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Seasonal recurrence of transient hypothyroidism in a patient with autoimmune thyroiditis.

Two postpartum and 7 spontaneous episodes of transient hypothyroidism developed during 5 years of observation in a florist with autoimmune thyroiditis and seasonal allergic rhinitis. The spontaneous episodes recurred twice a year regularly in spring and in autumn, the seasons of her allergic rhinitis. In most of these episodes as well as in the postpartum ones, hypothyroidism was preceded by transient thyrotoxicosis. In addition to the similarity in the clinical course, the changes in antimicrosomal antibody titers in pregnancy-unrelated episodes were almost identical to those in postpartum episodes. Throughout the observation periods, she had supranormal serum total immunoglobulin (Ig) E concentrations and high antigen-specific Ig E levels for various pollen extracts such as cedar and ragweed. However, we failed to demonstrate a correlation between thyroid function and total or any antigen-specific Ig E level. The present findings suggest that the pregnancy-unrelated thyroid dysfunction in our patient developed as a result of silent thyroiditis and through similar immunological mechanisms to those in postpartum thyroiditis. And it is suspected, though unproved, that the seasonal recurrence of pregnancy-unrelated thyroiditis has some causal relation to her allergic disease.

Adult↗

The differential diagnostic problems in unilateral euthyroid Graves' ophthalmopathy.

Nine consecutive patients with unilateral ophthalmopathy with suspected endocrine pathogenesis were investigated with a TRH test, a T3 suppression-test, thyroid autoantibodies and a subsequent computerized tomography (CT)-scan. All patients were clinically and biochemically euthyroid. Seven of 9 patients had a normal TRH test and 6 of 7 had a normal T3 suppression test. Slightly to moderately elevated microsomal and thyroglobulin (determined with radioimmunoassay) autoantibodies were found in 5 of 8 patients and in 1 patient thyroid stimulating immunoglobulins (TSI) were found. Three of the patients had normal thyroid function tests and no detectable thyroid autoantibodies. The subsequent CT-scan revealed that one of these had a maxillary tumour protruding into the orbita. The remaining 8 patients had enlargement of one (3 patients) or more (5 patients) eye muscles. Two of the 8 patients had bilaterally enlarged eye muscles, one of which was the patient with positive TSI. The remaining 6 patients had unilateral extraocular muscle enlargement. Thus, 2 of 9 patients had ophthalmopathy without thyroid dysfunction so-called isolated autoimmune ophthalmopathy or Graves' ophthalmopathy. Thyroid function tests seem to be of limited value in the diagnosis between endocrine and non-endocrine eye disease, and we recommend the use of diagnostic imaging (e.g. CT-scan) in patients with unilateral exophthalmus in order to diagnose malignant processes.

Antibodies↗

Antithyroid antibodies during amiodarone treatment.

In 44 euthyroid and goitre-free patients, 23 treated with amiodarone (group A) and 21 treated with other antiarrhythmic drugs (group B), antimicrosomal antibodies and antithyroglobulin antibodies were determined before the beginning of treatment and after 7, 15, 30, 60, and 180 days. In group A, none of the patients had antithyroid antibodies before treatment. 1 of 15 patients (6.7%) had antimicrosomal antibodies (titre 1:100) on day 7 only, and 1 of 18 (5.5%) had antithyroglobulin antibodies (titre 1:80) on day 180. In group B. 1 of 21 patients (4.8%) had antimicrosomal antibodies (IgG class) at titre 1:400 before the beginning of treatment, which was negative on day 180, and 2 of 17 (11.8%) had antimicrosomal antibodies (titre 1:100) on day 60 only. None of these patients showed clinical and/or laboratory signs of hyper- or hypothyroidism. These data indicated that antithyroid antibodies rarely appear in amiodarone-treated patients and do not differ significantly from patients treated with other antiarrhythmic drugs. The role of autoimmunity and the meaning of antithyroid antibodies in the pathogenesis of amiodarone-induced thyroid dysfunction (mainly of hypothyroidism) in patients without pre-existent thyroid diseases is still unclear.

Aged↗

Thyroid peroxidase autoantibodies predict poor metabolic control and need for thyroid treatment in pregnant IDDM women.

