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Parity and the risk of autoimmune thyroid disease: a community-based study.

CONTEXT: Recent studies have suggested that fetal microchimerism (transplacental passage of fetal cells followed by engraftment into maternal tissues) may play a role in the pathogenesis of autoimmune thyroid disease. If that is true, then parity should be a risk factor for autoimmune thyroid disease. OBJECTIVE: The objective of this study was to examine parity as a risk factor for autoimmune thyroid disease. DESIGN, SETTING, AND PARTICIPANTS: TSH, thyroid peroxidase antibody, and thyroglobulin antibody concentrations were measured on archived sera from 1045 female participants in a 1981 community health survey in Busselton, Western Australia. OUTCOME MEASURES: Odds ratios (ORs) for positive thyroid antibodies (increased concentration of either antibody) or thyroid dysfunction (abnormal serum TSH) were used. RESULTS: After adjustment for age, women who had previously been pregnant did not have a significantly increased risk of positive thyroid antibodies [OR, 1.20; 95% confidence interval (CI), 0.74-1.97; P = 0.46], raised TSH (OR, 0.93; 95% CI, 0.46-1.87; P = 0.84), or reduced TSH (OR, 0.87; 95% CI, 0.33-2.30; P = 0.79) compared with women who had never been pregnant. For each additional pregnancy, the OR was 1.02 (95% CI, 0.94-1.11; P = 0.57) for positive antibodies, 1.02 (95% CI, 0.91-1.14; P = 0.67) for raised TSH, and 1.03 (95% CI, 0.87-1.22; P = 0.73) for reduced TSH. Analysis using number of live births gave similar results. The results were similar in younger and older women. CONCLUSIONS: Parity is not a risk factor for thyroid autoimmunity or thyroid dysfunction. These data do not support a key pathogenic role for fetal microchimerism in chronic autoimmune thyroid disease.

Adult↗

Optimisation of thyroid hormone replacement using an automated thyroid register.

The high prevalence of thyroid dysfunction requires an efficient and effective means of monitoring and adjustment. We compared the current network of 12,524 patients with thyroid dysfunction with register data prior to 1991 to examine the precision of thyroxine replacement in patients with hypothyroidism and assess locally changing trends in treatment of hyperthyroidism. Since 1991, due to the associated adverse effects of a suppressed thyroid-stimulating hormone (TSH) (<0.03 mU/l), the network has facilitated a significant reduction in the proportion of thyroxine-treated patients with TSH suppression from 58.5% before 1991 to 9.2 +/- 3.8% thereafter. Since 1991, there has been an increased use of radioiodine by 14.3% [95% confidence interval (95% CI): 10.6-17.8] and a reduced use of thyroidectomy by 12.3% (95% CI: 8.8-15.8) to treat hyperthyroid patients compared with before 1991. Between the two treatments, there were no differences in subsequent rates of hypothyroidism or mean thyroxine dosage.

Aged↗

Disturbances of thyroid function in the elderly.

Disturbances of thyroid function occur more often in the elderly than in the young. This short review gives an up-to-date overview of this topic. After discussing the difference in epidemiology of thyroid dysfunction in elderly persons in areas with different iodine nutrient status, the physiologic age-induced changes of the hypothalamic-pituitary-thyroid axis are discussed, especially with regard to their consequences on normal ranges of thyroid hormones. Although slight decreases in thyrotropin (TSH) and free triiodothyronine (T3) have been described as occurring in healthy elderly persons, it is concluded from the available data that abnormal values of thyroid hormones in serum of old people should be further investigated, since none of the described changes lead to values outside the normal range. Special emphasis is given to the fact that disturbances of thyroid function are oligosymptomatic or may even be asymptomatic in old persons. Therefore, laboratory screening for thyroid dysfunction in patients over 65 years of age seems to be justified. Lastly, differences of treatment in comparison with younger patients with hyper- or hypothyroidism are presented. The impact of subclinical disturbances of thyroid function in the elderly and their possible therapeutic consequences are also included in this discussion.

Aged↗

Thyroid disease in diabetics.

Among a diabetic clinic population of 5,000 there were 113 patients (1.1%) with concurrent clinical thyroid dysfunction (56 hyperthyroid, 57 hypothyroid). Seventy-one (62.8%) of these patients were insulin-dependent and diabetes preceded thyroid disease in 85 (75.2%). Twenty patients were given carbimazole for two or more years and of these 15 (75%) relapsed, a percentage not significantly different from that seen in non-diabetic patients. The value of screening diabetic patients for evidence of thyroid dysfunction is discussed.

