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Effects of chronic iodine excess in a cohort of long-term American workers in West Africa.

A cross-sectional survey of 102 Peace Corps volunteers in Niger, West Africa, in 1998 had previously demonstrated a high rate of thyroid dysfunction and goiter attributable to excess iodine from their water filters. The Peace Corps volunteers were followed-up a mean of 30 wk after they ceased using iodine-based water filtration systems. Goiter was present in 44% of subjects during excess iodine ingestion and in 30% after removal of excess iodine. Mean serum iodine decreased from 293 micro g/liter during excess iodine ingestion to 84 micro g/liter after cessation of excess iodine. Mean total serum T(4) values increased from 100.4 to 113.3 nmol/liter (7.8 to 8.8 micro g/dl). Mean serum free T(4) increased from 32.2 to 34.7 pmol/liter (2.5 to 2.7 ng/dl). Mean serum TSH decreased from 4.9 to 1.8 mU/liter. Mean serum thyroid peroxidase antibody levels decreased from 33,000 to 22,000 IU/liter (33 to 22 IU/ml). We found that during prolonged excess iodine exposure there were marked increases in serum total iodine concentrations, and the prevalence of goiter, elevated serum TSH values, and elevated serum thyroid peroxidase antibody values increased. The prevalence of all abnormalities decreased after removal of excess iodine from the drinking water system.

Adult↗

Increase in peripheral large granular lymphocytes in postpartum autoimmune thyroiditis.

In order to elucidate the mechanism of postpartum aggravation of autoimmune thyroid disease (AITD), we serially examined the change in the proportion of peripheral large granular lymphocytes (LGL), which have activities of NK, K and/or cytotoxic T cells, in their postpartum period. Within 6 months postpartum, the percentage of LGL increased transiently in patients with AITD who remained euthyroid, or developed destructive thyrotoxicosis and/or hypothyroidism due to thyroiditis and even in normal controls. These changes in the LGL percentage were more obvious in the patients who had marked postpartum thyroid dysfunction. In contrast, we did not find a definite increase in the LGL percentage within 6 months postpartum in patients with Graves' disease who relapsed into Graves' thyrotoxicosis. These deta suggest that the increase in LGL in the postpartum period may be related to the induction of postpartum destructive thyrotoxicosis and/or hypothyroidism in AITD.

Female↗

[Euthyroid Graves' disease (problems of diagnosis and treatment)].

Twenty-six patients with endocrine ophthalmopathy without signs of thyroid disease (according to ultrasonic scanning, measurements of free thyroxin and thyrotropic hormone-TTH) were examined. Edematous exophthalmos in the compensated stage was diagnosed in 13 patients, subclinical stage of this condition in 10, and endocrine myopathy in 3 patients. Russian drug thyroliberin was used for accurate diagnosis of thyroid dysfunction; injection of this drugs to normal subjects leads to a drastic (3.5-5-fold) increase of TTH level. After measurement of TTH, the drug was infused intravenously by jet injection in a dose of 500 micrograms. Ten normal subjects were controls. 30 min after thyroliberin injection, TTH was measured. It was sharply increased in half of patients and in the control group. In one-third of cases (mainly with edematous exophthalmos) TTH level increased negligibly or even decreased after the test. After 1.5-2 years, signs of hyperthyrosis manifested in one-third of this group of patients. The authors consider that patients with the so-called Graves' disease are at a high risk of thyroid abnormalities and should be regularly consulted by both ophthalmologist and endocrinologist.

Adult↗

Smoking and thyroid disorders--a meta-analysis.

