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Aggregation of High-Normal Thyroid-Stimulating Hormone in Hypertensive Families

Endocrinology, Diabetes, and Hypertension Division (O.G., S.H., U.C.N., G.H.W.), and Division of Cardiology (T.S.P.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115; Cardiovascular Genetics, Cardiology Division, University of Utah (P.N.H.), Salt Lake City, Utah 84108; and Department of Genetics and Clinical Investigation Center, Hôpital Européen Georges Pompidou (X.J.), Paris 75908, France

Address all correspondence and requests for reprints to: Dr. Gordon H. Williams, Endocrinology, Diabetes, and Hypertension Division, 221 Longwood Avenue, RFB-2, Boston, Massachusetts 02115. E-mail: gwilliams{at}partners.org.

Background: Studies suggest that there are genetic variants that influence both blood pressure regulation and serum TSH levels. We investigated whether high-normal TSH values aggregate in hypertensive families. The influence of hypertension family history on serum TSH levels in healthy normotensive individuals was also examined.

Methods: All subjects were euthyroid (TSH, 0.5–5.0 mIU/liter). The study subjects were 333 hypertensives, including 229 members of multiple sibling families. The subjects had blood samples for serum TSH determination drawn in the morning after overnight bed rest. High-normal TSH was defined as values above 2.0 mIU/liter and equal to or less than 5.0 mIU/liter. Thirty-one healthy normotensives provided information about their family history of hypertension by telephone.

Results: The concordance for high-normal TSH values among hypertensive, multiple sibling families was greater than expected by chance (P = 0.009). There were nearly twice as many families concordant for high-normal TSH status as expected (13.2% vs. 7.0%), whereas the observed proportion concordant for normal TSH status was similar to that expected (58.3% vs. 54.1%). Family membership explained a significant proportion of variance in TSH status (P = 0.038). Healthy normotensives with a family history of hypertension had significantly higher TSH values (2.2 ± 1.2 mIU/liter) than those with a negative family history of hypertension (TSH 1.3 ± 0.7 mIU/liter) independent of other characteristics (P = 0.025).

Conclusions: There is familial aggregation of high-normal TSH values in hypertensive families, and a hypertension family history influences serum TSH levels in healthy individuals. These findings are consistent with the existence of genetic variants affecting both blood pressure regulation and serum TSH levels.

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