OBJECTIVE: To study whether the presence of antithyroid peroxidase antibodies (TPO-Abs) before gestation in IDDM affects thyroid function and metabolic control during pregnancy and early postpartum as well as neonatal outcome. RESEARCH DESIGN AND METHODS: A prospective study at an outpatient endocrine-obstetric unit was carried out in 20 pregnant IDDM women. Free T4 (thyroxine), thyroid-stimulating hormone (TSH), TPO-Abs, and HbA1c were assayed before gestation; during the first, second, and third trimester of pregnancy; and 3 months postpartum. RESULTS: HbA1c was significantly higher in TPO-Ab+ women than in those who were TPO-Ab- during the second (P < 0.01) and third (P < 0.05) trimesters. HbA1c levels significantly decreased in TPO-Ab- patients when the second (P < 0.01) and third (P < 0.05) trimesters were compared with before the pregnancy and the first trimester. There was a significant increase in the dosage of insulin for TPO-Ab+ versus TPO-Ab- patients during the second (P < 0.05) and third (P < 0.01) trimesters and 3 months postpartum (P < 0.05). TSH was significantly increased in the second (P < 0.001) and third (P < 0.05) trimesters and 3 months postpartum (P < 0.01) when compared with TPO-Ab- patients; 7.6% of the TPO-Ab- group and 29% in the TPO-Ab+ group presented postpartum thyroid dysfunction, and 42% of the TPO-Ab+ women required thyroid treatment. CONCLUSIONS: Pregnant women with IDDM who have a positive test for TPO-Abs before gestation have poorer glucose control and a high prevalence of hypothyroidism. Therefore we recommend that prepregnant IDDM patients be screened for anti-TPO-Abs. Those with a positive result should be followed with serial monitoring of free T4 and TSH levels during each trimester as well as the postpartum period.

Adult↗

[Physiopathology of iodine: current interest of its measurement in biological fluids].

Iodine plays a central role in thyroid physiology, being both a major constituent of thyroid hormones and a regulator of thyroid gland functions. Iodine intakes considerably vary according to subjects. Inappropriate iodine intakes are worrying in term of public health regarding iodine deficiency (western world currently is not exempt) and regarding the frequency of iatrogen iodine overloads. Iodine disorders induce a biological and/or clinical expression of thyroid dysfunction, and in some cases can disclose pre-existent thyroid abnormalities. Determination of serum and urine iodine levels is an useful marker in the biological investigation of the thyroid function, can contribute to undertake an appropriate therapeutics and follow its efficacy.

Humans↗

[A rare case of differential diagnosis of myopathy].

Relationship among thyroid dysfunction and musculoskeletal symptoms has been known for years. Autoimmunic thyroiditis is the most common cause of hypothyrosis. A patient who suffered from myopathy secondary to autoimmunic thyroiditis and hypothyrosis is described in this article. Attention has been drawn to proximal muscle weakness and general fatigue which is common in such cases. Significant elevation of muscle enzymes is typical. Usually no specific signs can be found on muscle biopsy. Much efforts should be put to distinguish myopathy secondary to hypothyrosis from polymyalgia rheumatica, polymyositis or myopathies caused by other diseases. Similar data of literature are reviewed in the article.

Diagnosis, Differential↗

[Extrahepatic manifestations of hepatitis C virus: the thyroid disorders].

The prevalence of thyroid disorders has been studied in patients with chronic hepatitis C virus (HCV) infection by many studies. In general, thyroid dysfunction in chronic C hepatitis may include all forms of thyroid alterations, i.e. hypothyroidism and hyperthyroidism, Hashimoto's disease and isolated increases in antithyroid autoantibodies. The prevalence of various thyroid disorders and serum anti-thyroid autoantibodies is generally higher in chronic hepatitis type C than in hepatitis B or D or control series. The results of most studies in patients with hepatitis C confirm a higher prevalence of autoimmune thyroid involvement and hypothyroidism than in controls. More recently, some epidemiological studies have suggested a possible association between HCV and thyroid cancer. These last data need to be confirmed by other studies, but seem to be sufficient to suggest careful thyroid monitoring during the follow-up of patients with HCV infection.

Europe↗

[Comparative results of thyroid ultrasound and laboratory studies in patients exposed to radiation].

