We propose to investigate in Graves' disease, the most common type of hyperthyroidism. Our preliminary study used a higher degree of standardization and comprehensiveness than did previous studies. We found that prominent symptoms of depression and anxiety, and subtle deficits in memory and attention, improved significantly when subjects became euthyroid. In addition, while beta-blocking drugs are routinely used for symptomatic relief of thyrotoxicosis before hormone levels are normalized, we were the first to show that propranolol treatment alone was associated with significant improvement of psychiatric symptoms concurrent with improvement of peripheral hyperthyroid symptoms. Excess thyroid hormones interact with catecholamines to produce the hyperadrenergic state in Graves' disease. Human and animal research suggests that beta-adrenergic receptor supersensitivity is involved. We hypothesize that the behavioral symptoms of Graves' disease are in part mediated by thyroid hormone-induced changes of CNS beta adrenergic receptors. We hope to demonstrate this by comparing effects of three (3) different conditions of beta-blockade. We propose to study 45 subjects at 3 stages - (1) untreated hyperthyroid, (2) beta-blocked and (3) euthyroid - using standardized endocrine, psychiatric and cognitive tests. A double- blind comparison of propranolol (enters the CNS), atenolol largely peripheral) and placebo should determine if our preliminary findings with propranolol are indeed related to CNS beta-blockade. Our study should advance the understanding of the interaction between thyroid hormones and catecholamines regarding the pathogenesis of psychiatric and cognitive symptoms, specifically focused on beta-adrenergic activity.
| Olson, B R; Klein, I; Benner, R et al. (1991) Hyperthyroid myopathy and the response to treatment. Thyroid 1:137-41 |
