We have evaluated the association between smoking, Graves' disease and endocrine ophthalmopathy in a case-control study of 208 patients with newly diagnosed Graves' disease and carried out a retrospective survey of 72 patients treated for Graves' disease and admitted to our ward because of endocrine ophthalmopathy. In the prospective study, patients with Graves' disease smoked significantly more than their healthy controls (41% vs 30%, p<0.01 for current smokers, odds ratio 1.6, 95% confidence interval 1.1-2.3, and p<0.05 for patients with a history of smoking, odds ratio: 1.4, 95% confidence interval 1.0-1.9). Among the patients with endocrine ophthalmopathy at diagnosis, there were slightly more patients with a history of smoking (p <0.05, odds ratio 2.1, 95% confidence interval 1.1-3.9), but not more current smokers when compared with the remaining group. The patients with eye problems tended to have a more active disease with higher levels of thyroxine and TSH-receptor antibodies, but no difference was seen in thyrogastric autoantibodies. No effect of smoking on thyroid hormone and autoantibody levels could be detected. In the retrospective survey we found 64%, 71% and 87% smokers among patients with moderate, severe and malignant eye disease, respectively. In summary, the results show that smoking is associated with an increased risk of contracting Graves' disease and that it enhances the severity of the eye disease in cases that develop endocrine ophthalmopathy during the course of treatment.
Brita Winsa, Agneta Mandahl and F Anders Karlsson
Brita Winsa, Per Anders Dahlberg, Rolf Jansson, Hans Ågren and F. Anders Karlsson
In patients with Graves' disease, thyrostatic drug treatment may induce definitive remission without the need of more aggressive measures such as surgery or radioiodine. Following drug therapy, however, relapses often occur. In the present study, a multivariate analysis of pretreatment variables was performed, in order to identify individuals running a high risk of an unfavourable outcome of thyrostatic drug therapy. We studied 109 consecutive patients with a mean age of 38 years, range 20–70, over a mean follow-up period of 5.3 years after cessation of therapy. The analysis showed that goitre size, age, thyroid hormone levels, HLA-DR 3 haplotype, and TSH receptor antibody levels were of prognostic significance, whereas HLA-B8 haplotype, a lymphocytic infiltrate at fine needle biopsy, thyroglobulin, and microsomal antibodies had no such value. In particular, patients characterized by young age, large goitre and high hormone values were found to be associated with an unfavourable course.
Rolf Jansson, Per Anders Dahlberg, Brita Winsa, Olav Meirik, Jan Säfwenberg and Anders Karlsson
Abstract. In the present study, 93 consecutive women, 20–40 years of age, referred to our clinic from 1976–85 with Graves' disease, were examined with respect to a possible relation between onset of disease and previous pregnancy. An increased relative risk of 6.5 (3.8–11.0, 95% confidence interval) of developing Graves' disease within one year following delivery was found. After excluding the nulliparous women, almost 2 out of 3 women who developed Graves' disease in the principal child-bearing age of 20–35 years had a postpartum onset, suggesting an important role of immunomodulatory events following delivery for the development of this disease in young women. Future studies will ascertain to which extent the recognition of postpartum Graves' disease has implications on the choice of therapy in this group of women.
Brita Winsa, Jonas Rastad, Göran Åkerström, Henry Johansson, Kerstin Westermark and F Anders Karlsson
Winsa B, Rastad J, Åkerström G, Johansson H, Westermark K, Karlsson FA. Retrospective evaluation of subtotal and total thyroidectomy in Graves' disease with and without endocrine ophthalmopathy. Eur J Endocrinol 1995;132:406–12. ISSN 0804–4643
A retrospective analysis was performed in 173 consecutive patients with Graves' disease (GD) with the principal aim of evaluating the influences of subtotal (N = 157) and total (N = 19) thyroidectomy on postoperative recurrence rates, endocrine ophthalmopathy (EO) and thyrotropin receptor antibody (TSH-R-ab) titres. Postoperatively recurrent disease, identified by increased thyroid hormone levels, occurred in 32 patients (20%) who underwent subtotal resection. These recurrences were associated with over-representation of preoperative EO (p < 0.001) as well as high TSH-R-ab levels post-operatively (p < 0.05–0.01). Subtotal and total resections were followed by an aggravation of preoperative EO in nine (16%) and one (6%), and by a development of EO in two and none of the patients, respectively. Persistently elevated TSH-R-ab titers during thyrostatic therapy became close to normalized in seven (32%) and 15 (88%) of the patients undergoing subtotal or total thyroidectomies, respectively, which illustrates a thyroid tissue dependency of the autoantibody production. Among the total material of 173 patients, altogether 75 cases exhibited persistent or progressive EO and/or TSH-R-ab elevation after more than 1 year of preoperative thyrostatic treatment. In this group, recurrent GD or aggravated EO occurred in 23 (39%) of those operated with subtotal resection and in one (6%) of those undergoing total thyroidectomy (p < 0.05). The results thus indicate that EO, particularly at the time of surgery, and prevailing TSH-R-ab titers are associated with an increased risk of recurrent GD and suggest that patients exhibiting these characteristics should benefit from total rather than subtotal thyroidectomy.
Brita Winsa, Department of Internal Medicine, University Hospital, S-751 85 Uppsala, Sweden