Hyperthyroidism is a condition of excess thyroid hormone production. It may be caused by intrinsic thyroid dysfunction or, rarely, by excessive stimulation of the thyroid gland by an autonomous source of thyroid-stimulating hormone (TSH). The prevalence of hyperthyroidism in the US is about 1.2%. Approximately 70% of cases result from Graves’ disease, in which autoantibodies to the TSH receptor continually stimulate the thyroid gland to overproduce thyroid hormone. Other common causes include toxic multinodular thyroid, toxic adenoma, and thyroiditis. Hyperthyroidism may also be caused by excessive ingestion of exogenous thyroid hormone or iodine. Rarely, hyperthyroidism may be caused by a TSH-secreting anterior pituitary adenoma or struma ovarii. Symptoms may also result when physiologically high doses of levothyroxine are used during treatment for thyroid malignancy in order to suppress TSH.
Clinical manifestations of hyperthyroidism vary significantly from patient to patient, with symptom severity often correlating with circulating thyroid hormone concentrations. Common signs and symptoms include tachycardia, palpitations, heat intolerance, weight loss, menstrual irregularities, nausea, vomiting, restlessness, anxiety, tremor, and atrial fibrillation. Further signs and symptoms depend on the etiology and severity of hyperthyroidism. In Graves’ disease, for example, typical symptoms include a diffuse, symmetric goiter; orbitopathy (including lid lag and irreversible exophthalmos); and dermopathy (including pretibial myxedema, a thickening and redness of the pretibial skin). Graves’ hyperthyroidism may be associated with other autoimmune diseases, including Addison disease and type 1 diabetes mellitus.
Thyroid storm is a rare and life-threatening form of hyperthyroidism. It can be precipitated by several factors in individuals with thyrotoxicosis and may be the first sign of this condition. Risk factors include major stress (e.g., infection, trauma), radioactive iodine therapy, or thyroidectomy for thyrotoxic state. One of the most common inciting factors is noncompliance with antithyroid medication. Clinical presentation may include hyperpyrexia (104-106 F), severe nausea, vomiting, jaundice, rigidity, and altered mental status, including agitation, delirium, or stupor. These symptoms may progress to seizures, coma, tachycardia or atrial fibrillation, congestive heart failure, shock, and death.
Sex. Hyperthyroidism is more common in females.
Genetics. Certain HLA-D subtypes increase risk for Graves’ disease.
Iodine. Excess dietary iodine intake and iodine-rich medication (e.g., amiodarone) use may cause hyperthyroidism. Amiodarone may also cause thyroiditis.
Physical findings may include a rapid heart rate and an enlarged thyroid. TSH is the most cost-effective assay for hyperthyroidism and should be the initial screening test. TSH is decreased in all types of hyperthyroidism, except when pituitary tumors produce TSH or the thyroid hormone feedback loop malfunctions.
Free T4 concentration is increased; the magnitude of T4 elevation is correlated with the degree of biochemical disease. If TSH and T3 are elevated but T4 is normal, Graves’ disease or thyroid adenoma are likely causes. A total T3:T4 ratio greater than 20 is common in Graves’ disease.
Once hyperthyroidism has been diagnosed, further testing can determine the underlying etiology. Thyroid stimulating immunoglobulins, antithyroglobin, and antithyroid peroxidase levels are often elevated in Graves’ disease. A 24-hour radioactive iodine uptake scan is often necessary for diagnosis of Graves’ disease and exclusion of other disorders. Uptake is increased in Graves’ disease, toxic adenoma, and multinodular goiter and is decreased in thyroiditis, excessive iodine consumption, and overmedication with thyroid hormone supplementation.
Radioimaging can define the shape and size of the thyroid and determine where “hot” nodules are distributed (iodine will concentrate in “hot” nodules). Functional nodules may represent toxic adenoma or multinodular goiter. Diffuse uptake is seen in Graves’ disease. Absence of uptake strongly suggests thyroiditis, exogenous thyroid hormone ingestion, or rarely, struma ovarii.
Initial therapy often uses a beta-blocker to oppose the adrenergic effects of thyroid hormone.
