Plasma total homocysteine levels during short-term iatrogenic hypothyroidism

Hypothyroidism is associated with increased cardiovascular morbidity, which cannot be fully explained by the atherogenic lipid profile observed in the se patients. We have previously found elevated levels of the cardiovascular risk factor, plasma total homocysteine (tHcy), in hypothyroidism. We conducted a longitudinal study on 17 patients who had undergone total th yroidectomy for thyroid cancer. During 6 weeks of discontinued T-4 substitu tion before radioscintigraphy (phase I), they attained a hypothyroid state, which was reversed by resupplementation (phase II). Plasma tHcy, serum cre atinine, serum and red blood cell folate, serum cobalamin, and serum choles terol were determined at a-week intervals throughout phases I and II. There was a progressive and parallel increase in tHcy (mean, 27%), serum cr eatinine (37%), and serum cholesterol (100%)during phase I, and these value s returned to the original level within 4-6 weeks after reinitiating T-4 th erapy. Serum and red blood cell folate levels showed only minor, but statis tically significant, changes. In a bivariate model, serum creatinine and se rum cholesterol were strongly associated with the changes observed in tHcy during short term hypothyroidism. In conclusion, we found a transient increase in both plasma tHcy and serum cholesterol during short term iatrogenic hypothyroidism, and the tHcy respo nse is probably mainly explained by concurrent changes in renal function. T he increase in both plasma tHcy and serum cholesterol may confer increased cardiovascular risk in hypothyroid patients.