THERAPY OF PRIMARY HYPOTHYROIDISM WITH L‐TRIIODOTHYRONINE: DISCORDANT CARDIAC AND PITUITARY RESPONSES

Cardiac systolic time intervals were studied in ten patients with primary hypo‐thyroidism before and during therapy with increasing doses of oral L‐triiodo‐thyronine (L‐T3). Therapy was increased sequentially from 10, 20, 25 to 50 μg of L‐T3 daily on a monthly basis. On L‐T3, 20 to 25 μg/day, cardiac systolic time intervals and other peripheral responses to thyroid hormone including serum cholesterol concentration, serum creatine phosphokinase (CPK) activity, and basal metabolic rate had normalized. However, serum thyrotrophin (TSH) levels and peak TSH responses to thyrotrophin‐releasing hormone (TRH) remained elevated on these doses of L‐T3. As the dose of L‐T3 was increased from 20 to 50 μg/day, mean basal serum TSH levels decreased from 55 to 16 μu/ml, and the peak TSH response to TRH decreased from 243 to 58 μu/ml (P < 0.001) while systolic time intervals did not decrease further. Changing to L‐thyroxine (L‐T4) therapy at this point resulted in further suppression of TSH secretion, without significantly altering systolic time intervals or the other peripheral responses to thyroid hormone. These data suggest (a) that some biological responses to thyroid hormone were normalized on lower doses of L‐T3 than were required to normalize TSH secretion, and (b) that higher doses of L‐T3 or substituting L‐T4 therapy could suppress TSH secretion further without altering the other peripheral responses to thyroid hormone.