Objective: The association between established hypothyroidism and high cholesterol levels is well known. The aim of the present study was to investigate the effect of thyroxine (T 4 ) administration on cholesterol levels in hypercholesterolemic subjects with TSH levels within the normal range ('highnormal' TSH compared with 'low-normal' TSH). Design and Methods: We determined TSH levels in 110 consecutive patients referred for hypercholesterolemia (serum cholesterol >7.5 mmol/l). Those with 'high-normal' TSH (2.0-4.0 mU/ml) as well as those with 'low-normal' TSH (0.40-1.99 mU/ml) were randomly assigned to receive either 25 or 50 mg T 4 daily for two months. Thus, groups A and B (low-normal TSH) received 25 and 50 mg T 4 respectively and groups C and D (high-normal TSH) received 25 and 50 mg T 4 respectively. Serum T 4 , tri-iodothyronine (T 3 ), TSH, free thyroxine index, resin T 3 uptake and thyroid autoantibodies (ThAab) as well as total cholesterol, high and low density lipoprotein cholesterol (HDL, LDL), and triglycerides were determined before and at the end of the two-month treatment period. Results: TSH levels were reduced in all groups. The most striking effect was observed in group D (TSH levels before: 2.77 Ϯ 0.55, after: 1.41 Ϯ 0.85 mU/ml, P < 0:01). Subjects in groups C and D had a higher probability of having positive ThAabs. A significant reduction in total cholesterol (P < 0:01) and LDL (P < 0:01) was observed after treatment only in group D. In those subjects in group D who were ThAab negative, there was no significant effect of thyroxine on cholesterol levels. Conclusions: Subjects with high-normal TSH levels combined with ThAabs may, in fact, have subclinical hypothyroidism presenting with elevated cholesterol levels. It is possible that these patients might benefit from thyroxine administration.

Serum thyroid hormones and antithyroid autoantibodies (AAB) were assayed in 87 randomly selected hypercholesterolemic persons compared to 80 controls with normal serum total cholesterol (TC). Of the 87 hypercholesterolemic persons 22 (25%) had positive AAB compared to 5 (6%) controls. Furthermore, 8 of the hypercholesterolemic patients had a serum TSH level above 5 mU/l, i.e. the had subclinical hypothyroidism, not diagnosed before, whereas thyroid function was normal in all normocholesterolemic persons. The new and unexpected finding was that the hypercholesterolemic persons had on average a significantly higher serum TSH than the controls, and this was true even when persons with positive AAB were excluded. There was a significant correlation between TC and serum TSH. It is concluded that hypothyroidism may not be an all-or-none phenomenon, and that many hypercholesterolemic persons with thyroid tests within the conventional normal range may have a slight impairment of their thyroid function.

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