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The natural history of autoimmune thyroid disease.

The autoimmune thyroid diseases have several clinical forms and undergo considerable variation in time in clinical, functional, and serological expression. These variations may best be understood in the light of a number of variables which interact in determining the nature of the disorder in each individual. These variable include subtle differences in genetics between one disorder and another, the magnitude of the organ-specific immunoregulatory defect and the superimposed influence of environmental factors (including hormonal factors) on the overall immune system. The latter influence may be of major importance in bringing about the remarkable variations observed over time in many patients in the expression of their conditions.

Autoimmune Diseases↗

Computed tomography in the evaluation of thyroid disease.

Traditionally, thyroid imaging has been performed primarily using radionuclide scanning. High-resolution computed tomography (CT) was performed in 18 patients to evaluate the CT appearance of various thyroid abnormalities including diffuse toxic goiter, multinodular goiter, Hashimoto thyroiditis, thyroid adenoma, and malignant thyroid tumors. CT images of the thyroid were correlated with radionuclide scanning, surgical findings, and clinical and laboratory results. CT provided a complementary method for evaluation of the thyroid by defining the morphology of the thyroid gland and more precisely defining the anatomic extent of thyroid abnormalities in relation to the normal structures of the neck and mediastinum.

Adolescent↗

Thyroid disease and pregnancy.

Thyroid disease is the most common pre-existing endocrine complaint occurring in pregnancy, reflecting in part its predilection for women of childbearing age. It is the fifth most frequent disorder in our general obstetric medicine clinic. When optimal management is achieved, a good outcome is likely for both the mother and child.

Adult↗

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↗

[99mTc uptake and TSH receptor autoantibodies--comparative study in Basedow's disease and other thyroid diseases].

In 255 patients (normals: group I, n = 30; nontoxic goitres: group II, n = 134; toxic goitres without ophthalmopathy: group III, n = 63; Graves' disease: group IV, n = 28) a TSH-receptor-autoantibody-assay (TRAK assay) for detection of thyrotropin-binding inhibiting antibodies (TBIAb) was tested and 99mTcO4-uptake (TcTU) was measured. Normal TcTU (range: 1.5-5.5%) and normal TRAK values (normal limit: F less than 11%) were only found in group I. An increased TcTU was found in group II in 22.4% (increased TRAK values only in 2.2%). In group III an increased TcTU was measured in 34.9% of the patients (all with normal TRAK titers). The stimulation of the TSH-receptor in immunogenic hyperthyroidism by TBIAb could be demonstrated by increased TRAK values in 71.4% of the patients with Graves' disease. In correlation, TcTU was also increased in 82.1% of the patients in group IV. As the measurement of TcTU can be helpful in differential diagnosis, the functional imaging with gamma camera and computer is today a conditio sine qua non, especially in suspected hyperthyroidism.

Autoantibodies↗

Thyroid disease in the elderly.

Thyroid disease in the aged, both hypothyroidism and hyperthyroidism, may be subtle or may be present with no clinical symptoms and signs, and is therefore difficult to diagnose on the basis of clinical evaluation. The help of the laboratory is essential in making the diagnosis of disease of the thyroid. Therapeutic strategies are different in the aged than in the younger adult with thyroid disease. It is essential for geriatricians, and all clinicians who care for the elderly, to have a solid understanding of thyroid function and dysfunctions in this group of patients so that they diagnose diseases of the thyroid correctly and treat them appropriately.

Aged↗

[Subclinical thyroid diseases].

The term "subclinical thyroid diseases" describes conditions characterized by low or elevated thyroid-stimulating hormone (TSH), normal levels of circulating thyroid hormones (thyroxine and triiodothyronine), and few or no definite clinical signs or symptoms of thyroid dysfunction. Therefore, it is a diagnosis based on laboratory evaluation, not on clinical criteria. Because the risk of subclinical thyroid disease increases with age, the number of cases should increase as population ages. Their importance lies in the possible adverse effects on the heart, lipids, bone mineral density, quality of life and mortality. Although the subclinical thyroid diseases tend to progress to overt disease, TSH levels in some subjects return to the reference range. However there is controversy about the definition, clinical importance, consequences of untreated disease, whom to screen and when to initiate treatment. We reviewed the literature and our recommendations about screening and treatment are based upon the existing evidence and the author's experience.

Humans↗

Coexistence of primary hyperparathyroidism and thyroid disease.

