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Thyroid disease and male reproductive function.

Despite the high prevalence of thyroid diseases in the general population, male reproductive function in patients with thyroid disease has been the subject of only a few studies. Hyperthyroidism appears to cause sperm abnormalities (mainly reduction in motility), which reverse after restoration of euthyroidism. Radioiodine therapy for hyperthyroidism or thyroid cancer may cause transient reductions in sperm count and motility, but there appears to be little risk of permanent effects provided that the cumulative dose is less than 14 MBq. The effects of hypothyroidism on male reproduction appear to be more subtle than those of hyperthyroidism and reversible. Severe, prolonged hypothyroidism in childhood may be associated with permanent abnormalities in gonadal function.

Humans↗

3,3'-Diindolylmethane, a cruciferous vegetable derived synthetic anti-proliferative compound in thyroid disease.

Considerable epidemiological evidence exists to link thyroid disease with differing patterns of dietary consumption, in particular, cruciferous vegetables. We have been studying the anti-thyroid cancer (TCa) activity of indole-3-carbinol (I3C) found in cruciferous vegetables and its acid catalyzed dimer, 3,3'-diindolylmethane (DIM). There are no studies as yet to elucidate the effect of these compounds on the altered proliferative patterns in goiter or thyroid neoplasia. In this study, we tested the anti-proliferative effects of I3C and DIM on four different thyroid cancer cell lines representative of papillary (B-CPAP and 8505-C) and follicular carcinoma of the thyroid (CGTH-W-1 and ML-1), and primary human goiter cells. Cell survival and IC50 values for I3C and DIM were calculated by the XTT assay and cell cycle distribution analysis was done by flow cytometry. DIM was found to be a better anti-proliferative agent than I3C in both papillary and follicular TCa resulting in a greater cytotoxic effect at a concentration over three fold lower than predicted by the molar ratio of DIM and I3C. The anti-proliferative activity of DIM in follicular TCa was mediated by a G1 arrest followed by induction of apoptosis. DIM also inhibited the growth of primary goiter cells by 70% compared to untreated controls. Contrary to traditional belief that cruciferous vegetables are "goitrogenic", DIM has anti-proliferative effects in glandular thyroid proliferative disease. Our preclinical studies provide a strong rationale for the clinical exploration of DIM as an adjuvant to surgery in thyroid proliferative disease.

Anticarcinogenic Agents↗

The antibody response in human autoimmune thyroid disease.

1. The analysis of the antibody response in autoimmune thyroid disease has followed several historical trends. It was the investigation of thyroid-reactive antibody that allowed the initial characterization of the three principle thyroid autoantigens, thyroglobulin, thyroid peroxidase and the thyroid stimulating hormone receptor. 2. Analysis can be grouped under two broad areas: analysis of the physiological and pathological effects of the antibody, and analysis of the structure of the antibodies themselves. This review will focus on the latter. 3. Within recent years there has been a great increase in knowledge of thyroid-reactive antibody structure, principally through the adoption of phage display combinatorial library methodologies. While this latter technique has established some general principles for antibodies to thyroglobin and especially thyroid peroxidase, there is still a substantial gap in our knowledge of the antibody response to the thyroid stimulating hormone receptor. 4. Thyroid peroxidase antibodies have a relatively restricted V-region usage, and there is a correlation between the V-regions used and the epitope on thyroid peroxidase bound. In particular the V kappa light chain V kappa I(O12), is associated with reactivity to one epitope. 5. The purpose of this review is to bring together the latest results concerning the molecular analysis of the antibody response in autoimmune thyroid disease, to highlight areas of ignorance and conflict, and to discuss the methods adopted to circumvent the problems associated with analysis of the antibody response.

Antibody Formation↗

Prevalence of pernicious anaemia in patients with Type 1 diabetes mellitus and autoimmune thyroid disease.

