Thyroid associated ophthalmopathy (TAO)
	Kahaly et al., Mainz, Germany, report on 122 orbital surgical decompressions in 67 euthyroid patients, median age 48 years, 49 female, with severe TAO. Results were followed with a median of 5 years. Endonasal approach was performed in 60%, endonasal-transmaxillar in 16%, and the endonasal-coronal technique in 24%. Median exophthalmus decreased with 7 mm, visual acuity improved from 0.4 to 0.8 in patients with optic neuropathy. In 60% of patients chemosis was present before surgery and disappeared in all two years later. Intraocular pressure in upgaze decreased from median 24 to 17 mmHg and lid aperture from 15 to 11.5 mm. Normalization of perimetry was observed in all 50 patients with scotomas. Severity of TAO (Donaldson score) decreased from 8-2.5 points. The novo diplopia developed in 33%, but was surgically successfully corrected. In 15% transient infraorbital hypoesthesia developed. Fallahi et al., Pisa, Italy, studied the prevalence of non-organ specific autoantibodies in patients with TAO before and after treatment with corticoids or intravenous immunoglobulin (IVIG). In 14/65 patients anti-nuclear antibodies (FAN) were positive, Ds-DNA antibodies in 2/50, anti-smooth muscle antibodies (ASMA) in 8/39, anti-mitochondrial antibodies in 1/39, RA factor in 2/39, antibodies to Sm, RNP, SS-A, and SS-B were negative in 39/39 patients. FAN and ASMA were re-evaluated after 6 and 9 months of treatment with corticoids and IVIG respectively, and 6-12 months later. FAN and ASMA disappeared in most patients with either treatment, but re-appeared in some after treatment, while patients who were initially negative showed positive ASMA and/or FAN after treatment. The authors conclude that TAO is associated with a high prevalence of non-organ specific autoantibodies that are modulated by corticosteroids or immunoglobulin treatment and secondly, that the appearance of ASMA and/or FAN in patients who were initially negative indicates an ongoing autoimmune process. Dattatreya et al., Cleveland, OH, USA, evaluated the effect of 131 therapy for hyperthyro>id Graves' disease on TAO. Twenty consecutive patients were treated with a mean dose of 15.5 mCi and were followed for 6 months with clinical evaluation and MRI both at baseline and during follow-up. Replacement L-T4 was started after sustained elevation of TSH. At baseline 6/20 patients showed clinical evidence of TAO and 8/20 showed only evidence of TAO by MRI. Total muscular volume (TMV) correlated significantly with Hertel score. Two months after 131 a small but significant increase in volume of the rectus inferior was seen that was not clinically evident and did not progress. TMV remained unchanged after therapy during the 6-months study period. They conclude that the hypothetical risk for 131-induced TAO must be small. (Comment: Two remarks must be made: In the first place the conclusion seems a little bit premature because only a small number of patients was investigated and secondly, the degree of TAO was not mentioned other than that only a subgroup of patients had clinical evidence of TAO.) Gordon et al., Pittsburg, PA, USA, compared L-T4 replacement dose (L-T4 RD) in patients with different etiology of hypothyroidism. They compared 37 patients with post radioiodine hypothyroidism for Graves' disease (PRH) on a stable L-T4 RD at a mean time after therapy of 12 years, 36 patients with atrophic thyroiditis (AT), 36 patients with Hashimoto's hypothyroidism (HH), 36 patients with central hypothyroidism (CH), and 36 patients with hypothyroidism post near total thyroidectomy and 131 therapy for thyroid carcinoma (TC). Mean RD (µg/kg/day) in AT (1.26) was significantly lower than in HH (1.95) and PRH (1.56), which in turn were lower than in CH (1.88) and TC (2.08). It appeared that L-T4RD in PRH varies as a function of time and stabilized at approximately 7 years post 131. The authors conclude that the different RD’s depend on residual functioning thyroid tissue. (Comment: They do not state but I assume that suppressive doses of T4 were used in TC.) Ludgate et al., Brussels, Belgium, published in the past that mRNA of the TSH receptor (TSHR) was present in orbital adipose tissue of 1 patient with TAO. In the present report they investigated, using a monoclonal antibody against TSHR- protein, if expression of the TSHR is present in retroorbital tissue of patients with TAO and of controls. Six samples of extraocular muscle (EOM) and one of orbital adipose tissue (OAT) from patients with TAO were studied. EOM from 5 strabismus corrections and OAT from two normal retina donations were used as controls. They found that no TSHR-protein was present in controls tissues but was located in all patients tissues. The morphology and location of the TSHR- protein was consistent with being present in the preadipocyte. The authors conclude that further studies are necessary to show if the immunoreactivity is due to the TSHR-protein itself or a cross-reacting protein. Dutton et al., Rochester, MI, USA, and Munich, Germany, detected TSHR mRNA in uncultured orbital connective tissue (OCT) specimens from patients with TAO but not in OCT specimens of normals. Neither was it detected in late-passage normal or TAO orbital fibroblasts. Immunohistochemical studies demonstrated TSHR-like immunoreactivity in uncultured TAO OCT specimens and in primary- and second- passage TAO fibroblasts, but immunoreactivity was absent in the 5th passage TAO orbital fibroblasts. The authors conclude that the TSHR-protein is expressed in orbital connective tissue of patients with TAO. (Comment: This and the previous study are important and gradually a picture arises at the horizon, suggesting that the antigen i.e. the TSHR-protein that is involved in the pathogenesis of the hyperthyroidism of Graves' disease is the same that is involved in the pathogenesis of TAO. Further studies, however, are necessary to confirm this picture and to exactly specify the cellular location of the TSHR-protein in the orbit.) Förster et al., Mainz, Germany, studied the phenotype of 18 T-cell lines derived from retroorbital infiltrates of 6 patients with severe TAO. After culturing and stimulation of these 18 T-cell lines they found that the lymphocytes that recognize autologous retroorbital protein fractions were predominantly CD4+. The cytokine mRNA profiles suggested that both Th1 and Th2 lymphocytes are present in these retroorbital infiltrates and support a role for both T- and B-cell autoimmunity in the development of TAO.