Hyperthyroidism is most commonly caused by Graves' disease, a chronic lymphocytic inflammatory condition with autoimmune components similar to Hashimoto's disease. One autoantibody, which is present in Graves' disease, but not in Hashimoto's thyroiditis, interacts with TSH receptors to cause increased secretion of thyroid hormones.
Only rarely is hyperthyroidism caused by a hyperfunctioning nodule in a multinodular goiter or by an isolated, autonomously functioning adenoma. Carcinoma of the thyroid is almost always nonfunctional. Hyperthyroidism secondary to hypersecretion of TSH is extremely rare.

Symptoms of hyperthyroidism include an elevated body temperature and sensitivity to heat with persistent perspiration; increased appetite, but weight loss; fatigability and muscle weakness; increased heart rate and blood pressure; marked irritability and nervousness with a fine tremor of the hands. Exophthalmus is found only in Graves' disease, but is not present in all cases.

Laboratory diagnosis of hyperthyroidism is currently based on finding depressed serum TSH concentration (remember that hyperthyoidism is secondary to pituitary, or ectopic, hypersecretion of TSH only exceedingly rarely) and increased fT4 in most cases as well. Earlier, TT3 was useful in that results were generally elevated more consistently and more markedly than were TT4 results. Graves' disease is specifically diagnosed by finding circulating antithyroid autoantibodies (antimicrosomal and/or antithyroglobulin) as well.

When inflammatory destruction of thyroid tissue or synthesis defects are sufficiently severe to preclude maintenance of normal thyroid hormone concentration, then frank symptomatic hypothyroidism develops. The symptoms include generalized edema with a high protein and mucopolysacharide content in the transudate (myxedema); intolerance to cold; fatigability and weakness; slowed movements, thought processes and speaking; thickened tongue; thick, dry, pale-yellow skin; and coarse, but sparse hair.
Serum cholesterol is typically increased since thyroid hormone controls levels of cell membrane receptors for low density lipoprotein in peripheral tissue. Hypothyroidism is one of the recognized causes of secondary type II hyperlipoproteinemia and is associated with increased risk for atherosclerosis.

Hypothyroidism in the adult most commonly results from the progression of chronic thyroiditis with eventual fibrous replacement of thyroid tissue.
Goiter is absent in hypothyroidism secondary to TSH deficiency and in such cases the thyroid is atrophic.
In cases of hypothyroidism from severe, chronic iodine deficiency or from complete enzyme deficiencies, the thyroid is hypertrophic and goiter is evident.

Neonatal hypothyroidism (cretinism) is most commonly caused by congenital abnormalities in the development of thyroid tissue or by enzyme deficiencies.

Laboratory diagnosis of primary hypothyroidism is made on the basis of elevated TSH and low fT4 values. TSH elevation is usually more marked than is the decrease in fT4, except, of course, for cases of hypothyroidism secondary to TSH deficiency. The end stage of chronic inflammatory thyroid disease is identified by the presence of antithyroglobulin and/or antimicroscomal antibodies at least up to the point where the thyroid is completely replaced by fibrous tissue.

The differential diagnosis of pituitary or hypothalamic insufficiency as the cause of TSH deficiency is based on results from the TRF stimulation test.

Early detection and treatment of neonatal hypothyroidism is essential for prevention of irreversible mental retardation. The incidence of cretinism is higher than that of phenylketonuria and most states have included measurement of T4 and TSH in screening newborns for inborn errors of metabolism.