrated for 42 days: two weeks before PTU injection and during PTU administration. The changes in serum thyroid hormone levels, serum male sex hormone levels, and testis antioxidant defense system were observed by histopathology of the thyroid gland, epididymis, prostate, and testis. The oral administrations of 125, 250, and 500 mg/kg of BH showed favorable effects compared to LF on hypothyroidism and related damages of reproductive organs through augmentation of the antioxidant defense system in the testis. In conclusion, BH is a promising new potent thyroid gland protecting agent.

Retrospective analysis of efficacy of radioactive iodine treatment of hyperthyroidism using a single calculated 131-I dose

Abstract: 211 Objectives To evaluate the success rate of therapeutic administration of a single calculated 131-I activity for eliminating hyperthyroidism. Methods After Internal Review Board approval with waiver of consent we retrospectively reviewed the clinical records of consecutive patients with hyperthyroidism treated with 131-I over an eight year period at the University of Michigan Nuclear Medicine Therapy Clinic. In preparation for radioactive iodine (RAI) treatment, patients underwent pinhole thyroid imaging, 24-hour radioactive iodine uptake (RAIU) measurements and clinical examination. All patients received a calculated 131-I activity of 0.2 mCi per estimated gram of thyroid tissue. The goal of RAI treatment was to eliminate hyperthyroidism and achieve hypothyroidism within 6 months of 131-I administration. Success of RAI therapy was assessed at 7 weeks and 3 months by clinical and biochemical follow-up with measurements of thyroid stimulating hormone (TSH), free tri-iodothyronine (FT3) and free thyroxine (FT4) levels. Successful treatment was defined as initiation of levothyroxine replacement after development of hypothyroidism. Results Data was obtained on 340 hyperthyroid patients (F258:M82, mean age 43.3 ± 17 y, 4-94); including 20 pediatric patients (5.9%) < 18 years), as follows: 323 patients (95%) with Graves’ disease, 14 patients (4%) with toxic multinodular goiter and 3 patients (1%) with an autonomously functioning thyroid nodule. Treatment history for hyperthyroidism prior to 131-I administration revealed: 190 patients (55.9%) had no prior therapeutic intervention (treatment-naive patients), 7 patients had prior RAI treatment at another medical center, 8 patients had prior thyroidectomy, and 135 (39.7%) had been treated with anti-thyroid medications, either propylthiouracil (PTU) or methimazole (MTZ) or both. The mean estimated thyroid gland size was 49.8 grams ± 18 range 15 - 100. Mean RAIU was 0.55 ± 18.1 (normal 0.7-0.30). RAI doses ranged from 5 to 113 mCi (mean dose = 19.3 mCi). Successful treatment of hyperthyroidism at our institution was obtained after a single therapeutic 131-I activity administration in 311 of 333 (93.4%) patients. Persistent hyperthyroidism was recorded in 22 patients (6.6%) who were subsequently managed as follows: 18 patients required two RAI treatments, 2 patients required three RAI treatments and 2 patients were referred for thyroidectomy with subsequent cure of their hyperthyroidism, due to patient decision after considering their treatment options. Multivariate logistic regression analysis demonstrated that failure of 131-I therapy was associated with age (p = 0.011), previous PTU therapy (p < 0.001) and size of the thyroid (p = 0.014), but not with MMZ therapy, interval between diagnosis and RAI treatment, dose of 131-I therapy or RAIU values before therapy. The mean response time after successful RAI therapy was 112.7 days, with 25% responding at 62 days, 50% by 84 days and 75% by 120 days post radioiodine administration. The mean response time for treatment naive patients (no prior antithyroid medications) was 137 days vs.181 days for patients managed with antithyroid medications (p=0.039). The mean time to respond for those on prior PTU was 240 days compared to 116 days for those on MMZ and 109 days for those not previously treated with antithyroid medications. Conclusions Successful single calculated 131-I activity therapy for hyperthyroidism can be achieved using 0.2 mCi of 131-I per estimated gram of thyroid tissue corrected for thyroidal 131-I uptake at 24 hours. Treatment failure occurs in 7% of patients and is mainly associated with and prior PTU medication treatment and larger thyroid glands. $$graphic_9E74D22B-CFD7-48DB-96C1-C19BE809F139$$