The paper presents the data of thyroid ultrasound and laboratory studies in 233 persons exposed to radiation: 63 X-ray physicians, 36 Chernobyl accident liquidators, 31 patients with lymphogranulomatosis, receiving radiotherapy, and 103 individuals (a control group) who were physicians of various specialties whose professional activity is unassociated with radiation factors. Thyroid changes were found in 67.7% of the examinees after gamma teletherapy and in 31% in the control group; among X-rat physicians and Chernobyl accident liquidators, the occurrence of thyroid changes was equal--44.4%. Direct radiation exposure of the thyroid in a dose of above 30 Gy led to the development of postradiation fibrosis (22.5%) and postradiation thyroiditis (32.3%) with thyroid dysfunction that is most commonly presented by hypothyroidism (22.45%). Autoimmune thyroiditis (11.1%) more predominantly with subclinical hypothyroidism, and diffuse thyroid hyperplasia (19.4%) resulted from mixed internal and external radiation. Thyroid changes revealed in X-ray physicians mainly appeared as nodular masses (22.2%) without functional impairments but to be followed up. It is recommended that the annual preventive examination protocol be supplemented by thyroid ultrasound studies in X-ray physicians.

Adult↗

[Postpartum thyroiditis: silent thyroiditis].

Endocrine and immune system explorations, systematically performed at the end of pregnancy for the last 15 years, have shown that in about 5 percent of women delivery is followed by thyroid dysfunction and goitrogenic episodes due to a painless or silent thyroiditis. In genetically predisposed subjects, this pathology is the expression of a hitherto asymptomatic chronic lymphocytic thyroiditis revealed by the generalized autoimmunity rebound that is characteristic of the postpartum period. Usually benign and transient, the thyroiditis may recur during subsequent pregnancies and eventually result in permanent hypothyroidism.

Female↗

Disturbances of thyroid function tests by drugs.

Commonly prescribed drugs can variously cause changes in measuring serum T3 and T4 concentrations. Thus spuriously normal thyroid hormone levels may result in moderate hypo- or hyperthyroidism, or the influence of pharmacological substances may lead to a false diagnosis of thyroid disease in euthyroid subjects. On the other hand numerous pharmacological agents, especially those interacting with neurotransmitters, may influence TSH secretion, too. While generally such drug-induced abnormal thyroid tests do not correspond to clinical features of thyroid dysfunction, iodine containing drugs, especially amiodarone, may result in overt thyroid disease.

Amiodarone↗

[Absorbed dose evaluation of thyroid during nasopharynx and breast carcinoma irradiation by in vivo dosimetry].

AIMS: The thyroid dysfunction after radiotherapy has led to evaluate the dose received by thyroid during nasopharynx and breast carcinoma irradiation. This evaluation was facilitated by in vivo dosimetry. The aims of this work were to evaluate the thyroid dose and to compare released dose at the reference point in the two localizations. PATIENTS AND METHODS: A total of 30 patients were evaluated: 18 patients with nasopharynx carcinoma and 12 patients with breast carcinoma were included in the final analysis. In the first group, the total thyroid but the isthmus was irradiated. On the other hand, in the second group, only one thyroid lobe was included into the target volume. All patients have been treated by gamma rays of cobalt 60 and the thyroid absorbed dose was measured by semiconductor dosimeters (Scanditronix DPD6). These dosimeters were calibrated in the same geometric conditions of the irradiation. RESULTS: The measured absorbed dose of the thyroid parenchyma was equal to the calculated absorbed dose at the target that has been specified at a depth of -3 cm. Under the block, the isthmus received 5.1 +/- 0.9 Gy (9.9 +/- 1.8%) in nasopharynx carcinoma irradiation. However, in breast carcinoma irradiation, the distal thyroid lobe and the isthmus received 2.9 +/- 0.7 Gy (6.55 +/- 1.56%) and 3.69 +/- 0.77 (8.39 +/- 1.76%), respectively. CONCLUSIONS: This study shows that the thyroid received a dose equal to the prescribed dose in both nasopharynx and breast cancer patients. It is recommended to follow the function of the thyroid gland in these patients.

Adult↗

Iodine-Induced hypothyroidism.

