Clinical features

The clinical features of hyperthyroidism may be dramatic and include:

Causes

Hyperthyroidism can result from:

Graves’ disease is the most common cause of hyperthyroidism, and is an autoimmune disease in which antibodies to the TSH receptor on the surface of thyroid cells appear to mimic the action of the pituitary hormone. The normal regulatory controls on T₄ synthesis and secretion are lacking. Pituitary secretion of TSH is completely inhibited by the high concentrations of thyroid hormones in the blood.

Although the eyelid retraction commonly seen in the patient with Graves’ disease (Fig 46.3) is due to the effects of high thyroid hormone concentration, not all of the eye signs are caused this way. Rather, the thyroid and orbital muscle may have a common antigen that is recognized by the circulating autoantibodies. The inflammatory process in the eye may lead to severe exophthalmos. This may even occur in the euthyroid patient.

Diagnosis

The demonstration of a suppressed TSH concentration and raised thyroid hormone concentration will confirm the diagnosis of primary hyperthyroidism. In particular, the finding that TSH is undetectable in one of the modern sensitive assays for this hormone strongly suggests that the symptomatic patient has primary hyperthyroidism.

Occasionally, biochemical confirmation of suspected hyperthyroidism will prove more difficult. The total T₄ concentration in a serum sample does not always reflect metabolic status, because of changes in binding protein concentration. In pregnancy, high circulating oestrogens cause stimulation of thyroid binding globulin (TBG) synthesis in the liver. Total T₄ concentrations will be above the reference interval although free T₄ will be normal (Fig 46.1). Congenital TBG deficiency can also cause confusion if a specimen is screened for thyroid hormones, even if thyroid disease is not suspected (Fig 46.1). TBG deficiency is encountered much less frequently than increased TBG.

Free T₄ assays are routinely used as first-line tests of thyroid dysfunction. TSH secretion is very sensitive to changes in free T₄, and many laboratories use TSH on its own to screen for thyroid disease. Free T₄ analyses are invaluable in diagnoses where binding proteins are altered, e.g. in pregnancy, in women on the oral contraceptive pill and in patients with the nephrotic syndrome (Table 46.1).

In a few patients with clinical features of hyperthyroidism, total T₄ concentration is found to be within the reference interval. Subsequent investigations reveal an elevated T₃ concentration. This is referred to as ‘T₃ toxicosis’. TSH is undetectable in these patients.

A strategy for the biochemical investigation of clinically suspected hyperthyroidism is shown in Figure 46.2.

Treatment

There are three methods for the treatment of Graves’ disease:

Thyroid function tests are important in the monitoring of all three treatments. In these circumstances it must be remembered that it takes a number of weeks before the tissue effects of thyroid hormones accurately reflect the concentration in the serum. In particular, TSH may take many weeks or months to adjust to its new level.