Adult↗

IgG subclass distribution and relative functional affinity of thyroid microsomal antibodies in postpartum thyroiditis.

An association between the development of postpartum hypothyroidism and high levels of IgG1 subclass microsomal (M) antibodies has been reported. Using an assay designed to detect reasonable levels of all the four IgG subclasses, we found no differences in the proportion of each IgG subclass in M antibodies of patients with postpartum hyperthyroidism or hypothyroidism compared with control postpartum patients with M antibodies but no thyroid dysfunction. However the total amount of M antibody of each IgG subclass was elevated above the controls in the patients with thyroid dysfunction. The relative functional affinity of M antibodies did not differ between controls and patients with hypothyroidism but declined 5 and 10-12 months after delivery compared to values at 2 months. These results do not support the suggestion that the amount of IgG1 subclass M antibodies particularly determines the course of postpartum thyroiditis. Rather, the total M antibody level, in all four subclasses, is associated with clinical outcome. Resolution of the disease, despite persisting M antibodies, may occur in part because the relative functional affinity of these antibodies declines after delivery.

Antibody Affinity↗

Prevalence of primary hyperparathyroidism in 13387 patients with thyroid diseases, newly diagnosed by screening of serum calcium.

Primary Hyperparathyroidism (PHP) often goes unrecognised. Evidence of the influence of thyroid diseases on parathyroid activity exists. In order to determine the prevalence of primary hyperparathyroidism (PHP) in patients with thyroid diseases, a series of patients referred to an outpatient department for patients with thyroid diseases were examined for additional PHP. In addition to screening for thyroid diseases, serum calcium concentration (S-Ca) was measured in a series of persons who came to our outpatients' service for patients with thyroid diseases during the period 1992 to 1998. 13387 persons, median age 48 y, m = 2367, f = 11020, among them 9017 patients with thyroid diseases and 4370 persons without thyroid dysfunction, were studied. In patients with S-Ca outside the normal range, further diagnostic tests relating to PHP were performed. 106/13387 persons showed S-Ca > or = 2.6 mmol/L, in 31 cases due to PHP. In comparison to persons without thyroid diseases, the occurrence of PHP was significantly higher in patients with thyroid diseases (4/4370 = 0.09% vs. 26/9017 = 0.29%). Furthermore, 2 patients with normal S-Ca were diagnosed as having PHP in addition to another endocrine disease (acromegaly, multiple endocrine neoplasia type IIa, resp.). 31 of the 54 persons with S-Ca > 2.6mmol/L and who showed no other reasons for hypercalcaemia were found to be in a hyperthyroid state. The prevalence of PHP was significantly higher in patients with euthyroid goitre (p < 0.05) and in patients with thyroid carcinoma (p = 0.01) as compared to other persons with thyroid diseases. The groups of patients did not differ with regard to age. However, patients without thyroid diseases were significantly younger (median age 38y). Above the age of 50, the prevalence of PHP became higher in patients with euthyroid goitre or thyroid carcinoma than in those with a healthy thyroid gland. In contrast, in persons of under 50 y, there was no difference between these groups. The percentage of males with PHP was higher than in the total population studied (30% vs. 21.5%). In conclusion, a high occurence of PHP could be demonstrated in patients with thyroid diseases (0.29%) as compared to persons without thyroid dysfunction (0.09%), the highest prevalence being in patients with thyroid carcinoma. A clinically not relevant influence of thyroid function on S-Ca was seen in some patients with hyperthyroidism. Determination of S-Ca is recommended for each patient referred to a thyroid outpatients' department because of the high number of PHP cases in this context.

Adolescent↗

The influence of long-term treatment with povidone-iodine on thyroid function.

Povidone-iodine (PVP-I) is generally very safe, but cases of thyroid dysfunction induced by PVP-I have been reported. The effect of long-term treatment with PVP-I on thyroid function was to be assessed. In 40 inpatients of the department of neurology, the status of the use of PVP-I preparations and their effects on serum inorganic iodine levels and thyroid functions were investigated. In 27 patients treated with PVP-I for a long term, inorganic iodine levels were significantly increased as compared to those in 13 patients without PVP-I treatment. Out of 27 patients treated with PVP-I in the long term, subclinical hypothroidism was seen in 3 patients, mild hyperthroidism was seen in 1 patient, and subclinical hyperthyroidism was suspected in 7 patients. Patients treated with PVP-I for a long time should be observed carefully for any manifestation of thyroid dysfunction.