Primary hyperparathyroidism (HPT) and thyroid disease are both relatively common diseases, which can coexist in the same patient. However, mere coincidence does not seem to be a satisfactory explanation for this association. Some factors like prior exposure to radiation may play a role in the association. The aim of this study was to determine the frequency of thyroid disease associated with HPT in 54 consecutive patients who underwent parathyroidectomy in our center from January 1990 to December 1997. Twenty-eight (52%) patients had thyroid disease associated to HPT. The patients had a mean age of 61+/-13 yr; they were predominantly postmenopausal women. Thyroid disease was detected preoperatively in 20 (71%) patients and during the surgical procedure in 8 (29%). Two patients had previous radiation exposure; one of them with papillary carcinoma of the thyroid. Two patients had hypothyroidism. UItrasonography was performed in the majority of patients in their preoperative evaluation. A multinodular goiter was seen to be the most frequent finding (76%). In addition to parathyroidectomy, 23 (82%) patients were also thyroidectomized. In conclusion, patients with HPT showed a high prevalence of thyroid disease, especially in postmenopausal women. Unsuspected thyroid lesions were found with sufficient frequency to warrant careful preoperative and intraoperative evaluation of both glands, in order to obviate reoperation. In experienced hands, combined surgery can be safely performed. Cervical ultrasonography is useful in the preoperative detection of nodular thyroid disease in these patients.

Adolescent↗

Geographic pathology of thyroid diseases.

The thyroid is one of the organs which demonstrates clearly the influence of extrinsic and especially geographically determined influences in the development of diseases. Endemic goiter and cretinism are the most typical examples. The question as to whether thyroid cancer arises more frequently in goiters that in normal thyroids, cannot be answered definitely as yet. But without doubt, the relative frequency of different types of thyroid neoplasms in goiter areas is not the same as in region without endemic goiter. The most common type of thyroid carcinoma observed in a nonendemic region is papillary carcinoma. Follicular and anaplastic carcinomas, however, are more often associated with goiter. Under the influence of iodine prophylaxis, the relative frequency of the different types of thyroid carcinoma approaches that of these carcinomas in nongoiter regions. The malignant hemangioendothelioma is observed nearly exclusively in some Alpine goiter areas. Since the introduction of preventive measures in Switzerland, its occurrence has diminished progressively. In contrast to endemic goiter, focal thyroiditis and even Hashimoto's disease seem to be on the increase since institution of iodine prophylaxis of endemic goiter. As the development of malignant lymphoma may be related to thyroiditis, a possible increase of such tumors should be considered.

Congenital Hypothyroidism↗

Immunohistochemical demonstration of thyroid peroxidase (TPO) in human thyroid tissues from various thyroid diseases.

Human thyroid peroxidase (hTPO) was detected immunohistochemically in 61 normal, benign and malignant thyroid tissues with a monoclonal antibody (38E) against hTPO using paraffin-embedded sections. Thyroid peroxidase was expressed intensely not only in tissues from Graves disease and hyperfunctioning adenomas, but also in those from carcinomas, adenomas and Hashimoto's thyroiditis. The staining pattern of TPO in the follicular cells was a diffuse and fine granular one in the normal thyroids, Graves' thyroids and adenomas, but abnormal coarse granular deposits of TPO were characteristically identified in most of the papillary carcinomas and Hashimoto's thyroiditis. These coarse granular deposits of TPO suggested that qualitative or structural changes in the TPO molecule are present in carcinomas and Hashimoto's thyroiditis. Consequently, these qualitative changes in TPO may be responsible for the lack of biochemically measured TPO activity in these diseases. This finding may also be useful in distinguishing between benign and malignant thyroid tumors.

Humans↗

Thyroid antibodies in children of mothers with auto-immune thyroid disease.

UNLABELLED: In a cross-sectional study, 29 children aged between 1 month and 15.3 years (average age 6.8 years) born to mothers with Graves disease or Hashimoto thyroiditis were examined clinically, biochemically, and by sonography of the thyroid gland. At the time of examination all children were clinically euthyroid. Tests of thyroid peroxidase antibody, thyroglobulin antibody, TSH receptor antibody and free thyroxine (fT4) gave normal results. In 3 children subclinical hypothyroidism with elevated TSH and normal fT4 concentrations were found; one of these children had a minor decrease of total thyroxine. Three children with otherwise normal test results had marginally elevated triiodothyronine concentrations. Increased antibody titres were present in 8 out of 29 children. TSH function-blocking antibodies were elevated in 8 cases. In addition, cytotoxic antibodies were found in one of the children. The distribution pattern of antibodies was different in each child and unrelated to the type of maternal thyroid disease. CONCLUSION: Children of mothers with auto-immune thyroid disease often have thyroid antibodies without signs of thyroid disease. Whether antibody-positive children have an increased risk of developing thyroid disorders later in life must be examined in a longitudinal study.

