The Effect of Postheparin Lipolytic Activity (PHLA) and Diet on Hyperlipoproteinemia in Hypothyroidism

Hypothyroidism has been shown to be accompanied by hyperlipoproteinemia. To examine the pathogenesis of hyperlipidemia in hypothyroidism, plasma cholesterol, triglyceride, lipoprotein electrophoresis on agarose gel and PHLA were measured in 8 patients with hypothyroidism before and during thyroid hormone replacement therapy. Lipoprotein lipase was measured as protamine-inactivated lipase activity; hepatic triglyceride lipase activity was measured as protamine-resistant lipase activity by the method of Krauss.Lipoprotein phenotyping revealed type IIa hyperlipoproteinemia in 3 patients, type III in 4 patients and type IV in 1 patient.The mean±S.E.M. of fasting plasma cholesterol and triglyceride were 258.8±25.2 and 191.5±51.1 mg/dl in the pretreatment period and were 199.9±19.9 and 131.1±30.4 mg/dl on thyroid hormone replacement, respectively.Hepatic triglyceride lipase was lower in the patients with hypothyroidism (4.51±0.65k moles FFA/ml/h) than in the controls (13.80±1.85, p<0.001) and increased (10.20±1.46, p<0.01) with treatment to levels comparable to those of the controls. However, lipoprotein lipase in the patients with hypothyroidism (2.76±0.43μ moles FFA/ml/h) was not different from that of the controls (3.56±0.76) and did not increase (3.33±0.69) significantly with treatment.The effects of a high carbohydrate diet and a high fat diet on lipoprotein metabolism were studied in 4 patients with hypothyroidism. Changing from a high carbohydrate diet to a high fat diet produced a mean decrease of plasma triglyceride (98.5 mg/dl) and a change of lipoprotein phenotype from type III to type IIa in 1 patient. Electrophoretograms in the other 3 patients (type IIa, 2 patients; type III, 1 patient) did not change.Two euthyroid volunteers were administered 300 μg of 1-thyroxine daily for two weeks and showed a significant increase in hepatic triglyceride lipase compared with their normal pretreatment levels.These results suggest that low hepatic triglyceride lipase is responsible for an abnormal VLDL conversion to LDL in hypothyroidism as Krauss et al. reported. Moreover, the nutritional state in addition to the low PHLA may produce either type II, type III or type IV hyperlipoproteinemia in hypothyroidism.