Erythrocyte sodium/potassium adenosine triphosphatase in thyroid disease and nonthyroidal illness

Thyroid hormone is known to modulate cell membrane sodium/potassium adenosine triphosphatase (Na/K-ATPase). To determine whether the activity of this enzyme differed in patients with nonthyroidal illness with low levels of circulating thyroid hormones and patients with documented clinical hypothyroidism, we measured Na/K-ATPase activity in red blood cells from patients with hypo- and hyperthyroidism, patients with nonthyroid disease with and without reduced circulating levels of thyroid hormone, and normal subjects. We also assessed whether the activity of this enzyme reflects decreased thyroid hormone action at the cellular level in patients with nonthyroidal illness. Hyperthyroidism was associated with decreased and hypothyroidism with increased erythrocyte Na/K-ATPase activity [142 +/- 24 (+/- SE) and 371 +/- 37 nmol Pi/mg X h; P less than 0.05 and P less than 0.01 compared to normal]. Enzyme activity in cells from patients with nonthyroidal illness and low levels of circulating T3 was significantly higher than that in cells from normal subjects (289 +/- 11 vs. 223 +/- 16 nmol Pi/mg X h; P less than 0.01), but was not significantly different from that in cells from hypothyroid patients. Red cell Na/K-ATPase activity in patients with nonthyroidal illness and normal thyroid function tests (185 +/- 38 nmol Pi/mg X h was indistinguishable from normal values. These data confirm that hyperthyroid patients have decreased red cell Na/K-ATPase activity and provide direct evidence that erythrocyte ATPase activity is increased in hypothyroid patients. The change in enzyme activity in patients with nonthyroidal illness and decreased circulating T3 levels was comparable to that in hypothyroidism. These results suggest that since red cell Na/K-ATPase activity does not distinguish between ill patients with low thyroid function tests and those with hypothyroidism, tissue hypothyroidism may exist in the former group of patients.