58 HYPERTHYROIDISM
Robert C. McIntyre Jr., M.D.

2. What causes hyperthyroidism?

3. How should hyperthyroidism be investigated?

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A thyroid stimulating hormone (TSH) level is the best intial test. A low TSH with a high serum level of thyroxine (T4) or triiodothyronine (T3) is diagnostic. A high TSH with an increase in free T4 indicates the rare patient with a thyrotropin-producing pituitary tumor.
After the diagnosis of hyperthyroidism is made, the radioactive iodine uptake (RAIU) can differentiate the many causes.

4. What are the three treatment options?

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Antithyroid drugs (ATD), radioiodine, and surgery.

5. Which drugs are useful for the treatment of hyperthyroidism? What are their mechanisms of action?

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Methimazole and propylthiouracil (PTU) are the mainstays of treatment. The goal of treatment is remission of Graves’ disease during therapy or euthyroidism before treatment with radioiodine or surgery. Both drugs inhibit organification of iodine and coupling of iodothyronines. PTU also inhibits the peripheral monodeiodination of T4 to T3. Treatment is started with 20 mg/day of methimazole or 100 mg of PTU 3 times/day. The dose may be reduced after 6 weeks of treatment as the patient shows clinical and biochemical improvement. Therapy is usually maintained for 2 years. Patients must be monitored for side effects, which include rash, pruritus, agranulocytosis, hepatitis, cholestatic jaundice, and lupus-like syndrome.

Beta-adrenergic antagonists ameliorate the signs and symptoms of disease. They should not be used alone except for short periods before radioiodine or surgical therapy. Nadolol (80 mg/day) and atenolol (100 mg/day) are the most common agents.
Iodine given as Lugol’s solution (5% iodine and 10% potassium iodide in water, 0.3 mL/day) or potassium iodide (60 mg 3 times/day) inhibits the release of thyroid hormone. It is useful for short-term therapy in preparation for surgery, after radioiodine therapy to hasten the decrease in hormone levels, and for treatment of thyroid storm.

6. What are the indications for and outcome of drug treatment?

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ATD therapy is reserved for mild hyperthyroidism and a small gland. Long-term remission of Graves’ hyperthyroidism during antithyroid drug therapy occurs in 50% of patients. Relapse is most common in the first 6 months after cessation of treatment.

7. What is the regimen of radioiodine treatment?

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Radioiodine is the most common therapy. The usual dose of radioiodine is 10 mCi. If hyperthyroidism is not cured, the dose should be repeated in 6 months. Pretreatment with antithyroid drug therapy should achieve a euthyroid state. Steroids prevent progression of ophthalmopathy. Prednisone is used at a dose of 0.5 mg/kg body weight, starting 3 days after radioiodine therapy and continuing for 1 month. The dose is tapered over 2 months.
Pregnancy is an absolute contraindication. Women of childbearing age should be evaluated with a pregnancy test before treatment and should avoid pregnancy for 6 months after treatment. Evidence indicates that radioiodine may exacerbate ophthalmopathy.

8. What is the outcome of radioiodine treatment?

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Euthyroidism is not achieved for months after treatment. After euthyroidism is achieved, recurrence of hyperthyroidism is rare. Hypothyroidism, the only serious side effect, is dose dependent. It occurs at a rate of 3% per year, affecting 50% of patients at 10 years, and nearly 100% at 25 years.

9. What are the indications for thyroidectomy for hyperthyroidism?

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* Pregnant patients who are difficult to treat medically
* Patients with large goiters and low radioiodine uptake
* Children
* Noncompliant patients
* Patients with nodules suspected to be cancerous
* Patients with compression of the trachea or esophagus
* Patients with cosmetic concerns
* Patients with ophthalmopathy

10. How should patients be prepared for surgery? Show answer
Any patient with hyperthyroidism should be rendered euthyroid before surgery. Patients may be treated with antithyroid medication and potassium iodine. Beta-adrenergic antagonists should also be used alone or in combination with the above regimen.

11. What is the extent of thyroidectomy?

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The two surgical options for Graves’ disease are subtotal thyroidectomy or near-total thyroidectomy. The goal of subtotal thyroidectomy is to preserve 8 g of well-vascularized thyroid tissue to avoid hypothyroidism. Because of the small risk of recurrence (10%), however, some surgeons prefer near-total thyroidectomy. In Plummer’s disease, lobectomy or partial thyroidectomy for unilateral lesions and contralateral subtotal thyroidectomy for multiple lesions render the patient euthyroid.

12. What is the incidence of hypothyroidism after surgery?

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All patients having a near-total thyroidectomy become hypothyroid and need thyroxine replacement. Hypothyroidism occurs in 50% of patients with subtotal thyroidectomy.
KEY POINTS: HYPERTHYROIDISM

1. A thyroid-stimulating hormone (TSH) level is the best initial test.
2. Methimazole and propylthiouracil are the mainstays of medical treatment.
3. The two surgical options for Graves’ disease are subtotal thyroidectomy and near-total thyroidectomy.

13. What is the appropriate treatment for toxic nodular goiter?

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Hyperthyroidism caused by toxic nodular goiter is permanent and without spontaneous remission; antithyroid drugs are not appropriate long-term therapy. Radioiodine is the most common form of therapy. Larger doses (50 mCi) minimize the risk of persistent hyperthyroidism in such patients, who tend to be older and to have prominent cardiovascular symptoms of hyperthyroidism.

14. What is the appropriate treatment for hyperthyroidism caused by thyroiditis?

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Subacute thyroiditis should be suspected if the patient has pain and tenderness in the thyroid region. The hyperthyroidism is usually mild and of short duration (i.e., weeks). Patients are treated with a beta-adrenergic antagonist and salicylate or glucocorticoid. Hypothyroidism may occur but is usually not permanent.

15. What is the appropriate treatment for thyroid storm?

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Thyrotoxic crisis should be treated in the intensive care unit. General measures include hydration, antipyresis (acetaminophen), and nutrition. Specific measures include inhibition of T4 synthesis and conversion to T3 with PTU at a dose of 100 mg orally, via nasogastric tube, or rectally every 6 hours. Iodides inhibit T4 release (saturated solution of potassium iodide, 5 drops by mouth or nasogastric tube every 6 hours). Steroids (dexamethasone, 2 mg every 6 hours) also inhibit T4 release and conversion to T3. Beta-adrenergic antagonists (propranolol or esmolol) may control cardiovascular manifestations. The last-resort management option is T4 removal by plasmapheresis, hemoperfusion, or dialysis.

16. Who performed the first thyroidectomy?

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Johann von Mikulicz-Radecki performed the first thyroidectomy in 1885.

17. Which surgeon won the Nobel Prize for his work with thyroid disease?

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Theodor Kocher won the Nobel Prize in medicine in 1909. He was successful in reducing the high mortality rate of thyroidectomy to less than 1%. His most significant achievement was in describing postoperative hypothyroidism as cachexia strumipriva.

References
BIBLIOGRAPHY
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