- LOOK FOR OTHER ENDOCRINE PATHOLOGIES
- HYPERTHYROID PT. WITH DETECTABLE TSH SHOULD ALWAYS BE EVALUATED FOR INAPPROPRIATE TSH SECRETION( EITHER A TSH TUMOR OR THYROID HORMONE RESISTANCE ).
Medical Care
With the exception of low I-123 uptake hyperthyroidism (eg, subacute thyroiditis; see Thyrotoxicosis), the treatment of hyperthyroidism includes symptom relief and therapy with antithyroid medications, therapy with radioactive iodine 131 (I-131), or thyroidectomy.
Symptom relief: Many of the neurological and cardiovascular symptoms of thyrotoxicosis are relieved by beta-blocker therapy. Prior to therapy, examine the patient for signs and symptoms of dehydration that often occur with hyperthyroidism. After oral rehydration, beta-blocker therapy can be started. Do not administer beta-blocker therapy to a patient with a significant history of asthma. Calcium channel blockers can be used for the same purposes when beta-blockers are contraindicated or poorly tolerated.
Antithyroid drugs: Antithyroid drugs (eg, methimazole, propylthiouracil) have been used for hyperthyroidism since their introduction in the 1940s. These drugs inhibit multiple steps in the synthesis of T4 and T3, leading to a gradual reduction in thyroid hormone levels over 2-8 weeks or longer. Titrate the antithyroid drug dose every 4 weeks until thyroid functions normalize. Some patients with Graves disease go into a remission after treatment for 12-18 months, and the drug can be discontinued. Notably, half the patients who go into remission have another recurrence of hyperthyroidism within the following year. Nodular forms of hyperthyroidism (toxic multinodular goiter and toxic adenoma) are permanent conditions and will not go into remission.
Antithyroid medications inhibit formation and coupling of iodotyrosines in thyroglobulin, which are necessary for thyroid hormone synthesis.
A second therapeutic action of propylthiouracil, but not methimazole, is the inhibition of conversion of T4 to T3. T3 is a more biologically active form of thyroid hormone. A quick reduction in T3 is associated with a clinically significant improvement in thyrotoxic symptoms.
The antithyroid medications are used for the long-term control of hyperthyroidism in children, adolescents, and pregnant women (propylthiouracil only for pregnancy). In women who are not pregnant, the medications are used to control hyperthyroidism prior to definitive therapy with radioactive iodine. In surveys of thyroid specialists in the United States, the preferred treatment of hyperthyroidism is radioactive iodine therapy.
The choice between propylthiouracil and methimazole is somewhat arbitrary. Methimazole is a more potent and longer-acting drug. Often, patient compliance is better with methimazole taken once or twice daily than with propylthiouracil given 3 or 4 times daily. Propylthiouracil often is the drug of choice in severe thyrotoxicosis because of the additional benefit of inhibition of T4 to T3 conversion. Administer propylthiouracil every 6-8 hours. The reduction in T3, which is 20-100 times more potent than T4, theoretically helps reduce the thyrotoxic symptoms more quickly that methimazole.
Adverse effects of antithyroid medications: The most common effects are allergic reactions of fever, rash, urticaria, and arthralgia, which occur in 1-5% of patients usually within the first few weeks of treatment. Serious adverse effects include agranulocytosis, aplastic anemia, hepatitis, polyarthritis, and a lupuslike vasculitis. All of these adverse effects, except agranulocytosis, occur more frequently with propylthiouracil. Agranulocytosis occurs in 0.2-0.5% of patients, with an equal frequency for both drugs. Patients with agranulocytosis usually present with fever and pharyngitis. After the drug is stopped, granulocyte counts usually start to rise within several days but may not normalize for 10-14 days. Granulocyte colony-stimulating factor (G-CSF) appears to accelerate recovery in patients with a bone marrow aspiration showing a granulocyte-to-erythrocyte (G:E) ratio of 1:2 or greater than 0.5.
Other drugs: In severe thyrotoxicosis from Graves disease or subacute thyroiditis, iodine or iodinated contrast agents have been administered to block T4 conversion to T3 and the release of thyroid hormone from the gland. This therapy is reserved for severe thyrotoxicosis because its use prevents definitive therapy of Graves thyrotoxicosis with radioactive iodine for many weeks. Either a saturated solution of potassium iodide (SSKI) at 10 gtt twice daily or iopanoic acid/ipodate (1 g/d) can be administered with rapid reduction in T3 levels. Take care to not administer these drugs to patients with toxic multinodular goiter or toxic adenomas. The autonomous nature of these conditions can lead to worsening of the thyrotoxicosis in the presence of pharmacological levels of iodide, a substrate in thyroid hormone synthesis.
Radioactive iodine therapy: Radioactive iodine therapy is the most common treatment of hyperthyroidism in adults in the United States. Although the effect is less rapid than antithyroid medication or thyroidectomy, it is effective, safe, and does not require hospitalization. It is administered orally as a single dose, in capsule or liquid form. The radioactive iodine is quickly absorbed and taken up by the thyroid. No other tissue or organ in the body is capable of retaining the radioactive iodine and, therefore, very few adverse effects are associated with this therapy.
The treatment results in a thyroid-specific inflammatory response, causing fibrosis and destruction of the thyroid over weeks to many months.
