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The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey.

BACKGROUND AND OBJECTIVE: The original Whickham Survey documented the prevalence of thyroid disorders in a randomly selected sample of 2779 adults which matched the population of Great Britain in age, sex and social class. The aim of the twenty-year follow-up survey was to determine the incidence and natural history of thyroid disease in this cohort. DESIGN, PATIENTS AND MEASUREMENTS: Subjects were traced at follow-up via the Electoral Register, General Practice registers, Gateshead Family Health Services Authority register and Office of Population Censuses and Surveys. Eight hundred and twenty-five subjects (30% of the sample) had died and, in addition to death certificates, two-thirds had information from either hospital/General Practitioner notes or post-mortem reports to document morbidity prior to death. Of the 1877 known survivors, 96% participated in the follow-up study and 91% were tested for clinical, biochemical and immunological evidence of thyroid dysfunction. RESULTS: Outcomes in terms of morbidity and mortality were determined for over 97% of the original sample. The mean incidence (with 95% confidence intervals) of spontaneous hypothyroidism in women was 3.5/1000 survivors/year (2.8-4.5) rising to 4.1/1000 survivors/year (3.3-5.0) for all causes of hypothyroidism and in men was 0.6/1000 survivors/year (0.3-1.2). The mean incidence of hyperthyroidism in women was 0.8/1000 survivors/year (0.5-1.4) and was negligible in men. Similar incidence rates were calculated for the deceased subjects. An estimate of the probability of the development of hypothyroidism and hyperthyroidism at a particular time, i.e. the hazard rate, showed an increase with age in hypothyroidism but no age relation in hyperthyroidism. The frequency of goitre decreased with age with 10% of women and 2% of men having a goitre at follow-up, as compared to 23% and 5% in the same subjects respectively at the first survey. The presence of a goitre at either survey was not associated with any clinical or biochemical evidence of thyroid dysfunction. In women, an association was found between the development of a goitre and thyroid-antibody status at follow-up, but not initially. The risk of having developed hypothyroidism at follow-up was examined with respect to risk factors identified at first survey. The odds ratios (with 95% confidence intervals) of developing hypothyroidism with (a) raised serum TSH alone were 8 (3-20) for women and 44 (19-104) for men; (b) positive anti-thyroid antibodies alone were 8 (5-15) for women and 25 (10-63) for men; (c) both raised serum TSH and positive anti-thyroid antibodies were 38 (22-65) for women and 173 (81-370) for men. A logit model indicated that increasing values of serum TSH above 2mU/l at first survey increased the probability of developing hypothyroidism which was further increased in the presence of anti-thyroid antibodies. Neither a positive family history of any form of thyroid disease nor parity of women at first survey was associated with increased risk of developing hypothyroidism. Fasting cholesterol and triglyceride levels at first survey when corrected for age showed no association with the development of hypothyroidism in women. CONCLUSIONS: This historical cohort study has provided incidence data for thyroid disease over a twenty-year period for a representative cross-sectional sample of the population, and has allowed the determination of the importance of prognostic risk factors for thyroid disease identified twenty years earlier.

Adult↗

Autoimmune thyroid disease in pregnant women and their offspring.