AIMS: To determine the prevalence of pernicious anaemia in patients with Type 1 diabetes mellitus and autoimmune thyroid disease. METHODS: A randomly selected asymptomatic group of 63 patients with Type 1 diabetes who also had autoimmune thyroid disease was studied. Blood samples were taken and assayed for serum B12. Those subjects with serum B12 concentrations below the reference range had a further blood sample taken for determination of intrinsic factor antibody. RESULTS: One patient had been diagnosed previously to have pernicious anaemia. Three patients had low serum B12 concentration and positive intrinsic factor antibody, confirming the diagnosis of pernicious anaemia. The prevalence of pernicious anaemia in this population with Type 1 diabetes and concomitant autoimmune thyroid disease was 6.3%. In female patients the prevalence of pernicious anaemia was 8.5%. CONCLUSIONS: Patients who have both Type 1 diabetes mellitus and autoimmune thyroid disease are at risk of developing pernicious anaemia.

Aged↗

A national study on biopsy-confirmed thyroid diseases among Koreans: an analysis of 7758 cases.

In order to determine the incidence and to understand recent trend of thyroid neoplasm and other thyroid diseases among Korean, a nation-wide collection of biopsy-confirmed and surgically removed thyroid lesions from 30 pathology laboratories of university and general hospitals was made over a 3-year-period from 1986 to 1988. These tumors and tumor-like lesions of the thyroid were classified according to the WHO classification. Results of this study were compared with those of the previous in Korea and other countries. Among the 7758 collected cases from 7449 patients, adenomatous goiter was the most common, comprising 2681 cases (34.6%), followed by follicular adenoma, 1868 cases (24.1%) and papillary carcinoma, 1474 cases (19%). Neoplastic condition comprised 48.8% (3786 cases). Of malignant tumors, papillary carcinoma was the most frequent accounting for 79.8%. The female to male ratio was 7.5:1 with female predominance. This female predominance was noted in all but two thyroid diseases. Medullary carcinoma showed equal distribution in both sexes, and two cases of malignant lymphoma developed in males. Thyroid diseases were common at the 3rd to 6th decades with peak incidence at the 4th decade. The right lobe of the thyroid was more frequently involved than the left lobe (1.6:1). The diagnoses were made largely on the surgically excised specimen (85.3%). Multiplicity of the lesions revealed single lesion in 64%, multiple and diffuse lesion in 36% of cases investigated. Average size of the lesion was in the range of 1-5 cm in diameter (62%).

Adenoma↗

Zinc, copper, manganese, and selenium metabolism in thyroid disease.

This study was designed to evaluate trace metal metabolism in adults with thyroid diseases. Erythrocyte zinc values were significantly lower than normal in hyperthyroidism and higher in hypothyroidism. A significantly higher than normal urinary excretion of zinc was observed in hyperthyroidism. The mean concentrations of plasma and erythrocyte copper were significantly above normal in hyperthyroidism. Plasma selenium levels were significantly lower than normal in hyperthyroidism. No statistically significant difference was found in plasma zinc, erythrocyte manganese, or urine copper values between patients with thyroid diseases and healthy controls. The erythrocyte manganese content correlated well with thyroxine and triiodothyronine levels. Plasma prealbumin and retinol-binding protein correlated well with the erythrocyte zinc content but not with plasma zinc levels. There was no correlation between erythrocyte superoxide dismutase activity and erythrocyte copper or zinc concentrations. The results of this study suggest that the metabolism of zinc, copper, manganese, and selenium is abnormal in thyroid diseases.

Adolescent↗

Polyendocrine autoimmunity in thyroid diseases.

Anti-adrenal and anti-pituitary autoantibodies have been determined in 45 patients with autoimmune diseases of the thyroid, including 25 patients with Graves' disease and 20 patients with hypothyroidism of autoimmune origin. The determinations were carried out with the use of solid-phase RIA methods previously developed by us, involving polyethylene tubes coated with the solubilized microsomal fractions obtained from human adrenal and pituitary glands. In the majority of patients with autoimmune diseases of the thyroid the presence of both anti-adrenal and anti-pituitary autoantibodies was detected. In 13 among 20 patients with hypothyroidism of autoimmune origin, the presence of anti-adrenal autoantibodies, and in 12 the presence of anti-pituitary autoantibodies was found. Among 25 patients with Graves' disease, 19 had both anti-adrenal and anti-pituitary autoantibodies. In the majority of patients with autoimmune diseases of the thyroid the titers of autoantibodies of both types were high but in no case were the clinical symptoms of adrenal or pituitary hypofunction observed. Our studies indicate that the thyroid diseases of autoimmune origin can be regarded as manifestation of some more generalized autoimmunization process.

