Thyroid hormone therapy adverse effects

Therapy with levothyroxine is very safe, provided that thyroid hormone levels are monitored and maintained within the normal range. Excess doses of T4 are associated with a loss of bone mass. A meta-analysis of 41 controlled studies on the impact of thyroid hormone therapy on bone mineral density (Uzzan et al., 1996) has shown that doses of T4 that suppress thyrotropin (TSH) secretion are associated with a significant loss of bone in the lumbar spine and hip in postmenopausal women. Another review of the evidence of the thyroid hormone effect of on skeletal integrity concluded that hyperthyroidism and the use of thyroid hormone to suppress TSH seem to have an adverse effect on bone, especially in postmenopausal women (Greenspan and Greenspan, 1999) however, thyroid hormone replacement seems to have a minimal effect on bone. 

In patients with longstanding hypothyroidism and those with ischemic heart disease, rapid correction of hypothyroidism may precipitate angina, cardiac arrhythmias, or other adverse effects. For these patients, replacement therapy should be started at low initial doses, followed by slow titration to full replacement as tolerated over several months. If hypothyroidism and some degree of adrenal insufficiency coexist, an appropriate adjustment of the corticosteroid replacement must be initiated prior to thyroid hormone replacement therapy. This prevents acute adrenocortical insufficiency that could otherwise arise from a thyroid hormone-induced increase in the metabolic clearance rate of adrenocortical hormones. 

L All of the following are common adverse effects associated with drug overdose of thyroid hormone replacement therapy EXCEPT... 

Inadvertent excessive use of thyroid hormones (for example, by eating ground beef contaminated with thyroid hormones (64), the incorrect use of these drugs for the treatment of obesity (65), excessive thyroid substitution therapy, and factitious use of thyroid hormones for psychiatric reasons (66)) result in mild hyperthyroidism, but serious short-term adverse effects are rare. 

Adverse effects of thyroid hormone parallel the increase in metabolic rate. The symptoms and signs are those of hyperthyroidism. Symptoms of myocardial ischaemia, atrial fibrillation or heart failure are liable to be provoked by too vigorous therapy or in patients having serious ischaemic heart disease who may even be unable to tolerate optimal therapy. Should they occur levothyroxine must be discontinued for at least a week and begim again at lower dosage. Only slight overdose is needed to precipitate atrial fibrillation in patients over 60 years. 

In contrast to other protein-bound drugs for which a loading dose is given to achieve rapid steady-state concentrations, a slow and stepwise increase in thyroid hormone replacement therapy is advisable. This is preferred mainly to avoid sudden cardiac adverse effects, especially in older patients with long-standing myxedema. Moreover, since thyroid hormone substitution can change the metabolic clearance of this drug, steady-state concentrations are obtained only after several months (SEDA-6, 363). 

Radioactive iodine ablation therapy for hyperthyroidism is relatively inexpensive, does not require hospitalization, and is relatively free of adverse effects. It is associated with a high incidence of permanent hypothyroidism, and all patients must be warned of this and followed therecffer for the onset of hypothyroidism. Because thyroid hormone replacement therapy is generally well accepted by the patient, many specialists prefer to treat with relatively higher doses to rapidly... 

Endocrine In patients receiving the minimum dose of amiodarone, thyroid abnormalities were observed at a rate between 14% and 18%. The effects on the thyroid gland are variable. Amiodarone may cause abnormal thyroid function detected only by laboratory test as well as clinically manifested thyroid dysfunction. The mechanism of this adverse effect is complex. Amiodarone inhibits the action of deiodinase and decreases peripheral conversion of thyroid hormones. Moreover, it decreases their renal elimination and inhibits their entry to peripheral tissues. The level of T4 increases by 40% within 1-4 months of amiodarone therapy. The deiodinase activity inhibition can be noticed after 3 months of treatment. It leads to an increase in the level of thyroid stimulating hormones. Amiodarone and its metabolite have a direct cytotoxic effect on thyroid follicular cells, which results in destructive thyroiditis. Amiodarone-induced thyroid damage can lead either to hypo- or hyperthyroidism. The latter can be of two types. Type 1 usually occurs in patients with prior thyroid damage. In this type, iodine excess causes excessive synthesis of thyroid hormones whereas in type 2 the inflammatory process is followed by destruction. A destructive thyroiditis leads to the release of hormones from damaged thyroid follicular cells. This mechanism occurs in patients with no history of thyroid disorders [15]. 

---