OBJECTIVE: To present an overview of autoimmune thyroid disease (AITD) that can occur in pregnancy. METHODS: The major thyroid antibodies that can traverse the maternal-fetal circulation and affect the fetus are summarized, those women at risk of having affected fetuses are identified, and the diagnosis, course, and treatment of AITD in maternal and neonatal patients are discussed. SUMMARY: AITD, including Graves' disease and autoimmune thyroiditis, is common in women of childbearing age. Rarely, the fetus can be affected because of transplacental passage of maternal IgG. Of the thyroid autoantibodies found in AITD, only those directed against the thyroid-stimulating hormone (TSH) receptor have been shown to cause fetal thyroid dysfunction. Both transient neonatal hyperthyroidism and hypothyroidism have been described, as has delayed onset of neonatal hyperthyroidism due to the coexistence of stimulating and blocking TSH receptor antibodies. In general, affected infants are those born to mothers with the most potent antibody activity, and the duration of the neonatal thyroid dysfunction is dependent on the antibody titer and the rate of metabolic clearance from the infant's circulation. If fetal hyperthyroidism is suspected, maternal TSH receptor antibodies should be measured during the third trimester of pregnancy. For neonatal hypothyroidism, this measurement in the mother or baby soon after birth will suffice. Screening for the presence of TSH receptor antibodies by radioreceptor assay is the most cost-effective approach. If results are positive, bioassay should be done to determine the nature of the antibody activity. Women at risk of having babies with neonatal hyperthyroidism include those with a history of previous affected infants, with difficult to control thyrotoxicosis, or with a history of Graves' disease and development of hypothyroidism either spontaneously or as a result of thyroid gland ablation. Transient neonatal hypothyroidism due to TSH receptor-blocking antibodies should be suspected in any infant with hypothyroidism born to a mother with AITD (particularly those with previously affected offspring). CONCLUSION: Treatment of maternal hyperthyroidism must consider both maternal and fetal thyroid status. In general, the lowest dose of antithyroid medication sufficient to produce maternal euthyroidism or slight hyperthyroidism is used. In pregnant women with hypothyroidism, doses of L-thyroxine should be sufficient to normalize maternal thyroid function without regard to the fetus. Identification and treatment of affected infants soon after birth will ensure a normal outcome. Whether inadequately treated maternal hypothyroidism is associated with a permanent intellectual deficit in the offspring is currently unknown.

Journal Article↗

Comparative screening for thyroid disorders in old age in areas of iodine deficiency, long-term iodine prophylaxis and abundant iodine intake.

OBJECTIVE: To investigate the effect of varying amounts of iodine intake on the prevalence of thyroid dysfunction, autoimmunity and goitre in old age. DESIGN: The first screening study where elderly subjects with varying amounts of iodine supply but from the same geographical and ethnographical region (Carpathian basin) were compared, and all hormone measurements and ultrasonography were performed by the same laboratory or person. PATIENTS: Nursing home residents were screened for thyroid disorders from: (A) an iodine-deficient area, Northern Hungary (n = 119; median age 81 years; median iodine excretion (MIE) 0.065 mumol/mmol creatinine (equivalent to 72 micrograms/g creatinine); (B) an area of obligatory iodinated salt prophylaxis since the 1950s, Slovakia (n = 135; median age 81 years, MIE 0.090 mumol/mmol creatinine (equivalent to 100 micrograms/g creatinine)) and (C) an abundant iodine intake area, Eastern Hungary (n = 92; median age 78 years; MIE 0.462 mumol/mmol creatinine (equivalent to 513 micrograms/g creatinine)). MEASUREMENTS: TSH, T4, free T4, T3, thyroglobulin (Tg), antibodies to Tg (AbTg) and to thyroid peroxidase (AbTPO), iodine excretion, ultrasonography of the thyroid gland. RESULTS: In regions A, B, and C, the prevalence of unsuspected clinical hypothyroidism was 0.8%, 1.5% and 7.6% (P = 0.006), with all cases except one being antibody positive (Ab+). The occurrence of subclinical hypothyroidism was 4.2% in region A, 10.4% in region B and 23.9% in region C (P < 0.001), but only 3 of 22 cases with subclinical hypothyroidism from region C were Ab+. The overall prevalence of Ab positivity (either antiTg+ or antiTPO+) was similar in the three regions (A, 19.3%; B, 24.4%; C, 22.8%). The occurrence of hyperthyroidism (clinical plus subclinical) was 3.4% in region A, 3.0% in region B and 0% in region C (not significant). The rate of elevated Tg levels was similar in the three regions. The prevalence of goitre was 39.4%, 16.4% and 12.2% (P < 0.001), respectively in regions A, B and C. In euthyroid subjects the mean ultrasonographically determined thyroid volume was 21.9 ml in region A, 13.6 ml in region B and 15.1 ml in region C (ANOVA F = 5.76; P = 0.0038). There was no significant difference in the occurrence of cases with hypoechogenic echotexture of the thyroid gland. CONCLUSIONS: The screening for hypothyroidism in nursing home residents living in iodine-rich regions is justified by the high prevalence of unsuspected clinical hypothyroidism. The high prevalence of antibody positivity in old age is independent of the iodine supply, but iodine supply has a determining role in the development of autoimmune hypothyroidism in the aged. Most cases of subclinical hypothyroidism in iodine-rich regions are not of autoimmune origin. In old age, hypoechogenic texture of the thyroid gland is not predictive of thyroid dysfunction.