Adolescent↗

Prevalence of fractures in postmenopausal women with thyroid disease.

We interviewed 300 white postmenopausal women (160 with thyroid disease, 140 without thyroid disease) to investigate whether having thyroid disease or taking thyroid hormone increased the prevalence of having a hip, vertebral, or forearm fracture. Thirty-seven (23%) women with thyroid disease and 45 (32%) women without thyroid disease had had a fracture, and there were no significant differences between these groups in the number or type of fractures. Dose of thyroid hormone and duration of therapy or disease did not affect fracture occurrence in women with thyroid disease. Women with a history of hyperthyroidism (9 of 32) or thyroid cancer (2 of 11) appeared to have their first fracture earlier (p < 0.01) than women without thyroid disease. In summary, women taking thyroid hormone for a variety of thyroid disorders do not appear to have an enhanced prevalence of a hip, vertebral, or forearm fractures, but women with a history of hyperthyroidism may have a propensity for their fractures to occur earlier in life.

Aged↗

Thyroid peroxidase activity-inhibiting immunoglobulins in patients with autoimmune thyroid disease.

The thyroid microsomal antibody (M-Ab) has been found to be an antibody against thyroid peroxidase (TPO), and such antibodies have been reported not only to bind TPO but also to directly inhibit TPO activity. In this study we investigated the relationship between TPO activity-inhibiting immunoglobulin (TPII) and thyroid function in 55 untreated patients with hyperthyroidism due to Graves' disease and 35 untreated patients with Hashimoto's disease. TPO partially purified from the microsomal fraction of Graves' thyroid tissue by Sephacryl S-300 gel filtration was incubated with immunoglobulin (Ig) fractions of serum prepared by precipitation with 15% polyethylene glycol. At the end of incubation, TPO activity was measured by a guaiacol assay. The TPII level was expressed as the TPII index, defined as the inhibition of TPO activity by patient Ig divided by inhibition produced by a known positive Ig. We also measured serum free T4, free T3, and TSH concentrations and anti-M-Ab titers, the latter by a microenzyme-linked immunosorbent assay. When a positive TPII index was defined as more than the mean + 2 SD of the TPII index (0.38) for 15 normal subjects, 13 patients with Graves' disease and 14 patients with Hashimoto's disease had positive TPII index values. There was a positive correlation between the TPII index values and the M-Ab titers in patients with either Graves' disease (r = 0.38; P less than 0.01) or Hashimoto's disease (r = 0.52; P less than 0.01). The mean TPII index in patients with Hashimoto's disease was significantly higher than that in patients with Graves' disease [0.38 +/- 0.42 (+/- SD) vs. 0.19 +/- 0.41; P less than 0.05]. The slope of the regression line between the TPII index values and the M-Ab titers for patients with Hashimoto's disease was steeper than that for patients with Graves' disease. The mean serum free T4 concentration was significantly lower in those patients with Hashimoto's disease who had positive TPII index values than in those with negative TPII index values (14.0 +/- 5.0 vs. 9.6 +/- 3.7 pmol/L; P less than 0.01). There was no significant difference in thyroid function between the patients with Graves' disease with positive and negative TPII index values. TPII appears to inhibit thyroid function in some patients, but no simple relationship between TPII and thyroid function in autoimmune thyroid disease was demonstrated. Understanding the factors that control access of anti-TPO antibody to its antigen may help to elucidate the significance of circulating anti-TPO antibody.

Adolescent↗

Detection of thyrotropin-receptor messenger ribonucleic acid (mRNA) and thyroglobulin mRNA transcripts in peripheral blood of patients with thyroid disease: sensitive and specific markers for thyroid cancer.

Because thyroid cancer cells express functional TSH receptors (TSHR), TSHR-mRNA in peripheral blood might serve as a tissue-/cancer-specific marker. We measured circulating TSHR-mRNA by RT-PCR in 51 normal controls, 27 patients with benign thyroid disease, 67 patients with treated differentiated thyroid cancer (DTC), and eight patients with newly diagnosed DTC, preoperatively. Results were compared with thyroglobulin (Tg) mRNA and serum Tg levels. TSHR-mRNA signals were not detected in normal controls and in 24 of 27 (89%) patients with benign thyroid disease. All 19 patients with treated DTC with evidence of distant or local disease tested positive for TSHR-mRNA (sensitivity 100%). Among patients with no evidence of disease, TSHR-mRNA was detected in 1 in 48 (specificity 98%). Six of the eight newly diagnosed DTC patients tested preoperatively were positive for TSHR-mRNA. The concordance between TSHR-mRNA and Tg-mRNA and between TSHR-mRNA and serum Tg was 95%. Fourteen patients with DTC (21%) had Tg antibodies, three with local disease (all positive for TSHR-mRNA), and 11 with no evidence of disease (all negative for TSHR-mRNA). Our results indicate that TSHR-mRNA and/or Tg-mRNA in peripheral blood are both equally sensitive and specific markers for monitoring thyroid cancer patients. Their principal value resides in the Tg antibody-positive patients in whom a positive or a negative mRNA value might have indicated or obviated the need for a whole-body scan. Furthermore, the high specificity combined with their ability to predict thyroid cancer preoperatively suggests a potential role in detecting thyroid cancer in patients with thyroid nodules.

