Background: Diplopia identifies patients with eye muscle involvement in Graves' ophthalmopathy (GO). Objective: To identify clinical parameters that could eliminate the need for magnetic resonance imaging (MRI) to assess the activity of inflammation in the eye muscles of GO patients with diplopia. Methods: In 43 patients with GO with recently developed diplopia, orbital ultrasound and MRI were performed. Muscle diameters and MRI T2 relaxation times were measured, and the amount of orbital connective tissue was calculated from MRI scans and compared with ultrasound readings, diplopia grades, degree of protrusion, ocular pressure, tear production, antibody levels and hormonal parameters of thyroid function. Results: No correlation was found between diameters of 233 extraocular muscles measured by MRI and by ultrasound. For each of the four muscles, there was a diameter above which ultrasound was always unreliable. MRI data were used in further analysis. Of the muscles examined, the inferior rectuses were the most frequently enlarged -at least one, in 93% of cases. Medial, lateral and superior rectuses were enlarged in 59%, 37% and 34% of the orbits respectively. The pattern of muscle involvement of the two orbits tended to be symmetric (r ¼ 0.49, P ¼ 0.003), particularly for the medial rectuses (r ¼ 0.90, P ¼ 0.000). Proptosis correlated with the sum of the muscle diameters for a given eye (right eye: r ¼ 0.54, P ¼ 0.003; left eye: r ¼ 0.57, P ¼ 0.001), but it failed to correlate with the amount of orbital connective tissue. In 53% of the patients, normal T2 relaxation times were found in all eight muscles. There was only a weak correlation between muscle thickness and T2 relaxation time (r ¼ 0.49, P ¼ 0.003), indicating that muscle enlargement alone is not a sign of disease activity. The severity of diplopia was independent of T2 relaxation time. The amount of orbital connective tissue showed a negative correlation with the greatest T2 relaxation time for a given eye (r ¼ ¹ 0.52, P ¼ 0.004); this suggests that disease types exist that have predominant muscle involvement and predominant connective tissue expansion. No correlation between connective tissue expansion and proptosis, diplopia grade, muscle thickness or disease duration was found -that is, connective tissue expansion is not a major factor in diplopia. Both muscle and connective tissue findings were independent of thyroid function. Conclusion: Ultrasound and MRI eye muscle diameter readings do not correlate, because of the inherent inaccuracy of orbital ultrasound. Muscle enlargement alone does not mean oedematous swelling and active disease. Neither ultrasound, nor any combination of 11 clinical and laboratory parameters provided the degree of information on muscles and connective tissue that was obtainable by MRI. In unclear cases of recently developed diplopia, before orbital decompression surgery, in the case of treatment failure or if, for any other reason, imaging is needed in GO, MRI is the method of choice.

No abstract

No abstract

Various diagnostic techniques have been successfully used in the clinical management of cold nodules; however, the decision on whether to employ surgery or a conservative treatment is not always easy. This study was designed to appraise the diagnostic value of technetium-99m methoxyisobutylisonitrile (MIBI) scintigraphy in the assessment of cold nodules detected using (99m)Tc-pertechnetate. Fifty-two patients were included in the study. All had already been selected for surgery, based on their clinical and laboratory findings, including fine-needle aspiration biopsy. The total number of cold nodules on (99m)Tc-pertechnetate scans was 59. The thyroid scan was performed 20-40 min after i.v. injection of 400 MBq of (99m)Tc-MIBI. Uptake of MIBI in thyroid nodules was compared with that in the surrounding normal thyroid tissue, and a score of between 0 and 3 was assigned to each nodule as follows: 0, cold; 1, decreased; 2, equal; 3, hot. Definitive histology revealed nodular goitre in 24 cases, adenoma in 19, thyroiditis in 1, differentiated cancer in 12, medullary cancer in 2, and anaplastic cancer in 1. None of the degenerative nodules were hot on MIBI scan, while the adenomas showed a variety of MIBI imaging patterns, most frequently the score 3 pattern. In the diagnosis of differentiated thyroid cancer the sensitivities of score 3 and score 2+3 MIBI uptake patterns were 83% (10/12) and 100%, respectively. The score 3 MIBI uptake pattern had a specificity of 100% and a positive predictive value of 100% with respect to thyroid (benign and malignant) neoplastic diseases, whereas a specificity of 72% and a positive predictive value of 43% were observed in the detection of differentiated cancer. After a cold nodule had been detected using (99m)Tc-pertechnetate, a second scan with high MIBI uptake increased by 7.8 times the probability that this nodule would be a differentiated cancer. In conclusion, (99m)Tc-MIBI scintigraphy is a useful method in the differential diagnosis of cold thyroid nodules if the primary aim is to differentiate degenerative from neoplastic diseases rather than to differentiate benign from malignant nodules. High MIBI uptake considerably increases the probability of a differentiated thyroid cancer and facilitates immediate surgical removal, while decreased uptake actually excludes it. We suggest a combination of fine-needle aspiration biopsy and MIBI scan as a routine diagnostic approach to cold thyroid nodules.

Over the past few years increasing evidence has suggested the nongenomic effects of thyroid hormone, such as the activation of the signal transduction pathways and the activation of nuclear factor-B by the induction of oxidative stress. The present study was undertaken to investigate the effect of thyroid hormone on human polymorphonuclear leukocytes (PMNLs) which are known as important sources of reactive oxygen species in the circulation. The production of superoxide anion (O 2 ) and the activity of myeloperoxidase were determined in the presence and absence of several inhibitors of the signalling pathway. -Thyroxine (T 4 ), L-3,5,3 -tri-iodothyronine (T 3 ) and L-3,5-di-iodothyronine (T 2 ) stimulated O 2 production in PMNLs in a dose-dependent manner within a few minutes of addition to cells. Thyroid hormone-stimulated O 2 production was partially inhibited by pertussis toxin, an inhibitor of GTP-binding G protein, and was completely abolished by the protein kinase C inhibitors calphostin C and Ro-32-0432, and by a calcium chelator (BAPTA; bis-(o-aminophenoxy)ethane-N,N,N ,N -tetraacetic acid). Thyroid hormone stimulated myeloperoxidase activity and induced 125 I incorporation into PMNLs. Furthermore, thyroid hormone pre-incubation enhanced O 2 production for n-formyl-methionyl-leucylphenylalanine (FMLP) stimulation. In conclusion, novel nongenomic actions of thyroid hormone, the induction of superoxide anion production and the stimulation of myeloperoxidase activity in PMNLs were demonstrated. The induction of O 2 production requires calcium and is mediated by a pertussis toxin-sensitive G protein via stimulation of protein kinase C(s). These results suggest the existence of a membrane-bound binding site for thyroid hormone in PMNLs and a physiological role for thyroid hormone in the cellular defence mechanisms by stimulating free-radical production.