Aged↗

[Prevalence of hypothyroidism and hyperthyroidism in temporal arteritis and rhizomelic pseudopolyarthritis. A controlled study of 104 cases].

The aim of this study was to assess the prevalence of hyperthyroidism and hypothyroidism in giant cell arteritis and polymyalgia rheumatica. The prevalence of thyroid dysfunction in giant cell arteritis and polymyalgia rheumatica patients was determined retrospectively from 1976 through 1984 and prospectively from 1984 through 1991. A control group was composed of patients over 55 years of age consecutively admitted to the same hospital department for another condition. Patients were screened for thyroid dysfunction using a thyrotropin assay. Abnormal results were evaluated by T3 and T4 assays and, if needed, a TRH test. Among the 68 giant cell arteritis patients (mean age 72.6 +/- 7 years), of which 41 were included in the prospective arm of the study, 6 had hypothyroidism and 3 had hyperthyroidism. Corresponding figures were 4 and 4 among the 36 patients with polymyalgia rheumatica (mean age 71.7 +/- 8.3 years), of which 18 were evaluated prospectively. Among the 305 controls (mean age 71.6 +/- 9.4 years), 16 had hypothyroidism and 10 had hyperthyroidism. Prevalences of hypothyroidism, hyperthyroidism, and antithyroid antibodies were not significantly different in the control and case groups. Data fail to support previous suggestions that giant cell arteritis or polymyalgia rheumatica patients may be an increased risk for hypothyroidism or hyperthyroidism. They lend no indirect support to the hypothesis that giant cell arteritis and polymyalgia rheumatica may be autoimmune disorders.

Aged↗

Thyroid function in children after cytostatic treatment for acute leukemia.

Sixty-one children were examined for thyroid dysfunction as an adverse late effect after cessation of antileukemic treatment. The aim of the study was to contribute to clarifying which types of therapy can cause this endocrine disorder. Our treatment protocols do not include cranial irradiation as CNS prophylaxis, but we give relatively intensive intrathecal methotrexate treatment. The results indicate that this cytostatic regimen alone does not cause thyroid dysfunction as an adverse late effect.

Adolescent↗

Oncostatin M: a new potent inhibitor of iodine metabolism inhibits thyroid peroxidase gene expression but not DNA synthesis in porcine thyroid cells in culture.

The functions of thyroid cells are regulated by a number of cytokines and growth factors in addition to TSH. Recent studies have revealed that several cytokines including interleukin (IL)-6 are involved in thyroid dysfunction. Oncostatin M (OSM) is a glycoprotein belonging to the same family of cytokines as IL-6, to which it is related by sequence and structural homology and the use of the signal-transducing receptor component gp130. We, therefore, studied the effect of OSM on iodide uptake and DNA synthesis by porcine thyroid cells in culture. OSM increased c-fos and c-jun mRNA levels but did not stimulate DNA synthesis. OSM inhibited iodide uptake stimulated by TSH; while IL-6 also inhibited iodide uptake, it was only about one-tenth as potent. IL-6 had about the same potency as OSM when it was added with soluble IL-6 receptor. OSM had no effect on cAMP production but inhibited iodide uptake stimulated by 8-bromo-cAMP and forskolin. These findings suggest that OSM exerts its inhibitory effects at the post-cAMP production step(s). OSM also inhibited thyroid peroxidase mRNA levels but had little effect on thyroglobulin mRNA levels. Investigations of the signal transduction system showed that gp130 and leukemia inhibitory factor (LIF) receptor beta subunit mRNA were detectable in porcine thyroid cells by reverse transcription (RT)-polymerase chain reaction (PCR). Together with the report that serum OSM and IL-6 concentrations are elevated to the same levels in patients with sepsis, these results suggest that OSM may contribute to the thyroid dysfunction in this condition.

Animals↗

[Monitoring of thyroid function in patients treated for cancer of the upper respiratory and digestive tract].