Adrenal Glands↗

[Cardiovascular consequences of thyroid diseases, their prevalence and treatment, particularly in cases with subclinical hyper- and hypothyroidism].

Cardiovascular consequences of thyroid diseases, their prevalence and treatment, particularly in cases with subclinical hyper- and hypothyroidism. The aim of the study was to draw attention to an association between the thyroid and cardiovascular diseases. The main topic was to lay emphasis on the importance of cardiovascular diseases caused by subclinical hyper- and hypothyroidism in the relation to the practice. The subclinical states precede the overt hyper- and hypothyroidism, and they are often present during their treatments. The changes in the levels of thyrotropin demonstrating subclinical thyroid diseases, could be detected in different non-thyroid diseases and resulted from the effect of some drugs. Particularly, the subclinical thyroid diseases become more frequent in older age. In the background of the high prevalences of atrial fibrillation, hypertension and psychosomatic events subclinical hyperthyroidism could be revealed. Subclinical hypothyroidism is characterized by an increased prevalence of elevated serum lipid levels, atherosclerosis, ischemic heart disease and hypertension often associating with the presence of anti-thyroid antibodies. It is important to reveal subclinical thyroid diseases in time for the effective treatment and for stopping of the cardiovascular damages before manifestations of cardiovascular diseases. The paper gives advice for the practice and the rational management. At the end, a survey of the association between thyroid and heart diseases in own department of internal medicine at the last three years is given.

Aged↗

Anti-cardiolipin antibodies in autoimmune thyroid diseases.

OBJECTIVE: In recent years anti-phospholipid antibodies have gained much attention since they are frequently associated with thrombosis, recurrent abortion, and thrombocytopenia. Besides disease-specific autoantibodies, other autoantibodies reactive with both organ and non-organ specific autoantigens have been found in patients with autoimmune thyroid diseases. Therefore the objective of this study was to evaluate the presence and significance of anti-phospholipid antibodies in untreated patients with different forms of autoimmune thyroid diseases. PATIENTS AND METHODS: Thirty-one patients (26 females, five males; mean age 42.5 years) affected by different autoimmune thyroid diseases were studied. Fourteen patients were affected by Graves' disease, eight by silent thyroiditis, five by Hashimoto's thyroiditis. Four patients with Graves' disease in remission were also evaluated. Anti-cardiolipin antibodies were detected by enzyme linked immunosorbent assay. In five Graves' disease patients anti-cardiolipin antibodies were evaluated before and after 3 months of therapy with methimazole. RESULTS: Seventeen out of 31 patients were positive for IgG and/or IgM anti-cardiolipin antibodies, the highest levels occurring in three Graves' disease patients with severe thyrotoxicosis. In four of five Graves' patients evaluated before and after methimazole therapy, anticardiolipin antibodies decreased following treatment. None of the patients with increased IgG and/or IgM anticardiolipin antibodies showed clinical manifestations of the anti-phospholipid syndrome during our observation which ranged from 1 to 5 years. CONCLUSIONS: Our results showed an increased incidence of anti-cardiolipin antibodies in patients affected by autoimmune thyroid diseases. However, these autoantibodies seem merely to represent a non-specific marker of immune dysregulation.

Adult↗

Development of thyroid disease during therapy of chronic viral hepatitis with interferon alfa.

Six of 237 (2.5%) patients with chronic viral hepatitis who were treated with recombinant interferon alfa developed thyroid disease while on treatment. Three patients developed hyperthyroidism, two of whom developed detectable levels of thyroid-stimulating immunoglobulin; three patients developed hypothyroidism in association with high titers of antithyroglobulin and/or antimicrosomal antibodies. The thyroid disease did not remit when interferon therapy was stopped, and all six patients required definitive therapy for the thyroid disease. These findings suggest that a small proportion of patients treated with interferon alfa develop autoimmune reactions and can develop autoimmune thyroid disease.

