Amiodarone-Induced thyroid dysfunction and ventricular tachyarrhythmias during long-term therapy in Japan.
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In 232 Japanese patients receiving long-term amiodarone therapy for life-threatening ventricular tachyarrhythmias, hyperthyroidism and hypothyroidism developed in 29 patients (12.5%) and 25 patients (10.8%), respectively. In patients with hyperthyroidism, the recurrence of sustained ventricular tachycardia was significantly higher with thyrotoxicosis than in the euthyroid period (31% vs 3%, p<0.01). Holter monitoring showed that the average heart rate and ventricular premature complexes significantly increased with hyperthyroidism. On the other hand, there was no increase in the recurrence of ventricular tachyarrhythmia with hypothyroidism. There was no change in the dose or the plasma concentration of amiodarone or desethylamiodarone in the euthyroid period or when hyperthyroidism or hypothyroidism manifested. It is important to monitor for arrhythmia when hyperthyroidism develops during amiodarone therapy. (+info)
A targeted dominant negative mutation of the thyroid hormone alpha 1 receptor causes increased mortality, infertility, and dwarfism in mice.
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Mutations in the thyroid hormone receptor beta (TRbeta) gene result in resistance to thyroid hormone. However, it is unknown whether mutations in the TRalpha gene could lead to a similar disease. To address this question, we prepared mutant mice by targeting mutant thyroid hormone receptor kindred PV (PV) mutation to the TRalpha gene locus by means of homologous recombination (TRalpha1PV mice). The PV mutation was derived from a patient with severe resistance to thyroid hormone that has a frameshift of the C-terminal 14 aa of TRbeta1. We knocked in the same PV mutation to the corresponding TRalpha gene locus to compare the phenotypes of TRalpha1(PV/+) mice with those of TRbeta(PV/+) mice. TRalpha1(PV/+) mice were viable, indicating that the mutation of the TRalpha gene is not embryonic lethal. In drastic contrast to the TRbeta(PV/+) mice, which do not exhibit a growth abnormality, TRalpha1(PV/+) mice were dwarfs. These dwarfs exhibited increased mortality and reduced fertility. In contrast to TRbeta(PV/+) mice, which have a hyperactive thyroid, TRalpha1(PV/+) mice exhibited mild thyroid failure. The in vivo pattern of abnormal regulation of T3 target genes in TRalpha1(PV/+) mice was unique from those of TRbeta(PV/+) mice. The distinct phenotypes exhibited by TRalpha1(PV/+) and TRbeta(PV/+) mice indicate that the in vivo functions of TR mutants are isoform-dependent. The TRalpha1(PV/+) mice may be used as a tool to uncover human diseases associated with mutations in the TRalpha gene and, furthermore, to understand the molecular mechanisms by which TR isoforms exert their biological activities. (+info)
Incidence of endocrine disease among residents of New York areas of concern.
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There are six Areas of Concern, as identified by the International Joint Commission, located in New York State. Three are contiguous in western New York and have similar contaminants (Buffalo River, Niagara River, and 18 Mile Creek). We used the Statewide Planning and Research Cooperative System database, which records diagnoses according to the (italic)International Classification of Disease, Ninth Revision(/italic) codes for all patients admitted to state-regulated hospital facilities, to compare incidence of selected diseases reported in hospitalized patients who reside in ZIP codes that are within 15 miles of any of these sites to those of residents of three different control populations: all residents of the rest of New York State (including New York City), all residents of ZIP codes outside New York City that do not contain any site identified as a federal or state Superfund site, and all residents of ZIP codes outside New York City that contain a federal or state Superfund site that does not have one or more persistent organic pollutants listed as a major contaminant. We found a significant elevation of disorders of the thyroid gland in women, but not in men, of all ages greater than 25 years on all three comparisons, as well as an increased incidence of morbidity from diseases of the female genital tract in women between age 25 to greater than 75 years for all comparison groups. There was also a significant elevation in incidence of endometriosis in women 25-44 years of age. All these elevations were significant at the 99% confidence level. Incidence of diseases of ovaries and testes and female infertility were not different from those in the rest of New York State. Although many factors influence incidence of thyroid and genital diseases, our results are consistent with the hypothesis that exposure to environmental contaminants through residence near polluted sites may be a factor. (+info)
Of jugglers, mechanics, communities, and the thyroid gland: how do we achieve good quality data to improve public health?
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Our knowledge about the distribution of exposures to toxic chemicals in various communities is limited. Only about 6% of approximately 1,400 toxic chemicals have been identified in surveys. Even for those chemicals that are measured, information is often insufficient to identify smaller populations at high risk. The question is whether information about the distribution of diseases in communities can help identify environmental risks, indicate areas of concern, and thus substitute exposure information. Thyroid disorders represent a large group of diseases that cannot be recorded into registries because of the lack of clear caseness; community-based monitoring of subtle health effects is needed. Thus, to identify potential health risks in communities, epidemiologic studies including effect and human exposure monitoring are necessary. However, to overcome the limitation of nonsystematic case studies, the development of a network of exposed communities concerned about exposures is proposed. A network would provide assessments of exposures and health outcomes, with different communities mutually serving as exposed and control groups. Such a network would foster communication and prevention measures within communities often left out of the dissemination of information about risks identified in studies conducted with residents of these communities. (+info)
Parity is associated with increased thyroid volume solely among smokers in an area with moderate to mild iodine deficiency.