Adult↗

Increased specificity and sensitivity of insulin antibody measurements in autoimmune thyroid disease and type I diabetes.

Insulin autoantibodies (IAA), a marker for insulin-dependent diabetes mellitus (IDDM), have been reported in other diseases such as thyroid disease and after treatment with sulfhydryl containing medications. Reported prevalences of IAA in non-diabetics vary widely, probably due in part to methodological differences between laboratories. In addition, certain sera may have a high non-specific binding to insulin. We compared a radioimmunoassay (RIA) for IAA which included non-specific binding with an RIA that incorporated a competitive displacement with cold insulin to remove non-specific binding. Using the RIA which measured specific plus non-specific binding, IAA positivity was found in 22/92 (23.9%) of sera from thyroid disease patients, 16/124 (12.9%) of random masked sera from a hospital laboratory, 27/335 (8.1%) of first degree relatives of IDDM patients, 63/178 (35.4%) of subjects with newly diagnosed IDDM, and 0/92 (0%) of normal controls. Insulin antibodies (IA) were found in 80/99 (80.8%) of insulin-treated diabetic subjects. In contrast, using the displacement assay which allowed measurement of specific binding, the frequency of IAA positivity was lower for subjects with thyroid disease (7/92 (7.6%)), random hospital sera (12/124 (9.8%)), and for first degree relatives of IDDM patients (8/335 (2.4%)), while higher for subjects with newly diagnosed IDDM (71/178 (39.9%)). Subjects with insulin-treated diabetes (78/99 (78.8%)) and normal subjects (1/92 (1.1%)) showed little change. Strikingly, three of the eight (37.5%) relatives of IDDM patients that were positive in the RIA measuring specific binding were detected only because cold displacement was utilized. We conclude: (1) subjects with thyroid disease and first degree relatives of IDDM patients frequently have high non-specific binding for IAA in an RIA not employing a cold displacement step, (2) in some newly diagnosed IDDM patients and first degree relatives of IDDM patients, IAA may be missed by an assay not optimized to measure specific binding, and (3) displacement with cold insulin increases both the specificity and sensitivity of RIAs measuring insulin autoantibodies.

Antibody Specificity↗

Autoantibodies to p53 in sera of patients with autoimmune thyroid disease.

Mutations in the tumor suppressor gene, p53, lead to intracellular accumulation of abnormal p53 protein and are associated with p53 autoantibodies. p53 also accumulates in autoimmune diseases and Hashimoto's thyroiditis, but it is unknown if p53 autoantibodies occur in the latter. We measured p53 autoantibodies in the sera of 93 patients with thyroid disease and 19 patients without thyroid disease. Anti-p53 antibodies were detected in the sera from 4.2% (2/48) of patients with autoimmune thyroid disease, including one patient with Hashimoto's thyroiditis (3.7%, 1/27) and one with Graves' disease (4.8%, 1/21). A third patient with pseudohypoparathyroidism, but without thyroid disease, was also positive (1/19; 5.2%). None of 19 patients with differentiated thyroid cancer had anti-p53 antibodies. We conclude that anti-p53 antibodies can be detected in the sera from approximately 4% of patients with autoimmune thyroid disease. This finding suggests that increased DNA damage and apoptosis may be associated with autoimmune thyroid disease.

Adolescent↗

Thyroid disease in patients with dementia of the Alzheimer type.

The authors compared the frequencies of prior thyroid disease, thyroid medication use, and abnormal serum thyroxine levels in 61 patients with dementia of the Alzheimer type (DAT) with those of 38 control subjects. They found that the 33 women with DAT had a 24.2% frequency of prior thyroid disease, comparable with that found in a previous epidemiologic study. The 19 female controls, however, had a similar frequency, failing to support a previously reported association between DAT and thyroid disease.

Aged↗