Amyotrophic Lateral Sclerosis↗

Thyroid function, morphology and prevalence of thyroid disease in a population-based study of Danish centenarians.

OBJECTIVES: To investigate thyroid function, morphology, and autoimmunity in relation to physical function in an unselected population of centenarians. DESIGN: A population-based survey. SETTING: Denmark. PARTICIPANTS: All persons living in Denmark who celebrated their 100th anniversary during the period April 1, 1995 to May 31, 1996, a total of 276 persons. MAIN OUTCOME MEASUREMENTS: Thyroid hormones (TSH, T4, FT4I, T3, FT3I, and T3RU), thyroid autoantibodies (TPOab and Tgab), thyroid volume, activities of daily living according to the Katz Index of ADL. RESULTS: In all, 207 (75%) of the 276 eligible subjects participated, and 148 agreed to blood tests. Among the participants, 2.9% had previously known hyperthyroidism, and the same proportion had previously known hypothyroidism. The blood tests did not reveal any undiagnosed cases of overt thyroid dysfunction. However 7.2% had a subnormal serum TSH, and 2.9% had an elevated serum TSH; all had normal serum T3 and serum T4 levels. Thyroid autoantibodies were detected in 26 (17.6%) centenarians (11.5% had Tgab and 9.5% had TPOab). Among relatively independent centenarians, low serum T3 was significantly associated with high comorbidity (P = .029), whereas both low serum T3 and thyroid autoantibodies were significantly associated with ADL-dependency (P < .001 and P = .030, respectively). Ultrasonography (n = 50) revealed a small gland with a median volume of 8.3 mL (range 3.2-27.9) compared with an expected volume of 20 mL (14-26) (P < .001). There was no significant relationship to body weight. When examined by ultrasound, only 26% had significant morphological alterations. CONCLUSIONS: Thyroid dysfunction does not seem to be more prevalent among centenarians than among younger old people. Low serum T3 is related to poor physical function and co-morbidity, whereas thyroid autoimmunity is related only to poor physical functioning. Despite atrophy of the thyroid gland, these findings suggest that thyroid function is well preserved in centenarians.

Activities of Daily Living↗

Reproductive manifestations of thyroid disease.

Thyroid function and reproductive function have many interactions, the scope and mechanism of which are not fully understood. These functions are of greatest clinical importance for veterinarians working with breeders of purebred dogs. Thyroid dysfunction does not always result in clinical signs of reproductive disorders or in subfertility. It seems that animals with overt thyroid dysfunction are those most likely to manifest reproduction problems.

Animals↗

An association between depression, anxiety and thyroid function--a clinical fact or an artefact?

OBJECTIVE: The aim of the study was to examine the association between depression, anxiety and thyroid dysfunction. METHOD: The study is part of the HUNT-study. Individuals aged 40-89 years (n = 30,589) with thyroid assays, and self-rating of depression and anxiety--Hospital Anxiety and Depression Scale (HADS)--were divided in six categories according to thyroid function. Relations were investigated with logistic regression analysis. RESULTS: The group with biochemical hypothyroidism had significantly lower risk for depression and anxiety compared with the reference group with normal thyroid function. Subclinical hypothyroidism, and latent and overt biochemical hyperthyroidism were not risk factors for depression or anxiety. When individuals with former known thyroid disease were excluded from the analyses, the results were essentially identical, but this group had an increased risk of both anxiety and depression, independent of thyroid function. CONCLUSION: In this large, unselected population, we found no statistical association between thyroid dysfunction, and the presence of depression or anxiety disorder.

Adult↗

Low concentrations of maternal thyroxin during early gestation: a risk factor of breech presentation?

