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The effect of D-thyroxine on lipoprotein lipids and apolipoproteins in primary type IIa hyperlipoproteinemia.

The effect of 3 months' treatment with D-thyroxine on the lipoprotein lipids and apolipoproteins AI and B was investigated in 12 patients with type IIa hyperlipoproteinemia. VLDL, LDL and HDL were separated by preparative ultracentrifugation. Both apolipoproteins were measured in serum by electroimmunoassay procedures with monospecific antisera. There was a significant decrease of cholesterol, phospholipids and apolipoprotein B in serum and of all lipids in the LDL class. VLDL and HDL lipids and apolipoprotein AI showed no significant alterations. The atherogenic ratios LDL/HDL lipids and apolipoprotein B/apolipoprotein AI were lowered with the most pronounced effect on the ratio between the two apoliopoproteins. It is concluded that there is an effective reduction of LDL particles by D-thyroxine. Further investigations are necessary to evaluate whether lipoprotein lipids or apolipoproteins are a better discriminator of the influence on atherosclerotic risk in type IIa hyperlipoproteinemia.

Adult↗

Effects of dextro-thyroxine, a preparation almost free of levo-thyroxine, on thyroid function, serum lipids and apolipoprotein A-I in "double pre-beta lipoproteinemia".

Eight subjects, belonging to a large family kindred repeatedly showing the electrophoretic pattern of the "double pre-beta lipoproteinemia", were studied. In seven of them thyroid function, serum lipids and apolipoprotein A-I were determined before and after treatment with dextro-thyroxine, preparation almost free of levo-thyroxine. In most of the patients, total-T4 levels and free-T4 Index were in the lower normal range, but basal TSH levels and the TSH response to TRH were normal. Dextro-thyroxine was effective in reducing both serum total cholesterol and triglycerides, but the percentage decrease in serum triglycerides was definitely greater than that of serum total cholesterol. This marked, unexpected hypotriglyceridemic effect is similar to that observed in a group of obese, hypertriglyceridemic hypothyroid patients treated with levo-thyroxine. Besides serum total cholesterol and triglycerides, the VLDL cholesterol/triglycerides ratio and the electrophoretic "slow moving" pre-beta component were also significantly reduced after treatment, suggesting that dextro-thyroxine can remove efficiently "remnant" VLDL particles from the plasma. Following dextro-thyroxine therapy, the relatively low pretreatment values of apolipoprotein A-I were significantly increased, being restored to normal.

Adult↗

Treatment of common lipoprotein disorders.

The pathogenesis of arteriosclerosis is not yet fully understood. The growing body of scientific information strongly indicates that the plasma lipoproteins are playing a crucial role in the development of this disease. We now have conclusive information that dietary cholesterol can produce arteriosclerosis in animals and its removal from the diet can result in regression of these lesions. Most importantly, we know that reducing plasma cholesterol in humans will prevent mortality and morbidity related to the clinical sequelae of arteriosclerosis. A diet can be prescribed that can produce profound reductions in lipoprotein levels in many individuals. The rate of success in achieving modifications that reduce plasma cholesterol is very high. Most patients over time find a diet with reduced cholesterol and saturated fat to be quite palatable. As food suppliers become more active in emphasizing low fat, low cholesterol products, and as restaurants see a demand for healthier entrees, the task for the physician and nutritionist will become much easier. Achieving sustained weight reduction is a much more difficult problem, but this too can be accomplished in many patients if the health professionals maintain a hopeful supportive approach. Ultimately, it is the patient's responsibility to bring about these lifestyle changes. It is the physician's and nutritionist's job to monitor the process and provide sound information and encouragement. For individuals with severe lipoprotein disorders such as familial hypercholesterolemia where diet therapy is helpful but not adequate, the use of medications is now indicated (bile acid binding resins and nicotinic acid). Other medications that promise additional effectiveness and safety are under development (Compactin, Mevinolin). It is our belief that control of coronary heart disease and stroke requires appropriate treatment of lipoprotein disorders and the methods for a strong beginning in this endeavor are at hand.

Adult↗

Effects of thyroxine and its related compounds on cerebral GABA receptors: inhibitory action on benzodiazepine recognition site in GABAA receptor complex.