Management of hyperthyroidism in pregnancy

Abstract: Hyperthyroidism in pregnancy is associated with adverse foetal, maternal and obstetrical outcome. Untreated or inadequately treated hyperthyroidism may precipitate pre eclampsia and congestive cardiac failure in mother. It also increases the risk of miscarriage, abruption placentae and premature delivery in such patients. Maintaining euthyroidism in these patients is of utmost importance. Antithyroid medications are used as first line treatment for such patients to restore euthyroid status at the earliest. Radioactive iodine is absolutely contraindicated in pregnancy and surgery often requires pre-treatment with anti thyroid medications. Two drugs are available –carbimazole and propylthiouracil. Use of carbimazole/methimazole in pregnancy is not only associated with increased incidence of scalp defect(aplasia cutis ) in the infants, but some specific congenital malformation like choanal atresia, oesophageal atresia, trachea-oesophageal fistula, patent vitello intestinal duct, omphalocele, dysmorphic facial features and growth retardation do occur. These malformations represent carbimazole /methimazole embryopathy. Due to the association of foetal teratogenicity with carbimazole /methimazole, propylthiouracil is recommended as the drug of choice in first trimester of pregnancy. However, as its use is associated with risk of hepatotoxicity, it should be changed to carbimazole/methimazole thereafter.

Drug utilization in treatment of thyroid disorders during pregnancy in serbia.

Abstract: Introduction. Depleted uranium radiation and pollution with polychlorinated biphenyls resulting from bombings the territories of Serbia as well as the additional long-term stress may have affected the function of thyroid gland. The objective of this study was to determine the trend of drug utilization in the treatment of thyroid dysfunction during pregnancy in Novi Sad. Material and Methods. Women who had given birth at the Department of Gynecology in 1989, 1999, 2007 and 2011 were interviewed during a one-month period about thyroid diseases in the pregnancy as well as the drugs they had taken. Results. Not a single pregnant woman was reported to have a thyroid disorder in 1989 and 1999, while in 2007 four women were reported to have a thyroid dysfunction. In 2011, fourteen out of 18 women with thyroid dysfunction were using levothyroxine and in most cases hypothyroidism was diagnosed as autoimmune Hashimoto thyroiditis. Conclusion. The study results suggest the necessity of performing more detailed analyses of the correlation between the frequency of the thyroid gland dysfunction and the effects of environmental pollution in Serbia. [Projekat Ministarstva nauke Republike Srbije, br. 41012]

The onset of systemic lupus erythematosus and thyroid dysfunction following Graves’ disease – A case report and literature review.

Abstract: Introduction. Graves’ disease is a multifactorial autoimmune thyroid disease, with the presence of typical circulating autoantibodies that can activate the thyroid hormone receptors, resulting in hyperthyroidism, goiter, and ophthalmopathy. Systemic lupus erythematosus is a multi-systemic autoimmune disease that involves almost all the organs of the human body and is characterized by autoantibodies formation. Several studies have reported that autoimmune thyroid and rheumatic disorders can present an unusual relationship. Case Outline. We report a case of a middle-aged woman who presented with systemic lupus erythematosus one year after being diagnosed with Graves’ disease. Prednisone and cyclophosphamide were administered to control the development of systemic lupus erythematosus. Furthermore, a percutaneous thyroid biopsy was performed for further confirmation of Graves’ disease. Methimazole instead of propylthiouracil was added into the therapeutic scheme. A month later, the patient’s clinical manifestation and laboratory tests got significant improvement, except that new thyr o id dysfunction appeared opposite to the original one. The administration of anti-thyroid drug was discontinued. With a period of decreased administration of prednisone, the patient’s thyroid function gradually got back to normal levels without any levothyroxine replacement. Conclusion. In conclusion, the clinical use of prednisone and antithyroid drugs may result in instability of the hypothalamus-pituitary-thyroid axis, and thyroid function should be carefully monitored in such patients. This article has been corrected. Link to the correction 10.2298/SARH1702101E