A study was carried out at Hôpital Boucicaut to determine the incidence of iatrogenic biological thyroid dysfunction in patients treated for cancer of the upper digestive and respiratory tracts, and to define the risk profile (tumor localisations, practical therapeutical procedures). Two studies were conducted: a prospective on including 18 patients and a retrospective one including 58 patients. Only partial results are currently available. They permit emphasizing the frequency of biological thyroid dysfunction associated both with combination surgical and radiotherapeutical regimens and radiotherapy or radiotherapy alone for the treatment of lesions of the piriform sinus, although they fail to provide conclusive evidence regarding the real frequency of this type pathology or the time of its occurrence.

Carcinoma, Squamous Cell↗

Cardiovascular hemodynamics and exercise tolerance in thyroid disease.

The heart is an organ sensitive to the action of thyroid hormone, and measurable changes in cardiovascular performance are detected with small variations in thyroid hormone serum concentrations. Most patients with thyroid disease experience cardiovascular manifestations, and the most serious complications of thyroid dysfunction occur as a result of cardiac involvement. The increased metabolic state and oxygen consumption that occur in hyperthyroid patients require an increased supply of oxygen and removal of metabolic products from the periphery. This is accomplished by increasing the cardiac output to meet the needs of the periphery. Circulation time is decreased in hyperthyroid patients, and a lowered arterial resistance and increased venous resistance promote the return of blood to the heart. Thyroid hormones may significantly decrease the strength of respiratory and skeletal muscles and affect regulatory mechanisms of adaptation to incremental effort. In hyperthyroidism, cardiovascular exercise testing and analysis of respiratory gas exchange demonstrate low efficiency of cardiopulmonary function as well as impaired chronotropic, contractile, and vasodilatatory reserves, which are reversible when euthyroidism is restored. During exercise, the increment (delta) of minute ventilation (respiratory rate x tidal volume), and oxygen pulse (oxygen uptake per heart beat) are significantly lower in dysthyroidism versus euthyroidism. Especially in older patients with thyroid dysfunction, markedly reduced workload, delta ejection fraction, and delta heart rate, both at the anaerobic threshold as well as at maximal exercise, are observed. In thyrotoxicosis, mitochondria oxidative dysfunction during exercise mostly causes intracellular acidosis, whereas in hypothyroidism, inadequate cardiovascular support appears to be one of the principal factors involved. These abnormalities partly explain why subjects with dysthyroidism are intolerant to exertion. Thus, in thyroid disease, both cardiac structures and function may remain normal at rest, however impaired cardiovascular and respiratory adaptation to effort becomes unmasked during exercise.

Age Factors↗

Thyroid function in pediatric patients after neck irradiation for Hodgkin disease.

Thyroid function was evaluated in a consecutively treated group of children and adolescents with Hodgkin disease who received incidental radiation to the thyroid gland. Ten of 27 (36.7%) were found to have elevated concentrations of thyroid-stimulating hormone (TSH). Two groups of patients had an increased incidence of thyroid dysfunction - those who had not had a pretreatment lymphangiogram and those who were less than 13 years of age at the time of neck irradiation. The estimated percentage of patients who did not have a pretreatment lymphangiogram who will develop TSH elevation was 67.7% and of patients who were 13 years of age or less when irradiated, 64.8%. Thyroid dysfunction developed in 6/7 patients who had both of these risk factors present.

Adolescent↗

Sensitive thyrotropin and free thyroxine testing in outpatients. Are both necessary?

