Apoptosis: its pathophysiology and monitoring. The role of apoptosis in the radioiodine therapy of hyperthyroidism.

The review aims to give an up to date understanding of the mechanisms of apoptosis (programmed cell death), the methods of detecting apoptosis, in particular with regard to imaging such changes non-invasively. Radioiodine (I-131) is a gamma and beta emitting radionuclide and is commonplace in the treatment of hyperthyroidism. I-131 therapy relies on the destruction of thyroid tissue by beta radiation, and such destruction is proposed to be partly as a result of apoptosis. The review undertakes to explore and provoke research into the mechanisms of thyroid cell destruction by I-131, and whether such changes are able to be detected or monitored. Current knowledge concerning apoptosis in the thyroid gland in diseased states (including cancer) are described. The clinical significance of monitoring and modifying apoptosis are emphasized. Furthermore, overt and late destruction of thyroid tissue following I-131 therapy requires elaboration, and the relevance of detecting and modifying thyroid cell apoptosis following I-131 are questioned.

The value of estimating serum aproptotic marker concentrations in monitoring and prognosis of 131I--therapy in Graves' disease. Preliminary report.

BACKGROUND: The effect of radioiodine (131I) in Graves' disease (GD) is probably due to the direct physical destruction of thyrocytes by beta radiation, and by the indirect action through stimulation of apoptosis in these cells. The aim of our study was to investigate the changes in serum concentrations of sFas and sFasL as stimulators of apoptosis, and Bcl-2 as an inhibitor of apoptosis in patients with GD following 131I administration. MATERIAL AND METHODS: The study was performed on 30 patients with GD (29 female and 1 male aged 25-45). All patients were euthyroid (biochemical and clinical) prior to radioiodine therapy. The target absorbed dose ranged between 90 and 160 Gy. We assessed markers of apoptosis and hormone concentrations (fT3, fT4 and TSH) in the following manner: before 131I administration, then two weeks, one month, two, three, four, and five months after 131I administration. RESULTS: After four months, the concentrations of sFas and sFasL rose by 50% and decreased during the next month. Pretherapeutic concentrations of Bcl-2 were elevated, and peaked two weeks after ingestion, showing a gradual decrease with time. We found a significant increase in serum TSH, and a decrease of fT3 and fT4 concentrations by the end of the third month of radioiodine therapy. CONCLUSIONS: Decreases in serum levels of sFas and sFasL and increases of Bcl-2 are regarded as characteristic for GD patients before radioiodine therapy. Radioiodine therapy reverses the ratio of estimated markers after four months. The concentrations of hormones reflect actual thyroid function, whereas concentrations of markers of apoptosis may suggest morphological changes.