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

Paul W. Ladenson, Paul D. Goldenheim and E. Chester Ridgway

From the Thyroid and Pulmonary Units (P.D.G.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114

Address reprint requests to: Dr. Paul W. Ladenson, Thyroid Unit, Massachusetts General Hospital, Boston, Massachusetts 02114.

Acute cardiovascular, renal, pulmonary, metabolic, and pituitary responses to therapy of hypothyroidism with 25 µg iv T₃ (group I, G-I, n = 11) or 50 µg 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 ng/dl and 229 ± 19 ng/dl, respectively. Myocardial performance, noninvasively assessed by the pulse wave arrival time (QK_d) and the phonocardiographic systolic time interval ratio was significantly altered after 1 day of therapy (QKd for G-I = –10 ± 4 msec, P < 0.05; and for G-II = –18 ± 14 msec, P < 0.01). After 7 treatment days, both the mean QK_d (203 ± 7 msec, P < 0.001) and phonocardiographic systolic time interval ratio (0.41 ± 0.02, P < 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 < 0.05; and G-II, 89 ± 5%, P < 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 < 0.02) and 70% (P < 0.001) of their respective pretreatment values. After 7 days of therapy, the mean basal TSH levels had declined to 75% (P < 0.001) and 5% (P < 0.001%) of pretreatment, respectively.

In comparison with previous observations of responses to 100 µg/day iv T₄ for 1 week, the 25 µg 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 µg/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. (J Clin Endocrinol Metab 56: 1252,1983)

^* Supported in part by Grants RR-1066, AM-16791, and HL-07354 from the National Institutes of Health. An abstract based on a portion of this study was presented at the Eastern Section Meeting of the American Federation for Clinical Research, Boston, MA, October, 1981.

Recipient of fellowships from the American College of Physicians and the American Philosophical Society.

Received August 13, 1982.

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