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 
triiodothyronine (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 (AIPh), 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).