EFFECTS OF THYROXINE EXCESS ON PERIPHERAL ORGANS

Aim of this paper is to review the effects of T4 excess due to exogeno us thyroid hormone administration on target organs, with particular re gard to heart, bone, liver and pituitary. Therapy with TSH-suppressive doses of T4 has been shown in a cross sectional echocardiographic stu dy to increase left ventricular contractility and to induce mild myoca rdial hypertrophy. Whether the latter represents a risk for the patien ts remains a matter of debate. Clinically it does not seem to be impor tant. The long-term evaluation of T4-therapy has provided controversia l results. Some have reported that T4-treated patients under the age o f 65 have an increased risk of ischemic heart disease, whereas others were unable to find any change in morbidity, mortality and quality of life, including cardiovascular events. Thyroid hormones enhance both o steoblastic and osteoclastic activities in cortical and trabecular bon e. Overt hyperthyroidism is well known to represent a risk factor for osteoporosis. Studies in the late eighties have suggested a reduced bo ne density in T4-treated patients, with a particular risk for cortical bone in postmenopausal women. More recent studies have failed to show any substantial T4-related change in bone mass. Taken together the ev idence of the literature suggests that TSH-suppressive therapy with T4 is, if well controlled, probably not associated with significant loss of bone mass at least in premenopausal women. A mild elevation of the activity of hepatic enzymes (glutathione-S-transferase, gamma glutamy ltransferase, alanine amino-transferase, angiotensin-converting enzyme ) has been observed in patients under T4 treatment in TSH-suppressive doses. The clinical relevance of such subtle changes in liver protein or enzyme levels seem to be very modest. There is a relevant proportio n of both athyreotic and goitrous T4-treated patients who have elevate d free T4 serum concentrations in the presence of unsuppressed TSH lev els. Therefore an increase of free T4 alone does not indicate per se a n overdose of exogenous T4. It is, furthermore, argued that the pituit ary has a greater sensitivity to thyroid hormone action and that there fore ''pituitary'' thyrotoxicosis does not necessarily mean thyrotoxic osis at the level of other tissues. Summarizing the discussed evidence in the literature, it is suggested that overt clinical thyrotoxicosis and/or m ore severe degrees of subclinical hyperthyroidism should be avoided when treating with L-T4. A careful monitoring by measuring ser um concentrations of free T3 (the probably most reliable indicator of tissue thyrotoxicosis), which should always be kept within the normal limits, is most helpful in this respect.