BACKGROUND: Smoking has been associated with Graves' disease, but it remains unclear if the association is present in other thyroid disorders. OUTCOME VARIABLES: Graves' disease, Graves' ophthalmopathy, toxic nodular goitre, non-toxic goitre, post-partum thyroid disease, Hashimoto's thyroiditis, or hypothyroidism. MATERIAL AND METHODS: A search of MEDLINE identified 25 studies on the association between smoking and thyroid diseases. RESULTS: In Graves' disease eight studies were available showing an odds ratio (OR) of 3.30 (95% confidence interval (CI): 2.09-5.22) in current smokers compared with never smokers. In ex-smokers there was no significant excess risk of Graves' disease (OR=1.41, 95% CI: 0.77-2.58). The OR associated with ever smoking in Graves' ophthalmopathy (4.40, 95% CI: 2.88-6.73, six studies) was significantly higher than in Graves' disease (1.90, 95% CI: 1.42-2.55, two-sided P-value <0.01). Ever smoking was not associated with toxic nodular goitre (OR=1.27, 95% CI: 0.69-2.33, three studies), while there was an increased risk of non-toxic goitre in smokers if men were excluded (OR=1.29, 95% CI: 1.01-1.65, eight studies). The risk associated with smoking was significantly lower in men than in women for both Graves' disease and non-toxic goitre. Hashimoto's thyroiditis and post-partum thyroid dysfunction were also associated with smoking while the association with hypothyroidism did not reach statistical significance. CONCLUSIONS: Cessation of smoking seems associated with a lower risk of Graves' disease than current smoking. Smoking increases the risk of Graves' ophthalmopathy beyond the risk associated with Graves' disease alone. Smoking cessation may lead to a decrease in morbidity from Graves' disease, especially in women.

Female↗

[Metabolic and endocrine effects of water and/or food deprivation in rats].

Metabolic and endocrine effects of water and/or food deprivation in rats. We aim at studying the effect of water deprivation, food deprivation and their combination for three days on adrenal cortex, pituitary-thyroid axis and vasopressinergic system activity in rats. Corticosterone level was determined by fluorimetric method. The levels of free thyroxine (FT4) and thyroid stimulating hormone (TSH) were determined by immunoenzymatic assay and vasopressin (AVP) level was determined by radio-immunoassay. In all three groups, basal levels of plasma corticosterone were increased. A thyroid dysfunction was shown after water deprivation, food deprivation and their combination reflected by a significant decrease in FT4 levels. Paradoxically, a significant decrease in TSH level was observed in food-deprived rats and in rats subjected to simultaneous food and water deprivation, while a slight and not significant decrease in TSH level was shown in water-deprived rats. A significant increase in plasma AVP level was observed after water deprivation and simultaneous water and food deprivation, while no change was found after food deprivation. The data indicated that water deprivation, food deprivation and their combination stimulated the adrenal cortex, thereby suggesting a stress state. On the other hand, it seems that nutritional stress modifies the pituitary-thyroid axis through mechanisms different from those of osmotic stress. Moreover, it seems that food deprivation partially prevented the stimulatory effect of water deprivation on vasopressinergic system.

Adrenal Cortex↗

[Autoimmune thyroid disease diagnosed during puerperium: evaluation 2 years later].

This is a 2 years follow-up study of seventeen women who were found to have mild goiter and post-partum thyroid disease two years earlier in order to establish if post-partum thyroid disease is a self-limited entity or the relapse of a chronic pre-existing disease. When first studied, the 17 women had thyroid dysfunction (15 with hyperthyroidism and 2 with hypothyroidism). Eight women had also elevated antimicrosomal antibodies (AMA) titers and 9 were negative for AMA. In the present study, all women were reexamined for the presence of goiter, and free thyroxine index (FT4I), TSH and AMA were determined. Mild (grade I-II, less than 30 g) goiter was found in 11 women. Six out seventeen women, still had altered functional tests (3 with hypothyroidism and 3 with hyperthyroidism). The elevated AMA titers seen in 8 patients in the first study, remained high in 6 (1:100-1:25600). None of the 9 patients who in the first study had negative AMA changed to positive titers. Results indicate that post-partum thyroid disease is not always a self-limited entity. The presence of elevated AMA titers in the initial post-partum period can express a chronic thyroid disease compromise. In these patients a longterm clinical and biochemical follow-up is recommended.