OBJECTIVE: To evaluate the relation between breech position at term (>37 weeks of gestation) and low maternal fT4 levels during gestation in women not suffering from overt thyroid dysfunction. DESIGN: A prospective cohort study of pregnant women. SETTING: Community-based study. POPULATION/SAMPLE: At random selected pregnant women of the general population. METHODS: At antenatal booking, based on thyroid function assessed at 12 weeks of gestation in a large cohort of pregnant women, two groups of participants were defined: women with low fT4 levels-below the 10th centile (n= 135) and women with fT4-between the 50th and 90th centiles at 12 weeks of gestation (n= 135). Women with clinical thyroid dysfunction (fT4 and TSH outside reference range) at 12 weeks of gestation were excluded. Maternal thyroid function (fT4 and TSH) was subsequently assessed at 24 and 32 weeks of gestation. Analysis refers to 204 women who met the inclusion and exclusion criteria and in whom all thyroid parameters were assessed. MAIN OUTCOME MEASURES: Fetal presentation (cephalic-breech) at delivery in women with term gestation (>37 weeks of gestation) in relation to maternal thyroid function at 12, 24 and 34 weeks of gestation. RESULTS: Breech presentation at term delivery was independently related to fT4 levels <10th centile at 12 weeks of gestation (OR = 4.7, 95% CI 1.1-19 [but not to an fT4 level below the 10th centile at 24 and 32 weeks of gestation]) as well as primiparity (OR = 4.7, 95% CI 1.3-15). CONCLUSIONS: Women with hypothyroxinaemia (fT4 level at the lowest 10th centile) during early gestation but without overt thyroid function are at risk for fetal breech presentation at term (>37 weeks of gestation).

Biomarkers↗

Effects of age and health on the euthyroid reference ranges for serum free thyroxine and free triiodothyronine.

Age-related trends in serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations were measured in 7248 euthyroid subjects (age-range 3 months to 106 years). 5700 were patients referred to hospitals for investigation of suspected thyroid dysfunction, but who were diagnosed euthyroid. 1548 were healthy blood donors (age-range 18-63 years) with no indication of thyroid dysfunction. FT4 concentrations were little affected by the age, the sex or the state of health of the subjects in either group. Serum FT3 concentrations were significantly affected by both age and health factors. The upper limit of the euthyroid reference range for young subjects up to 15 years was about 20% higher (10.4 pmol/l) than for adult subjects older than 25 years (8.8 pmol/l). The change in the upper limits typical of young subjects to that typical of adults occurred steadily over the decade 15-25 years. After this age, little further change occurred, especially in healthy subjects. Additionally, the lower limit of the euthyroid range for FT3 was extended by the inclusion in the reference group of patients referred to hospitals. Compared with the lower limit of the FT3 range for healthy subjects (5 pmol/l), the corresponding limit for referred subjects (young or adult) was 3.5-3.8 pmol/l. Broadening of the FT3 reference range was probably brought about by a significant number of patients in the hospital-referred group with the "low-T3 syndrome" of mild non-thyroidal illness. Accordingly, FT3 was inferior to FT4 in the discrimination of hypothyroidism, as FT4 was unaffected by this phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Goiters and thyroid function disorders in pregnancy].

Thyroid function abnormalities during pregnancy can affect up to 10% of all women. The mother's thyroid dysfunctions have an influence on fetal development, not only iodine deficiency, but also hyperthyroidism, hypothyroidism, and immunological disorders or inappropriate production of hCG. This review focuses on all thyroid dysfunctions during pregnancy.

Female↗

Thyroid function and anti-thyroid antibodies in MS patients screened for interferon treatment. A multicenter study.

Interferon beta (IFNB) treatment for multiple sclerosis (MS) has been associated with thyroid disorders (TD), in particular in patients with subclinical TD or anti-thyroid (AT) autoantibodies (autoAb) before starting treatment. TD and AT autoAb frequency was reported increased in MS. To determine whether MS patients have subclinical thyroid function abnormalities or anti-thyroid autoimmunity predisposing to develop TD, we performed a prospective multicenter screening of thyroid function and autoimmunity in 152 relapsing-remitting (RR) MS patients selected to receive IFNB treatment and in 437 healthy normothyroidal controls. Thyroid-related hormones and anti-thyroid microsomal antigen (anti-TMA) autoAb were tested with sensitive immunoradiometric or chromatographic assays. Cases were stratified for different progressively decreasing or increasing cutoff values of thyroid-stimulating hormone (TSH) (0.3, 0.2, 0.1, 3 and 5 mIU/l), and odds ratios (OR) with 95% confidence intervals (CI) calculated using logistic regression adjusted for gender, age, and anti-TMA autoAb positivity. The frequency of cases below or above the TSH cutoff values was not significantly different in MS patients and controls, and the risk to have an abnormal TSH level was not significantly increased in MS patients (OR ranging 0.37-0.84; CI, 0.05-3.01), even if anti-TMA autoAb positive (OR ranging 0.35-0.85; CI, 0.04-3.00). Frequencies of subclinical hypothyroidism and of anti-TMA autoAb positivity were, however, trending higher in MS men (ranging 5-7%) than in controls (3%). MS patients do not have an increased risk of subtle thyroid function abnormalities, subclinical TD, or anti-TMA autoAb positivity that may predispose to develop thyroid dysfunction during IFNB treatment. The positive trend for subclinical hypothyroidism and anti-TMA autoAb positivity, however, advises a longitudinal study of thyroid function and autoimmunity during IFNB treatment to see whether patients with baseline subclinical thyroid dysfunction develop clinically significant alteration during treatment.

