Sequential occurrence of toxic nodular goiter followed by Graves' disease.

OBJECTIVE: To present the first case of Graves' disease occurring after toxic nodular goiter in a patient who had not received radioiodine therapy. METHODS: We describe the clinical, laboratory, and radiologic findings in a 65-year-old woman with toxic nodular goiter followed by Graves' disease and review related reports in the literature. RESULTS: Although isolated case reports have documented the sequential occurrence of toxic nodular goiter or toxic adenoma and Graves' disease, no definite connection currently exists between these two types of hyperthyroidism. In cases previously described, Graves' disease appeared after the use of radioiodine for the treatment of the toxic nodular goiter. In our current patient, toxic nodular goiter was treated surgically, followed by the occurrence of Graves' disease 3 years later. CONCLUSION: This is the first published case of sequential toxic nodular goiter and Graves' disease in which radioiodine was not used for treatment of the goiter and thus cannot be implicated as the inciting event for the subsequent development of Graves' disease.

Relationship of the parameters of body cholesterol metabolism with plasma levels of HDL cholesterol and the major HDL apoproteins.

The inverse relationship between plasma levels of high density lipoprotein (HDL) and coronary heart disease rates has suggested that HDL might influence body stores of cholesterol. Therefore, we have investigated potential relationships between the parameters of body cholesterol metabolism and the plasma levels of HDL cholesterol and the major HDL apoproteins. The study involved 55 human subjects who underwent long-term cholesterol turnover studies, as well as plasma lipoprotein and apolipoprotein assays. In order to maximize the likelihood of detecting existing relationships, the subjects were selected to span a wide range of plasma levels of lipids, lipoproteins, and apolipoproteins. Single univariate correlation analyses suggested weak but statistically significant inverse relationships of HDL cholesterol and apoA-I levels with the following model parameters: production rate (PR), the mass of rapidly exchanging body cholesterol (M1), the minimum estimate of the mass of slowly exchanging body cholesterol (M3min), and of the mass of total exchangeable body cholesterol (Mtotmin). These correlations, however, were quantitatively quite small (/r/ = 0.28-0.42) in comparison to the strength of the univariate relationships between body weight and PR (r = 0.76), M1 (r = 0.61), M3min (r = 0.58), and Mtotmin (r = 0.78). Correlations for apoA-II and apoE levels were even smaller than those for apoA-I and HDL cholesterol. In additional analyses using multivariate approaches, HDL cholesterol, apoA-I, apoA-II, and apoE levels were all found not to be independent determinants of the parameters of body cholesterol metabolism (/partial r/ less than 0.17, P greater than 0.3 in all cases). Thus the weak univariate correlations reflect relationships of HDL cholesterol and apoA-I levels with physiological variables, such as body size, which are primarily related to the model parameters. We conclude that plasma levels of HDL cholesterol and apoproteins A-I, A-II, and E are not quantitatively important independent determinants of the mass of slowly exchanging body cholesterol or of other parameters of long-term cholesterol turnover in humans. These studies give no support to the hypothesis that the inverse relationship between HDL cholesterol levels and coronary heart disease rates is mediated via an influence of HDL on body stores of cholesterol.

Comparison of the effects of colestipol hydrochloride and clofibrate on plasma lipids and lipoproteins in the treatment of hypercholesterolemia.

The effects of colestipol HCl resin and clofibrate on plasma lipid and lipoprotein levels were compared in 65 patients with primary hypercholesterolemia. Patients were randomly assigned to treatment with colestipol (in progressive doses of 15, 20, and 30 g/day), clofibrate (2 g/day), or placebo resin; lipoprotein levels were determined at months 0, 2, 4, 6, and 9. The colestipol group received both colestipol and clofibrate during months 7 through 9 of the study. After 6 months of treatment, mean plasma total cholesterol fell from 333 to 266 (P less than 0.01) on colestipol, and from 329 to 270 (P less than 0.05) on clofibrate. More patients responded, however, to colestipol than to clofibrate. Both drugs also produced significant reductions in LDL cholesterol levels, and clofibrate lowered plasma triglycerides as well. HDL cholesterol level did not change significantly on either medication. The placebo group showed no change in any of the parameters studied. A significant difference was not observed between the effects of 15 g/day of colestipol and those of the higher doses studies. Addition of clofibrate to colestipol did not enhance the latter's hypocholesterolemic action.

