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

Brokken, Leon LU ; Scheenhart, J W ; Wiersinga, W M and Prummel, M F (2001) In Journal of Clinical Endocrinology and Metabolism 86(10). p.4814-4817
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... (More)
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. (Less)
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; ; and
organization
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type
Contribution to journal
publication status
published
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in
Journal of Clinical Endocrinology and Metabolism
volume
86
issue
10
pages
4814 - 4817
publisher
Oxford University Press
external identifiers
  • wos:000171755400042
  • scopus:0034751152
ISSN
1945-7197
language
English
LU publication?
yes
id
f4463b3d-3036-41e9-959a-25ac342537d6 (old id 1297122)
alternative location
http://jcem.endojournals.org/cgi/content/full/86/10/4814
date added to LUP
2016-04-01 16:23:12
date last changed
2025-10-14 11:52:55
@article{f4463b3d-3036-41e9-959a-25ac342537d6,
  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 &lt; 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 &lt; 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.}},
  author       = {{Brokken, Leon and Scheenhart, J W and Wiersinga, W M and Prummel, M F}},
  issn         = {{1945-7197}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{4814--4817}},
  publisher    = {{Oxford University Press}},
  series       = {{Journal of Clinical Endocrinology and Metabolism}},
  title        = {{Suppression of serum TSH by Graves' Ig: evidence for a functional pituitary TSH receptor}},
  url          = {{http://jcem.endojournals.org/cgi/content/full/86/10/4814}},
  volume       = {{86}},
  year         = {{2001}},
}