Adolescent↗

Thyroid nodular disease after radiotherapy to the neck for childhood Hodgkin's disease.

Patients who receive radiotherapy to the neck are at risk of developing thyroid dysfunction. This prospective study of patients whose treatment for Hodgkin's disease in childhood included radiotherapy to the neck aimed to investigate the incidence and natural history of thyroid dysfunction and the morphological changes of the gland demonstrated on ultrasound. Forty-seven patients were investigated by clinical examination, thyroid function tests and thyroid ultrasound. Only six patients had a clinically detectable abnormality, but 64% had abnormal thyroid function tests. All patients had an abnormal thyroid ultrasound scan and 42% had at least one focal abnormality. A significant association was found between the presence of a focal lesion on ultrasound and young age at radiotherapy, longer follow-up and the length of time that the thyroid-stimulating hormone (TSH) level had been elevated. During follow-up, 65% of patients not on thyroxine developed new focal abnormalities. The longest time interval between radiotherapy and an increase in TSH level was 94 months, and from radiotherapy to the appearance of a focal abnormality on thyroid ultrasound was over 18 years. Three patients were found to have a thyroid carcinoma. These findings indicate the importance of long-term follow-up for patients treated by neck irradiation for Hodgkin's disease in childhood.

Adolescent↗

In vitro testing of thyroid function: a review.

Triiodothyronine (T(3)) is the major thyroid hormone and thyroxine (T(4)) may be only a "prohormone". A normal serum T(3) concentration can compensate for a low serum T(4) to maintain euthyroidism and on the other hand hyperthyroidism can exist in spite of a normal T(4) if the T(3) concentration is increased ("T(3)-toxicosis"). A raised serum thyroid stimulating hormone (TSH) concentration is the present most sensitive indicator of thyroidal hypothyroidism and the level can be used to titrate replacement therapy to the individual's own requirements. TSH concentration is classically low in hypothyroidism secondary to pituitary or to hypothalamic disorder and synthetic thyrotrophin release hormone can then be used to identify which of these two sites is at fault. Thyroxine is the best form of thyroid replacement for hypothyroidism because it produces more consistently physiological concentrations of T(3). Full replacement is achieved with 0.1 - 0.2 mg of T(4)/day and doses above this, as formerly widely used, may cause over-replacement. New reliable kit tests are available which give in one quick procedure a measure of free-thyroxine even in the presence of abnormalities of protein-binding. These kit tests are suitable for the routine screening of the whole spectrum of thyroid dysfunction and when combined, in appropriate instances, with radioimmunoassay procedures for serum T(3) and TSH, provide a battery of tests which will help in the diagnosis of the great majority of causes of thyroid dysfunction.

Female↗

Antithyroid hormone antibodies induced by interferon-alpha.

A 40-yr-old woman known for a multinodular goiter had hyperthyroidism. Treatment with antithyroid drugs and iodine therapy was effective. One year later, she received interferon-alpha for treatment of essential cryoglobulinemia. At that time, the patient was euthyroid. Testing for antithyroglobulin, antimicrosome, anti-TSH receptor, and antithyroid hormone antibodies was negative. After a 1-yr course of interferon-alpha, goiter enlargement was noticed. Apparently elevated free T3 and T4 serum values were measured by RIA, contrasting with clinical euthyroidism and normal TSH values. High serum levels of antithyroid hormone antibodies were found in the patient's serum, using a radiolabeled hormone immunoprecipitation assay. Antithyroglobulin and antimicrosome antibodies titers were also elevated and paralleled antithyroid hormone antibodies. After cessation of interferon-alpha therapy, clinical status and TSH levels remained normal, while thyroid hormone values and antithyroid hormone antibody levels progressively normalized. To our knowledge, this is the first report of antithyroid hormone antibodies induced by interferon-alpha. Since thyroid dysfunction is described in 10-15% of treated patients, the fact that interferon-alpha can induce antithyroid hormone antibodies has important implications: 1) the prevalence or intensity of thyroid dysfunction could be overestimated; and 2) artifactually elevated free T3 and T4 serum values could lead to inappropriate therapy of thyroid disease or cessation of interferon treatment.

Adult↗