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OBJECTIVE: Pregnancy has been suggested as part of the explanation of the gender difference in the prevalence of goitre, but opposing results have been reported on the association between pregnancy and goitre. We investigated the association between parity and thyroid volume and a possible impact of iodine deficiency and tobacco smoking on this association. DESIGN: A comparative, cross-sectional study of 3712 women randomly sampled from the general population in two geographical areas with moderate and mild iodine deficiency. METHODS: The participants answered questionnaires with an obstetric anamnesis, and ultrasonography of the thyroid was performed. Data were analysed in linear models and logistic regression analysis to adjust for age, iodine status, use of oral contraceptives and smoking habits. Women with present or recent pregnancies were excluded from the analyses. RESULTS: A higher thyroid volume was found among parous than among nulliparous women (P=0.007). The association between parity and thyroid volume was strongest in the youngest age groups, in the region with the most severe iodine deficiency, and among smokers. No association was found between parity and the prevalence of solitary or multiple thyroid nodules. Number of births, age at menarche or menopause, the number of fertile years, and age at first childbirth were not associated with thyroid volume. CONCLUSION: Pregnancy increases thyroid volume, particularly when combined with tobacco smoking and iodine deficiency. The effect is probably reversible seen over a spectrum of several years. (+info)
Improved diagnosis of "nondelineated" thyroid nodules by oblique scintillation scanning and echography.
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The scan of the thyroid gland in oblique projections has enabled us to visualize 11 "cold" thyroid nodules which were not delineated on a traditional anterior view among 825 patients studied in a 2-yr period. Accurate localization of the nodule in the oblique projection facilitated accurate placement of the transducer for echography. The combination of the isotope imaging studies and ultrasound then permitted one to differentiate solid and cystic "cold" nodules. Diagnosis and choice of therapy are therefore enhanced by the addition of oblique views, when needed, and echography. (+info)
Urinary iodine levels and thyroid diseases in children; comparison between Nagasaki and Chernobyl.
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We evaluated the incidence of childhood thyroid diseases and urinary iodine levels in Nagasaki, Japan and in Gomel, Belarus, which was greatly radio-contaminated by the Chernobyl accident, in order to obtain the comparative data of thyroid diseases between iodine-rich (Japan) and -deficient (Belarus) areas. In Nagasaki, the median level of urinary iodine, measured by ammonium persulfate digestion in microplate method, was 362.9 microg/L. In order to evaluate the geographical differences in Japan, other samples were collected in Hamamatsu and in South Kayabe, Hokkaido, where the median levels were 208.4 microg/L and 1015.5 microg/L, respectively. Furthermore, thyroid screening by ultrasound (US) in Nagasaki revealed only four cases that showed goiter (1.6%) and two cases (0.8%) that had cystic degeneration and single thyroid cyst. There was no evidence of thyroid nodule detected by US examination. In contrast, the median of urinary iodine level was 41.3 microg/L in Gomel. The incidences of goiter (13.6%) and echogenic abnormality (1.74%) in Gomel were much higher than in Nagasaki, suggesting the critical involvement of iodine deficiency in increased childhood thyroid abnormality around Chernobyl. Radioactive iodine released just after the Chernobyl accident may have influenced predominantly children residing in iodine-deficient areas. Our results suggest that management of thyroid screening for schoolchildren at ordinary times may be beneficial for monitoring the adverse effects of radioactive iodine from the standpoint of future prospective study. (+info)
The effect of formulation on reduced radioiodide thyroid uptake.
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This investigation compared in vitro dissolution profiles from sodium iodide capsules with radioiodide thyroid uptake in patients with thyroid abnormalities, using sodium iodide capsules prepared with a formulation exhibiting complete release of radioiodide in vitro and a formulation exhibiting incomplete release. METHODS: In vitro dissolution profiles for radioactive sodium iodide capsules with 2 different formulations were determined using the U.S. Pharmacopeia (USP) XXIV dissolution test. The 2 formulations studied in vitro were sodium phosphate dibasic powder with 1% magnesium stearate and calcium phosphate dibasic powder with 3% magnesium stearate. The thyroid uptake of radioiodide from capsules exhibiting complete release or incomplete release of radioiodide was determined in patients with thyroid disorders. RESULTS: In the dissolution studies, by 20 min after initiation of the test, >95% of the radioactive iodide was released from capsules of sodium phosphate dibasic powder. The capsules of calcium phosphate dibasic powder reached 75% at 65 min, with no further release occurring thereafter. In the in vivo studies, the mean thyroid uptake at 1 h for sodium phosphate dibasic powder with 1% magnesium stearate (complete-release formulation) was 12.7%, compared with 9.3% for calcium phosphate dibasic powder with 3% magnesium stearate (incomplete-release formulation) (P < 0.05). At 24 h, the value was 56.6% for the complete-release formulation, compared with 50.3% for the incomplete-release formulation (P < 0.01, Wilcoxon signed rank test). At 1 h, the abdominal activity for the complete-release formulation was 3.4%, compared with 8.8% for the incomplete-release formulation (P < 0.01). At 24 h, the value was 0.4% for the complete-release formulation, compared with 1.0% for the incomplete-release formulation (P < 0.01). CONCLUSION: The data suggest that the incomplete dissolution profile observed in vitro may correlate with reduced bioavailability of radioiodide in vivo. The USP dissolution test can be applied to radioiodide sodium iodide capsules as a quality assurance procedure. (+info)