Clinical Thyroid Dysfunction Research Articles

Impact of long-term administration of amiodarone on the thyroid function of patients with Chagas' disease.

The effect of long-term treatment with amiodarone on patients with Chagas' disease has seldom been reported. This nonrandomized observational study attempted to analyze the follow-up of patients with Chagas' disease regarding their clinical evolution, thyroid dysfunction, and goiter. We compared 72 patients with long-term use (11 +/- 5 years) of amiodarone, including 22 patients who developed goiter, to 33 patients who did not use amiodarone, followed-up for 2 to 20 years (7 +/- 11 years). Follow-up of 72 patients for 9 +/- 5.4 years with periodic cardiac and thyroid function evaluations showed that only 26 maintained normal serum thyrotropin (TSH) levels; 24 presented with elevated levels; 4 had low levels, and 18 patients presented with fluctuations of TSH level. Among the 22 patients with goiter, only 3 (14%) patients maintained normal TSH, 8 (36%) had elevated TSH, 2 (9%) had low TSH, and 9 (41%) patients presented with fluctuating serum TSH levels. Most individuals remained clinically euthyroid with no evidence of cardiac impairment that could be attributed to thyroid dysfunction and the arrhythmias were adequately controlled by amiodarone. We suggest that amiodarone treatment may be continued for patients with Chagas' disease with arrhythmias, even in those who develop thyroid function abnormalities or goiter.

Thyroid dysfunction after bone marrow transplantation for primary immunodeficiency without the use of total body irradiation in conditioning.

Thyroid dysfunction, a common long-term complication following bone marrow transplantation (BMT), is frequently associated with total body irradiation (TBI) given in the pre-BMT conditioning protocol. We report our preliminary observation of the prevalence of thyroid dysfunction in children transplanted for primary immunodeficiency (PID) who were given cytoreductive conditioning with busulphan and cyclophosphamide, but without TBI. We evaluated thyroid-stimulating hormone (TSH) and free thyroxine (fT4) in 83 survivors transplanted between 1987 and 2002. We found nine children (10.8%) with clinical and/or biochemical thyroid dysfunction at 4 months to 4.5 years post-BMT of which three had positive antithyroid microsomal antibodies. Two patients were classified as primary and seven as compensated hypothyroidism (hyperthyrotropinaemia). Four patients with clinical features of hypothyroidism received replacement thyroxine, while five of the seven patients with compensated hypothyroidism remain off thyroxine because we suspect this may be a transient phenomenon. Abnormalities of thyroid function including severe primary hypothyroidism may occur post-BMT in children receiving chemotherapy conditioning without TBI. Thyroid function should be assessed regularly in this group of patients.

Níveis de hormônios tireoideanos em pacientes com dissecção aórtica: comparação com controles e correlação com a porcentagem de área da camada média composta por depósitos mixóides

Deposits of myxoid material, similar to myxedema related to thyroid disease, are described in the medial layer of aortas with dissection. We analyzed the clinical or subclinical thyroid dysfunction of patients with this disease and analyzed whether a correlation exists between serum levels of thyroid-related hormones and the myxoid content of the aortic media. We measured, with standard methods, serum levels of triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) in 28 patients who underwent aortic dissection and free T4 in 20 of them. The same hormones were quantified in 20 control patients matched by sex and age. Results were compared by using the Mann-Whitney test. We also measured the percentage of the aortic media occupied by myxoid material in the surgical specimens of 25 of the patients with aortic dissection and analyzed its correlation with hormone levels by using the Pearson test. In the 20 pairs in which the amount of hormones was compared, the mean values for T3, T4, free T4, and TSH were 1.22ng/mL, 9.89mcg/dL, 1.18ng/dL, and 5.45 microIU/mL in study patients and 1.15ng/mL, 8.57mcg/dL, 1.32ng/dL, and 2.15 microIU/mL in controls. Neither these differences nor the correlation between the percentage of myxoid content (mean=30%) and the values for T3, T4, free T4, and TSH (mean 1.22ng/mL, 9.44mcg/dL, 1.20ng/dL, and 5.08 microIU/mL, respectively; n= 25) were significant. Our data suggest that serum levels of thyroid hormones have no relation with the myxoid content in the aortic media in cases of aortic dissection.

Thyroid autoimmunity in chronic idiopathic urticaria: implications for therapy.

