Atrophic Hypothyroidism Research Articles

Painful Thyroiditis and Subsequent Atrophic Hypothyroidism After Cord Blood Transfusion

Painful Thyroiditis and Subsequent Atrophic Hypothyroidism After Cord Blood Transfusion

Calcitonin deficiency in early stages of chronic autoimmune thyroiditis.

Although calcitonin (Ct) deficiency has been described in chronic autoimmune thyroiditis (CAT) it is unclear at what stage in the disease it develops. We have analysed the Ct secretory responses of patients in two different evolutionary stages of CAT, namely the goitrous and atrophic phases. We studied the Ct response to combined calcium (2 mg/kg) and pentagastrin (0.5 microgram/kg) intravenous infusion in 27 patients with CAT and 30 normal adult controls. The cases were divided into two groups. The first comprised eleven women with CAT and goitrous subclinical hypothyroidism (GH), aged 28.6 +/- 10.1 years--at diagnosis they had increased thyroid autoantibody titres and cytological features compatible with stages 1 and 2 of Hashimoto's thyroiditis. The second comprised 16 females with CAT and an atrophic thyroid confirmed by ultrasound scan, aged 38.0 +/- 9.2 years--these patients were severely hypothyroid at diagnosis and were termed AH (atrophic hypothyroidism). Both groups (GH and AH) received replacement doses of thyroxine sufficient to restore euthyroidism for at least six months before the stimulation tests. Control group (C) consisted of 20 healthy women (A), aged 30.0 +/- 9.6 years, and 10 healthy men (B), aged 34.7 +/- 8.0 years. Serum Ct was measured by IRMA. The Ct secretory response was related to thyroid size and cytological data, when available. Basal Ct concentrations in groups GH (0.08 ng/l, median) and AH (0.07 ng/l, median) were significantly lower than those of female controls (0.58 ng/l, median). Stimulated Ct peak values in groups GH (0.08 ng/l, median) and AH (0.19 ng/l, median) were significantly lower than those of female controls (13.61 ng/l, median). Also, both basal (2.72 ng/l, median) and stimulated Ct levels (35.73 ng/l, median) in male controls were significantly higher than in female controls given already. A positive correlation between the Ct secretory reserve and thyroid dimensions, evaluated by ultrasound scan, was found only in patients with thyroid atrophy (AH; rs = 0.61, P < 0.05). We have found low basal and stimulated calcitonin values in patients with chronic autoimmune thyroiditis and thyroid enlargement, which represents an early phase of chronic autoimmune thyroiditis. Our data have also confirmed previous findings of deficient calcitonin secretion in advanced stages of chronic autoimmune thyroiditis in which thyroid atrophy is usually found. These findings may be associated with C-cell destruction following progressive, nonspecific follicular cell damage caused by lymphocytic infiltration and fibrosis of the gland.

Reassurance About Bioequivalence of Generic Thyroxine in the United Kingdom

AbstractIn New Zealand the approval of registration of generic L-thyroxine has recently been considered. The bioequivalence of two generic brands of L-thyroxine available in the United Kingdom was studied in comparison with the brand leader Eltroxin (Glaxo) in five female patients with primary atrophic hypothyroidism. Each patient was randomly allocated, double blind, each of the three brands in their usual dose for a period of one month before the estimation of serum total thyroxine (Tq), free, serum total triiodothyronine (T3), free T4 and serum sensitive thyrotrophin (sTSH) estimations before and at 0.5, 1, 2, 8 and 24 hours after the morning dose at 0900 hours. Using multivariate analysis there was no significant difference in those levels between the brand leader and the two generic products. There is therefore some reassurance concerning the bioequivalence of some of the generic products of L-thyroxine but it is important that individual studies of generic products are undertaken prior to their intr...

Low Prevalence of Thyrotropin Receptor Antibody in Primary Hypothyroidism in Japan

The prevalence of TSH receptor antibody (TRAb), measured by RRA assay (TSH-binding inhibitor immunoglobulin, TBII) and biological stimulation-blocking assay (thyroid-stimulation blocking antibody, TSBAb), was examined in 134 consecutive patients with primary hypothyroidism due to autoimmune thyroiditis [83 patients with goitrous Hashimoto's disease (group A) and 51 with primary atrophic hypothyroidism (group B)]. In group A, TBII was detected in 6 patients (7%), TSBAb in 7 (8%), and both in 4 (5%). Similarly, in group B, TBII was detected in 7 patients (14%), TSBAb in 7 (14%), and both in 5 (10%). TBII with TSBAb activity was low or moderate in group A, but strongly positive in group B. No relationship was apparent in either group between TBII or TSBAb activity and any clinical or laboratory parameter examined. Moreover, no clinical or laboratory findings distinguished patients with TRAb from those without. The low prevalence of TRAb in primary hypothyroidism suggests that intrathyroidal cell-mediated destructive mechanisms may be more important in the pathogenesis of hypothyroidism in autoimmune thyroiditis.

