Suppression of serum TSH by Graves' Ig: evidence for a functional pituitary TSH receptor.
Antithyroid treatment for Graves' hyperthyroidism restores euthyroidism clinically 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. However, we recently showed that the pituitary contains a TSH receptor through which TSH secretion may be down-regulated via a paracrine feedback loop. In Graves' disease, TSH receptor autoantibodies may also bind this pituitary receptor, thus causing continued TSH suppression. This hypothesis was tested in a rat model. Rat thyroids were blocked by methimazole, and the animals were supplemented with L-T(4). They were then injected with purified human IgG 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 in 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 intermediate strength TSH receptor autoantibody-treated animals had levels in between the other two groups (13.5 +/- 2.0 ng/ml). We conclude that TSH receptor autoantibodies can directly suppress TSH levels independently of circulating thyroid hormone levels, suggesting a functioning pituitary TSH receptor.
Brokken
L J
LJ
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. l.j.brokken@amc.uva.nl
Scheenhart
J W
JW
Wiersinga
W M
WM
Prummel
M F
MF
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D005260:Female; D006111:Graves Disease / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D010902:Pituitary Gland / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011989:Receptors, Thyrotropin / Q000276:immunology / Q000502:physiology*; D013972:Thyrotropin / Q000037:antagonists & inhibitors* / Q000097:blood
D001323:Autoantibodies; D007074:Immunoglobulin G; D011989:Receptors, Thyrotropin; D013972:Thyrotropin