Autoantibodies↗

[Hypothyroidism following cervical irradiation in the management of carcinoma of the nasopharynx and of the breast: a prospective study on eighty-four cases].

PURPOSE: 1/ To evaluate the incidence of hypothyroidism following radiotherapy in the management of breast and nasopharyngeal carcinomas, 2/ to define the role of a systematic post therapeutic screening. PATIENTS AND METHODS: From January 1996 through March 2001 a systematic evaluation of the clinical and the biological thyroid function was performed on a cohort of 84 patients that received supraclavicular irradiation. Selected patients had either a mammary (37 cases) or a nasopharyngeal (47 cases) carcinoma. Initial work up included thyroid inspection and palpation, and biological tests: serum FT4 and TSH levels, radioimmunochemistry, completed by dynamic thyroid stimulation, using TRH, in case of border line low T4 or isolated high TSH levels. Tests were repeated every three months the first year, and then every six months. Replacement therapy with L Thyroxin was administered in case of hypothyroidism. RESULTS: All selected patients had a normal function initially. With a mean two years follow up (1-5 years), 24 patients (29%) experienced hypothyroidism, half of whom (13 cases) being purely biological. Five patients (11%), with a nasopharyngeal carcinoma, presented also with associated pituitary failure. Clinical symptoms were minor or mild in all cases. Hypothyroidism was detected at a mean 21 months follow up. In 2 patients, hypothyroidism disappeared spontaneously within 6 months. Possible predictive factors were evaluated: age of the time of radiation, gender, percentage of irradiated thyroid, total dose, dose per fraction, tumour type and chemotherapy. Only age appeared significantly correlated with thyroid dysfunction (range: 10-30 years, P=0.002). CONCLUSION: Hypothyroidism is a frequent and certainly underestimated complication following radiotherapy of the neck. In such patients, a systematic clinical and biological evaluation every three months the first year, and then every six months until five years is recommended.

Adolescent↗

[Acute suppurative thyroiditis. Report of a case and review of the literature].

The authors present a case of acute suppurative thyroiditis complicated by acute dyspnoea with asphyxia in a patient of geriatric age. In this patient there were present possible infectious focuses like multiple dental abscesses and contamination of the urinary tract. Histological examination highlighted a focus of papillifer carcinoma in the context of the gland. We have a review of the literature on this observation and description. Acute suppurative thyroiditis is currently a pathology of rare observation. This rarity is due, apart from the availability of antibiotic therapy, to an intrinsic resistance of the thyroid gland to contamination. In most cases we are talking of bacterial infections, but in immunodepressed subjects fungal etiology is noteworthy. The infection could arise from primitive focuses present in any bodily district with propagation to the thyroid across different ways. Expressive is the anamnestic observation of preexisting thyroid dysfunction. After an attentive evaluation of the clinical findings, usually characteristic, it is important to complete the diagnostic course with some instrumental investigations. In particular cervical sonography, possibly associated with agobiopsy is fundamental. Initially therapy is medical (basically antibiotic). The surgical resolution foresees the drainage of the purulent abscess or the thyroidectomy if it is associated with a struma.

Acute Disease↗

[Late complications of radiation therapy in patients with malignant lymphoma].

The improvement on the treatment of malignant lymphoma have led to prolonged survival for many patients. However, they are at risk of late complications of the disease and treatment. Impaired function due to radiation-induced injury of normal tissues, such as cardiac, pulmonary, or thyroid dysfunction, becoming manifest at few months to years after treatment. Fortunately, only a small portion of these are major complications, causing severe, or permanent disability. The frequency of secondary leukemia (AML) occurring in patients treated for malignant lymphoma is highest in those patients receiving many courses of combination chemotherapy and is low in those receiving radiation therapy alone.

