GRAVES AND THYROTOXICOSIS : LIPIDS, PROTEIN METABOLISM

[ling]

Graves’ Disease and the Manifestations of Thyrotoxicosis

DeGroot LJ.

ncbi.nlm.nih.gov/books/NBK2...

LIPIDS

The serum cholesterol level is depressed in thyrotoxicosis. There is an increase both in synthesis and in degradation, but the balance results in a new lower steady-state concentration in the serum. The cholesterol pool in the body is altered by thyroid hormone in different directions, depending on the species involved, and does not necessarily parallel the serum cholesterol level. Hypocholesterolemia may be produced without a distinct decrease in total body or liver cholesterol [418-428]. Part of the cholesterol-lowering action of thyroid hormone may be due to the effects of malnutrition and weight loss, and part may be simply a manifestation of hypermetabolism, since agents that elevate metabolism, such as salicylates, also lower serum lipid levels.

Thyroid hormone directly enhances conversion of cholesterol to bile acids and their excretion in the bile. This metabolic route accounts for the disposal of 70-90% of the cholesterol formed in the body [421]. Thyroid hormone may also affect cholesterol metabolism by directly increasing the number of membrane surface low-density lipoprotein (LDL) receptors [422]. The increased cholesterol synthesis, and even more enhanced clearance rate in hyperthyroidism has been confirmed in a recent study. Hepatic lypogenesis is also strikingly increased, probably both by direct action of thyroid hormones and an increase in insulin. Triglyceride levels tend to be slightly elevated (423).

Levels of the other serum lipid components are lowered [424-429]. Plasma triglycerides are in the low normal range, and the clearance rate of infused triglycerides may be elevated. Postheparin lipolytic activity [425,426] may be low or normal. Hyperthyroidism causes lower levels of apo(a), HDL, and ratio of total/HDL cholesterol [420,426]. Plasma leptin levels are normal in hyperthyroid patients (427). The free tocopherol level of the plasma changes in parallel with the cholesterol alterations in thyrotoxicosis [429].

Rich et al. [430]found the level of nonesterified fatty acids elevated in thyrotoxic patients. This response can be seen within six hours after administration of L-T3 to normal subjects, and might be related to the observation that ketosis occurs more readily in thyrotoxic patients than in normal subjects.

PROTEIN METABOLISM

Protein formation and destruction are both accelerated in hyperthyroidism. Nitrogen excretion is increased, and nitrogen balance may be normal or negative, depending on whether intake meets the demands of increased catabolism. Testosterone is able to exert its anabolic effects in thyrotoxicosis.

Lewallen et al [431] found that administration of thyroid hormone increases albumin synthesis and degradation in normal subjects, increases the fractional rate of degradation, and reduces the quantity of exchangeable albumin.

Thyroid hormone in vivo [432] or in vitro [433], as reviewed in Chapter 2, exerts its basic action through stimulation of transcription and mRNA translation. Thyroid hormone stimulates incorporation of amino acids into protein by liver microsomes. This action is at least partially explained by increased production of mRNA and by an increased transfer of soluble tRNA- bound amino acids into microsomal protein [434]. Clinically, a great excess of thyroid hormone appears to have the opposite effect. Crispell et al. found that protein synthesis may be depressed by feeding thyroid hormone to normal humans [432]. Catabolism of collagen is increased, [435]and urinary hypodroxyproline excretion is characteristically increased. Gluconeogenesis from alanine is stimulated by thyroid hormone [436]. Probably the elevated somatomedin levels found in thyrotoxicosis [296] contribute to augmented protein synthesis.

L-carnitine feeding has been shown to reverse some of the metabolic abnormalities in Graves’ disease. In a randomized double-blind study, L-carnitine, in a dose of 2-4 grams/day also reversed or prevented some of the adverse effects of excess thyroid hormone on bone mineralization. Presumably this occurs because hyperthyroidism has depleted body stores of carnitine (437).

cAMP Metabolism

Basal cAMP levels are on average elevated in serum of thyrotoxic humans , and there is hyperresponsiveness to stimuli such as epinephrine and glucagon [438]. Urinary cAMP is likewise increased [439]. Treatment with propranolol (in some studies) lowers basal cAMP toward, but not to, normal [440]. Adrenergic receptors are increased in number, and responses are enhanced as compared to the normal state (see Chapter 2).

Vitamin Metabolism

The absorption of vitamin A is increased and conversion of carotene to vitamin A is accelerated in thyrotoxicosis. The requirements of the body are likewise increased, and low blood concentrations of vitamin A may be found.

Requirements for thiamine and vitamin B6 are increased [441]. Lack of the B vitamins has been implicated as a cause of liver damage in thyrotoxicosis. It has been demonstrated that vitamin B12 requirements are increased in experimental thyrotoxicosis.

Radiosensitivity

Radiosensitivity of animal and human tumors may be enhanced by administration of L-T3 [442].

[Trixie64]

ling -thanks for all your interesting posts.

[ling in reply to Trixie64]

You are most welcome Trixie : )