The effects of thyroxine and its related derivatives on gamma-aminobutyric acid (GABA) receptors in the rat brain were examined. D-Thyroxine strongly inhibited [3H]flunitrazepam binding to benzodiazepine receptor in crude synaptic membrane from the rat brain. The Scatchard analysis of the [3H]flunitrazepam binding in the presence of D-thyroxine indicated the decreases in the affinity and maximum number of binding site. Furthermore, D-thyroxine inhibited the enhancing effect of flunitrazepam on GABA-stimulated 36Cl- influx into membrane vesicles, although GABA-stimulated 36Cl- influx alone was not affected by D-thyroxine. On the other hand, the effects of thyroxine and its related derivatives on cerebral GABAB receptor binding were not noted. These results suggest that D-thyroxine may be a drug which is able to modulate the function of GABAA receptor complex via the inhibitory action on benzodiazepine recognition site.

Animals↗

Maintenance of brain thyroid hormone level during peripheral hypothyroid condition in adult rat.

Thyroid hormones are essential for normal functioning of adult mammalian brain. The present investigation deals with the understanding of the time course of thyroid hormone homeostasis in adult rat brain. Animals were rendered hypothyroid by PTU injections (2 mg/100 g bw) for 30 consecutive days. Serum and synaptosomal T3/T4 content, synaptosomal AChE and Na+-K+-ATPase activities were determined on alternate days. While serum T4 level initially increased on the second day compared to control, serum T3 declined in a triphasic pattern; the first phase lasting from the second day to the 6th day, the second phase ended on the 14th day and last phase continued till the 30th day. Cerebro-cortical synaptosomal T3 level increased on the 2nd day from the control, attained a peak on the 4th day, remained stable until the 18th day, and abruptly declined on the 20th day. Synaptosomal T4 content remained negligible or undetected throughout. Synaptosomal membrane Na+-K+-ATPase and AChE activity exhibited an inverse relationship during the experimental regime, being much more prominent on the 2nd, 18th and 20th day coinciding with the variations in brain T3 level. Thus, the study identifies the onset of central homeostasis between the first and second day, its continuation for about 16-18 days and its termination between the 18th and 20th day.

Acetylcholinesterase↗

Xanthomas and hyperlipidemias.

The ability to recognize diverse clinical forms of xanthomas, such as tuberous, planar, eruptive and tendinous, is important in the detection of underlying systemic disease. A variety of primary genetic disorders, as well as numerous secondary conditions such as diabetes, obstructive liver disease, thyroid disease, renal disease, and pancreatitis, can lead to hyperlipoproteinemia that results in the formation not only of xanthomas but also of life-threatening vascular atherosclerosis. An understanding of the pathogenesis of the underlying lipoprotein alterations provides a rational approach to therapy utilizing dietary manipulations and drugs. Such treatment is capable of correcting most disorders of lipid metabolism, and, if appropriate therapy is initiated at the first sign of xanthoma evolution, it may prevent progression of atherosclerosis, provide resolution of xanthomas, and in some instances prevent serious pancreatitis.

Apoproteins↗

Influence of D-thyroxine on plasma thyroid hormone levels and TSH secretion.

Triiodothyronine (T3), thyroxine (T4), basal TSH and TSH after stimulation with TRH were determined in healthy subjects and patients treated with D-thyroxine (DT4). After a dosage of 6 mg DT4 the D/L T4 plasma concentration rose about 4-fold 4 hours after application and was only moderately elevated 14 hours later. To achieve constantly elevated T4 levels 3 mg DT4 were applied in the further experiment every 12 hours. The D/L T4 plasma concentration rose 2.5-4-fold and there was a small but significant increase of the D/L T3 plasma concentration. 74 hours after onset of treatment basal TSH was below detectable limits and the increase of TSH 30 min after injection of 200 mug TRH (TRH test) was only about 15% compared to zero time. The time course of TSH suppression was investigated after treatment with DT4 and LT4 (single dosage of 3 mg). TRH-tests were performed before, 10, 26, 50 and 74 hours after the first dosage of D or LT4. There was no difference in the time course of basal TSH and TSH stimulated by TRH. In 10 patients on DT4 long-term therapy, basal and stimulated TSH were found to be below the detectable limits of 0.4 mug/ml. Our results show that (1) plasma half-life of DT4 is less than 1 day, (2) TSH suppression after D and LT4 treatment is very similar, and (3) in patients on long-term DT4 treatment, TSH plasma concentration is below detectable limits even after stimulation with TRH.

Dextrothyroxine↗