The association between thyroid autoimmunity and chronic idiopathic urticaria has long been recognized, although prevalence rates differ in the studies reported to date (from 12 to 29%). There is, therefore, a strong indication to screen patients affected by chronic urticaria of unknown origin for thyroid antibodies (antithyroperoxidase and antithyroglobulin) and, when positive, for serum thyrotropin to assess thyroid functional status. Less clear is the implication of thyroid autoimmunity for therapy, as most patients with urticaria who have associated thyroid autoimmunity are euthyroid. There is no doubt that cases with clinical or subclinical thyroid dysfunction should undergo treatment with either levothyroxine or antithyroid drugs for hypo- or hyper-function, respectively. Although the best remission rates for symptoms of urticaria have so far been obtained with levothyroxine in patients who are euthyroid, monitoring of thyroid function through serum thyrotropin determination is highly recommended because of the risk of hyperthyroidism, especially in the elderly.

Thyroid autoantibodies in Thai type 1 diabetic patients: clinical significance and their relationship with glutamic acid decarboxylase antibodies

Objective: To study the clinical significance of thyroid autoantibodies in Thai patients with type 1 diabetes and their relationship with glutamic acid decarboxylase antibodies (GAD 65Ab). Methods: Thyroglobulin antibodies (TG-Ab) and thyroid peroxidase antibodies (TPO-Ab) were measured in 50 Thai type 1 diabetic patients. Forty-four patients also had GAD 65Ab measured. Serum thyrotropin (TSH) was measured in all patients who had no history of thyroid disease regardless of thyroid antibody status. Clinical data including sex, age at onset and duration of diabetes, family history of diabetes, fasting c-peptide levels as well as frequencies of GAD 65Ab were compared between patients with and without thyroid antibodies. GAD 65Ab was also measured in 29 non-diabetic patients with hyperthyroid Graves’ disease or Hashimoto thyroiditis as a control group. Results: TG-Ab and TPO-Ab were positive in nine (18%) and 15 (30%) patients, respectively. Eight patients (16%) were positive for both antibodies. Two of 16 patients who were positive for TG-Ab or TPO-Ab had a previous history of hyperthyroidism prior to diabetes onset. Of the remainder, two were newly diagnosed with hyperthyroidism and one was found to have clinical hypothyroidism at the time of the study. None of 34 patients without thyroid antibodies had thyroid dysfunction. Eight patients with positive thyroid antibodies but without clinical thyroid dysfunction and 21 patients without thyroid antibodies were followed for up to 3 years, two patients of the first group developed hypothyroidism, whereas none of the latter developed thyroid dysfunction. The frequency of thyroid dysfunction at the time of initial study was significantly higher in patients with positive thyroid antibodies (3/14 vs. 0/34; P=0.021) and these patients who were initially euthyroid tended to have a higher risk of developing thyroid dysfunction (2/8 vs. 0/21; P=0.069). The frequency of thyroid antibodies was significantly increased in females and in those who had positive GAD 65Ab. GAD 65Ab was negative in all of the non-diabetic patients with autoimmune thyroid disease. Conclusions: About one-fourth of Thai patients with type 1 diabetes without thyroid disease had thyroid antibodies. The frequency of thyroid antibodies was increased in female and in GAD 65Ab positive patients. The presence of thyroid antibodies is associated with a higher frequency of and may predict a higher risk for thyroid dysfunction in Thai type 1 diabetic patients.

The prevalence of thyroid dysfunction in a population with borderline iodine deficiency.

We lack information on the influence of borderline iodine deficiency on the occurrence of thyroid dysfunction. Iodine deficiency has been reported to facilitate the development of toxic nodular goitre, whereas a high iodine intake may increase the prevalence of autoimmune hypothyroidism. In a cross-sectional study of a random sample of the general population in our region with borderline iodine deficiency 2656 (65%) of 4073 men and women aged 41 to 71 years participated. Records were made of previous thyroidal illness. Blood samples were drawn for thyroid parameters and TPO Ab values. Iodine and creatinine was assessed in casual urine samples. Previous or present hyperthyroidism was reported by 1.4% of the participants whereas 0.6% had unknown biochemical hyperthyroidism. All cases of undiagnosed hyperthyroidism were among women. Previously diagnosed and treated hypothyroidism was reported by 1.0% and undiagnosed hypothyroidism was found in 0.4%. Subclinical hyperthyroidism was found in 1.3% and subclinical hypothyroidism in 0.7%. TPO Ab titres >200 kU/l were found in 16.9% of the women and 6.6% of the men, and 83% of participants with TSH >5 mU/l had TPO Ab titres >200 kU/l. Participants with TPO Ab titres between 100 and 200 kU/l had no increased frequency of thyroid dysfunction. The median iodine excretion rate was estimated as 103 microg/day. Serum TSH values were higher in women than in men and showed higher dispersion in women as well as in old age. Serum free T3 was found to be higher in women than in men and increased with age. Serum free T4 showed no sex difference but values increased with increasing age. In our region with borderline iodine deficiency more than 5% of the general population has clinical or subclinical thyroid dysfunction. We found a relatively high prevalence of hyperthyroidism, especially previously undiagnosed disease, but a low prevalence of hypothyroidism as would be expected in an area of iodine deficiency. Hypothyroidism was related to TPO Ab titres of >200 kU/l. Thyroid hormone levels varied with age and sex.

