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Summary objective To investigate whether variations over time of TSH-receptor antibodies (TRAb) and antibodies against G2s (G2sAb) and extraocular muscles (EMAb) can predict worsening of ophthalmopathy in Graves’ patients treated with intravenous glucocorticoid (IVGC) therapy. patients Of 65 consecutive patients with treated Graves’ disease and severe and active ophthalmopathy (GO) chosen to undergo IVGC treatment, only 57 patients, persistently euthyroid under methimazole therapy, were studied longitudinally for ocular parameters, TRAb, G2sAb and EMAb before therapy, at the end of therapy and, subsequently, every month for 21 months. measurements TRAb was detected by radioimmunoassay (RIA), G2sAb by enzyme-linked immunosorbent assay (ELISA) and EMAb by indirect immunofluorescence. results Forty-three out of 57 patients (75·4%, group 1) responded positively to therapy [improvement in diplopia and decrease in proptosis and clinical activity score (CAS)] but 14 (24·6%) did not (group 2). During follow-up after IVGC therapy, 12 out of 43 patients in group 1 (28%) showed a worsening in GO (group 1a), while 31 (72%) had stable ocular conditions or further improvement (group 1b). At the start of the study, TRAb, G2sAb and EMAb were not significantly different among the three groups. At the end of IVGC therapy TRAb levels decreased significantly with respect to starting values in all three groups of patients, whereas G2sAb and EMAb decreased significantly in groups 1a and 1b but not in group 2. During the subsequent follow-up, 10 patients in group 1a one/two months before and all 12 patients at the time of GO worsening showed an increase in G2sAb and EMAb but not in TRAb, which were consistently absent or present at low titre in all patients in this group. In group 1b TRAb, G2sAb and EMAb further decreased or became negative during the follow-up period. In all patients, TRAb were positively correlated with both CAS and proptosis only at the start of the study; by contrast, a significant correlation between both G2sAb and EMAb and diplopia was observed in groups 1a and 1b at all the times during the study, except one/two months before the worsening of GO in group 1a. conclusions Our results indicate that TRAb, G2sAb and EMAb can be considered sensitive markers of Graves’ ophthalmopathy during the initial stages of ophthalmopathy, but that only G2sAb and EMAb seem to be good predictive markers of the outcome in patients after corticosteroid therapy. Thus, taking into account the cost/benefit ratio, a longitudinal evaluation of either EMAb or G2sAb could be useful in monitoring the intravenous glucocorticoid therapy in patients with severe and active ophthalmopathy to predict a possible worsening of Graves’ ophthalmopathy.

Summary Objective In order to investigate whether somatotrophs are the target of antipituitary antibodies (APA) in adult patients with growth hormone deficiency (GHD), we studied the sera of 37 APA positive patients. Patients Patients were grouped as follows: nine patients with APA at high titre (> 1 : 8) affected by apparently idiopathic GHD; four of them (group 1a) with isolated GHD diagnosed during childhood and five with GHD diagnosed during adulthood associated with autoimmune endocrine diseases (group 1b), and 28 patients with autoimmune endocrine diseases without pituitary impairment, previously found positive for APA at low titre (1 : 8, group 2). Measurements APA were evaluated by a four-layer double indirect immunofluorescence technique. Results In group 1a patients, APA immunostained exclusively GH-producing cells. In group 1b patients, APA were directed not only to GH- but also to other pituitary hormone-producing cells. In group 2 patients, APA were directed selectively to PRL-producing cells and rarely to some GH-producing cells. Conclusions In the present study, we demonstrated that GH-secreting cells are the target of the autoimmune reaction in autoimmune GHD and that the immunostaining of only the somatotrophs is typical of isolated GHD. In contrast, the finding of diffuse staining of APA indicates the need to search for other autoimmune diseases. Finally, the presence of APA at low titre directed against PRL-secreting cells in patients with autoimmune endocrine diseases in the absence of pituitary impairment, seems to be only a nonspecific marker of pituitary autoimmunity. A longitudinal study would be useful to clarify the relationship between the different pituitary cell involvement and the natural history of pituitary dysfunction in autoimmune hypophysitis.