BACKGROUND: The appropriate use of specific thyroid function tests to detect thyroid dysfunction remains controversial; some experts recommend both a sensitive thyrotropin (sTSH) test and a free thyroxine (FT4) test, while others recommend an sTSH test alone. OBJECTIVE: To determine how often sTSH and FT4 tests are ordered simultaneously, how often the results are discordant, and under what circumstances a single test of thyroid function may be sufficient to rule out thyroid dysfunction. METHODS: Retrospective descriptive study of all sTSH and FT4 tests performed on adult outpatients during a 6-month period. If both sTSH and FT4 tests were performed on a single serum specimen, the results were classified as concordant (both tests indicating hypothyroidism, hyperthyroidism, or euthyroidism) or discordant. Chart review was performed on patients with normal sTSH results and abnormal FT4 results. RESULTS: A total of 6551 sTSH and 3518 FT4 tests were performed during the study period. Both sTSH and FT4 tests were ordered together on 3143 specimens (48% and 89% of the total number of sTSH and FT4 tests ordered, respectively) from 2629 patients. Of the sTSH results, 69.8% were within the normal range, and 92.7% of the FT4 results were normal. The concordance between sTSH and FT4 results was 74.3%. Among the 1835 specimens with normal sTSH results, FT4 level was low in 11 patients (0.6%; 95% confidence interval, 0.3%-0.9%) and high in 24 (1.3%; 95% confidence interval, 0.8%-1.8%). Chart review did not disclose any instances when an abnormal FT4 results contributed to the treatment of an individual with a normal sTSH result. CONCLUSIONS: The sTSH test alone, and not the combination of sTSH and FT4 tests, should be ordered in most outpatients. An FT4 test should not be routinely ordered if the sTSH result is normal; at our institution this approach would obviate the need for at least half of the FT4 tests performed each year.

Adult↗

RAPID ESTIMATION OF THYROID FUNCTION BY PHOTOMOTOGRAPHY.

The usefulness of photomotographic determination of the duration of the ankle reflex in the diagnosis of thyroid dysfunction was studied. Diagnoses by photomotography and I(131) uptake were in accord in 28 normals (260-380 milliseconds), 14 hypothyroid (390-600) and 21 hyperthyroid patients (160-250). Euthyroid reflex duration did not vary in 141 healthy persons when considered in terms of race, sex, age and pregnancy. In 172 patients, psychiatric or neuromuscular illness, heart failure, fever or several drugs had no effect. Hyperthyroidism was erroneously diagnosed in seven euthyroid subjects; there were no false hypothyroid values. Photomotography is helpful in the diagnosis of thyroid dysfunction, especially hypothyroidism.

Achilles Tendon↗

Innate and acquired immune system in patients developing interferon-alpha-related autoimmune thyroiditis: a prospective study.

OBJECTIVE: In this prospective study, we investigated whether the development of interferon (IFN)-alpha-related autoimmune thyroiditis (IFN-AT) was correlated with the sequential changes of cytokine pattern induced by IFNalpha in the peripheral lymphocytes. PATIENTS AND METHODS: We enrolled 18 hepatitis C virus (HCV)-positive patients who developed IFN-AT, eight patients with euthyroidism [IFN-AT(Eu)] and 10 with thyroid dysfunction [IFN-AT(Dy)]. Twenty HCV-positive patients without IFN-AT acted as control group (Co-HCV+). Intracellular expression of IFNgamma and IL-4 was evaluated by multicolor flow-cytometry analysis in peripheral lymphocytes in vitro stimulated by phorbol-12-myristate-13-acetate (PMA) (25 ng/ml) and ionomycin (1 mug/ml) in presence of monensin (5 microm). RESULTS: At the appearance of thyroid disease, both IFN-AT(Eu) and IFN-AT(Dy) patients showed a significant increase of IFNgamma expression in CD3+CD56+ and CD3-CD56+ cells but not in CD4+ and CD8+ cells. At this time point, IFN-AT(Eu) but not IFN-AT(Dy) patients also showed an increase of IL-4 expression in CD3+CD56+ cells and CD4+ cells. Six months later, IFN-AT(Eu) patients maintained high expression of IL-4 in CD4+ and CD3+CD56+ cells without any further increase in IFNgamma expression. By contrast, IFN-AT(Dy) patients showed an increase of IFNgamma expression in CD4+ and CD8+ cells, with a concomitant decrease of IL-4 expression in CD4+ cells. CONCLUSIONS: Type 2 immune response is activated early and specifically in patients with IFN-AT who remain euthyroid throughout the follow-up. Predominant in patients developing thyroid dysfunction, by contrast, is the type 1 immune response that seems to occur earlier in innate than acquired immune system.

Adult↗

Thyroid hormone levels in panic disorder.