Síndrome de Down e hipertiroidismo.: Comunicación de 3 casos

We report three patients with Down syndrome that developed a hyperthyroidism. A 25 years old female and a 18 years old male had Basedow Graves disease and were treated with radioiodine. A 19 years old male had a Hashitoxicosis and is presently being treated with propylthiouracyl. Clinical and subclinical thyroid dysfunction is frequent in patients with Down syndrome and the risk increases with age. Therefore a surveillance with yearly TSH measurements should be done in these patients, since signs and symptoms of thyroid disease are barely detected in them. Hypothyroidism is the most frequent dysfunction but hyperthyroidism is also associated to Down syndrome.

Longitudinal study of iodine in toenails following IV administration of an iodine-containing contrast agent

The literature on the relationship between diet and thyroid cancer (TC) risk and the higher incidence of TC among Asian immigrants to the US compared to second and third generation subgroups has prompted epidemiologists to hypothesize that increased levels of iodine consumption may be associated with TC risk, particularly among persons with a history of clinical or subclinical thyroid dysfunction. At the University of Missouri Research Reactor (MURR), we have applied epiboron neutron activation analysis to investigate human nails as a dietary monitor for iodine. Preliminary studies have indicated a positive correlation between dietary iodine intake and the concentration of iodine in toenails. However, these studies are confounded by high iodine levels (up to 30 ppm) in approximately 5% of the nails studied. We hypothesize that, in the subjects we have studied, the high iodine levels may be due to iodine-containing medications, in particular contrast-agents containing iopamidol. This paper will report on longitudinal studies using contrast agent subjects who were followed-up for almost two years compared to a longitudinal control and a population mean. Based on this study, we suggest that iodine-containing contrast agents contaminate nail samples via non-specific binding in the short term followed by incorporation in the nail as a result of absorption.

Thyroid autoantibodies and thyroid dysfunction during treatment with interferon-α for chronic hepatitis C

Interferon-alpha (2a or 2b) is increasingly used for treatment of chronic hepatitis C virus (HCV) infection. Recent reports suggested a correlation between increases in thyroid autoantibodies and the development of thyroid dysfunction during interferon-alpha therapy. In this study, we analyzed thyroid hormones and antithyroid antibodies at monthly intervals in 53 patients who received interferon alpha for chronic active hepatitis C infection. Of five patients with initially elevated levels of antithyroid peroxydase antibodies (anti-TPO), the antibodies increased further in two of them. Ten patients, who started interferon therapy with normal antibody levels, developed elevated anti-TPO antibodies for limited times during treatment. Levels of anti-TPO antibodies showed a marked fluctuation, and only three patients had increased anti-TPO antibodies persisting for longer than 3 mo. Antithyroglobulin antibodies appeared in four patients, all of whom were also positive for anti-TPO antibodies. No changes in TRAB levels were observed. All of these patients with elevated antithyroid antibodies remained in an euthyroid state. One patient with normal antithyroid antibodies developed thyroiditis with severe thyrotoxicosis after 9 wk of interferon therapy. These findings suggest that the induction of antithyroid antibodies during treatment with interferon-alpha does not indicate clinical relevant thyroid dysfunction. Routine measurement of antithyroid antibodies during interferon-alpha therapy does not seem to be mandatory.

The Incidence of Clinical Thyroid Dysfunction in an Unselected Group of Pregnant and Post Partum Women

This study has examined the incidence of thyroid dysfunction during pregnancy and up to six months post partum in 65 women attending an antenatal clinic in the West of Scotland. Five were found to be positive for thyroid antibodies at presentation and in these the antibody titre fluctuated during pregnancy and in the post partum period. One patient developed thyroglobulin antibodies post partum. Mean total T3 and total T4 levels rose during pregnancy but had normalised by six weeks post partum. The changes in FT4 and TBG levels observed during pregnancy did not normalise until after six weeks post partum. Only one patient developed any biochemical evidence of thyrotoxicosis post partum and this was not found to be associated with the presence of thyroid antibodies. No patient showed any evidence of hypothyroidism.

