ON THE EFFECT OF THYROTROPIN AND IMMUNOGLOBULINS RELATED TO GRAVES' DISEASE ON THYROTROPIN SYNTHESIS AND SECRETION

The effect of exogenous thyroxine (T₄), thyrotropin (TSH), long acting thyroid stimulator (LATS), immunoglobulin G fractions from (a) thyrotoxic sera without LATS and (b) sera from patients with ophthalmic Graves' disease, upon serum TSH concentration and pituitary TSH content has been investigated in the guinea‐pig. Pituitary TSH content was significantly lower in animals injected with T₄ (1.80 mU), TSH (2.80 mU) and LATS (3.20 mU) than that in the controls (6.40 mU). Thyroidectomy caused a significant elevation in serum TSH concentration (22.30 mU/dl vs 6.67 in sham operated controls) but no significant alteration in pituitary TSH content (4.40 mU vs 3.80 mU in sham operated controls). TSH injections in thyroidectomised animals induced a significant increase in serum TSH concentration (31.60 mU/dl) and the pituitary TSH content (6.50 mU). Two out of four IgG samples from patients with ophthalmic Graves' disease caused a fall in serum TSH concentration (12.90 and 14.40 mU/dl) with a concomitant rise in pituitary TSH content (9.00 and 9.30 mU) in thyroidectomized animals. It is concluded (1) that exogenous TSH induces an enhanced TSH synthesis and release in thyroidectomised guinea‐pigs which suggests the presence of a positive ‘short loop’ feedback for TSH and (2) that IgG fractions from some sera of ophthalmic Graves' disease may have the ability to inhibit TSH release from the pituitary. This inhibitory effect, hitherto not described, may be responsible for the diminished TRH induced TSH release in some patients with euthyroid Graves' disease.