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Prevalence of thyroid disease, thyroid dysfunction and thyroid peroxidase antibodies in a large, unselected population. The Health Study of Nord-Trondelag (HUNT).

OBJECTIVE: To examine the prevalence of thyroid disease and dysfunction including thyroid autoimmunity in Norway. MATERIALS AND METHODS: All inhabitants 20 years and older (94009) in Nord-Trondelag were invited to participate in a health survey with a questionnaire and blood samples. RESULTS: The prevalence of former diagnosed hyperthyroidism was 2.5% in females and 0.6% in males, hypothyroidism 4.8% and 0.9%, and goitre 2.9% and 0.4% respectively. In both sexes the prevalence increased with age. In individuals without a history of thyroid disease the median, 2.5 and 97.5 percentiles for TSH (mU/l) were 1.80 and 0.49-5.70 for females and 1. 50 and 0.56-4.60 for males. The TSH values increased with age. When excluding individuals with positive thyroid peroxidase antibodies (TPOAb) (>200U/ml), the 97.5 percentiles dropped to 3.60 mU/l and 3. 40 mU/l respectively. The prevalence of pathological TSH values in females and males were TSH >/=10mU/l 0.90% and 0.37%; TSH 4.1-9. 9mU/l 5.1% and 3.7%; and TSH</=0.05mU/l 0.45% and 0.20% respectively. The prevalence of positive TPOAb (>200U/ml) was 13.9% in females and 2.8% in males. In females the lowest percentage (7.9%) of positive TPOAb was seen with TSH 0.2-1.9mU/l and increased both with lower and higher levels of TSH. The percentage of males with positive TPOAb was lower than in females in all TSH groups except for those with TSH>10mU/l (85% TPOAb positive). CONCLUSIONS: In spite of a high prevalence of recognised thyroid disease in the population a considerable number of inhabitants have undiagnosed thyroid dysfunction and also positive TPOAb.

Adult↗

Endocrine-skin interactions. Cutaneous manifestations of pituitary disease, thyroid disease, calcium disorders, and diabetes.

Endocrinologic disorders occasionally manifest themselves by their associated or induced cutaneous abnormalities. In some instances the initial and most prominent complaints of the patient are related to alterations in the skin, and thus the dermatologist will at times be the first physician consulted. In this article we describe the cutaneous lesions that occur in patients with acromegaly, hypopituitarism, hypothyroidism, hyperthyroidism, diabetes mellitus, glucagonomas, hypercalcemia, hypoparathyroidism, and fibrous dysplasia. In addition, we also discuss the role of the skin in vitamin D metabolism. Whenever possible and where known, we have attempted to point out the pathophysiologic mechanisms that account for the cutaneous changes.

Calcium Metabolism Disorders↗

[Antigen receptor V beta gene usage of T lymphocytes in diseased thyroids in patients with autoimmune thyroid diseases].

OBJECTIVE: To explore the patterns of TCR V beta gene families and the preferentially used V beta genes in intrathyroidal T lymphocytes (ITL) of patients with Graves disease and Hashimoto thyroiditis. METHODS: Thyroid tissues of 12 patients with Graves disease, and 15 patients with Hashimotos thyroiditis were used for RNA extraction. Then, the RNA was used as templates for RT-PCR with a panel of primers including 24 oligonucleotides specific for TCR V beta gene families as upstream primers and one oligonucleotide specific for C beta as downstream primer. The amplified products were subjected to electrophoresis in agarose gels and observed under UV light. The positive expression of TCR V beta gene was identified by comparing the products with the size of the designed V beta genes. The matched peripheral blood samples of 5 Graves patients, 5 Hashimoto thyroiditis patients and 7 normal subjects were also obtained and used as controls. RESULTS: In 24 TCR V beta gene families tested for each individual sample, their average expressions were 5.3 +/- 1.2 and 13.4 +/- 3.0 in thyroid specimens of patients with Graves disease and Hashimoto thyroiditis, respectively, while those in the matched peripheral blood lymphocytes of the above two groups and normal controls were 23.0 +/- 1.0, 22.2 +/- 1.3 and 22.4 +/- 1.7, respectively. In addition, some of the TCR V beta genes such as V beta 3, V beta 5 and V beta 8 were more frequently used by intrathyroidal lymphocytes of Graves disease. CONCLUSIONS: These data indicate the oligoclonality of the intrathyroidal T cell populations in patients with Graves disease. Also, those of the preferentially used TCR V beta genes can be regarded as molecular targets for specific immune intervention. In contrast, the loss of restriction of TCR V beta gene utilization exists in Hashimoto thyroiditis, which may be related to the recruitment of T lymphocytes in thyroid glands through this mechanism.

Adult↗

[Significance of circulating anti-thyroid stimulating hormone (TSH) receptor antibodies in patients with autoimmune thyroid diseases--thyroid stimulation blocking antibody in patients with Graves' disease].

