Impaired Na⁺,K⁺ATPase activity in red blood cells in euthyroid women treated with levothyroxine after total thyroidectomy for Graves' disease

Abstract 

In patients suffering from hyperthyroidism dependent on Graves' disease, a reduction in Na⁺,K⁺ATPase activity has been demonstrated in red blood cells (RBCs), as well as an inverse correlation between this enzymatic action and free triidothyronine (FT₃) levels. The restoration of normal FT₃ values also brings about a normalization of Na⁺,K⁺ATPase activity in erythrocytes. These results have made it possible to hypothesize that the thyroid hormones control Na⁺,K⁺ATPase activity and that this control is manifested by means of variations in the number of ouabain-binding sites. For this reason, the measurement of the activity of the Na/K pump can be considered as a further indicator of the peripheral effects of thyroid hormones. With a view to assess the relation between the course of treated hyperthyroidism and Na⁺,K⁺ATPase activity during antithyroid therapy and after surgical thyroidectomy followed by replacement therapy, we studied 24 patients affected by Graves' disease (group Graves [GG]). They were compared with 24 female Graves' patients who underwent total thyroidectomy for nontoxic and diffuse nodular goiter (NDNG) (group control [GC]) and with 24 normal healthy women (group normal [GN]). When Graves' hyperthyroidism was diagnosed, the Na⁺,K⁺ATPase activity in RBCs was impaired in all GG patients. Thionamide treatment restored the normal activity of the Na/K pump, accompanied by normalization of the number of ouabain-binding sites. One hundred eighty days after thyroidectomy, in conditions of clinical and biochemical euthyroidism due to replacement therapy with levothyroxine, the activity of Na⁺,K⁺ATPase in RBCs was once again reduced in GG, while appearing normal in GC and GN (1.77 ± 0.16 mmol Pi h⁻¹ · L⁻¹ RBCs v 2.09 ± 0.26 v 2.09 ± 0.24, P < .05). Different instrumental or biochemical parameters, such as glycemia, serum lipids, ions, serum alkaline phosphatase (AlPh), serum creatine phosphokinase (CPK), blood pressure, and heart rate, were evaluated and appeared normalized in GG and GC 180 days after surgery. We conclude that (1) in patients suffering from Graves' disease, subjected to total thyroidectomy followed by levothyroxine replacement therapy, there is a reduction in the activity of the Na⁺,K⁺ATPase on erythrocytes 6 months after the surgical approach; and (2) a similar alteration is not observed in patients subjected to thyroidectomy for NDNG. These findings allow the formulation of the hypothesis that (1) treatment with levothyroxine for 180 days after thyroidectomy in GG is not long enough to restore the normality of all the peripheral indicators of action of the thyroid hormones; and (2) levothyroxine replacement therapy is unable to guarantee euthyroidism in all the tissues in GG (eg, during hematopoiesis in the bone marrow).

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