KATHLEEN R. REEDY, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20857
H. LESTER REED, Department of Medicine, Madigan Army Medical Center, Tacoma, Washington 98431
McMurdo Station, Antarctica, has a year-round population of science support staff from which 17 people have volunteered to participate in this year's (October 1997 to August 1998) study of the metabolic changes that occur in humans in response to the polar environment. This study is designed to identify the mechanism of these changes and follows the report of 16 subjects who participated in a study the previous year (October 1996 to August 1997) at McMurdo (Do et al. 1997).
The 17 subjects are randomized into two groups, closely matched in age, weight, height, body surface area, body mass index, body temperature, resting heart rate, maximum capacity of oxygen use, with gender balance. This subject pool is representative of typical antarctic residents: indoor and outdoor workers, day and night workers, and a wide age range. This study is a double blind, in which one group will receive placebo, the other a daily 50-microgram thyroxine supplement. In contrast, last year's study group was randomized to two well-matched groups, both of which received placebo for the first 4 months, single blind, and for the remaining 7 months of antarctic residence, double blind; one group continued to receive placebo, and the other group received a daily supplement of 50 micrograms of thyroxine. We were able to observe the early stages (Do, Lemar, and Reed 1996) of cold-adaptation mechanisms in all subjects, then see differences in the two groups after intervention.
Among other things, thyroid hormones, which include triiodothyronine (T3) and thyroxine (T4), regulate energy expenditure. Production and tissue uptake of T3 are dramatically increased during antarctic residence (Reed et al. 1990). These increases are not consistent for all tissues and appear to be greatly increased in skeletal muscle, while in tissues such as brain and central nervous system sites the level may decrease (Reed et al. 1988; Harford et al. 1993). We interpret this change in relative thyroid content as a shift in distribution function, which results in a phenomenon we call the "Polar T3 Syndrome" (Harford et al. 1993).
For this year's project, each subject will complete a monthly measure of body temperature with an aural thermometer, resting metabolic rate (RMR), and energy requirement for a fixed submaximal work task on a cycle ergometer measured by oxygen uptake with a metabolic cart (Gibson et al. 1993; Do et al. 1997). Short-term memory is measured with a "matching to sample" exercise on a computer screen.
A small tissue sample from the anterior thigh will be examined to determine fiber typing and the level of T3 in the skeletal muscle. Samples at the beginning and end of the year of antarctic residence will be compared to determine changes in muscle T3 level during extreme cold adaptation and between the placebo and thyroxine supplemented treatment groups.
Employing these 17 volunteer subjects, we will execute thyroid hormone kinetics studies at the beginning, midway, and the end of their winter-over year. TSH, bound and free T3 and T4 levels, T3 production and distribution (Reed et al. 1990) will be measured and the progress tracked by introducing a bolus of T3 into the venous system of each subject and withdrawing small (3-milliliter) samples of blood several times the first hour, twice an hour for 4 hours, then hourly to 12 hours and each 12 hours to 72 hours. These kinetic studies will help define the stage of adaptation (Do et al. 1996), the mechanism of change affected by length of antarctic residence, and the effect of thyroxine supplementation.
This is acknowledgment of the collaborating scientists participating in the execution of these protocols: Nhan Van Do, Lawrence Palinkas, John Thomas, Nancy Finney, Rick Seip, Samuel Case, and Liz Mino.
This research is supported by National Science Foundation grant OPP 89-22832.
Do, N., H. LeMar, and H. Reed. 1996. Thyroid hormone responses to environmental cold exposure and seasonal change: A proposed model. Endocrinology and Metabolism, 3, 7-16.
Do, N., M. Staudaucher, S. Case, K. Reedy, H. LeMar, N. Finney, P. Newbauer, C. McLain, and H. Reed. 1997. Changes in skeletal muscle efficiency and resting oxygen use after four months of antarctic residence: Physiological significance of the Polar T3 Syndrome. 1997 Thyroid, 7(suppl 1), S36. [Abstract]
Gibson, C., R. Jones, D. Bunner, J. Lance, and H. Reed. 1993. Submaximal cycloergometry to determine changing metabolic parameters following 131I therapy for thyrotoxicosis. Endocrine Society 75th Meeting. Bethesda, Maryland: Endocrine Society Press. [Abstract]
Harford, R., H. Reed, M. Morris, I. Sapien, R. Warden, and M. D'Alesandro. 1993. Relationship between changes in serum thyrotropin and total lipoprotein cholesterol with prolonged antarctic residence. Metabolism, 42, 1159-1163.
Reed, H., D. Brice, K. Shakir, K. Burman, M. D'Alesandro, and J. O'Brian. 1990. Decreased free fraction of thyroid hormones after prolonged antarctic residence. Journal of Applied Physiology, 69, 1467-1472.
Reed, H., K. Burman, K. Shakir, and J. O'Brian. 1986. Alterations in the hypothalamic-pituitary-thyroid axis after prolonged residence in Antarctica. Clinical Endocrinology (OXF), 25, 55-65.
Reed, H., J. Ferreiro, K. Shakir, K. Burman, and J. O'Brian. 1988. Pituitary and peripheral hormone responses to T3 administration during antarctic residence. American Journal of Physiology, 254, E733-E739.
Reed, H., E. Silverman, K. Shakir, R. Dons, K. Burman, and J. O'Brian. 1990. Changes in serum triiodothyronine (T3) kinetics after prolonged antarctic residence: The Polar T3Syndrome. Journal of Clinical Endocrinology and Metabolism, 70, 965-974.