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Comment on Thyrotropin Receptor Gene and Mitral Valve Prolapse

Hyogo Prefectural Amagasaki Hospital Hyogo, Japan

Donald F. Sellitti and

Uniformed Services University of Health Sciences Bethesda, Maryland

Sonia Q. Doi, Takashi Akamizu and Kazuwa Nakao

Kyoto University Graduate School of Medicine Kyoto, Japan

In a recent article, Khoo et al. (1) reported a family, in which activating TSH receptor (TSH-R) mutation is associated with mitral valve prolapse. They concluded that TSH-R activation may increase the clinical expression of mitral valve prolapse in genetically predisposed individuals.

As the authors stated, mitral valve prolapse in a relatively common disorder, but its real prevalence as a disease entity is controversial. It was earlier reported by Channick et al. (2) that mitral valve prolapse is associated with hyperthyroidism due to Graves’ disease, which was confirmed by other investigators (3). Because the affected members with gain-of-function mutations of the TSH-R described by Khoo et al. were all thyrotoxic, it is reasonable to speculate that mitral valve prolapse is secondary to thyrotoxicosis caused by TSH-R activation. In this context, it seems likely that mitral valve prolapse is not specific to the TSH-R mutation.

The cardiac manifestations in hyperthyroidism have been attributed to the direct effects of thyroid hormone or its indirect effects through catecholamines on the heart. As Khoo et al. commented in their discussion (1), Drvota et al. (4) and we (5, 6) have reported the presence of TSH-R in the heart. We postulate that cardiomyopathy is another clinical presentation of Graves’ disease, which may be mediated through autoimmunity against the TSH-R (5). The involvement of adjacent myocardium is suggested in some cases with mitral valve prolapse (2). Considering that mitral valve prolapse is associated with Hashimoto’s thyroiditis (7), it remains possible that some autoimmune mechanisms may underlie the mitral valve prolapse, as well as cardiomyopathy, associated with autoimmune thyroid diseases.

Footnotes

Address all correspondence to: Dr. Hiroyuki Koshiyama, Division of Endocrinology and Metabolism, Department of Internal Medicine, Hyogo Prefectural Amagasaki Hospital, 1-1-1 Higashi-Damitosu-cho, Amagasaki, Hyogo 660-0828, Japan.

Received May 11, 1999.

References

1. Khoo DHC, Parma J, Rajasoorya C, Vassart G. 1999 A germline mutation of thyrotropin receptor gene associated with thyrotoxicosis and mitral valve prolapse in a Chinese family. J Clin Endocrinol Metab. 84:1459–1462.[Abstract/Free Full Text]
2. Channick BJ, Adlin EV, Marks AD, et al. 1981 Hyperthyroidism and mitral-valve prolapse. N Engl J Med. 305:497–500.[Medline]
3. Brauman A, Algom M, Gilboa Y, Ramot Y, Golik A, Stryjer D. 1985 Mitral valve prolapse in hyperthyroidism of two different origins. Br J Med 53:374–377.
4. Drvota V, Janson A, Norman C, et al. 1995 Evidence for the presence of functional thyrotropin receptor in cardiac muscle. Biochem Biophys Res Commun. 211:426–431.[CrossRef][Medline]
5. Koshiyama H, Sellitti DF, Akamizu T, et al. 1996 Cardiomyopathy associated with Graves’ disease. Clin Endocrinol (Oxf). 45:111–116.[CrossRef][Medline]
6. Sellitti DF, Hill R, Doi SQ, et al. 1997 Differential expression of thyrotropin receptor mRNA in the porcine heart. Thyroid. 7:641–645.[Medline]
7. Marks AD, Channick BJ, Adlin EV, Kessler RK, Braiman LE, Denenberg BS. 1985 Chronic thyroiditis and mitral valve prolapse. Ann Intern Med. 102:479–483.

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