Effects of lipoproteins on plasma viscosity.

Patients with hypertriglyceridemia and mixed hyperlipidemia have been found to have mean plasma viscosities significantly higher than controls (P less than 0.005). In a group of 70 hyperlipidemic patients and controls, plasma viscosity was correlated with plasma triglyceride concentration (r = 0.56, P less than 0.01) and to a lesser extent with the concentration of plasma cholesterol (r = 0.29, P less than 0.05). When isolated lipoprotein fractions were added to lipoprotein-free plasma in increasing concentration over a physiological range, a highly significant linear relationship between plasma viscosity and chylomicron concentrations (r = 0.98, P less than 0.001) was apparent. Furthermore, when chylomicrons were removed by ultracentrifugation, viscosity returned to baseline levels. Added VLDL produced a lesser effect (r = 0.70, P less than 0.001) and added LDL, over the range of cholesterol concentration studied, had no influence on viscosity. These studies indicate that chylomicrons in particular can increase plasma viscosity. Viscosity increases of the magnitude demonstrated may in turn alter blood flow and thus contribute to symptoms such as intermittent claudication. Chylomicron-induced increases in plasma viscosity and subsequent decreases in local pancreatic blood flow may be one of the factors involved in the known relationship between severe chylomicronemia and acute pancreatitis.

Prediction of the parameters of whole body cholesterol metabolism in humans.

Total body turnover of cholesterol was studied in 54 subjects by fitting a three-pool mathematical model to plasma decay curves of 32--49 weeks duration following [14C]cholesterol injection. Fifteen subjects were normal, 10 hypercholesterolemic, 21 hypertriglyceridemic, and 8 had both hypercholesterolemia and hypertriglyceridemia; 21 had a familial form of hyperlipidemia. In every subject in this heterogeneous population, the three-pool model gave the best fit for the data. An extensive search was conducted for relationships between model parameters and physiological variables (body size, serum lipid levels, age, and sex). Both linear and nonlinear relationships, and those involving interactions between pairs of variables, were explored. Fifty different forms of the model parameters and 53 forms of the physiological variables were examined. To guard against declaring statistical significance when none was present, subjects were first randomly divided into two matched groups. In the first (hypothesis-generating) group of 36 subjects, more than 100,000 regression equations were considered for each form of the model parameters. Twenty-one highly significant equations were found that were then tested in the second group (hypothesis-testing, 18 subjects). Eighteen of the 21 equations were found to be significant; of these, 6 were selected that accounted for a large part of the observed variation in the four model parameters for which equations were found (production rate (PR), and the sizes of pool 1, pool 3, and total exchangeable body cholesterol). The major determinant of cholesterol PR was body weight alone (r = 0.80). No function of serum lipid levels significantly influenced PR. Both body weight and serum cholesterol level entered into the equations for cholesterol mass. Age influenced the size of pool 3. Serum triglyceride level only had an effect on the size of pool 1. Since these equations were generated in one group of subjects and tested in another, they can be considered a confirmed set of predictive equations.

Normal levels of fibrinopeptide A in patients with primary hyperlipidemia.

Fibrinopeptide A (FPA) levels were measured in a group of 130 controls and patients with various types of primary hyperlipidemia to investigate whether an increased steady state level of thrombin activity is present in hyperlipidemic patients. In a subset of 56 subjects, levels of clotting factors II, VII, and X were measured as well. FPA levels in hyperlipidemic patients were not significantly different from those of control subjects. Furthermore, on multiple regression analysis, no significant relationships were found between FPA levels and the concentrations of serum cholesterol or triglyceride, or log triglyceride levels. Statistically significant relationships were found between all three clotting factor levels and triglyceride concentration. The correlation coefficients for these relationships, however, were low, so that the correlations are of questionable pathophysiological significance. A weak relationship also was found between the plasma levels of cholesterol and of factor II. Thus, although small increases in various clotting factors may be found in patients with hyperlipidemia, plasma FPA levels are normal. These data indicate that hyperlipidemia is not associated with a steady state of increased thrombin activity in vivo in humans.