Creatine Kinase Elevation during Antithyroid Treatment of a Patient with Graves’ Disease: A Case Report and Review of Literature

Abstract: Thionamides (methimazole and propylthiouracil), which have been used in the treatment of graves’ disease since 1940, inhibit the organification of iodine and coupling of iodotyrosines, thus blocking the synthesis of hormones. Myalgia is a rare side effect of these drugs. CK is the muscle specific kinase. The measurement of serum concentration of CK is useful to estimate the muscles’ breakdown. We present a young male patient with Graves’ disease who had abnormal increase of CK level during treatment with methimazole (MMI). He experienced myalgia and elevated CK level 1 month after initiation of MMI. In the beginning of the myalgia, his free T4 level decreased to normal range. After dose reduction of MMI, CK level decreased and his symptoms were resolved. Although the mechanisms for this effect are not yet clear, it is thought that rapid decrease in thyroid hormone by antithyroid treatment in susceptible patients with graves’ disease can be the cause of CK elevation. Measuring CK level in Graves disease patients presented with myalgia during treatment with antithyroid drugs would be a useful diagnostic tool.

Current status of screening and management of thyroid diseases during pregnancy

Abstract: Objective To investigate the current status of screening and management of thyroid diseases during pregnancy, and to provide evidence for further improvement of clinical management. Methods Clinical data of 5 981 pregnant women who delivered at Peking University First Hospital between September 1, 2013 and September 30, 2014 were analyzed retrospectively. Their average age was (30±4) years (18-47 years) and average gestational week was (39.2±1.6) weeks (25.5-42.0 weeks). The reference range of thyroid stimulating hormone (TSH) was 0.1-2.5 mU/L recommended by the American Thyroid Association (ATA). The reference range of free thyroxine (FT4) was 11.48-22.70 pmol/L and the cut-off value of thyroid peroxidase antibody (TPOAb) was 34 U/ml both recommended by the kit. The specific reference range of TSH was obtained from normal pregnant women in this study (0.23-4.08 mU/L in the first trimester). Pregnant women with hypothyroidism were divided into two groups according to their TSH level at the first trimester: TSH≥2.5-<4.08 mU/L group and TSH≥4.08 mU/L group. T test, Chi-square or Fisher's exact test were applied for statistical analysis. Results (1) Screening status: Of the 5 981 pregnant women, there were 13 cases (0.2%) of hyperthyroidism and 146 cases (2.4%) of hypothyroidism diagnosed before conception (133 cases of Hashimoto thyroiditis, eight cases after operation for thyroid cancer, and five cases after 131I therapy because of hyperthyroidism). Among the 5 822 cases requiring screening, 4 044 cases (69.5%) received screening tests of TSH, FT4 and TPOAb during early pregnancy according to Chinese Guidelines, and 1 778 cases received neither standard screening nor screening test. (2) Treatment of hypothyroidism: Hypothyroidism treatment rate was only 61.5% (107/174) according to the reference range recommended by the ATA, lower than that of 88.1% (52/59) according to the reference range of this study (χ2=14.430, P<0.05). There were 60 cases receiving no treatment in TSH≥2.5-<4.08 mU/L group. Forty-three of these cases were reexamined, and one of them was abnormal, with a rate of 2.3% (1/43). There were seven cases without treatment in TSH≥4.08 mU/L group; six of them were reexamined among which one was abnormal, with a rate of 1/6. (3) Thyrotoxicosis: Among the 4 044 pregnant women, 99 cases had TSH <0.1 mU/L, including 11 cases with FT4 ≥22.70 pmol/L (22.82-60.96 pmol/L). Only three cases were positive for thyrotrophin receptor antibody, and then diagnosed as hyperthyroidism and treated with propylthiouracil. (4) Thyroid cancer: Among the 5 981 pregnant women, six cases were diagnosed as thyroid cancer during pregnancy and lactation, with an incidence of 100.3/100 000. Of the six cases, five were diagnosed during pregnancy, and one at one month postpartum. All of the six cases underwent operation and were confirmed to be papillocarcinoma by pathology. Conclusions The screening rate of thyroid diseases during pregnancy is high, but the clinical management is not fully standardized. We suggested that each center should established its own normal reference range for thyroid function test. The incidence of thyroid cancer during pregnancy is increasing, thus attention should be paid to its diagnosis. Key words: Thyroid diseases; Pregnancy complications; Thyrotropin; Thyroxine; Iodide peroxidase; Reference values

