Drug responses in hyperthyroid children suggesting an endogenous false transmitter.

Abstract

Alpha methyl dopa (AMD) is ineffective as a treatment for increased cardiovascular activity in hyperthyroid children. Reserpine produces some vascular improvement, but is less effective than thyroidectomy or propylthiouracil. During periods of AMD treatment, reserpine treatment, and no treatment, hyperthyroid patients were infused with norepinephrine (NE) and tyramine and their systolic blood pressure (BP) responses were measured. These infusions were repeated when the patients were euthyroid. AMD increased responses to tyramine in hyperthyroidism, as it does in normal and hypertensive states, but it did not affect response to NE. Reserpine treatment diminished responses to tyramine in hyperthyroidism and increased responses to NE, as it does in other conditions. In the untreated hyperthyroid state, as compared to the euthyroid state, responses to both tyramine and NE were increased. These clinical observations and evoked drug responses in hyperthyroidism can be explained by postulating the accumulation of the false transmitter octopamine in sympathetic nerves. The conditions which lead to octopamine accumulation in animals‐monoamine oxidase inhibition and tyramine increase‐are present in hyperthyroid human beings. We suggest that AMD has no beneficial effect on cardiovascular dynamics in hyperthyroidism because the AMD metabolite, alpha methyl NE, though a weak transmitter, is a more potent one than the false transmitter, octopamine, already present, which it partly replaces. The finding that BP response to tyramine (as well as to NE) is enhanced in untreated hyperthyroidism suggests increased total NE storage in nerve ends. This is consistent with the postulated accumulation of octopamine.