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

L. J. Brokken, J. W. Scheenhart, W. M. Wiersinga, M. F. Prummel

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)4814-4817
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Volume86
Issue number10
DOIs
Publication statusPublished - 2001-Oct-01
Externally publishedYes

Swedish Standard Keywords

  • Endocrinology and Diabetes (30205)

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