It is a well-known fact that a thyroid stimulation blocking antibody (TSBAb) may play an important role in primary hypothyroidism. However, it has rarely been reported that TSBAb appears in only a few cases of Graves' disease which became hypothyroidism in their clinical courses. We examined TSBAb in 120 sera from 79 cases with Graves' disease before or while under methimazole (MMI)-treatment. TSBAb value was expressed as the percentage inhibition of TSH-stimulated cAMP response of porcine thyroid cells by the patient's IgG. TSBAb was positive in 9 cases (11.4%) of 79 cases of Graves' disease. In 6 of the 9 cases, TSBAb was detected at the untreated period. In the other 2 of the 9 cases, it was detected during the exacerbation related with their pregnancy. It was difficult to control Graves' disease in all 9 cases. These results suggest that TSBAb appears not only in primary hypothyroidism but also even in the hyperthyroid state of Graves' disease, and that the combination of TSAb and TSBAb may regulate the pathogenesis of Graves' disease.

Adult↗

Possible role of IL-1, TNF-alpha, and IL-6 in insulin-dependent diabetes mellitus and autoimmune thyroid disease. Thyroid Cell Group.

Recent experiments indicate a central role of macrophages (M phi), and natural killer (NK) cells, and their products IL-1, IL-6 and TNF alpha in autoimmune endocrine diseases. Intermediate levels of IL-1 alpha/beta inhibit the function of pancreatic beta-cells and thyrocytes, an effect potentiated by TNF alpha. In contrast, low levels of IL-1 potentiate the secretion of insulin and thyroid hormones, and intermediate levels of IL-6 double glucose-induced insulin production by beta-cells. Intermediate and high levels of IL-1 and IL-6 are cytotoxic to normal beta-cells. IL-1 induces IL-6 in isolated islets and in thyrocytes. The cytokines may play a role in the physiological regulation of endocrine functions, for instance during conditions of stress. The genes for TNF alpha and -beta, both located in the MHC region, and IL-6 are polymorphic, and specific alleles may control the amount of cytokine produced. Specific TNF alpha/beta alleles may be in linkage disequilibrium with HLA alleles known to be positively or negatively associated with endocrine and other autoimmune diseases.

Animals↗

Molecular genetics of benign thyroid disease.

Thyroid diseases include forms amenable to alterations in genes involved in functional regulatory processes, morphofunctional development, hormogenesis and hormone functional expression. A number of genetic diseases are consequent of a point mutation, the cause of the replacement of a single nucleotide which may alter the chromosome number structure and morphology. Among structural anomalies there is deletion, duplication, inversion, translocation and isochromosome formation. Among thyroid diseases, the underlying cause of some of them is represented by alterations in genes regulating the thyroid function, alterations in genes of thyroid differentiation. Less common are the alterations in genes connected with the synthesis of proteins involved in hormone transport while alteration in genes encoding thyroid hormone receptors and in genes involved in thyroid neoplastic transformation are extensively described in literature. The studies of molecular biology will allow in-dept knowledge of the pathogenesis of thyroid disease associated to genetic alterations.

Chromosome Aberrations↗

Drug metabolism in thyroid disease.

Thyroid dysfunction can influence the physiological disposition of drugs. Depending on the pharmacokinetic properties of the individual drug, changes in the rate of metabolism ranging from profound to moderate or negligible have been observed. Since renal function is also influenced by thyroid disease, changes in renal elimination of drugs which are excreted in the urine mainly as unchanged drugs have to be considered as another reason for altered drugs disposition in thyroid disease. In patients with thyrotoxicosis lower, and in patients with myxoedema, higher, digitalis plasma levels have been observed. The altered disposition of cardiac glycosides in thyroid dysfunction can be attributed to changes in renal elimination and metabolism. These findings may be the kinetic correlate for the clinical observation that larger than the usual dose of digitalis is required in thyrotoxic patients and lower in hypothyroid patients. Antipyrene half-lives are very much shortened during hyperthyroidism and prolonged appreciably during hypothyroidism. The alterations in the disposition of these drugs seen during thyroid dysfunction can be ascribed to changes in its rate of metabolism which is controlled by the levels of circulating thyroid hormones. N-demethylation of aminopyrine is depressed both in hyper- and hypothyroid patients as compared with euthyroid subjects. Changes in the half-life of this drug were observed only during hypothyroidism. The physiological disposition of the antithyroid drug propylthiouracil is not changed during thyrotoxicosis. A decrease in plasma half-life of methimazole is however, observed during hyperthyroidism, whereas in hypothyroid patients half-life is increased. The few data available so far do not allow general prediction of how thyroid disease could alter drug metabolism in man.

Administration, Oral↗

Antithyroid peroxidase autoantibodies in thyroid diseases.