Recovery of the thyroid function in patients with atrophic hypothyroidism and blocking type TSH binding inhibitor immunoglobulin

The prognosis of atrophic hypothyroidism with blocking type TSH-binding inhibitor immunoglobulin was studied. Among 45 patients (16 males and 29 females) with overt hypothyroidism (serum TSH greater than 40 mU/l) without goitre, thyroid autoantibody to microsomal antigen was positive in 38 or 84.4%, and 4 or 8.9% had TSH-binding inhibitor immunoglobulin, which was shown to be a TSH-stimulation blocking antibody by cAMP production assay using cultured porcine thyroid cells. Thyroidal radioactive iodine uptake was low and thyroid hormone replacement therapy was required. Long-term follow up of 2 patients with strongly positive TSH-binding inhibitor immunoglobulin for 2 to 7 years, however, revealed recovery of the thyroid function after steroid therapy or spontaneously with iodide restriction, respectively, correlating with decrease in both TSH-binding inhibitor immunoglobulin and TSH-stimulation blocking antibody activities. Thyroidal radioactive iodine uptake became normal and histological examination of the thyroid in one patient revealed well-preserved thyroid follicles with lymphocytic infiltration. Recovery of thyroid function can be expected with a decrease in TSH-binding inhibitor immunoglobulin activity in atrophic hypothyroidism, which is not necessarily the end stage of chronic thyroiditis.

Secretor Status and Infection in Patients with Graves' Disease

We have demonstrated that the inability to secrete the water soluble glycoprotein form of the ABO blood group antigens into saliva is significantly more common in patients with Graves' disease than control subjects (40% vs 27%: P less than 0.025) but not among those with Hashimoto's thyroiditis or spontaneous primary atrophic hypothyroidism. Non-secretion is associated with increased susceptibility to infection and to asymptomatic carriage of some microorganisms. Although Yersinia enterocolitica has been found to express antigen cross reactive with the TSH receptor, we did not find an increased prevalence of Yersinia species in the faeces of 107 patients with Graves' disease. The isolation rate (less than 1%) was similar to that observed in the local population with diarrhoeal illness. Salivary IgA levels determined by whole cell ELISA with Y. enterocolitica 03 were not elevated in the majority of specimens examined. The results suggest that in contrast to reports from Scandinavia, there is no strong evidence that yersiniae play a role in the pathogenesis of Graves' disease among patients in South east Scotland. Non-secretors are significantly over represented among patients with several other autoimmune diseases; however, with the exception of antitubulin antibodies, non-secretors with Graves' disease did not have more antibodies to other human antigens than secretor patients.

Effective Method for Prediction of Transient Hypothyroidism in Neonates Born to Mothers with Chronic Thyroiditis

An effective method of prediction of neonatal transient hypothyroidism was examined in 105 neonates (including a pair of twins) born to mothers with chronic thyroiditis (92 mothers with goitrous Hashimoto's disease and 12 with primary atrophic hypothyroidism). Antithyroid microsomal antibody was measured by a hemagglutination technique (MCHA), and antithyroid-stimulating hormone (TSH) receptor antibody by both radioreceptor assay (TBII) and biologic thyroid-stimulation blocking assay (TSBAb). For generalization of predictive criteria, the expression of TBII activity was standardized using standard serum made taking units of MRC-LATS-standard B as a reference, and that of TSBAb activity was standardized as the degree of dilution with normal pooled serum to attain 50% inhibition of TSH (100 microU/ml)-induced cyclic adenosine monophosphate increase (TSBAb50). The MCHA titer in maternal serum at delivery correlated well with that of the corresponding cord serum, but not with the free thyroxine (T4) index or the TSH level in cord serum. TBII activity was positive in only 4 of 12 mothers with primary atrophic hypothyroidism, TSBAb activity was also positive only in these four mothers, and neonatal thyroid dysfunction was observed in three of their neonates. Two of these neonates developed transient hypothyroidism requiring T4 treatment, and the t third developed mild transient hyperthyrotropinemia with normal T4 and triidothyronine levels. The mothers whose neonates showed transient hypothyroidism had TBII activities of more than 300 U/ml and TSBAb50 activities of more than 300. Ninety-two mothers with goitrous Hashimoto's disease had neither TBII nor TSBAb activity, irrespective of their thyroid function, and delivered euthyroid babies.(ABSTRACT TRUNCATED AT 250 WORDS)

