Conclusions

There is a key role for both the endocrinologist and endocrine surgeon in the management of hyperthyroidism due to Graves' and Plummer's diseases, and therapy involves a team approach. The three basic treatment modalities—antithyroid therapy, radioactive iodine therapy, and surgery—each have their advantages and disadvantages. Surgery is an excellent therapy for both diseases because there is no mortality, and there are few complications or recurrences. It allows a rapid and consistent method of achieving euthyroidism and avoids the long-term risks of radioactive iodine. However, experience is important. The Hartley-Dunhill procedure is the treatment of choice.

Patients should be rendered euthyroid before operation. It can be technically difficult because of gland vascularity. Radioactive iodine ablation should be considered for disease recurrence after surgery.

Acknowledgmen ts

The authors owe many thanks to the following individuals, without whom preparation of this chapter would not have been possible:

Gloria Graham, MD, Associate Professor, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, for her expert guidance on the dermatologic manifestations of thyroid diseases

Kenneth Greer, MD, Associate Professor, Department of Dermatology, University of Virginia Health Systems, Charlottesville, Virginia, for generously providing prize photographs of the systemic manifestations of Graves' disease

Nat Watson, Jr, MD, Associate Professor, Radiological Sciences— Radiology, Wake Forest University School of Medicine, for his indispensable guidance on nuclear medicine and graciously providing radiologic images

Paige Clark, MD, Associate Professor, Radiological Sciences—Radiology, Wake Forest University School of Medicine, for providing technetium 99m radionuclide scans

Phyllis Easter, Secretarial Assistant, Department of Surgery, Wake Forest University School of Medicine, for her endless devotion in assisting with the preparation of this chapter

Andrea Hassell, Secretarial Assistant, Division of Surgery, Wake Forest University School of Medicine, for her wonderful assistance

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27. Cooper DS. Antithyroid drugs for the treatment of hyperthyroidism caused by Graves' disease. Endocrinol Metab Clin North Am 1998:27:225.

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Use and Abuse of Thyroid-Stimulating Hormone Suppressive Therapy in Patients with Nodular Goiter and Benign or Malignant Thyroid Neoplasms

Niall O'Higgins, MCh ■ Andrew P. Zbar, MB ■ Susannah E. Harte, MD

Nodular disease of the thyroid gland is common. The medical suppressive treatment of goiter relies heavily on the ability to distinguish benign from malignant disease, largely through the use of high-resolution thyroid ultrasonography and fine-needle aspiration cytology of solitary and dominant thyroid masses.

Thyroid nodules occur in approximately 0.8% of adult men and in as many as 5% of adult women in iodine-replete areas; there is a steady increase in detectable incidence after 45 years of age.1 The prevalence of thyroid nodules is population dependent and is markedly higher in areas of endemic iodine deficiency.2 Exposure to low-dose ionizing radiation early in life increases the incidence of both benign and malignant nodules.34 Thyroid cancer is the most common endocrine malignancy, with an annual incidence of 10,000 new cases in the United States.5 Thyroid glands that are normal by palpation frequently have one or more nodules demonstrable at autopsy, and as many as 4% of patients at autopsy harbor microscopic, so-called occult, carcinomas of the thyroid.6-7

Ultrasonography in high-risk cases has produced a further dilemma in management with the discovery of impalpable nodules as small as 1 mm. The natural history and significance of these subclinical masses are unknown.8

Nodular goiter, on the other hand, is probably the most common endocrine "problem" in the world, and delineation of the value of thyroid suppression therapy in patients at low risk for carcinoma has significant implications for global health care costs.9-10 The use of thyroid-stimulating hormone (TSH; thyrotropin) suppressive therapy after thyroidectomy for benign and malignant disease remains controversial largely because of the heterogeneity of disorders for which it has been advocated and because the natural history of malignant disease is long.

Unfortunately, few randomized, controlled clinical trials exist for specific disorders such as solitary nodular disease, multinodular goiter, and differentiated carcinoma to support unequivocally the value of long-term suppressive therapy. The failure to monitor adequately the suppression of TSH in patients, to establish the compliance with suppression medication, and to evaluate nodular size objectively have also contributed to difficulties in interpreting the results in patients receiving suppressive therapy. It is clear, however, that despite an overall increase in the detectable incidence of differentiated thyroid cancer over the last 30 years, there has been a steady decrease in mortality, and this may be explained by both earlier diagnosis and more widespread use of TSH suppressive treatment.11-12

The introduction of highly sensitive thyrotropin immu-noenzymometric assays has led to a standardization of TSH suppression and permitted closer monitoring of both the efficacy of and problems with thyroxine (T4) treatment. However, these assays, although sufficiently sensitive to allow more accurate quantification of subnormal values, are still not routinely used in certain parts of the United States.13 Measurement of serum TSH permits precise levothyroxine dosage in both replacement therapy and TSH suppressive therapy when supraphysiologic doses of levothyroxine are given to maintain TSH levels below normal. Evidence of the delayed complications of overzealous and minimally monitored T4 replacement in both overt and subclinical hypothyroidism, most notably in inducing bone demineraliza-tion, altering serum lipid profiles, and contributing to cardiac morbidity, particularly in elderly patients, has raised concerns about the dangers of T4 therapy when used in the long term in supraphysiologic doses to suppress TSH in both benign and malignant disease.14 Decreased bone mineral density and an accelerated rate of bone loss have been reported in the literature in both pre- and postmenopausal women who are receiving doses of levothyroxine sufficient to produce subnormal serum TSH levels.15'18 A better understanding of growth factors that affect normal thyrocyte function and that may explain TSH independence of autonomous nodules, as well as a more selective individual approach to suppressive therapy of tumors in patients deemed to have a poor prognosis, will be of value in limiting the number of patients receiving long-term suppression. Excessive levothyroxine therapy, either intentional or inadvertent, is not as innocuous as once was supposed, and studies have shown that as many as 50% of patients treated with levothyroxine therapy, who were clinically euthyroid, were overtreated based on their serum TSH concentration.19'20

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