High-dose external irradiation therapy, that is, more than 2000 rad, does not confer safety from thyroid carcinoma, as was previously thought (16). Rather, an increased prevalence of thyroid carcinoma, usually papillary cancer, has been found, particularly in patients with Hodgkin’s disease and other lymphomas who received upper mantle irradiation that included the thyroid gland. Usually a dose of about 4000 to 5000 rad was given. Both benign and malignant thyroid nodules are being recognized now that these persons survive for longer periods (17). If a thyroid mass appears, it should be treated aggressively. These patients should also be observed carefully for the development of hypothyroidism.

RISK OF IONIZING RADIATION

Sixty years after Hiroshima and 20 years after Chernobyl, there continues to be an increase in both benign and malignant nodules (18a, 18b). Children in the area of the Chernobyl nuclear accident have been shown to have at least a 30-fold increase in papillary thyroid cancer (18c). This cancer may also be more aggressive than the usual papillary carcinoma. It is thought to be the result of exposure to iodine isotopes that were inhaled or that entered the food chain. The mechanism of radiation-induced thyroid cancer is thought to be caused by rearrangements in tyrosine kinase domains of the RET and TRK genes (19). DIAGNOSIS OF THYROID NODULES Excellent review articles concerning the diagnosis of thyroid nodules have recently been published (20a, 20b). A number of diagnostic modalities have been used in the past, but currently most have been superseded by FNA of the mass with cytologic analysis (20c). In the hands of a good thyroid cytologist, more than 90% of nodules can be categorized histologically. Approximately 65% to 70% are found to be compatible with a colloid nodule. Twenty percent demonstrate sheets of follicular cells with little or no colloid. These are called a possible follicular neoplasm or an indeterminate nodule. Five percent to 10% are malignant, and less than 10% are non-diagnostic.

All patients who have malignant cytologic results should be operated on. False-positive diagnoses are rare.

All patients with sheets of follicular cells with little or no colloid should also undergo surgery, because their findings are compatible with a follicular neoplasm. Most, up to 90%, prove to be benign; however, a follicular carcinoma exhibits the same cytologic characteristics and cannot be differentiated by this technique. Only by careful histologic examination, after operative removal of the nodule, can follicular carcinoma and adenoma be differentiated, because follicular cancers exhibit capsular and/or vascular invasion (20d).

When the diagnosis of colloid nodule is made cytologically, the patient should be observed and not operated on unless tracheal compression or a substernal goiter is present, or unless the patient desires the benign mass to be removed. Finally, if an inadequate specimen is obtained, FNA with cytologic examination should be repeated. With small, non-palpable masses, FNA should be performed under ultrasound guidance. Thus, FNA with cytologic assessment is the most powerful tool in our armamentarium for the diagnosis of a thyroid nodule (21).

In summary, the algorithm for the diagnosis of a thyroid nodule with isotope scintigraphy and ultrasonography as initial steps (Fig. 10) has been replaced in most hospitals, including our own, by emphasizing the importance of early cytologic examination of the needle aspirate (Fig. 11). Far fewer isotope scans are currently being done because carcinomas represent only 5% to 10% of all cold nodules. This test is usually reserved for diagnosis of a “hot” nodule.

Most patients undergoing a thyroid operation are euthyroid and require no specific preoperative preparation related to their thyroid gland. Determination of the serum calcium level may be helpful, and endoscopic laryngoscopy should definitely be performed in those who are hoarse and in others who have had a prior thyroid or parathyroid operation in order to detect the possibility of a recurrent laryngeal nerve injury.

Modest hypothyroidism is of little concern when treating a surgical patient; however, severe hypothyroidism can be a significant risk factor. Severe hypothyroidism can be diagnosed clinically by myxedema, as well as by slowness of affect, speech, and reflexes (22). Circulating thyroxine and triiodothyronine values are low. The serum thyroid-stimulating hormone (TSH) level is high in all cases of hypothyroidism that are not caused by pituitary insufficiency, and it is the best test of thyroid function. In the presence of severe hypothyroidism, both the morbidity and the mortality of surgery are increased as a result of the effects of both the anesthesia and the operation. Such patients have a higher incidence of perioperative hypotension, cardiovascular problems, gastrointestinal hypomotility, prolonged anesthetic recovery, and neuropsychiatric disturbances. They metabolize drugs slowly and are very sensitive to all medications. Therefore, when severe myxedema is present, it is preferable to defer elective surgery until a euthyroid state is achieved.