Thyroid microsomal antibodies (anti-M Ab) have been recently proven to be directed to thyroid peroxidase (TPO). Methods to detect anti-TPO antibodies (anti-TPO Ab) employing purified antigen have been developed, but the available information on the clinical usefulness of this technique is still limited to small patient series. In the present investigation anti-TPO Ab were assayed by a newly developed monoclonal antibody-assisted RIA in a large number (n = 715) of subjects, including 119 normal controls and 596 patients with different autoimmune or nonautoimmune thyroid disease: Anti-TPO Ab were detected in 10 of 119 (8.4%; range, 11-210 U/mL) normal controls, 134 of 181 (74%; range, 11-74.000 U/mL) patients with Graves' disease, all but 1 of 144 (99.3%; range, 11-90.000 U/mL) with Hashimoto's thyroiditis (n - 98) or idiopathic myxedema (n = 46), 20 of 180 (11.1%; range, 11-6.700 U/mL) with miscellaneous nonautoimmune thyroid diseases, 16 of 83 (19.2%; range, 11-6.600 U/mL) patients with differentiated thyroid carcinoma, and in none of 8 patients with subacute thyroiditis. The highest anti-TPO Ab concentrations were found in untreated hypothyroid Hashimoto's thyroiditis, but no simple relationship between anti-TPO Ab levels and thyroid function was observed. Anti-TPO Ab significantly decreased in patients with Graves' disease after treatment with methimazole and in those with hypothyroid Hashimoto's thyroiditis or idiopathic myxedema during L-T4 administration. A highly significant positive correlation (r = 0.979; P less than 0.001) was found between anti-M Ab titers by passive hemagglutination (PH; available in 650 sera) and the corresponding average anti-TPO Ab by RIA; discrepant results were almost exclusively limited to sera with negative or low (1:100-1:400) anti-M Ab titers. Analysis of these discrepant data indicated higher autoimmune disease specificity and sensitivity of anti-TPO Ab RIA tests compared to anti-M Ab by PH. Absorption studies showed that interference of anti-Tg Ab was responsible for anti-M Ab-positive tests in occasional anti-TPO Ab-negative/anti-M Ab-positive sera from autoimmune thyroid disease patients. Anti-TPO Ab determination by RIA was unaffected by circulating thyroglobulin concentrations up to more than 10,000 ng/mL. In conclusion, anti-TPO Ab assay by monoclonal antibody-assisted RIA appears to be more sensitive and specific for thyroid autoimmune diseases than anti-M Ab determination by PH. Since the assay is easy to perform and employs only tracer amounts of purified antigen, these characteristics should allow its rapid diffusion to the clinical routine.

Adolescent↗

Humic substances in drinking water and the epidemiology of thyroid disease.

Thyroid diseases are common in all populations but the type and frequency depends on environmental factors. In Denmark geographical differences in iodine intake are caused by different iodine contents of drinking water, which varies from < 1 to 139 microg iodine per litre. Comparative epidemiologic studies have demonstrated considerable differences in type and occurrence of thyroid disease with more goitre and hyperthyroidism in Aalborg with water iodine content around 5 microg/L, and more hypothyroidism in Copenhagen with water iodine around 20 microg/L. In Denmark, iodine in ground water is bound in humic substances, which have probably leached from marine sediments in the aquifers. Interestingly, humic substances in water from other parts of the world have goitrogenic properties, especially humic substances from coal and shale. Humic substances are heterogeneous mixtures of naturally occurring molecules, produced by decomposition of plant and animal tissues. The effect of humic substances in drinking water on the epidemiology of thyroid disease probably depends on the source of aquifer sediments.

Chelating Agents↗

Occult thyroid pathology in the young adult: an autopsy study of 138 patients without clinical thyroid disease.

Thyroid glands from autopsies on 138 adults, ages 20 to 40 years, with no known clinical or laboratory evidence of thyroid disease, were serially sectioned at 2 mm intervals and microscopically examined for occult thyroid disease and anatomic variations. Occult papillary carcinoma was found in 3% of the glands, along with a single case of medullary carcinoma. The prevalence of occult thyroid carcinoma in this group of young adults is significantly less than that reported in the literature in people over forty (P less than .001). The glands demonstrated a number of other morphologic changes of importance to surgical pathologists. The thyroid capsule was incomplete in 62% of the glands. Thyroid follicles were found in the capsule in 14% of cases and thyroid follicles or nodules were outside the gland in perithyroid connective tissue in 88% of cases. Thyroid follicles were identified in 7% of cases in perithyroid strap muscles attached to the pyramidal lobe. A number of other, less common anatomic variations were also seen.

Adenoma↗

Pregnancy complicated by thyroid disease.