Screening of Geriatric Patients for Thyroid Dysfunction with Thyrotropin-Releasing-Hormone Test, Sensitive Thyrotropin and Free Thyroxine Estimation

Hospitalized geriatric patients (N = 354) from an iodine-deficient area were screened with sensitive thyrotropin (TSH), free and total thyroxine (FT4, T4) and total triiodothyronine (T3) to determine the occurrence rate of clinical and subclinical thyroid dysfunction. The diagnostic value of the tests was compared to each other and to that of the thyrotropin-releasing-hormone test (TRH-test) in order to find the optimal first line screening test in geriatric patients. Clinical hyperthyroidism was found in 13, subclinical hyperthyroidism in 10, overt hypothyroidism in 6 and subclinical hypothyroidism in 8 cases. 20.6% of the patients were euthyroid but had subnormal TSH response to TRH, as a sign of possible thyroid autonomy. The low occurrence rate of clinical thyroid disorders (4.8%) does not justify the screening of geriatric patients in general, but the high probability of thyroid autonomy makes reasonable the investigation of every geriatric patient before iodine administration. Suppressed basal TSH and high FT4 were found to be both sensitive and specific in diagnosing clinical hyperthyroidism, but the predictive value was insufficient; elevated T4 and T3 are specific, but not sensitive. Basal TSH is sensitive, specific and has a good predictive value in diagnosing euthyroidism, whereas normal T4, FT4 or T3 are not specific enough for euthyroidism. Basal TSH is better as a first line test of thyroid function than FT4. A normal basal TSH confirms euthyroidism by itself. Other tests (TRH test, T4, FT4, T3) are necessary to elucidate the clinical importance of a subnormal or suppressed basal TSH.

Chronic administration of amiodarone and thyroid function: A follow-up study

In order to evaluate the effects of amiodarone on thyroid function in chronically treated patients, 43 consecutive patients, who had been taking a mean weekly dose of 1420 ± 488 mg for more than 9 months (mean 16.5 months), were studied. In a first evaluation, three patients with hypothyroidism and two with hyperthyroidism were discovered. In the remaining 38 patients, mean T 4 (131 ± 38 nmol/L) and rT 3 (0.85 ± 0.3 nmol/L) levels were significantly higher than reference values ( p < 0.05 and p < 0.001, respectively), and mean T 3 levels (1.89 ± 0.73 nmol/L) were significantly lower ( p < 0.001). Thirteen patients showed hyperresponsiveness to thyrotropin-releasing hormone (TRH) stimulation testing. In a second evaluation, performed 12 to 18 months later, two new cases of hypothyroidism were discovered. T 3 levels showed significantly lower values ( p < 0.02) than in the first evaluation, whereas basal thyroid-stimulating hormone levels and levels 30 and 60 minutes after TRH stimulation were significantly higher than those in the first evaluation ( p < 0.001). Five new hyperresponders to TRH were found. In the present series, the progressive appearance of clinical thyroid dysfunction with an elevated total incidence (16%) is demonstrated. Moreover, a progressively high prevalence of hyperresponsiveness to TRH stimulation is shown. These findings indicate that chronic amiodarone administration may carry a high risk of thyroid dysfunction.

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.

Cyclical combination chemotherapy and thyroid function in patients with advanced Hodgkin's disease.

Clinical and biochemical assessment of thyroid function was undertaken in patients with Hodgkin's disease at designated points following diagnosis. At diagnosis, two of 20 patients had either abnormally low routine thyroid indices, or elevated thyroid stimulating hormone (TSH) levels that were not due to iodine-based investigations. Following lymphography, 76.5% of patients had TSH levels that remained elevated for a median period of 3 months. No detectable thyroid dysfunction was induced during chemotherapy. Fifty-four patients were studied at a median time of 35 months after chemotherapy. One euthyroid patient had a nodular goitre, and one had abnormal thyroid indices. Tsh levels were elevated in 44% of patients, although the median TSH level for the group was normal. Half the patients had abnormal TRH stimulation tests. Sixty patients were studied after irradiation and chemotherapy. Four patients had clinical thyroid dysfunction, and 10% of routine thyroid indices were abnormal. TSH levels were abnormal in 80%, with a markedly elevated median level. All thyroid releasing hormone stimulation tests were abnormal.

THYROIDAL I-131 UPTAKE PATTERNS FOLLOWING IODIDES.

Clinical thyroid dysfunction produced by chronic iodide uptake in euthyroid individuals is rare but well established. The abnormalities so produced include goiter, 1,2 goiter with myxedema, 1-12 and, more rarely, myxedema without goiter formation. 3,4,13 Although many studies have been performed to determine the mechanisms by which iodides produce their effects upon the thyroid gland and upon the thyroid-pituitary axis, the precise loci of this halide's action remain imperfectly understood. The various hypotheses proposed on the subject have been recently reviewed. 3,9 Three main types of radioiodine uptake abnormalities have been noted in patients on iodide medication. The best known is transient depression of the 24-hour I 131 uptake. In those patients who developed clinical evidence of thyroid dysfunction, two other less well-recognized patterns were described. 4,7,9-12 One was an abnormally high 24-hour radioiodine uptake occurring 1 to 12 days following discontinuance of iodides. The other was a high two-hour uptake with subsequent rapid fall indicating