The Impact of Maternal Thyrotoxicosis and Antithyroid Drug Exposure on Fetal/Neonatal Brain Development

Abstract: Elevated maternal thyroid hormone levels during pregnancy, as well as antithyroid drugs, can influence fetal and neonatal brain development. Elevated thyroid hormone levels in pregnancy are associated with an increased risk of miscarriage, preterm delivery, intrauterine growth restriction, preeclampsia, and heart failure. Fetal exposure to excessive maternal thyroid hormone is associated with inhibition of the fetal hypothalamic–pituitary–thyroid axis, impaired maturation of pituitary thyrotrophs and thyroid gland development, and potential disruption of neurologic development. Early diagnosis and treatment of maternal hyperthyroidism during pregnancy with antithyroid drugs improves pregnancy outcomes, fetal growth, and neurologic development. The antithyroid drugs methimazole (MMI) and carbimazole (CAB), however, are associated with a rare embryopathy that may include aplasia cutis, choanal atresia, tracheoesophageal fistulas, omphalocele, omphalomesenteric duct anomalies, and facial abnormalities. Although the number of reported cases is small relative to the number of women taking MMI or CAB at the time of conception, similar congenital abnormalities have not been reported in association with exposure to the antithyroid drug propylthiouracil (PTU). Developmental delay has been described in a subset of cases of MMI/CAB-related embryopathy, potentially due to the perinatal hypoxia associated with bilateral choanal atresia. PTU has been associated with severe maternal hepatotoxicity. The current guidelines for treatment of hyperthyroidism in pregnancy reconcile the adverse profile of antithyroid drugs in pregnancy by recommending PTU in the first trimester, to minimize the risk for embryopathy, and MMI in the second and third trimesters, to minimize the risk of liver failure.

Analysis of iodine-131-induced early thyroid hormone variations in Graves' disease.

Abstract: OBJECTIVE This prospective study aimed to assess iodine-131 (I)-induced early thyroid hormone variations in Graves' disease (GD) and determine the associated factors. MATERIALS AND METHODS One hundred and seventy-one GD patients treated with I were evaluated (47 men, 124 women). I was administered at 9.0±4.9 mCi on average. Serum free triiodothyronine and free thyroxin were measured within 24 h before treatment and 8 (3-14) days after treatment. Patients were divided into increase, no change, and decrease groups, respectively, on the basis of hormone variations after treatment. χ-Test, analysis of variance, and the Kruskal-Wallis test were used to compare groups in terms of sex, age, course of disease, thyroid stimulating hormone receptor antibodies, antithyroid drug (ATD) pretreatment time, time of ATD discontinuation before I treatment, 24 h thyroid I uptake, thyroid weight, I activity, and I activity/thyroid weight (μCi/g). The Spearman method was used for correlation analyses. RESULTS Twenty-seven, 20, and 124 cases were assigned to increase, no change, and decrease groups, respectively. Significant differences were found among groups in the time of ATD discontinuation before I treatment [the median duration for methimazole was 11 (5-26), 16 (10-30), and 21 (1-30) days, P=0.000, the median duration for propylthiouracil was 12.5 (5-24), 22 (11-26), and 26 (21-30) days, P=0.000], thyroid weight (93.5±33.6, 90.3±48.8, and 74.1±26.0 g, P=0.003), and μCi/g (84.8±11.8, 100.4±24.9, and 121.1±44.0 μCi/g, P=0.000). Interestingly, μCi/g was negatively and positively correlated to the possibility of hormone increase and decrease, respectively. No significant differences were found in the other parameters assessed. CONCLUSION At the early stage of I treatment for GD, few patients showed increased thyroid hormone levels. Key factors may include time of ATD discontinuation before I treatment and μCi/g. High μCi/g might decrease thyroid hormone levels in early treatment, making it safe.