Iodine is an essential element for thyroid hormone synthesis. The thyroid gland has the capacity and holds the machinery to handle the iodine efficiently when the availability of iodine becomes scarce, as well as when iodine is available in excessive quantities. The latter situation is handled by the thyroid by acutely inhibiting the organification of iodine, the so-called acute Wolff-Chaikoff effect, by a mechanism not well understood 52 years after the original description. It is proposed that iodopeptide(s) are formed that temporarily inhibit thyroid peroxidase (TPO) mRNA and protein synthesis and, therefore, thyroglobulin iodinations. The Wolff-Chaikoff effect is an effective means of rejecting the large quantities of iodide and therefore preventing the thyroid from synthesizing large quantities of thyroid hormones. The acute Wolff-Chaikoff effect lasts for few a days and then, through the so-called "escape" phenomenon, the organification of intrathyroidal iodide resumes and the normal synthesis of thyroxine (T4) and triiodothyronine (T3) returns. This is achieved by decreasing the intrathyroidal inorganic iodine concentration by down regulation of the sodium iodine symporter (NIS) and therefore permits the TPO-H202 system to resume normal activity. However, in a few apparently normal individuals, in newborns and fetuses, in some patients with chronic systemic diseases, euthyroid patients with autoimmune thyroiditis, and Graves' disease patients previously treated with radioimmunoassay (RAI), surgery or antithyroid drugs, the escape from the inhibitory effect of large doses of iodides is not achieved and clinical or subclinical hypothyroidism ensues. Iodide-induced hypothyroidism has also been observed in patients with a history of postpartum thyroiditis, in euthyroid patients after a previous episode of subacute thyroiditis, and in patients treated with recombinant interferon-alpha who developed transient thyroid dysfunction during interferon-a treatment. The hypothyroidism is transient and thyroid function returns to normal in 2 to 3 weeks after iodide withdrawal, but transient T4 replacement therapy may be required in some patients. The patients who develop transient iodine-induced hypothyroidism must be followed long term thereafter because many will develop permanent primary hypothyroidism.

Amiodarone↗

Why measure thyroglobulin autoantibodies rather than thyroid peroxidase autoantibodies?

Autoantibodies to thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) are of immunoglobulin G (IgG) class and have high affinities for their respective autoantigens. Both autoantibodies are markers of thyroid autoimmunity and they can be measured by a variety of assays. From the clinical perspective, TgAb are less prevalent than TPOAb and less useful than TPOAb for prediction of thyroid dysfunction. Moreover, TgAb interfere with Tg measurements to monitor metastases in thyroid cancer. However, increasing evidence suggests that these TgAb provide a surrogate for Tg. In terms of disease pathogenesis, Tg has been suggested to play a role in Graves' ophthalmopathy. Pending further studies, TgAb epitopes could distinguish between individuals who are euthyroid or who have clinical disease. A final, intriguing reason for measuring and characterizing TgAb is the interest these autoantibodies have rekindled in their autoantigen. It is conceivable that Tg polymorphisms, combined with the explosive mix of iodine, TPO and H2O2 necessary for thyroid hormone synthesis, inadvertently provide the trigger for the autoimmune thyroid response.

Autoantibodies↗

Development of a dried whole-blood spot thyroglobulin assay and its evaluation as an indicator of thyroid status in goitrous children receiving iodized salt.

BACKGROUND: Serum thyroglobulin appears to be a sensitive marker of thyroid dysfunction in endemic goiter. However, its value as an indicator of thyroid status in children after the introduction of iodized salt has not been tested. OBJECTIVE: The objective was to optimize and validate a thyroglobulin assay on dried whole blood spots and to evaluate thyroglobulin as an indicator of thyroid response to iodized salt. DESIGN: A standardized, commercially available, sandwich fluoroimmunometric serum thyroglobulin assay was adapted for use on blood spots and validated in Swiss children. In a 1-y prospective study in 377 goitrous Moroccan children aged 6-15 y, the assay was used to measure thyroglobulin before and after the introduction of iodized salt. Urinary iodine, thyroid volume, thyrotropin, and thyroxine were measured, and regression was done with thyroglobulin as the dependent variable. RESULTS: Correlation between the blood spot and serum assays was excellent (r = 0.98). The SD of the difference between the blood spot and serum assays was 3.8 micro g/L; the median CVs for the blood spot assay in controls and samples were 6.3% and 14.4%, respectively. Median thyroglobulin was 24.5 (range: 0-328.8) micro g/L at baseline and fell significantly after the introduction of iodized salt to 6.2 (0-83.1) and 4.4 (0-47.1) micro g/L at 5 and 12 mo, respectively (P < 0.0001). Regression of urinary iodine and thyroid volume on thyroglobulin was highly significant at baseline and at 5 mo (P < 0.001). CONCLUSION: Thyroglobulin, measured in dried whole blood spots, may be a valuable indicator of improving thyroid function in children after supplementation with iodized salt.

Adolescent↗

Case report: silent thyroiditis developed during alpha-interferon therapy.