Antineoplastic Combined Chemotherapy Protocols↗

Rational use of thyroid function tests.

In this era of cost containment, it is necessary to efficiently select the most important laboratory investigations for diagnostic and management purposes, with patient benefit as the ultimate objective. Thyroid function tests collectively represent a very costly item for laboratory services and have tended to be unselectively overutilized virtually until the present. Tests available for thyroid function testing include both in vitro and in vivo tests. Virtually all physicians are familiar with the free thyroxine (fT4) or its equivalents (fT4E), total and free triiodothyronine (TT3 and fT3), and sensitive thyrotrophin (TSH) assays, to which may be added plasma thyroglobulin (Tg), and thyroid autoantibodies (TAb) (including thyroid stimulating antibody [TSAb]). In vitro tests include thyroidal uptakes and scans, as well as other imaging techniques (e.g., ultrasound). Other less commonly used or obsolete techniques are not discussed. For screening or case finding where there is little probability that the patient(s) has thyroid dysfunction, a sensitive TSH assay is all that is initially required. If, however, the TSH result is elevated, a fT4E and TAb should then be performed. If the TSH is subnormal, then a fT4E, TT3, and (if still necessary) TSH response to TRH would determine if that patient was truly hyperthyroid (in elderly patients, a low TSH is often not associated with hyperthyroidism!). Conversely, not all patients with elevated fT4 are truly hyperthyroid. Uptakes and scans are primarily of importance in the correct diagnosis of unusual cases of hyperthyroidism and for nodular disease. When patients already diagnosed are being followed, proper selection of testing is again important, sometimes emphasizing one test over others (e.g., TT3); for example, in patients with Graves' Disease on anti-thyroid drugs, the fT4E and TSH values may not reflect the true status of the patient. On the one hand, the TSH may remain low for months after the patient has become euthyroid, and on the other hand, the fT4E may drop even below normal, whereas the T3 remains elevated (and the patient still hyperthyroid). The many other vagaries of these tests are also mentioned.

Autoantibodies↗

[Effect of experimental elevation and decrease of thyroxine level on catalepsy in rats].

Thyroid dysfunction is associated with mental disorders. The present study was aimed to reveal the effects of experimental decrease and increase of thyroxine level on expression of two types of extensive freezing: spontaneous and pinch-induced catalepsy, in Wistar rat males. Chronic administration of thyroxine synthesis inhibitor, propylthiouracil (5 mg/kg/day, 28 days), markedly decreased plasma hormone level and at the same time produced a significant increase in percentage of spontaneously cataleptic animals and immobility time, but had no effect on the expression of pinch-induced catalepsy. On the contrary, chronic thyroxin (0.1 mg/kg/day, 28 days) treatment produced no effect on spontaneous catalepsy expression, although it significantly increased percentage of cataleptic animals and immobility time of pinch-induced catalepsy. The results suggest that both the thyroid hormone deficit and excess provoke catalepsy in rats but enhance different forms of freezing reaction.

Animals↗

[Hormonal etiology of secondary amenorrhea].

Over a 12-month period we evaluated 185 patients who consulted our outpatient department with symptoms of secondary amenorrhoea. Hormonal levels and body mass index were determined and an assessment made, on the basis of specific questioning. of the occurrence of possible mental alterations in the patients before they became amenorrhoic. Of our collective, 36 patients (19.5%) showed normal hormonal values, 50 patients (26%) were hypoestrogenemic, 46 women (25%) had elevated androgens, 15 patients (8%) had increased gonadotropins, 4 patients (2%) suffered from hyperprolactinemia, and 2 women (1%) had thyroid dysfunction. The remaining 32 amenorrhoic patients (17.2%) demonstrated different combinations of altered hormone values. The hypoestrogenemic patients showed a significant difference (p < 0.043) in body mass index in comparison with patients demonstrating normal hormone values. In contrast to reports in the literature hypoestrogenemia was the most frequent cause of secondary amenorrhoea in our study.