Antithyroid drugs. Antithyroid drugs, such as methimazole and propylthiouracil, block thyroid hormone synthesis or conversion of active thyroid hormone. These drugs are typically first-line treatments and are usually very effective in reducing or normalizing thyroid levels; however, side effects often limit their use, especially over the long term. The most common side effects include rash, urticaria, and liver function test abnormalities. A very rare but serious side effect is suppression of white blood cells, which can weaken the body’s ability to fight infection. While taking these medications, patients need frequent blood monitoring of thyroid function. Antithyroid drugs are typically continued for up to 1-2 years. Spontaneous remission of hyperthyroidism occurs in less than 30% of patients.
Radioactive iodine (I131) to ablate thyroid tissue is a definitive treatment with excellent success rates, and it is the most commonly used treatment in the US. It cannot, however, be used in pregnancy, and breastfeeding mothers must pump and dispose of their milk for about 5 days after treatment. Radioiodine treatment can cause or worsen Graves’ orbitopathy. Complete destruction of the thyroid gland typically occurs within 8-10 weeks, at which point thyroid hormone replacement is necessary to reestablish a euthyroid state.
Surgical removal of the thyroid (thyroidectomy) is also an effective treatment. It is often indicated in hyperthyroid patients who have an obstructive goiter.
Lifelong thyroid hormone supplementation will be necessary after ablation or thyroidectomy due to resultant hypothyroidism.
Thyroid storm treatment is generally similar to that for hyperthyroidism but with closer monitoring and higher medication doses. Treatment with glucocorticoids or potassium iodine may be indicated (excess iodine reduces release of stored thyroid hormone into the circulation). Intensive care unit observation is essential.
In the Adventist Health Study-2, dietary patterns were shown to be associated with hyperthyroidism. Compared with omnivores, hyperthyroidism prevalence was 52% lower among participants following vegan diets, 35% lower among lacto-ovo-vegetarians, and 26% lower among those limiting their meat consumption to fish. The potential mechanism relates to environmental estrogens added to meat, eggs, and dairy triggering autoimmune reactions. Furthermore, vegan diets may downregulate insulin-like growth factor-1, which is a modulator of apoptosis and lymphocyte proliferation. Finally, polyphenols found in plants may protect against autoimmune diseases.
Iodine-induced hyperthyroidism has been reported in patients after treatment for previous thyroid diseases. Specifically, patients treated with antithyroid drugs for Graves’ disease are prone to develop iodine-induced hyperthyroidism. Excess iodine exposure may occur through drugs, antiseptics, food preservatives, and contrast media, in which iodine amounts can be several thousand times higher than what is recommended. Cow’s milk is a primary source of dietary iodine in the US. Certain breads, nori, and fish contain up to 198 µg, 232 µg, and 158 µg iodine per serving, respectively, which would provide a large excess when compared with the recommended dietary allowance for adults of 150 µg.
Patients with celiac disease have an increased prevalence of autoimmune disease, including Graves’ disease. It is unclear whether the association is due to a common genetic basis for the two conditions or to an unidentified cause-and-effect relationship. Limited evidence indicates that antithyroid antibody production abates in celiac patients after 3-6 months on a gluten-free diet.
See Basic Diet Orders chapter.
Nutrition consultation to assist patient in planning appropriate iodine intake.
What to Tell the Family
Hyperthyroidism is common and generally responds well to medical therapy. In some cases, the disease spontaneously remits. In others, radioactive iodine therapy, antithyroid drugs, or surgery is indicated to remove or destroy overactive thyroid cells, which may necessitate lifelong thyroid hormone replacement to maintain a normal hormone level.
Dietary factors, particularly plant-based diets, may play a role in prevention and treatment, but randomized clinical trials have yet to be conducted. Under medical supervision, patients with mild to moderate disease could attempt a trial period of avoiding animal-derived foods, as well as limiting intake of foods that contain high concentrations of iodine (including milk, yogurt, bread made with iodate dough conditioners, iodized salt, nori, fish, and shellfish) and foods that contain iodides, iodate, algin, alginates, carrageen, agar, and red dye number 3.
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