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Burumkulova et al., Moscow, Russia, investigated if there was a
difference in the normalization of left ventricular contractility (LVC)
in 30 patients with untreated Graves' disease, who subsequently received
15 mg methimazole per day as compared to 30 untreated patients, who were
subsequently treated with 30 mg methimazole per day. LVC was measured by
using two-dimensional echocardiography. Biochemical euthyroidism was reached
at the same time in both groups after 3 weeks, and at that time normalization
of the previously increased LVC was found in 87% in the low methimazole
group and in 93% in the high methimazole group. It is concluded that starting
with 15 mg methimazole as treatment for Graves' disease, is as effectively
as starting with 30 mg methimazole. It should be noted that both groups
were selected randomly.
Schuppert et al., Hannover, Germany and Bethesda, MD, USA, investigated the effect of pretreatment with iodide of patients with untreated Graves' disease on the expression of the major histocompatibility complex (MHC) class I and class II, as it has been previously suggested that increased expression of MHC I and II may play a role in the expression and perpetuation of autoimmune thyroid disease. They found that expression of MHC class I and II was lower in patients pretreated with iodide as to no-iodide pretreatment. The authors conclude that the therapeutical action of iodide may also be related to lowering of MHC gene expression in thyroid autoimmune disease. (Comment: The "classical" effect of iodide in Graves' disease has been attributed to its inhibitory action on thyroid hormone synthesis and release (Wolff-Chaikoff effect). However, after about 10 days, the thyroid escapes from this effect and thyroid hormone synthesis and release may be stimulated at an increased rate. The results of these authors are of interest, but at this moment it is not advocated to routinely use iodide as pretreatment in the routine medical approach of Graves' disease). Rippegather et al., Frankfurt, Germany, studied the role of intrathyroidal lymphocytes (ITL) on the pathogenesis of human autoimmune thyroid disease by injecting ITL from 9 patients with Graves' disease (GD) and 9 patients with non-toxic nodular goiter (NTG) into nude (athymic) mice which were 8 weeks previously grafted with normal human thyroid tissue. After injection of ITL a significantly higher number of CD3+ human lymphocytes was found in the transplant of GD-lymphocytes injected mice as compared to NTG-lymphocytes injected mice. In addition, a significant increase of HLA-class II, intracellular adhesion molecule-I (ICAM-I), vascular cell adhesion molecule-I (VCAM-I), and CD58-expression was seen, as well as a number of IgG presenting plasma cells only after injection of Graves' disease-lymphocytes. The authors conclude that in the nude mouse model, grafted GD-lymphocytes selectively migrate into human thyroid transplants and induce significant functional as well as histological changes, like in autoimmune human thyroid disease. The results suggest an important role of ITL in the etiopathology and clinical course of Graves' disease. Mühlberg et al., München and Leipzig, Germany, studied the effects of dexamethasone and UV-irradiation on cultured retroorbital fibroblasts of 3 patients with TAO on the induction of interleukin-1 (IL-1) and its antagonist IL-1 receptor antagonist (IL-1RA). They found that with increasing concentrations of dexamethasone IL-1RA gene expression was inhibited in a dose dependent manner. By contrast UV irradiation dose dependently upregulated IL-1RA expression and the authors conclude that induction of this antagonist to IL-1 may represent an important mechanism, by which orbital radiotherapy exerts its beneficial therapeutic actions in patients with active GO, because it is known that IL-1 plays a prominent role in the evolution of TAO by its capacity to stimulate cell proliferation, glycosaminoglycan synthesis and prostaglandin production. (Comment: corticosteroids, like dexamethasone, also have beneficial effects on development of TAO, apparently by a different mechanism than through its effects on IL-1RA.) |
