Hyperthyroidism

1

How common is hyperthyroidism?

Of the 1.2% prevalence of hyperthyroidism in the United States, 0.5% is overt, while 0.7% is subclinical. The incidence of overt disease is approximately 0.4 per 1000 women, and 0.1 per 1000 men, but varies significantly by age.

2

What are the signs and symptoms of hyperthyroidism?

• General: Heat intolerance, perspiration, flushing, tremor, sleep disturbance, or hair loss

• Psychologic: Nervousness, emotional lability, anxiety, aggressiveness, or delusions

• Cardiovascular: Palpitations, tachycardia, or supraventricular dysrhythmias

• Respiratory: Breathlessness or hoarseness

• Gastrointestinal: Increased appetite, weight loss, or increased frequency of bowel movements

• Reproductive: Gynecomastia, irregular menses

• Bone: Osteoporosis

• Other: Ophthalmopathy, dermopathy

3

What are the common causes of hyperthyroidism?

Graves’ disease, toxic multinodular goiter (TMNG), and toxic uninodular goiter (Plummer’s disease) are the three most common causes. Others include acute thyroiditis, subacute (de Quervain’s) thyroiditis, silent thyroiditis, amiodarone-induced thyroiditis, iatrogenic thyrotoxicosis, factitious ingestion of thyroid hormone, struma ovarii, trophoblastic disease, resistance to thyroid hormone, and extensive metastases from follicular thyroid cancer.

4

How should hyperthyroidism be investigated?

Serum thyroid-stimulating hormone (TSH) measurement is the most useful test in the evaluation of hyperthyroidism and should be used as an initial screening test. It has the highest sensitivity and specificity of any single blood test. A low TSH with a high serum level of free thyroxine (T ₄ ) or triiodothyronine (T ₃ ) is diagnostic. A high TSH with an increase in free T ₄ indicates the rare patient with a thyrotropin-producing pituitary tumor. Subclinical hyperthyroidism has suppressed TSH with a high-normal T ₄ or T ₃ .

After the diagnosis of hyperthyroidism is made, radioactive iodine uptake (RAIU) may be used to differentiate the many causes. It is most indicated when thyroid nodules are present or when the clinical presentation of thyrotoxicosis is not diagnostic of Graves’ disease. Uptake in the thyroid is usually measured at 4–6 hours then again at 24 hours.

• High uptake: Confirms hyperthyroidism resulting from overproduction of thyroid hormone

• Uniform uptake: Suggests Graves’ disease

• Patchy uptake: Suggests TMNG

• Unifocal area with suppression of the remaining thyroid: Diagnostic of a toxic solitary adenoma

• Diffuse, low uptake: Suggests thyroiditis, which can cause a self-limited course of hyperthyroidism secondary to release of preformed thyroid hormone

5

How is the diagnosis of Graves’ disease established?

Graves’ disease can almost always be diagnosed on the basis of the clinical findings that include symmetric thyroid enlargement, recent onset ophthalmopathy, and moderate to severe hyperthyroidism. Ophthalmopathy is unique to Graves’ disease and is the result of thyroid autoantibodies (particularly in smokers) that cross-react to the extraocular muscles. TSH will be low in association with an increased free T ₄ . If the free T ₄ is normal, a free T ₃ level is obtained to rule out T ₃ toxicosis. RAIU shows uniform increased uptake. Because Graves’ is an autoimmune disease that results in production of autoantibodies that stimulate the TSH receptor, TSH receptor antibody assays or thyroid-stimulating immunoglobulin (TSI) levels can be used to confirm the diagnosis.

6

What are the three treatment options for Graves’ disease?

Antithyroid drugs (ATDs), radioactive iodine (I ¹³¹ ) therapy, and surgery. Each has associated risks and benefits. In the United States, radioactive iodine (RAI) has been the preferred therapy.