Adult↗

Genetic analysis of 29 kindreds with generalized and pituitary resistance to thyroid hormone. Identification of thirteen novel mutations in the thyroid hormone receptor beta gene.

Resistance to thyroid hormone (RTH), with elevated serum free thyroid hormones and nonsuppressed thyrotropin levels, is either relatively asymptomatic, suggesting a generalized disorder (GRTH) or associated with thyrotoxic features, indicating possible selective pituitary resistance (PRTH). 20 GRTH and 9 PRTH cases, sporadic or dominantly inherited, were analyzed. Affected individuals were heterozygous for single nucleotide substitutions in the thyroid hormone receptor beta gene, except for a single case of a seven nucleotide insertion. With one exception, the corresponding 13 novel and 7 known codon changes localized to and extended the boundaries of two mutation clusters in the hormone-binding domain of the receptor. 15 kindreds shared 6 different mutations, and haplotype analyses of the mutant allele showed that they occurred independently. The majority (14 out of 19) of the recurrent but a minority (1 out of 10) of unique mutations were transitions of CpG dinucleotides. Mutant receptor binding to ligand was moderately or severely impaired and did not correlate with the magnitude of thyroid dysfunction. There was no association between clinical features and the nature or location of a receptor mutation. These observations suggest that GRTH and PRTH are phenotypic variants of the same genetic disorder, whose clinical expression may be modulated by other non-mutation-related factors.

Adolescent↗

Effects of chronic iodine administration on thyroid status in euthyroid subjects previously treated with antithyroid drugs for Graves' hyperthyroidism.

In view of the adverse effects of the administration of pharmacological quantities of iodine to euthyroid patients with a history of a wide variety of thyroid disorders, it has been suggested that iodine-containing medications and radioopaque dyes containing iodine should be avoided, if possible, in patients with underlying thyroid disease. We have now prospectively studied the effects of pharmacological doses of a saturated solution of potassium iodide (SSKI) on thyroid function in euthyroid patients with a previous history of hyperthyroid Graves' disease successfully treated with antithyroid drugs. Ten euthyroid women (mean age, 56 yr) who had hyperthyroid Graves' disease successfully treated with methimazole 36.4 +/- 4.7 months earlier were evaluated before, during, and after the administration of 10 drops SSKI daily for 90 days. The following thyroid function tests were obtained: serum T4, T3, TSH, TSH receptor antibody (TSH-RAb), and antithyroid peroxidase antibody (AbTPO) concentrations; TRH tests; and iodine perchlorate discharge tests. Serum T4, T3, basal and TRH-stimulated TSH, and TSH-RAb values were normal before SSKI administration, but serum AbTPO levels were markedly positive in 7 and iodine perchlorate discharge tests were positive in 4 of these 10 women. During SSKI administration, basal and TRH-stimulated serum TSH values increased above normal in 2 women with normal serum T4 and T3 concentrations; thyroid hormone values and TRH tests were normal in the other 8 patients and similar to values observed in 4 euthyroid women without a history of thyroid disease given SSKI. Serum AbTPO increased slightly, but significantly, during SSKI administration in the 7 women with positive values at baseline (P < 0.05). TSH-RAb remained undetectable. After SSKI withdrawal, the 10 women were reevaluated 60 and 120 days later. Two women developed a blunted TSH response to TRH, but normal serum T4 and T3 concentrations, and 2 women developed overt hyperthyroidism, with undetectable basal and TRH-stimulated serum TSH and elevated serum T4 and T3 concentrations, requiring methimazole therapy. All values in the remaining 6 women were similar to those present before SSKI administration. These results suggest that some euthyroid patients with a history of antithyroid drug therapy for Graves' disease may develop thyroid dysfunction during and after excess iodine administration. The development of subclinical hypothyroidism during SSKI administration was not clinically important, but the occurrence of overt hyperthyroidism after SSKI was discontinued did require antithyroid drug therapy. It is advisable, therefore, to avoid iodine-containing substances in euthyroid patients with a history of antithyroid drug therapy for Graves' disease.

