EFFECT OF THYROID SUBSTITUTION ON HYPERCHOLESTEROLEMIA IN PATIENTS WITH SUBCLINICAL HYPOTHYROIDISM - A REANALYSIS OF INTERVENTION STUDIES

OBJECTIVE The significance of mild hypercholesterolaemia in subclinica l hypothyroidism and whether there is beneficial reduction after thyro xine replacement, remain controversial. We aimed to describe the assoc iation between hypercholesterolaemia and subclinical hypothyroidism, a nd to quantify the effect of thyroid substitution therapy by an analys is of previously published intervention studies. DATA SOURCES Interven tion studies cited in the Medline database from January 1976 until Jan uary 1995, with index terms cholesterol, hypercholesterolaemia, hyperl ipidaemia, thyrotrophin (TSH), hypothyroidism, thyroid and human. A to tal of 148 studies were reviewed. DATA EXTRACTION We recorded the year of publication, study design, number of patients enrolled, mean age, duration of thyroid substitution, normal range of TSH levels, TSH leve ls pre and post-substitution treatment and total cholesterol in plasma before and after treatment. DATA ANALYSIS (1) Qualitative description of studies on the relationship between hypercholesterolaemia and hypo thyroidism, both subclinical and clinical. (2) Precision weighted pool ed estimates of the effect of thyroid substitution therapy on the plas ma levels of total cholesterol, in patients with subclinical and overt hypothyroidism. RESULTS Subclnical hypothyroidism was two to three ti mes more frequent in people with an elevated total plasma cholesterol. In addition, the total plasma cholesterol levels were slightly elevat ed in patients with subclinical dysfunction of the thyroid. Thyroid su bstitution therapy in patients with subclinical hypothyroidism, restor ing the TSH levels to normal, decreased total cholesterol by 0 . 4 mmo l/l (95% confidence interval (CI) 0 . 2-0 . 6 mmol/l) independently of the initial plasma level, The effect of thyroid substitution therapy on HDL-cholesterol in patients with subclinical hypothyroidism was not consistent. The effect of thyroid substitution in patients with overt hypothyroidism was highly dependent on the pretreatment levels of tot al cholesterol. In these patients substitution therapy decreased total cholesterol by 1 . 2 mmol/l (95% CI 0 . 9-1 . 5 mmol/l) when the plas ma levels were elevated up to 8 mmol/l, and by 3 . 4 mmol/l (95% CI 3 . 0-3 . 7) when plasma levels were higher than 8 mmol/l. The high dens ity lipoprotein (HDL)-cholesterol level decreased and amounted to 0 . 16 mmol/l (95% CI 0 . 07-0 . 24). CONCLUSIONS Thyroid substitution tre atment in patients with hypercholesterolaemia and subclinical hypothyr oidism decreases total plasma cholesterol by 0 . 4 mmol/l, but plasma levels remain elevated in most patients. Further treatment with dietar y restriction and cholesterol synthesis inhibitors should then be cons idered.