Causes of thyroid hormone excess include primary hyperthyroidism (Graves' disease, toxic multinodular goiter [MNG], toxic adenoma, iodine excess); thyroid destruction (subacute thyroiditis, silent thyroiditis, amiodarone, radiation); extrathyroidal sources of thyroid hormone (thyrotoxicosis factitia, struma ovarii, functioning follicular carcinoma); and secondary hyperthyroidism (TSH-secreting pituitary adenoma, thyroid hormone resistance syndrome, human chorionic gonadotropin [hCG]-secreting tumors, gestational thyrotoxicosis). Graves' disease, caused by activating TSH-receptor antibodies, is the most common cause of thyrotoxicosis and accounts for 60-80% of cases. Its prevalence in women is 10-fold higher than in men; its peak occurrence is at age 20-50 years.
Symptoms include nervousness, irritability, heat intolerance, excessive sweating, palpitations, fatigue and weakness, weight loss with increased appetite, frequent bowel movements, and oligomenorrhea. Pts are anxious, restless, and fidgety. Skin is warm and moist, and fingernails may separate from the nail bed (Plummer's nails). Eyelid retraction and lid lag may be present. Cardiovascular findings include tachycardia, systolic hypertension, systolic murmur, and atrial fibrillation. A fine tremor, hyperreflexia, and proximal muscle weakness also may be present. Long-standing thyrotoxicosis may lead to osteopenia. In the elderly, the classic signs of thyrotoxicosis may not be apparent, the main manifestations being weight loss and fatigue (“apathetic thyrotoxicosis”).
In Graves' disease, the thyroid is usually diffusely enlarged to two to three times its normal size, and a bruit or thrill may be present. Infiltrative ophthalmopathy (with variable degrees of proptosis, periorbital swelling, and ophthalmoplegia) and dermopathy (pretibial myxedema) also may be found; these are extrathyroidal manifestations of the autoimmune process. In subacute thyroiditis, the thyroid is exquisitely tender and enlarged with referred pain to the jaw or ear, and sometimes accompanied by fever and preceded by an upper respiratory tract infection. Solitary or multiple nodules may be present in toxic adenoma or toxic MNG.
Thyrotoxic crisis, or thyroid storm, is rare, presents as a life-threatening exacerbation of hyperthyroidism, and can be accompanied by fever, delirium, seizures, arrhythmias, coma, vomiting, diarrhea, and jaundice.
Investigations used to determine the existence and causes of thyrotoxicosis are summarized in Fig. 173-2. Evaluation of Thyrotoxicosis. Serum TSH is a sensitive marker of thyrotoxicosis caused by Graves' disease, autonomous thyroid nodules, thyroiditis, and exogenous levothyroxine treatment. Associated laboratory abnormalities include elevation of bilirubin, liver enzymes, and ferritin. Thyroid radioiodine uptake may be required to distinguish the various etiologies: high uptake in Graves' disease and nodular disease versus low uptake in thyroid destruction, iodine excess, and extrathyroidal sources of thyroid hormone. (Note: Radioiodine is the nuclide required for quantitative thyroid uptake, whereas technetium is sufficient for imaging purposes.) The ESR is elevated in subacute thyroiditis. TRAb measurement can also be used to diagnose Graves' disease and color-flow Doppler ultrasonography may distinguish between hyperthyroidism (with increased blood flow) and destructive thyroiditis.
| TREATMENT | ||
ThyrotoxicosisGraves' disease may be treated with antithyroid drugs or radioiodine; subtotal thyroidectomy is rarely indicated. The main antithyroid drugs are methimazole or carbimazole (10-20 mg two to three times a day initially, titrated to 2.5-10 mg/d) and propylthiouracil (PTU) (100-200 mg every 8 h initially, titrated to 50 mg once or twice a day). Methimazole is preferred in most pts because of easier dosing. Thyroid function tests should be checked 3-4 weeks after initiation of treatment, with adjustments to maintain a normal free T4 level. Since TSH recovery from suppression is delayed, serum TSH levels should not be used for dose adjustment in the first few months. The common side effects are rash, urticaria, fever, and arthralgia (1-5% of pts). Uncommon but major side effects include hepatitis, an SLE-like syndrome, and, rarely, agranulocytosis (<1%). All pts should be given written instructions regarding the symptoms of possible agranulocytosis (sore throat, fever, mouth ulcers) and the need to stop treatment pending a complete blood count to confirm that agranulocytosis is not present. Propranolol (20-40 mg every 6 h) or longer-acting beta blockers such as atenolol (50 mg/d) may be useful at the start of treatment to control adrenergic symptoms until euthyroidism is reached. Anticoagulation with warfarin should be considered in pts with atrial fibrillation. Radioiodine can also be used as initial treatment or in pts who do not undergo remission after a 1- to 2-year trial of antithyroid drugs. Antecedent treatment with antithyroid drugs and a beta blocker should be considered in elderly pts and those with cardiac problems, with cessation of antithyroid drugs 3-5 days prior to radioiodine administration. Radioiodine treatment is contraindicated in pregnancy; instead, symptoms and hormone levels should be monitored or controlled with the lowest effective dose of PTU. (Methimazole is not recommended in pregnancy because of reports of fetal agenesis cutis.) Radioactive iodine should generally be avoided in pts with moderate to severe eye disease. Corneal drying may be relieved with artificial tears and taping the eyelids shut during sleep. Progressive exophthalmos with chemosis, ophthalmoplegia, or vision loss is treated with large doses of prednisone (40-80 mg/d) and ophthalmologic referral; orbital decompression may be required. In thyroid storm, large doses of PTU (600-mg loading dose) should be administered orally, per nasogastric tube, or per rectum, followed 1 h later by five drops of saturated solution of KI (SSKI) q6h. PTU (200-300 mg every 6 h) should be continued, along with propranolol (40-60 mg PO q4h or 2 mg IV every 4 h) and dexamethasone (2 mg every 6 h). Any underlying precipitating cause should be identified and treated. Radioiodine is the treatment of choice for toxic nodules. Subacute thyroiditis in its thyrotoxic phase should be treated with NSAIDs and beta blockade to control symptoms, with monitoring of the TSH and free T4 levels every 4 weeks. Antithyroid drugs are not effective in thyroiditis. The clinical course of subacute thyroiditis is summarized in Fig. 173-3. Clinical Course of Subacute Thyroiditis. Transient levothyroxine replacement (50-100 µg/d) may be required if the hypothyroid phase is prolonged. Silent thyroiditis (or postpartum thyroiditis if within 3-6 months of delivery) should be treated with beta blockade during the thyrotoxic phase and levothyroxine in the hypothyroid phase, with withdrawal after 6-9 months to assess recovery. |