Technetium-99m-anti-tumour necrosis factor alpha scintigraphy as promising predictor of response to corticotherapy in chronic active Graves' ophthalmopathy.

It has been suggested that technetium-99m (99mTc)-anti-tumour necrosis factor alpha (TNF-α) scintigraphy (SCI) may be a useful diagnostic tool in Graves' ophthalmopathy (GO). This study evaluated whether orbit total radioactivity uptake on SCI could be used to predict corticosteroid therapy (CorT) responses in active-GO patients. A longitudinal study of patients with active GO defined by Clinical Active Score (CAS) >3/7 was done. Clinical, laboratory and SCI evaluations were performed at baseline and 3 months after concluding intravenous CorT. SCI (planar and tomographic) was assessed after intravenous injection of 10 mCi of 99mTc-anti-TNF-α. Orbits and cerebral hemispheres were defined as regions of interest (ROIs) to enable orbit/hemisphere ROI-ratios of total radioactive uptake. ROI-ratios were considered positive at >2·5. Average total radiation uptake (TRU) was also determined for each orbit (AVGROI ). Clinical, laboratory and SCI data were compared between responders (CAS became inactive) and non-responders to CorT (18 patients). At baseline, AVGROI were higher in active OG orbits (67·3 cps) than in inactive ones (33·6 cps; P<0·05). AVGROI (absolute values) reduced (-29·9 cps) in CorT responders and tended (P = 0·067) to differ from variations occurred in non-responders (+6·9 cps in patients with maintained CAS positivity post-treatment). Higher baseline ROI-ratios (4·9 versus 3·3; P = 0·056) and its pronounced reductions following CorT (-37% versus +56% in non-responders; P = 0·036) tended to be associated with good CorT responses in the subgroup of GO history ≥1 year. SCI showed a good association with active eye disease and may be an additional tool to identify CorT responders.

Successful Treatment for Severe Thyroid-associated Ophthalmopathy with Tocilizumab.

BACKGROUND AND OBJECTIVE: Thyroid-associated ophthalmopathy (TAO) is the most common extrathyroidal manifestation of Graves disease, occasionally severe and refractory to treatment, mainly in long-term disease. In these cases, one of the most important infiltrating cytokines in the orbital tissue is interleukin-6 (IL-6). METHODS: This is a case report, the methodology consisted of the application of tocilizumab in a patient with graves disease and the patient's follow-up. RESULTS: We present the case of a 54-year-old male with TAO who responded adequately to treatment with tocilizumab, an antibody directed against the IL-6 receptor. CONCLUSION: Tocilizumab could be an optional treatment in patients with TAO.

Changes of serum cytokines in hyperthyroid Graves' disease patients at diagnosis and during methimazole treatment.

OBJECTIVE: Cytokines are involved in the pathogenesis of Graves' disease (GD), but ambiguous serum cytokine results have been described. METHODS: We studied the changes in serum interleukin (IL)-1ß, soluble IL-2 receptor (sIL-2R), IL-5, IL-6 and tumor necrosis factor (TNF)-α concentrations in 29 untreated GD patients before and after restoration of euthyroidism with methimazole (MMI) treatment compared to 25 control subjects. Eleven out of 29 GD patients had active Graves' ophthalmopathy (GO). RESULTS: Compared to controls, untreated GD patients had significantly higher median levels of serum IL-1ß (18.7 vs. 34.0 pg/ml), sIL-2R (292.5 vs. 1,585.0 pg/ml), IL-5 (1.0 vs. 9.0 pg/ml), IL-6 (3.0 vs. 5.0 pg/ml) and TNF-α (8.1 vs. 16.0 pg/ml). In euthyroidism following MMI treatment, concentrations of IL-1ß (25.0 pg/ml), sIL-2R (362.0 pg/ml), IL-5 (3.0 pg/ml), IL-6 (3.0 pg/ml) and TNF-α (5.0 pg/ml) declined significantly and were similar to controls. The greatest reductions were noted in sIL-2R (76.9%), TNF-α (68.8%) and IL-5 (66.6%) levels. Serum sIL-2R, IL-5 and TNF-α levels in active GO patients were significantly elevated, but no significant differences were observed in GD patients without GO. Using a multiple linear regression analysis, serum IL-1ß was significantly associated with free thyroxine, sIL-2R with triiodothyronine and serum thyrotropin receptor antibody (TRAb) and TNF-α with TRAb. CONCLUSION: These results support the notion that serum cytokines could be used as a marker of GD activity, and the decrease in cytokine levels might be related to the achievement of euthyroidism and the immunomodulatory effects of MMI treatment.

