Abstract
BACKGROUND: Despite numerous recent studies linking height loss to the risk of cardiovascular disease, the underlying biological mechanisms are poorly understood. Subclinical hypothyroidism (SCH) has been positively associated with height loss in individuals with low-normal range free thyroxine (FT4) levels. This association may stem from impaired endothelial repair caused by an inadequate response to the increased thyroid hormone demand. Recent evidence has highlighted the clinical significance of thyroid cysts in terms of their endothelial-related activity. Consequently, it is plausible that thyroid cysts influence the relationship between SCH and height loss. METHOD: A prospective-study was conducted in 1,601 Japanese individuals aged 40-74 years with normal serum free triiodothyronine (T3) and free T4 levels. Height loss was defined as being in the highest quartile of annual height decrease. RESULTS: SCH was significantly and positively associated with height loss among individuals with thyroid cysts, but not among those without thyroid cysts; the sex- and age-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for height loss were 1.00 (0.56, 1.94) in individuals without thyroid cysts and 2.45 (1.03, 5.81) in those with thyroid cysts. After further adjustment for free T4, atherosclerosis, hypertension, and chronic kidney disease, these associations essentially remained, with adjusted ORs (95% CIs) of 1.00 (0.53, 1.83) and 2.75 (1.12, 6.74), respectively. CONCLUSION: Our findings clarify the biological basis of height loss as a cardiovascular risk factor. Endothelial dysfunction is associated with SCH and height loss. Given that urinary iodine concentration has previously been reported to be positively associated with the presence of thyroid cysts and that excess iodine intake is a major cause of SCH in the Japanese population, the observed relationship may reflect an inadequate thyroidal response to increased hormone demand following endothelial injury.