Thyrotoxicosis is a hypermetabolic state caused by elevated levels of free T3 and T4. It is often referred to as hyperthyroidism because it is caused most commonly by hyperfunction of the thyroid gland. When these elevated levels arise from hyperfunction of the thyroid as occurs in Graves disease, the thyrotoxicosis may correctly be called hyperthyroidism. When the increased hormone levels reflect excessive leakage of hormone out of a nonhyperactive gland, however it is properly referred to as thyrotoxicosis. Long usage often equates these terms. By either name the syndrome is manifested by nervousness, palpitations, rapid pulse, fatigability, muscular weakness, weight loss with good appetite, diarrhea heat intolerance, warm skin , excessive perspiration, emotional lability, menstrual changes, a fine tremor of the hand (particularly when outstretched), eye changes and variable enlargement of the thyroid gland. Throtoxicosis can be caused by a variety of disorders.

Diffuse hyperplasia of the thyroid associated with Graves disease (accounts for 85% of cases)
Ingestion of exogenous thyroid hormone (administered for hypothyroidism)
Hyperfunctional multinodular goiter
Hyperfunctional adenoma of the thyroid
Thyroiditis

The terms primary and secondary hyperthyroidism are sometimes used to designate hyperthyroidism arising from an intrinsic thyroid abnormality and that arising from process outside of the thyroid such as a TSH ?secreting pituitary tumor. Less common causes of secondary hyperthyroidism include secretion of excessinve amounts of thyroid hormone by ectopic thyroid arising in ovarian teratomas.

Clinical Course

The clinical manifestations of hyperthyroidism include changes referable to the hypermetabolic state induced by excess thyroid hormone as well as those related to overactivity of the sympathetic nervour system. Excessive levels of thyroid hormone result in an increase in the basal metabolic rate. Cardiac manifestations are among the earliest and most consistent features of hyperthyroidism. Patients with hyperthyroidism can have an increase in cardiac output owing to both increased cardiac contractility and increased peripheral oxygen requirement. Tachycardia, palpitations and cardiomegaly are common. Arrhythmias particularly in elderly patients with preexisting cardiac disease. Myocardial changes, such as foci of lymphocytic and eosinophilic infiltration mild fibrosis in the interstitium, fatty changes in myofibers and an increase in size and number of mitochondria have been described. These changes are not frequent and other possible concomitant pathogeneses have not been rigorously ruled out, so debate continues about so-called thyrotoxic cardiomyopathy.

Other findings throughout the body include atrophy and fatty infiltration of skeletal muscle sometimes with focal interstitial lymphocytic infiltrates; minimal fatty changes in the liver sometimes accompanied by mild periportal fibrosis and a mild lymphocytic infiltrate osteoporosis; and generalizedlyumphoid hyperplasia with lymphadenopathy.

Ocular changes often call attention to hyperthyroidism. A wide starting gaze and lid lag are present because of sympathetic overstimulation of the levator palpebrae superioris. Only patients with Graves disesase have ophthalmopathy.

In the neuromuscular system, overactivity of the sympathetic nervous system produces tremor , hyperactivity , emotional lability, anxiety, inability to concentrate, and insomnia. Proximal muscle weakness is common with decreased muscle mass.

The skin of thyrotoxic patients tends to be warm, moist and flushed because of increased blood flow and peripheral vasodilation to increase heat loss. Sweating is increased because of higher levels of calorigenesis. Infiltrative dermopathy is seen only in Graves hyperthyroidism.

The skeletal system is also affected in hyperthyroidism. Thyroid hormone stimulates bone resorption, resulting in increased porosity of cortical bone and reduced volume of trabecular bone. The net effect is osteoporosis and an increased risk of fractures in patients with chronic hyperthyroidism.