Fetal Goiter was Resolved with Decreasing Maternal Propylthiouracil Dose

Abstract: Fetal goiter is an uncommon, serious problem during pregnancy. Careful routine antenatal ultrasound screening can find out an intrauterine fetal goiter. Fetal goiter has an incidence of 1:40000 live births (1). 80% of cases are caused by dysgenesis of the thyroid gland. The rest 5% and 15% are due to hypothalamohypophyseal abnormalities and dyshormonogenesis, respectively. 8% of cases are due to hyperthyroid pregnant on antithyroid medication (2). The anti-thyroid antibody types and the medication status of the patient may cause hyper, hypo or euthyroid fetuses. Untreated intrauterine hypothyroidism may predispose to motor or cognitive deficits, or impaired intellectual development. A large mass on the anterior neck may lead to extension of fetal head and malpresentation (3). Our study reports a case of fetal goiter successfully treated with incrementally decreasing dose of maternal propylthiouracil (PTU). Maternal thyroid hormone-stimulating antibodies can stimulate a fetal thyroid to result in a goitrous hyperthyroidism. Fetal tachycardia and subsequent fetal hydrops may develop after fetal hyperthyroidism. Elevated maternal anti-thyroid peroxidase (antiTPO) and anti-thyroglobulin titers may give rise to suppression of thyroid hormone synthesis in the fetus. Furthermore, maternal antithyroid therapy may inhibit fetal thyroid peroxidase (2). Fetal hypothyroidism may lead to subsequent neurological impairment. The fetus may be hypothyroid, hyperthyroid or euthyroid when the fetal goiter is detected on the examination. Therefore, the evolution of fetal thyroid hormone levels is essential to decide whether to start early treatment (4). Especially when fetal goiter is diagnosed, serial amniocentesis should be done to check thyroid stimulating hormone (TSH) levels in the amniotic fluid reflecting fetal thyroid metabolism (5). Alternatively, cordocentesis, as the gold standard for the diagnosis, may be done for the assessment of the fetal thyroid hormone status (6). We report a case of fetal goiter diagnosed by detailed ultrasonography. A 33-year-old woman at twenty weeks of gestation was referred to our hospital for detailed ultrasonography. A fetal goiter was identified. She was receiving propylthiouracil (PTU) 100 mg daily for Graves’ disease. Amniocentesis was performed and fetal thyroid function was evaluated as normal. Her recent thyroid function tests were normal, but antithyroid antibodies were positive. The dose of PTU was reduced to 50 mg. However, at twenty six weeks of gestation, maternal thyroid-related autoantibodies became undetectable. A fetal magnetic resonance imaging demonstrated a slight shrinkage of the fetal goiter at 30 weeks. The fetus was delivered vaginally. Thyroid function tests of the neonate were normal, and neonatal goiter was nonpalpable. Fetal goiter is a rare disease. It can be spontaneously resolved by decreasing the maternal dose of PTU.