Hashitoxicosis

Abstract: The level of apoptosis has been investigated in thyroid tissue from eight patients with Graves's disease, one with Hashitoxicosis, three with Hashimoto's thyroiditis, and five patients with multinodular goitre, using flow cytometry and an in situ immunofluorescence technique. Cryostat sections have also been studied for Bcl-2 and APO-1/Fas expression in the thyrocytes and infiltrating lymphocytes, to determine their susceptibility to apoptosis. An increased level of apoptosis was detected in Hashimoto's glands. This was associated with decreased Bcl-2 staining and a patchy APO-1/Fas reactivity on thyrocytes. In addition, APO-1/Fas expression was noted within the germinal centres of lymphoid follicles. It is suggested that the dysregulation of apoptosis-related genes could be an important factor in the progression of destructive thyroid autoimmune disease.

Abstract: In a prospective multicentric study, 924 untreated hyperthyroid patients were investigated, coming consecutively within one year into 17 thyroid centers of 6 European countries. With the aid of clinical information, evaluation of thyroid scan and centrally assayed thyroid hormones, thyroid antibodies, TSH-binding inhibiting immunoglobulins (TBII), and urinary iodine, different types of hyperthyroidism could be shown. Two types of hyperthyroidism could be defined directly: autonomous adenoma in cases of hot nodules in thyroid scan and Graves’ disease, defined as hyperthyroidism with eye symptoms, and/or measurable TBII levels. The remainder, called “non-classifiable”, included TBII negative Graves’ patients, comprising of Hashitoxicosis, toxic nodular goiter, and other multifocal autonomies. 9.2% of the patients had an autonomous adenoma, 59.6% Graves’ disease, and 31,2% unclassified hyperthyroidism. The main and significant difference between these types were mean age, goiter size, nodularity, and severity of the disease, being especially expressed in Graves’ disease. Graves’ patients had significantly increased T3/T4 ratios. Using as additional criteria diffuse regular uptake and/or increased T3/T4 ratios for immunogenic types of hyperthyroidism at least half of the 31.2% unclassified hyperthyroidism are probably Graves’ disease. Forming two groups of iodine-deficient areas (IDA) and iodine-sufficient areas (ISA) according to the urinary iodine, it was possible to elucidate some characteristics independently of local factors. Autonomous adenoma was more frequent in IDA (10.1 %) than in ISA (3.2%). Differences in iodine supply are reflected in the three types of hyperthyroidism by a significant higher prevalence of goiter, thyroid nodularity, lower thyroid hormone concentrations, and a higher rate of T3 toxicosis in IDA. Increased thyroid autoantibodies were found significantly more often in the English centers, compared to the centers in central Europe. The most striking difference between the three types of hyperthyroidism in IDA and ISA was the incidence of iodine contamination, as defined as urinary iodine excretion ≥ 250 µg/g creatinine, being lowest in Graves’ disease (5.6%), and highest in unclassified hyperthyroidism (35%). This difference is probably due to the late diagnoses in non-Graves’ patients because presenting symptoms are less typical. The primary criteria of Graves’ disease could be especially evaluated in 271 patients. The highest prevalent single parameter of Graves’ disease is TBII (89%) followed by diffuse regular uptake (78%), diffuse consistency (75%), eye signs (47%), and thyroid autoantibodies (37%). All primary criteria together (group A) could be found only in 18.7% of patients in ISA versus 7.3% in IDA; only one criterion (group B) in 2.5%, and 8.4% resp. Patients of group A are younger, have a smaller goiter, and a more severe disease. Hashitoxicosis was assumed to exist in 4.2% of unclassified hyperthyroidism. We conclude: the different types of hyperthyroidism in 17 centers of 6 European countries are related to differences in immunological and nutritional status. This is reflected by a change in the distribution of the different types rather than by a change in the type of hyperthyroidism itself.