Clinics in Endocrinology and Metabolism最新文献

The effects of trace metal nutrition on the fetus and neonate have been described. Since very little research has been done with the human fetus and neonate, much of our knowledge must be extrapolated from animal studies. In addition, most of the work centres around the effects of copper and zinc nutrition. Nutritional requirements (when known) for both enteral and total parenteral feeding of certain trace metals, as well as the bioavailability, have been discussed. Finally, methods of assessment of trace metal nutritional status have been discussed. These include direct measurement of metal concentrations and determination of biochemical indicators, such as metal-dependent enzyme activities—both of which are static indicators of nutritional status, and functional assessment of nutritional status which is a dynamic measure of trace metal nutrition and includes tests measuring the effects of metal nutrition on the function of cells, tissues, organs, and the host in general.

The importance of cardiovascular system involvement in hyperthyroidism has been recognized for many years. In the middle-aged and elderly patient, often with mild but prolonged elevation of plasma thyroid hormones, symptoms and signs of heart failure and complicating atrial fibrillation may dominate the clinical picture and mask the more classical endocrine manifestations of the disease. Pitfalls in diagnosis and the importance of early recognition and treatment are discussed. Despite experimental evidence for a short-term isotropic action of thyroid hormone excess, clinical data support the existence of a reversible cardiomyopathy in hyperthyroidism with impaired contractile reserve. Enhanced myocardial performance at rest primarily reflects the peripheral actions of thyroid hormone excess. Most, if not all, of the cardiac abnormalities return to normal once a euthyroid state has been achieved, although atrial fibrillation may persist in a minority. Optimum treatment requires rapid and definitive antithyroid therapy, usually using a large dose of radio-iodine, and rapid control of heart failure. Systemic anti-coagulation is indicated in the presence of atrial fibrillation and should be continued until sinus rhythm has been present for at least three months, either spontaneously or after cardioversion.

Investigation of suspected hyperthyroidism is conventionally based on measurement of total or free T₄ as the initial test, followed in equivocal cases by total or free T₃, and the TRH test. Recent developments in techniques for measuring free hormones and TSH promise to change this approach. Free T₄ and free T₃ can now be rapidly and simply quantitated in whole serum using labelled analogue radioimmunoassays. Specific and highly sensitive assays using labelled monoclonal antibodies are now available for serum TSH that permit the suppressed levels found in most cases of hyperthyroidism to be distinguished from euthyroid levels. These newer assays are available at a cost per test that is often similar to that of the more established tests.

Available evidence indicates that measurement of basal serum TSH by a sensitive labelled antibody method can serve as a first line test, at least in uncomplicated cases of suspected hyperthyroidism. In patients with a suppressed TSH, a serum free T₄, and in equivocal cases free T₃, will distinguish the clinical and subclinical forms of hyperthyroidism. Such an approach would obviate the need for the TRH test. It must be emphasized, however, that experience with this new approach is limited. Caution is advised in the interpretation of low TSH and free hormone levels when there are associated complicating features, such as severe non-thyroidal illness, or pregnancy.

These developments mark a trend in thyroid function testing away from measurement of circulating total hormone levels. The newer tests provide an assessment of end organ (thyrotroph) response, and an assessment of biologically active (free) hormone to which the tissues are exposed. These complementary approaches have the potential to identify relatively minor degrees of thyroid dysfunction.

The abnormally increased thyroid activity that is characteristic of Graves' disease is caused by immunoglobulins which specifically interact with the thyroid cell and stimulate it. Increases and decreases in thyroid activity in Graves' disease can be clearly related to rise and fall of these immunoglobulin-mediated activities. The level of immunoglobulin stimulatory activity can be used for prediction of the likelihood of neonatal Graves' disease and of recurrence of disease after cessation of treatment with antithyroid drugs.

Investigation of patients with Graves' disease and their families has led to identification of particular human leukocyte antigens and genetically linked markers on immunoglobulins which both appear to incur increased susceptibility to certain autoimmune diseases. Differences in immune function, when compared with control populations, have been found in patients with these genetically linked markers. Protection against autoimmune disease-is maintained by purposeful inhibition of any self-directed activity within each function of the immune system and by the controlling interaction of other immune functions. No single deficiency of immune function can be selected as giving the major risk of autoimmune disease, but rather a sum of relative defects resulting in an increased risk. In some patients with Graves' disease the self-protection mechanisms regain sufficient control of the immune functions to reduce the activity of the autoimmune disease, and the patient may achieve clinical remission. Often, however, there is evidence that abnormal immune activity directed against thyroid tissue has persisted with liability to recurrence of the Graves' disease.