Rapid Pituitary and Peripheral Tissue Responses to Intravenous L-Triiodothyronine in Hypothyroidism*

Abstract

Acute cardiovascular, renal, pulmonary, metabolic, and pituitary responses to therapy of hypothyroidism with 25 micrograms iv T3 (group I G-I, n = 11) or 50 micrograms iv T3 (group II, G-II, n = 10)/day for 1 week have been studied. Serum T3 levels were acutely normalized in both groups with the mean basal serum T3 levels (X +/- SE) after 7 days, 98 +/- 10 micrograms/dl and 229 +/- 19 ng/dl, respectively. Myocardial performance, noninvasively assessed by the pulse wave arrival time (QKd) and the phonocardiographic systolic time interval ratio was significantly altered after 1 day of therapy (QKd for G-I = -10 +/- 4 msec, P less than 0.05; and for G-II = -18 +/- 14 msec, P less than 0.01). After 7 treatment days, both the mean QKd (203 +/- 7 msec, P less than 0.001) and phonocardiographic systolic time interval ratio (0.41 +/- 0.02, P less than 0.01) were within the normal range in G-II. Abnormal pretreatment renal excretion of an oral water load (G-I, 65 +/- 6%; and G-II, 57 +/- 6%) was also reversed after 1 week (G-I, 84 +/- 5%, P less than 0.05; and G-II, 89 +/- 5%, P less than 0.01). Patients with blunted hypercapnic (n = 6) and hypoxic (n = 4) ventilatory drives were improved in both groups after 6 days. The mean basal metabolic rate, serum cholesterol, and serum creatine phosphokinase were altered by the week of therapy in a dose-response manner, and were in the normal range in G-II. Pituitary TSH secretion was promptly suppressed in both groups. Two hours after the first T3 dose, the mean serum TSH for G-I and G-II decreased to 85% (P less than 0.02) and 70% (P less than 0.001) of their respective pretreatment values. After 7 days of therapy, the mean basal TSH levels had declined to 75% (P less than 0.001) and 5% (P less than 0.001%) of pretreatment, respectively. In comparison with previous observations of responses to 100 micrograms/day iv T4 for 1 week, the 25 micrograms dose T3 was equivalent in terms of changes in basal serum T3 and peripheral (nonpituitary) tissue responses, but less effective than T4 in lowering serum TSH. Based on these parameters, 50 micrograms/day iv T3 was the most effective of the three regimens within this time frame. The implications of these observations in the clinical management of severe complicated myxedema are discussed.