Alpha-interferon (IFN-alpha) was used for the treatment of chronic active hepatitis C in a 30-year-old woman who was euthyroid but had low titers of antithyroid antibodies before treatment. Two months after the initiation of IFN-alpha therapy she became thyrotoxic. She had nontender diffuse goiter. A laboratory examination revealed elevated levels of serum free thyroid hormones and a suppressed concentration of serum thyrotropin. Titers of antimicrosomal antibodies increased. The anti-thyrotropin receptor antibody was negative. A 99mTcO- scintigram of the thyroid showed reduced uptake. During the IFN therapy free thyroid-hormone levels started to decline. The IFN-alpha therapy was completed 1 month after the onset of thyrotoxicosis. Two months after the completion of the therapy the patient became euthyroid and 99mTcO- uptake was normalized. It is likely that preexisting chronic thyroiditis was exacerbated to cause silent thyroiditis during IFN-alpha therapy. None of the other 11 patients with chronic hepatitis C who had had no anti-thyroid antibodies and were treated with IFN-alpha showed anti-thyroid antibodies and thyroid dysfunction after the therapy. It is advisable to assess anti-thyroid antibodies and thyroid function in patients who are going to receive IFN-alpha treatment.

Adult↗

Growth and hormonal status of children treated for brain tumours.

The adult survivors of the treatment of brain tumours in childhood are often short. Several adverse factors contribute to the impaired growth of these children including growth hormone (GH) deficiency, impaired spinal growth following spinal irradiation, chemotherapy, poor nutritional intake and recurrent tumour. The GH deficiency is due to radiation-induced damage to the hypothalamic-pituitary axis. GH is always the first pituitary hormone to be affected by such radiation damage but panhypopituitarism may occur if the radiation dose is sufficiently great. Preliminary results suggest that GH therapy will improve the growth rate of children with radiation-induced GH deficiency. Additional endocrine complications, which may occur following spinal irradiation, include thyroid dysfunction and ovarian failure due to direct radiation damage to the thyroid and the ovary.

Adolescent↗

Three novel mutations at serine 314 in the thyroid hormone beta receptor differentially impair ligand binding in the syndrome of resistance to thyroid hormone.

The syndrome of resistance to thyroid hormone is associated with diverse mutations in the ligand-binding domain of the thyroid hormone beta receptor, localizing to three clusters around the hormone binding cavity. Here, we report three novel resistance to thyroid hormone mutations (S314C, S314F, and S314Y), due to different nucleotide substitutions in the same codon, occurring in six separate families. Functional characterization of these mutant receptors showed marked differences in their properties. S314F and S314Y receptor mutants exhibited significant transcriptional impairment in keeping with negligible ligand binding and were potent dominant negative inhibitors of wild-type receptor action. In contrast, the S314C mutant bound ligand with reduced affinity, such that its functional impairment and dominant negative activity manifest at low concentrations of thyroid hormone, but are more reversible at higher T3 concentrations. The degree of functional impairment of mutant receptors in vitro may correlate with the magnitude of thyroid dysfunction in vivo. Modelling these mutations using the crystal structure of thyroid hormone receptor beta shows why ligand binding is perturbed and why the phenylalanine/tyrosine mutations are more deleterious than cysteine.

Adolescent↗

Influence of lithium on cell function in two different cell systems.

Lithium is widely used in the treatment and prophylaxis of bipolar psychiatric disorders. It accumulates in the thyroid gland and can cause goitre or thyroid dysfunction. The mechanisms of various effects of the lithium ion on thyroid cells have not been completely clarified. The aim of our work was to establish whether lithium, in the presence or absence of TSH, stimulates the synthesis of cAMP; as model systems we used a strain of rat thyroid follicular cells FRTL-5 and a line of Chinese hamster ovary fibroblasts with the human TSH receptor (CHO-R). Lithium at concentrations of 0.35 mM, 1 mM, 1.4 mM, 1.7 mM and 2 mM without TSH and at selected concentrations with TSH stimulation significantly increased cAMP synthesis in FRTL-5 and in CHO-R cells when compared with controls without lithium. These results are different from the published data, which have been unable to confirm the influence of lithium on cAMP synthesis or have even reported the inhibition of cAMP synthesis. However, in most published investigations only lithium in combination with TSH was tested. In conclusion, lithium was found to stimulate cAMP synthesis in FRTL-5 cells and in CHO-R cells.

Animals↗