If urgent surgery is necessary, it should not be postponed simply for repletion of thyroid hormone. Endocrine consultation is imperative, and an excellent anesthesiologist is mandatory for success. In most cases, intravenous thyroxine can be started preoperatively and continued thereafter. In general, small doses of thyroxine are initially given to patients who are severely hypothyroid, and then the dose is gradually increased.

In the United States, most patients with thyrotoxicosis have Graves’ disease. In the United States, over 90% of all patients with Graves’ disease are treated with radioiodine therapy. Young patients, those with very large goiters, pregnant women, and those with thyroid nodules or severe ophthalmopathy are commonly operated upon. Radioiodine therapy may lead to worsening ophthalmopathy.

Persons with Graves’ disease or other thyrotoxic states should be treated preoperatively to restore a euthyroid state and to prevent thyroid storm, a severe accentuation of the symptoms and signs of hyperthyroidism that can occur during or after surgery. Thyroid storm results in tachycardia or cardiac arrhythmias, fever, disorientation, coma, and even death. In the early days of thyroid surgery, operations on the toxic gland were among the most dangerous surgical procedures because of the common occurrence of severe bleeding, as well as all the symptoms and signs of thyroid storm. Now, with proper preoperative preparation (23), operations on the thyroid gland in Graves’ disease can be performed with about the same degree of safety as operations for other thyroid conditions.

In mild cases of Graves’ disease with thyrotoxicosis, iodine therapy alone has been used for preoperative preparation, although we do not recommend this approach routinely (22). Lugol’s solution or a saturated solution of potassium iodide is given up to 8 to 10 days. Although only several drops per day are needed to block the release of thyroxine from the toxic thyroid gland, it is our practice to administer three drops two or three times daily. This medication is taken in milk or orange juice to make it more palatable.

Most of our patients with Graves’ disease are treated initially with the antithyroid drugs propylthiouracil or methimazole (Tapazole) until they approach a euthyroid state. Then, iodine is added to the regimen for 8 to 10 days before surgery. The iodine decreases the vascularity and increases the firmness of the gland. Sometimes thyroxine is added to this regimen to prevent hypothyroidism and to decrease the size of the gland. Beta-adrenergic blockers such as propranolol (Inderal) have increased the safety of thyroidectomy for patients with Graves’ disease (23). We use them commonly with antithyroid drugs to block beta-adrenergic receptors, and ameliorate the major signs of Graves’ disease by decreasing the patient’s pulse rate and eliminating the tremor. Some surgeons recommend preoperative use of propranolol alone or with iodine (24). These regimens, they believe, shorten the preparation time of patients with Graves’ disease for surgery and make the operation easier because the thyroid gland is smaller and less friable than it would otherwise be (24). We do not favor these regimens for routine preparation because they do not appear to offer the same degree of safety as do preoperative programs that restore a euthyroid state before surgery. Instances of fever and tachycardia have been reported in persons with Graves’ disease who were taking only propranolol. We have used propranolol therapy alone or with iodine without difficulty in some patients who are allergic to antithyroid medications. In such patients it is essential to continue the propranolol for 1 to 2 weeks postoperatively. Remember that they are still in a thyrotoxic state immediately after surgery, although the peripheral manifestations of their disease have been blocked.

The advantages and disadvantages of radioiodine vs. thyroidectomy as definitive treatment of Graves’ disease are listed in Table 1. In our patients we have never had a death from thyroidectomy in over 30 years. Surgical resection involves either subtotal thyroidectomy (Fig. 12) or lobectomy with contralateral subtotal lobectomy. Currently we leave about 2 g or less of thyroid tissue in the neck at the end of the operative procedure. Leaving more leads to a higher rate of recurrence (25). In children and adolescents, one should leave smaller remnants because the incidence of recurrence of thyrotoxicosis appears to be greater in this group. Finally, when operating for severe ophthalmopathy, we try to perform near-total or total thyroidectomy. The major benefits of thyroidectomy appear to be the speed with which normalization is achieved and possibly a lower rate of hypothyroidism than is seen after radioiodine therapy.