Adult↗

Prevalence and evaluation of B12 deficiency in patients with autoimmune thyroid disease.

BACKGROUND: Patients with autoimmune thyroid disease (AITD) have a higher prevalence of pernicious anemia compared with the general population. Clinical signs of B12 deficiency may be subtle and missed, particularly in patients with known autoimmune disease. We assessed the prevalence of vitamin B12 deficiency in patients with AITD and whether their evaluation may be simplified by measuring fasting gastrin levels. METHODS: Serum B12 levels was measured in 115 patients with AITD (7 men and 108 women), with a mean age of 47 +/- 15 years. In patients with low serum B12 levels (< or =133 pmol/L), fasting serum gastrin and parietal cell antibodies (PCA) were measured. RESULTS: Thirty-two patients (28%) with AITD had low B12 levels. Fasting serum gastrin was measured in 26 and was higher than normal in 8 patients. PCA were also measured in 27 patients with B12 deficiency and were positive in 8 patients. Five patients with high gastrin levels underwent gastroscopy with biopsy, and atrophic gastritis was diagnosed in all. The prevalence of pernicious anemia as assessed by high serum gastrin levels in patients with low B12 was 31%. CONCLUSIONS: Patients with AITD have a high prevalence of B12 deficiency and particularly of pernicious anemia. The evaluation of B12 deficiency can be simplified by measuring fasting serum gastrin and, if elevated, referring the patient for gastroscopy.

Adolescent↗

[The expression of G proteins alpha-subunit mRNA in different thyroid diseases].

OBJECTIVE: To investigate the expression of G proteins alpha subunit mRNA in different thyroid diseases. METHODS: Twenty-three thyroid specimens were obtained during surgery, 5 from patients with Graves' disease (GD), 7 from patients with multinodular goiter (MNG), 6 from patients with eufunctioning thyroid adenoma (EFTA) and 5 from patients with thyroid papillary cancer (TPC). The expression of stimulating and inhibiting G proteins alpha subunit mRNA were determined by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: (1) The expression of G(s)alpha mRNA in TPCs (1.67 +/- 0.25) was significantly higher than that in normal thyroids (1.10 +/- 0.14) and MNGs (0.96 +/- 0.31), P < 0.05 and P < 0.01. The expression in GDs (1.47 +/- 0.11) and EFTAs (1.36 +/- 0.28) was significantly higher than that in MNGs (P < 0.05), but comparable to that in normal thyroids. (2) The expression of G(i)alpha-2 mRNA in GDs (0.68 +/- 0.26) was lower than that in MNGs (1.15 +/- 0.35), P < 0.05, but there was no difference in the expression of G(i)alpha-1 and G(i)alpha-3 mRNA among different thyroid diseases. CONCLUSION: The results indicated that G(s)alpha could play an important role in the pathogenesis of thyroid papillary cancer and G proteins had different expression in different thyroid diseases.

Adenoma↗

Prevalence of psychiatric disorders in thyroid diseased patients.

Several studies have underlined the high prevalence of psychiatric symptoms and disorders in thyroid diseases. The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes, by means of a standardized instrument, i.e., the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised, Upjohn Version (SCID-UP-R). The results showed higher rates of panic disorder, simple phobia, obsessive-compulsive disorder, major depressive disorder, bipolar disorder and cyclothymia in thyroid patients than in the general population. These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities.

Adult↗

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↗

[Goiter and nodular thyroid disease: clinical guidelines for diagnosis and treatment. (Waiting? Hormone therapy? Surgery? radioiodine?)].

Nodular thyroid disease is a common problem. We present clinical guidelines for the management of patients with thyroid nodules, multinodular goiters and thyroid cysts for use by primary physicians. In the initial evaluation ultrasonography of the thyroid and fine-needle aspiration biopsy (FNAB) is recommended. FNAB has become the cornerstone in the evaluation of solitary thyroid nodules, cysts and dominant nodules within multinodular goiters. If the procedure is done properly, it should have a false-negative rate of less than 5% and a false-positive rate of not more than 1%. Thyroid radionuclide scans are less frequently used in the initial evaluation of a nodular goiter. Surgery is the primary therapy for patients with nodular thyroid disease. Other available treatment options are radioiodine and TSH-suppression with thyroxine. The main indications for surgery in euthyroid patients with thyroid nodule or with nontoxic multinodular goiter are recently documented or suspected malignancy, compression of the trachea and esophagus, significant growth of the nodule, recurrence of a cyst after aspiration, neck discomfort and cosmetic concern.

