David S. Cooper

It may be the experience of many clinicians, as it has been ours, that a very small group of patients with hypothyroidism are not entirely well on thyroxine replacement alone.¹ The concept of hormone replacement therapy is commonly credited to Brown-Sequard, who in 1889 at age 72 years injected himself with an extract of dog testicles and noted enhanced vitality and mental acuity.² The concept of “internal secretion” arose from these experiments, and soon thereafter Murray successfully treated myxedema with “juice” extracted from sheep thyroid glands.³ Replacement therapy with virtually all clinically relevant hormones has been possible since the middle of the 20th century. The challenge, however, is to administer these hormones in deficiency states in a way that precisely replicates the complex manner in which they are endogenously secreted. Insulin replacement in patients with type 1 diabetes is an obvious example of this difficulty. Even the most sophisticated patient using an external insulin pump and continuous glucose monitoring has difficulty mimicking normal insulin secretion without being subjected to potentially dangerous hypoglycemia.

Endogenous subclinical hyperthyroidism, defined by normal circulating levels of free T₄ and T₃ and low levels of TSH, is a common clinical entity and is typically caused by the same conditions that account for the majority of cases of overt hyperthyroidism: Graves’ disease, toxic multinodular goiter, and solitary autonomously functioning thyroid nodules. Subclinical hyperthyroidism has been associated with an increased risk of atrial fibrillation and mortality, decreased bone mineral density in postmenopausal women, and mild hyperthyroid symptoms. Treatment of subclinical hyperthyroidism remains controversial, given the lack of prospective randomized controlled trials showing clinical benefit with restoration of the euthyroid state. Nevertheless, it seems reasonable to treat older individuals whose serum TSH levels are less than 0.1 mU/liter and certain high-risk patients, even when the serum TSH is between 0.1 and the lower limit of the normal range.

Background.: Mucosa‐associated lymphoid tissue (MALT) lymphomas account for less than 1% of all primary thyroid malignancies. They typically arise as neoplastic transformations within areas of autoimmune thyroiditis. Although they tend to have an indolent course, these lymphomas present a diagnostic challenge requiring a high level of suspicion in patients at increased risk of development.Methods.: We retrospectively reviewed 3 cases of primary MALT thyroid lymphoma discovered in patients with a compressive goiter. This represents the experience at a single institution from 1996 to 2005. Hospital and clinic records were reviewed to identify the workup, treatment, and outcome.Results.: One of 3 patients underwent preoperative fine‐needle aspiration (FNA). All patients underwent total thyroidectomy to relieve compressive symptoms, and the final pathology revealed MALT lymphoma. Two patients subsequently underwent radiation therapy. All patients are alive without evidence of disease recurrence.Conclusions.: These cases are notable for the unexpected presentation of MALT lymphoma within a compressive goiter. © 2006 Wiley Periodicals, Inc. Head Neck, 2006

Antithyroid drugs, which have been available for more than half a century, are important in the management of hyperthyroidism, particularly in patients with Graves' disease, who have a high response rate. Since the responses of patients vary and these agents have potentially serious side effects, a working knowledge of their complex pharmacology is required. This review article considers recent pharmacologic and clinical data related to the use of these compounds.

In the realm of preventive medicine, there are three distinct types of prevention that can be defined. Primary prevention is the prevention of new disease in previously healthy individuals, usually achieved by decreasing risk factors for disease. Secondary prevention is the prevention of progression of mild or latent disease to more severe disease, and typically involves screening for occult disease. Tertiary prevention is the term used by some to describe medical care intended to improve already established disease. The role of primary prevention of thyroid disease in the United States is uncertain, because iodine deficiency is not clearly known to be a problem. In the case of secondary prevention of thyroid disease, this would necessarily involve screening of individuals for subclinical hyperthyroidism or hypothyroidism with thyrotropin (TSH) testing. Using data from a large prevalence study and from the 2000 U.S. Census, it can be calculated that approximately 15 million adults have unrecognized thyroid disease, mostly subclinical hypothyroidism. If detected, secondary prevention might also entail treatment with antithyroid drugs/radioiodine or thyroxine to prevent sequelae or progression to a more advanced degree of thyrotoxicosis or thyroid failure, respectively. Over the next 20 years, it can be calculated that approximately 5 million people, mostly with subclinical hypothyroidism, will progress to overt disease. Tertiary prevention of thyroid disease would involve avoiding iatrogenic disease, such as thyroid hormone overdose. From epidemiologic data it can be calculated that approximately 600,00 elderly individuals have iatrogenic hyperthyroidism from thyroid hormone overdose, putting them at risk for atrial fibrillation and osteoporosis. Together, these data suggest that the notion of preventive medicine in the United States should be expanded to include thyroid disease as a target for secondary and tertiary intervention.

This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author's clinical recommendations.A 59-year-old woman is found to have a serum thyrotropin level of 7 mU per liter on routine screening. Her only symptoms are mild fatigue, which has been present for more than 10 years, and difficulty losing weight. The results of the physical examination are normal, except for the finding of a small, firm thyroid with a slightly irregular surface. The serum cholesterol level is 220 mg per deciliter (5.69 mmol per liter), the low-density lipoprotein (LDL) cholesterol level is 140 mg per deciliter (3.62 mmol per liter), and a test for antibodies against thyroperoxidase is positive. Should treatment . . .