A history of thyroid dysfunction has been reported in patients with phobic disorders. There is also evidence of a blunted TSH response to TRH stimulation in patients with panic disorder. In this study, values of T3, T4 and T7 were compared between 26 patients with panic attacks and 20 normal controls. Patients were diagnosed according to DSM-III criteria and those with a clinical history of thyroid dysfunction were excluded. Patients were not on any medication when the blood samples were drawn. The mean values of T3, T4 and T7 did not significantly differ between the two groups, suggesting no evidence of hypo or hyperthyroidism; however, the variance of distribution of T3, T4 and T7 values was significantly different between the two groups (Fmax values for T3: 2.55, p value less than 0.05; T4: 3.15, p value less than 0.01; T7: 2.55, p value less than 0.05).

Adult↗

RET receptor signaling: dysfunction in thyroid cancer and Hirschsprung's disease.

Gain-of-function mutations within the receptor tyrosine kinase gene RET cause inherited and non-inherited thyroid cancer. Somatic gene rearrangements of RET have been found in papillary thyroid carcinoma and germline point mutations in multiple endocrine neoplasia (MEN) types 2A and 2B and familial medullary thyroid carcinoma (FMTC). Conversely, loss-of-function mutations are responsible for the development of Hirschsprung's disease, a congenital malformation of the enteric nervous system. Comparison between normal RET signaling activated by the RET ligand glial cell line-derived neurotrophic factor (GDNF) and abnormal RET signaling caused by various mutations has led to a deeper understanding of disease mechanisms. The focus of the present review is on recent progress in the study of RET signaling dysfunction in human diseases.

Animals↗

Protective effects of vitamin E against lead-induced deterioration of membrane associated type-I iodothyronine 5'-monodeiodinase (5'D-I) activity in male mice.

The protective role of vitamin E (vit E) on lead-induced thyroid dysfunction with special reference to type-I iodothyronine 5'-monodeiodinase (5'D-I) activity in mice liver was investigated. Daily intraperitoneal (i.p.) injection of lead acetate (0.5 mg/kg body weight) for 30 days significantly decreased serum 3,3',5-triiodothyronine (T3) concentration and hepatic 5'D-I activity. Furthermore, lead significantly increased peroxidative reactions involving membrane components (lipid peroxidation, LPO) while the activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) were decreased in mouse liver. Simultaneous administration of vit E (5 mg/kg body weight) and 0.5 mg/kg body weight of lead restored thyroid function in mice by maintaining normal hepatic 5'D-I activity and serum thyroid hormone concentrations. It also prevented increase in LPO and inhibition of SOD and CAT activities in liver. We suggest that the intact membrane structure is a must for 5'D-I activity and the administration of vit E may prevent the lead induced thyroid dysfunction by maintaining membrane architecture.

Animals↗

Clinical manifestations of postpartum thyroid disease.

Postpartum thyroiditis (PPT) occurs in 5%-9% of unselected postpartum women; hyperthyroidism and hypothyroidism develop, the latter being permanent, in up to 25 %-30% of women. PPT is strongly associated with antithyroid peroxidase (anti-TPO) antibodies, but 50% of anti-TPO positive women do not develop thyroid dysfunction. Symptom analysis has shown that lack of energy and irritability were the most frequent hyperthyroid symptoms whereas lack of energy, aches and pains, poor memory, dry skin, and cold intolerance were the significant hypothyroid features. Some of these symptoms were more frequently observed than in antibody-negative controls even when these patients were euthyroid and in anti-TPOAb positive women who did not develop PPT at all. The diagnosis of PPT is based on the observation of abnormal thyroid function tests in a postpartum anti-TPOAb-positive woman: transient hyperthyroidism occurs at 14 weeks and hypothyroidism at 19 weeks postpartum. Diffuse or multifocal hypoechogenicity of the thyroid is seen on echography and a thyroid destructive process is evidenced by an increase in serum thyroglobulin and urinary iodine excretion. In addition to the 25%-30% of women who develop permanent hypothyroidism at 3 years, recent data indicate that 50% of women who have developed PPT will be hypothyroid 7-9 years later. The long-term risk is only 5% for those anti-TPOAb positive women not developing thyroid dysfunction postpartum. The risk of recurrent PPT is 70% if previous PPT was experienced and 25% if the patient was euthyroid after the first pregnancy.

Female↗