Suppression of serum TSH by Graves' Ig: evidence for a functional pituitary TSH receptor
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1297122
- author
- Brokken, Leon LU ; Scheenhart, J W ; Wiersinga, W M and Prummel, M F
- organization
- publishing date
- 2001
- type
- Contribution to journal
- publication status
- published
- subject
- 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
- 2025-04-04 14:57:44
@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 < 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.}}, 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}}, }