Generally, the dose of I-131 administered is 75-200 Β΅Ci/g of estimated thyroid tissue divided by the percent of I-123 uptake in 24 hours. This dose is intended to render the patient hypothyroid. Lithium used in the weeks following radioactive iodine therapy may extend the retention of radioactive iodine and result in increased efficacy. However, studies looking at this are inconsistent, and benefits of lithium used with radioactive iodine must be weighed against the toxicities associated with lithium.
Hypothyroidism is considered by many experts to be the expected goal of radioactive iodine therapy. In several large epidemiological studies of radioactive iodine therapy in patients with Graves disease, no evidence indicated that radioactive iodine therapy caused the development of thyroid carcinoma. No evidence of increased mortality exists for any other form of cancer, including leukemia, with radioactive iodine therapy of hyperthyroidism.
Long-term follow-up data of children and adolescents treated with radioactive iodine are lacking. Because of this absence of data, long-term antithyroid medications usually are recommended in children rather than radioiodine therapy.
Radioactive iodine is never administered to pregnant or lactating women. Radioactive iodine can cross the placenta and be excreted into milk, which can ablate the infant's thyroid and result in hypothyroidism. Checking for pregnancy prior to radioactive iodine therapy and suggesting that the patient not become pregnant for at least 3-6 months after the treatment and until thyroid functions are normal are standard practice.
Retrospective reviews have demonstrated no excess in fetal malformations or miscarriage rates in women previously treated with radioactive iodine for hyperthyroidism.
Radioactive iodine usually is not administered to patients with severe ophthalmopathy because clinical evidence suggests that usually mild, but occasionally severe, worsening of thyroid eye disease occurs after radioactive iodine therapy. The risk of ophthalmopathy is worse in patients who smoke cigarettes, but, apparently, it can be reduced by glucocorticoid therapy (prednisone 0.4 mg/kg for 1 mo with subsequent taper) after the radioactive iodine therapy.
Surgical Care
Subtotal thyroidectomy is the oldest form of treatment of hyperthyroidism. Total thyroidectomy and combinations of hemithyroidectomies and contralateral subtotal thyroidectomies also have been used.
Because of excellent effectiveness in regulating thyroid function with antithyroid medications and radioactive iodine, thyroidectomy is reserved for special circumstances, including the following:
Severe hyperthyroidism in children
Pregnant women who are noncompliant or intolerant of antithyroid medication
Patients with very large goiters or severe ophthalmopathy
Patients who refuse radioactive iodine therapy
Refractory amiodarone-induced hyperthyroidism
Patients who require normalization of thyroid functions quickly, such as pregnant women, women who desire pregnancy in the next 6 months, or patients with unstable cardiac conditions
With current operative techniques, bilateral subtotal thyroidectomy should have a mortality rate approaching zero in patients who are properly prepared. Historically, the most common cause of thyroid storm, a physiological decompensation in patients who are severely thyrotoxic with a mortality of 50-100%, is operative stress.
Preoperative preparation includes antithyroid medication, stable (cold) iodine treatment (to decrease gland vascularity), and beta-blocker therapy.
Generally, antithyroid drug therapy should be administered until thyroid functions normalize (4-8 wk).
Titrate propranolol until the resting pulse rate is less than 80 bpm.
Finally, administer iodide as SSKI (1-2 drops bid for 10-14 d) before surgery.
An additional benefit from stable iodide therapy, besides the reduction in thyroid hormone excretion, is a demonstrated decrease in thyroid blood flow and possible reduction in blood loss during surgery.
Adverse effects of therapy include recurrent laryngeal nerve damage and hypoparathyroidism due to damage of local structures during surgery.
Consultations
Generally, thyrotoxicosis should be evaluated and treated by an endocrinologist.
Therapy including radioactive iodine and antithyroid medication requires careful follow-up, which is best performed by a specialist.
Generally, after definitive therapy is completed with radioactive iodine or surgical thyroidectomy, the patient can be cared for by the primary care doctor (with thyroid hormone replacement therapy if necessary).
Patients with Graves thyrotoxicosis should be examined by an ophthalmologist for thyroid eye disease, which occurs in some form in 50% of patients. Often the eye disease is subclinical and remits with time. The eye disease usually occurs within 1 year (before or after) of the diagnosis of hyperthyroidism, but new-onset has been detected decades later. Graves eye disease also can occur without the patient ever having developed hyperthyroidism.
Diet
No special diet must be followed by patients with thyroid disease.
Notably, excess amounts of iodide found in some expectorants, x-ray contrast dyes, seaweed tablets, and health food supplements should be avoided because the iodide interferes with or complicates the management of both antithyroid and radioactive iodine therapies.
Activity
Often, in otherwise healthy patients with hyperthyroidism, exercise tolerance is not affected significantly. For these people, no reduction in physical activity is necessary. For elderly patients or for those with cardiopulmonary comorbidities, a decrease in activity is prudent until hyperthyroidism is medically controlled.
Often with severe thyrotoxicosis, systolic and diastolic cardiac dysfunction manifested by dyspnea upon exertion exists.
Often, beta-blocker therapy greatly improves exercise tolerance until thyroid hormones levels are reduced by other therapies.