Antithyroid Agents↗

[Hashimoto's encephalitis].

Hashimoto's encephalitis was first described more than 30 years ago. The clinical picture is typically that of a subacute encephalopathy with a moderate to marked alteration of consciousness, seizures, myoclonus or tremulousness. Additional stroke-like episodes can occur along the course of the disease which may be monophasic or relapsing. The diagnosis of Hashimoto's encephalitis requires the presence of an elevated titer of antithyroid antibodies (mainly anti-thyroperoxidase and also anti-thyroglobulin) which is not necessarily associated with obvious thyroid dysfunction. The results of neurologic investigations are not specific and show typically a global slowing of the EEG, a moderately high CSF protein content and a normal or near normal imaging except in rare cases. The disorder is considered autoimmune and is remarkably responsive to corticosteroids which must be started as soon as possible after the diagnosis has been confirmed biologically. The long-term prognosis is usually good but some patients may die or present major neurologic sequelae.

Encephalitis↗

[The lipid metabolic characteristics of patients with thyroid pathology living in the European north of the USSR].

The blood content of total lipids, triglycerides, total cholesterol, alpha- and beta-lipoprotein cholesterol was measured in 79 patients with diffuse toxic goiter during treatment, in 25 patients with hypothyroidism, in 33 with thyroid hyperplasia, and in 54 healthy women aged 35-60 years from the group of native population of the European North. In all the forms of thyroid dysfunction, the patients manifested dyslipoproteinemia in the form of hypercholesterolemia with an increase of the concentration of beta-cholesterol, hypertriglyceridemia, and with a rise of the cholesterol atherogenic index to 4.0 and over. The signs of dyslipoproteinemia were marked to the greatest degree in thyrotoxicosis, at the stages of euthyroidism attainment or disease remissions.

Adult↗

Transient neonatal hypothyroidism after gestational exposure to amiodarone: a follow-up of two cases.

Amiodarone (AMD) is an antiarrhythmic drug which contains 37% of iodine. It can reach the fetus by transplacental passage and induce fetal hypothyroidism. Since in some pregnant women AMD represents a cardinal therapeutic opportunity, it is necessary to establish not only the risk of teratogenicity linked to fetal AMD exposure but also to evaluate the psychomotor development of children with neonatal thyroid dysfunction related to fetal AMD exposure. We report on two cases involving children with an AMD gestational exposure and transient neonatal hypothyroidism, who were followed-up until the age of 4 years 8 months and 5 years 6 months, respectively. Denver's developmental milestone test and Whechsler Preschool and Primary Scale of Intelligence (WPPSI) were administered to the patients in accordance to their age. A normal psychomotor development was observed in both patients with full scale IQ score, verbal and performance IQ scores within normal range. In conclusion, if these data were validated by larger studies, it might not be obligatory to discontinue AMD administration in cardiopathic pregnant women, since mental impairment may not necessarily occur in children with transient neonatal hypothyroidism caused by fetal AMD exposure. However, the evaluation of the thyroid function of these children is imperative.

Adult↗

Response to warfarin and other oral anticoagulants: effects of disease states.

BACKGROUND: Warfarin is associated with numerous drug and food interactions, and much attention has been appropriately focused on this subject. Because several disease states may also affect response to oral anticoagulants, we present a summary of the literature. METHODS: We searched MEDLINE for original articles on the effect of disease states on response to warfarin. RESULTS: Liver disease and thyroid dysfunction are well-documented as affecting warfarin response. Further study is needed to establish whether febrile illness, congestive heart failure, and other disease states enhance the effect of warfarin in some patients. CONCLUSION: Careful monitoring of anticoagulant therapy in patients with diseases that have the potential to affect warfarin response could increase safety and efficacy of this important agent.

Administration, Oral↗