Inhibition of 5' (outer ring) deiodination of T4
	The outer ring, or 5' deiodinase designated type 1, that is present predominantly in liver, kidney, thyroid and heart is a selenoprotein that catalyses the peripheral conversion of T4 to T3, and rT3 to 3,3'T2. This activity is markedly diminished in catabolic states and the enzyme is inhibited by numerous drugs (table 1) which lead to a decrease in the serum concentration of T3 and to an increase in the concentration of rT3, by inhibiting its further deiodination to 3,3'T2. By its effect on the type 1 deiodinase, amiodarone leads to a decrease in serum T3 and an increase in rT3 (Wiersinga, 1996), often associated with an increase in serum T4, an effect attributed to its diminished clearance. Various b-blockers differ in their effect on 5' deiodination. Propranolol in high doses diminishes the production of T3 in vitro and in vivo, but this action also occurs with the d-propranolol isomer which lacks b blocking activity, suggesting that the effect may be due to a quinidine-like membrane stabilizing effect, rather than specific b blockade. The T3 lowering effect is not seen with other b blockers such as atenolol or metaprolol, nor with labetalol, which has combined a and b blocking activity. The symptomatic benefit of b blockers in thyrotoxicosis appears to be independent of their influence on serum T3. Propranolol in high doses can also selectively increase serum T4 (Cooper et al, 1982); the effect may be due to diminished T4 clearance. Several iodinated compounds, including amiodarone and the oral cholecystographic contrast agents, inhibit both the type 1 and type 2, 5'deiodinases, resulting also in decreased formation of T3 in the pituitary, leading to a slight increase in serum TSH, which usually remains within the normal reference range. On the basis of its ability to rapidly lower serum T3, the oral cholecystographic contrast agent ipodate has been used as an additional in the management of thyrotoxicosis. In thyrotoxic subjects, where the half-life of T3 is less than one day, agents that inhibit the type 1 deiodinase can rapidly lower the increased serum T3 concentration. When a T3 lowering effect due to an associated illness or a medication can be identified, the diagnosis of thyrotoxicosis should not be dismissed on the grounds of normal serum T3, if this finding is associated with suppression of TSH and T4 excess in the face of suggestive clinical features.