Thyroid disorders during pregnancy can have potential adverse effects on the fetus, making recognition and treatment of paramount importance. Signs and symptoms of thyroid disease can be masked by pregnancy. Familiarity with thyroid function test values and their interpretation during normal pregnancy is necessary to discriminate between expected changes and pathological changes. Ongoing management of a pregnant woman with thyroid disease involves sign and symptom monitoring, thyroid function testing to adjust medication dosage, and patient education/counseling regarding the disease and its relationship to her pregnancy.

Counseling↗

Anemia in thyroid diseases.

Thyroid hormones generally stimulate erythropoiesis. These agents also increase erythrocyte 2,3-DPG concentrations, which serve to enhance the delivery of oxygen to tissues. In the absence of thyroid hormones, anemia frequently develops and may be normocytic, hypochromic-microcytic, or macrocytic. Anemia is an uncommon finding in hyperthyroidism but when present may be morphologically similar to that observed in hypothyroidism. Pernicious anemia has been strongly associated with hypothyroidism, hyperthyroidism, and thyroiditis. Complete correction of anemia often requires restoration of thyroid function as well as specific hematinic therapy. Continued attention to hematologic status is essential in the management of patients with thyroid diseases.

Anemia↗

Subclinical thyroid disease.

Thyroid disease can roughly be divided into functional and anatomical disorders. Subclinical disease is by definition not accompanied by symptoms or signs and usually goes unrecognized for the bearer (and the observer). In this communication an overview will be given of existing literature and some own results concerning subclinical hypothyroidism, subclinical thyrotoxicosis and thyroid incidentalomas. Apart from definitions, data on prevalence, clinical effects, prognostic significance and the need for and response to therapy will be discussed.

Humans↗

Reversible alteration of red cell lithium-sodium countertransport in patients with thyroid disease.

Thyroid hormones may alter red blood cell (RBC) sodium content and transport. The functional importance of lithium-sodium (Li-Na) countertransport in regulating sodium (Na) transport in vascular smooth muscle and kidney by Na-H countertransport and the potential effect of thyroid hormone on these processes led us to study Li-Na countertransport and other sodium transporters in RBCs of patients with thyroid dysfunction. Patients with untreated hypothyroidism (10) and hyperthyroidism (10) were studied, along with normal subjects (10). The mean value for Li-Na countertransport was significantly higher in the hypothyroid group [0.46 +/- 0.08 (+/- SE) mmol/L cell.h; P less than 0.05] and lower in the hyperthyroid group (0.15 +/- 0.04 mmol/L cell.h; P less than 0.05) compared to that in the normal subjects (0.25 +/- 0.03 mmol/L cell.h). When all groups were combined, significant negative correlations were found between Li-Na countertransport and serum T4 (r = -0.48; P less than 0.01), free T4 index (r = -0.42; P less than 0.05), and serum T3 (r = -0.38; P less than 0.05). Li-Na countertransport was positively correlated with serum triglyceride (r = 0.57; P less than 0.01), but not with serum cholesterol levels (r = 0.28; P = NS). The values became normal in subsets of the hypothyroid (n = 5) and hyperthyroid groups (n = 5) during treatment. We found a bidirectional effect of thyroid status on RBC Li-Na countertransport, which was reversible when serum thyroid hormone levels became normal. Changes in Li-Na countertransport, a pathway of Na-H exchange, may influence renal sodium handling and vascular tone in patients with thyroid disease and contribute to abnormalities such as hypertension that occur in patients with hypothyroidism.

Biological Transport↗

High prevalence of acquired von Willebrand's syndrome in patients with thyroid diseases undergoing thyroid surgery.

BACKGROUND AND OBJECTIVES: Various coagulation abnormalities occur in patients with thyroid diseases. These abnormalities range from subclinical laboratory findings to hemorrhage or thromboembolism. However, the prevalence of hemostatic abnormalities in patients with thyroid diseases is still unclear. DESIGN AND METHODS: Between January 1999 and December 2003, 1342 consecutive patients with various thyroid diseases who were candidates for thyroid surgery underwent preoperative screening of hemostatic parameters including prothrombin time, activated partial thromboplastin time and platelet-related hemostasis with the PFA-100 platelet-function analyzer. RESULTS: Thirty-nine patients (2.9%) had abnormalities of the coagulation screening tests. Of these, 35 patients had von Willebrand's disease (type 1 in 33 cases and type 2A in 2 cases), 2 patients had decreased platelet aggregability, and 2 patients had coagulation factor XI deficiency. As all patients with coagulation abnormalities responded to subcutaneous desmopressin injection (0.3 microg/Kg BW), this drug was successfully used as surgical prophylaxis. INTERPRETATION AND CONCLUSIONS: Up to 3% of patients with thyroid diseases undergoing thyroid surgery have coagulation abnormalities, in most cases resembling von Willebrand's disease. Coagulation screening tests are needed in order to identify those patients at increased risk of bleeding.

Adolescent↗