Algorithms↗

[Benign thyroid disease: 20-year experience in surgical therapy].

This retrospective study compares recurrence and postoperative complication rates after isthmo-lobectomy and subtotal thyroidectomy (group I) vs near-total and total thyroidectomy (group II) for benign thyroid disease. Seven hundred and forty-three patients were operated on for thyroid diseases over the period from 1977 to 1998. We considered 202 patients operated on for benign thyroid disease from 1988 to 1998. The follow-up ranged from 1 to 10 years (mean: 3.4 yrs). One hundred and thirty-two patients (65.3%) were operated on for bilateral nodular goitre, 35 (17.3%) for unilateral nodular goitre, 14 (6.9%) for toxic goitre and 21 (10.4%) for thyroiditis. Over the period 1988-1992, 19 patients underwent isthmo-lobectomy and 71 subtotal thyroidectomy (group I). From 1993 to 1998, 39 patients underwent near-total thyroidectomy and 61 total thyroidectomy (group II). The relapse rate was 14.4% in group I, while there were no recurrences in group II (p = 0.000064). Temporary hypocalcaemia was significantly higher (p = 0.000001) in group II (29%) than in group I (2.2%). Within group II, the rate was significantly higher (p = 0.0013) after total thyroidectomy (37.7%) than after near-total thyroidectomy (15.4%). In our experience, near-total and total thyroidectomy are an appropriate approach for preventing recurrence in patients with benign thyroid disease despite the fact that the risk of temporary hypocalcaemia is higher than after less radical surgery. Near-total thyroidectomy and the exercise of all due care in the surgical technique may help to reduce its incidence.

Adult↗

A review of thyroid disease in pregnancy.

Goitre is common and alterations in biochemical indices of thyroid function are invariable during pregnancy , but thyroid disease, of which hyperthyroidism is the most frequent (0,05% of 72,257 pregnancies at three Dublin Maternity Hospitals, 1979-81) is rare. Good results in terms of perinatal loss (4/112, 3.57%) has been achieved by one of us (MID) in 109 pregnancies using antithyroid drugs alone. Neonatal thyrotoxicosis occurs in one to two percent of babies born to mothers with thyroid disease. The condition is usually transient but a prolonged course may occur in up to 20 percent. Successful pregnancy is possible despite maternal hypothyroidism; three such pregnancies have been managed by one of us (MID). Clinical hyperthyroidism due to trophoblastic disease is very rare and is cured by evacuation of molar tissue. The course of thyroid cancer is not affected by pregnancy.

Antithyroid Agents↗

Thyroid disease, a risk factor for optic neuropathy mimicking normal-tension glaucoma.

The aethiology and pathogenesis of normal-tension glaucoma (NTG) is unknown but increasing evidence suggests multiple mechanisms of damage. Six out of 25 NTG patients (24%) had thyroid disease. The mean age of these patients was 66.5 +/- 9 years and of those without thyroid disease 60.7 +/- 9.6 years. The thyroid group was more hyperopic. The difference in mean intraocular pressure was not significant, but in the thyroid group the mean diurnal IOP variations were significantly smaller. The pattern VEP results indicated a correlation between optic neuropathy and prolonged latency of the P100 component in the group with thyroid disease and a correlation between optic neuropathy and lowered N80-P100 amplitudes in the group without. For one patient with hypothyroidism the delayed latency in the worse eye was normalized after thyroxine substitution. Due to overlapping the absolute values of P100 and the N80-P100 peak-peak amplitudes in pattern VEP cannot be used for differential diagnosis. These findings indicate that thyroid disease either causes optic neuropathy mimicking glaucomatous damage or is a risk factor for glaucoma.

Adult↗