Patogenia y tratamiento médico de la orbitopatía de graves / Pathogenesis and medical treatment of graves' orbitopathy

La Orbitopatía de Graves se presenta clínicamente en aproximadamente 50 por ciento de los casos de Enfermedad de Graves. La mayoría de las veces es leve y sólo en menos del 5 por ciento pone en riesgo la visión, pese a lo cual deteriora significativamente la calidad de vida de los pacientes. Hasta el momento no se conoce totalmente la patogenia, siendo posiblemente el receptor de TSH el blanco de la autoinmunidad. En cuanto al tratamiento, las medidas preventivas como lograr el eutiroidismo y la suspensión del tabaco son útiles en los distintos grados de la enfermedad. Para los casos más severos se han investigado diferentes medicamentos pero ninguno ha demostrado ser superior a los Glucocorticoides. Actualmente los consensos concuerdan en que es imprescindible clasificar al paciente según grado de actividad y severidad para orientar la terapia con mayor eficacia. Las investigaciones en curso pretenden encontrar una droga que supere el rendimiento existente

Graves' orbitopathy occurs clinically in approximately 50 percent of Graves' Disease. Most often it is mild and only less than 5 percent can threaten vision, despite which it significantly impairs the quality of life of this patients. So far its pathogenesis is not completely understood, but possibly TSH receptor is the target of autoimmunity. In relation to treatment, preventive measures such as achieving euthyroidism and the suspension of tobacco are useful in varying degrees of the disease. For more severe cases, different drugs have been investigated but none has shown superior efficacy to that of Glucocorticoids. Currently, different consensus agrees that it is essential to classify the patient according to levels of activity and severity to guide therapy more effectively. Ongoing investigations aim to find a drug that exceeds the existing performance

Estudio de las células natural killer como marcador inmunológico en pacientes con oftalmopatía distiroidea / Study of natural killer cells as an immune marker in patients with dysthyroid ophthalmopathy

Objetivo: analizar la correlación e influencia inmunológica de las células "Natural killer" con el desarrollo de la oftalmología distiroidea. Método: se incluyen 30 pacientes, estudiándose con tomografía computada de órbita y resonancia magnética, estudio hormonal e inmunológico. Resultados: 83.33 por ciento sexo femenino y 16.6 por ciento masculino. Edad promedio 39.97 años, 57.7 por ciento con enfermedad tiroidea controlada, complemento C3 11.16 y C4 26.54, natural killer basal 437.93 (rango 350-715) y posterior a tratamiento 308.1 (rango 188-405). Se demostró por imagen compromiso a músculos en el 77 por ciento sin diagnóstico. Conclusiones: la lesión muscular se correlacionó con el estado inmunológico del paciente incluso sin exoftalmos. La mejoría de las células NK con el tratamiento inmusupresor fue evidente y se sugiere una estrecha relación con el desarrollo de anomalías musculares y estrábica. Es importante distoroideo integrar un diagnóstico inmunológico y estrabológico temprano.

Objective: to analyze the immunological activity of natural killer cells in graves disease. Method: we studied 30 patients without strabismus. Orbital tomography, magnetic resonance hormonal and immunological test were incluided. Results: 83.33 per cent female, 16.6 per cent male. Age: 39.97 years old. 57.7 per cent of patients had normal hormonal levels. natural killer 437.93 pre-treatment, and 308.1 post treatment. Muscle damage was demostrated in 77 per cent of cases. Conclusion: we demonstrated a correlation between muscle damage and immunological disorders without an important exoftalmos. Improvement with corticoid therapy of natural killer alls levels was evident and a close relationship with de development of muscular anomalies and strabismus is suggested. In all graves patients it is important to integrate an early immunological and strabismological diagnosis.