Suppression of serum TSH by Graves' Ig: Evidence for a functional pituitary TSH receptor

Antithyroid treatment for Graves' hyperthyroidism restores euthyroidism cli nically within 1-2 months, but it is well known that TSH levels can remain suppressed for many months despite normal free T-4 and T-3 levels. This has been attributed to a delayed recovery of the pituitary-thyroid axis. Howev er, we recently showed that the pituitary contains a TSH receptor through w hich TSH secretion maybe down-regulated via a paracrine feedback loop. In G raves' disease, TSH receptor autoantibodies may also bind this pituitary re ceptor, thus causing continued TSH suppression. This hypothesis was tested in a rat model. Rat thyroids were blocked by methimazole, and the animals w ere supplemented with L-T-4. They were then injected with purified human Ig G from Graves' disease patients at two different titers or with IgG from a healthy control (thyroid hormone binding inhibitory Ig, 591, 127, and < 5 U /liter). Despite similar T-4 and T-3 levels, TSH levels were indeed lower i n the animals treated with high TSH receptor autoantibodies containing IgGs ; the 48-h mean TSH concentration (mean +/- SEM; n = 8) was 11.6 +/- 1.3 ng /ml compared with 16.2 +/- 0.9 ng/ml in the controls (P < 0.01). The interm ediate strength TSH receptor autoantibody-treated animals had levels in bet ween the other two groups (13.5 +/- 2.0 ng/ml). We conclude that TSH recept or autoantibodies can directly suppress TSH levels independently of circula ting thyroid hormone levels, suggesting a functioning pituitary TSH recepto r.