4 Autoimmunity and hypothyroidism

Hypothyroidism can be induced by various diseases. An autoimmune cause accounts for approximately 90% of adult hypothyroidism, mostly due to Hashimoto's disease. The majority of Hashimoto patients are women aged between 20 and 60 years old and nearly 10% show overt hypothyroidism. With time euthyroid patients progress to hypothyroidism and thus the prevalence of hypothyroidism is higher in elderly patients. Especially at 3 to 8 months postpartum, the prevalence of hypothyroidism is very high, up to 2-4%, but more than 90% of these cases are transient. Autoimmune destructive mechanisms, such as antibody dependent cytotoxicity, K and NK cell cytotoxicity, T lymphocyte cytotoxicity and lymphokine cytotoxicity, have been studied in vitro, but the most important factor in vivo is still unknown. A recent finding is that thyroid stimulation blocking antibody (TSBAb) may induce primary atrophic hypothyroidism. This antibody not only blocks TSH-induced cAMP production but also blocks TSH-induced DNA synthesis and iodine uptake in cultured thyroid cells. The prevalence of TSBAb in patients with primary atrophic hypothyroidism varies in different studies, from 0 to 47%. Reports on the relationship between TSBAb and TSH-binding inhibitory immunoglobulin (TBII) detected by radioreceptor assay are conflicting. The prevalence of TSBAb in patients with goitrous hypothyroidism is also controversial, varying from 0 to 20%. Transient hypothyroidism is observed frequently in the postpartum period and in the post-thyrotoxic phase of pregnancy-unrelated silent thyroiditis. Maternal TSBAb causes transient neonatal hypothyroidism when the activity is more than 1500 i.u./litre. The blocking and stimulatory types of anti-TSH receptor antibodies may both react with the same epitope(s) of TSH-receptor related antigens but the exact mechanisms that lead to the different effects are unknown. In some patients, including those with Graves' disease, stimulating and blocking antibodies co-exist and thyroid function may change from hyperthyroidism to hypothyroidism, or vice-versa, depending on the balance of stimulatory and blocking activities. Hypothyroidism in Graves' disease after treatment is thought to be induced in two ways: autoimmune thyroid destruction and the predominant appearance of TSBAb. Dietary iodine restriction is helpful in allowing recovery from hypothyroidism in more than half of the patients with spontaneously occurring primary hypothyroidism in Japan. Submaximal doses of T3 may be useful in differentiating transient from persistent hypothyroidism, since spontaneous recovery is detected by an increase of serum T4.(ABSTRACT TRUNCATED AT 400 WORDS)

Autoimmune Endocrine Disease

Publisher Summary This chapter discusses autoimmune endocrine disease. Many different definitions of autoimmune disease exist. From a pathophysiological point of view, autoimmune disease represents altered physiology as a direct result of antibodies or lymphocytes reacting with self antigens. From an immunological point of view, autoimmune disease should be transferable with antibodies or lymphocytes, and the disease process should be reenacted in normal transplanted tissue without evidence of tissue rejection. From a clinical point of view, autoimmune disease should be preventable or curable with immunotherapy. As the study of endocrine autoimmunity as well as other autoimmune diseases has progressed, many common themes link these various illnesses. There are three major pathogenic mechanisms in autoimmune endocrine disease. The most common cause of disease is the destruction of a specific gland or cell type (type I diabetes mellitus, thyroiditis, idiopathic primary adrenal insufficiency, idiopathic hypoparathyroidism, primary gonadal insufficiency, and hypophysitis). The next most common cause of autoimmune endocrine disease results from antibody interactions with cell-surface receptors either mimicking hormone action (Graves' disease, hypoglycemia with anti-insulin receptor antibodies) or blocking receptor function (atrophic hypothyroidism and insulin resistance secondary to anti-insulin receptor antibodies).