Thyroid Federation International - ThyroWorld -1.1 ThyroMobil

An Ounce of Prevention: A Pound of Cure

By Dr. David Cooper, Medical Adviser, Thyroid Federation International

From ThyroWorld, Volume 5, No. 1, Spring 2002

An old adage tells us that "an ounce of prevention is worth a pound of cure." In the following article, Dr. David Cooper puts a new spin on that folk wisdom by describing ways in which prevention might be applied to thyroid disease.

Dr. Cooper is Director, Division of Endocrinology, Sinai Hospital of Baltimore, Maryland as well as TFI's new Medical Adviser. He gave the sum and substance of this article in a special presentation to TFI members in Warsaw, Poland last August. We welcome Dr. Cooper and his insightful remarks on thyroid preventive measures."

Preventive medicine focuses on avoiding or lessening the impact of disease in a susceptible population. There are three distinct types of prevention: primary prevention is preventing new disease from occurring in previously healthy individuals. This typically includes common sense public health measures , such as following a healthy diet, getting vaccinations, and wearing seat belts. In the realm of thyroid disease, ensuring an adequate iodine intake is the major way to prevent thyroid disease in iodine-deficient areas of the world. Secondary prevention is preventing the progress of mild or latent disease to more severe disease. A prime example of secondary prevention would be the use of mammography screening to detect the earliest stages of breast cancer. In the case of thyroid disease, secondary prevention involves screening of individuals for mild or "subclinical" hypothyroidism. If mild hypothyroidism is detected, secondary prevention would also entail treatment with thyroxine to prevent progress to a more advanced degree of thyroid failure. Tertiary prevention is the term used to describe preventing an already present disease from becoming worse. This involves monitoring for disease progression with clinical and laboratory assessment, and, theoretically, avoiding iatrogenic disease (inadvertent illness induced by the doctor), such as prescribing too much thyroid hormone.

Primary Prevention

Although iodine deficiency is not, in all likelihood, a major public health problem in the United States, smoking is a known risk factor for thyroid disease. Goiter, as well as autoimmune thyroid disease (Graves' disease, Graves' eye disease, and Hashimoto's thyroiditis), have all been linked to smoking cigarettes. Therefore, stop smoking programs, if successful, will probably lead to a decrease in the prevalence of thyroid disease. Ironically however, two recent studies suggest that people who smoke tobacco may have a lower risk of thyroid cancer than is observed in nonsmokers. (Similar findings have been reported in people who consume alcohol versus abstainers). So it is difficult to predict if a decrease in smoking in the general population will lead to a decrease in the overall prevalence of thyroid disease.

Secondary Prevention

Secondary prevention of thyroid disease includes screening mildly affected "normal" people who generally have no obvious symptoms. The impact of a thyroid screening program in the United States can be assessed by examining the prevalence of mild hypothyroidism in a representative population sample, and applying the data to the entire U.S. population. One of the largest prevalence surveys for subclinical thyroid disease was the "Colorado Study". In this survey, over 25,000 people participated in a series of health fairs in the state of Colorado. Strictly speaking, this was not a true random population-based study, since the participants voluntarily went to the health fairs, and thus might be considered to have engaged in "health-seeking behaviour." Nevertheless, the prevalence of mild hypothyroidism, defined as having a normal blood level of free T4 and an elevated blood level of TSH, was 8.5%, similar to figures obtained in other smaller population-based studies.

As expected, the prevalence of mild hypothyroidism was approximately 4% in individuals aged 18 to 24, rising respectively to 16% and 22% in elderly men and women. Extending the figures from this study to the entire U.S. population using 1996 US Census data, and adjusting for the number of men and women in each age group, we can calculate that approximately 4.1 million men and 8 million women have subclinical hypothyroidism, or a total of 12 million people.

Whickham Survey

Approximately 30 years ago, Dr. Michael Tunbridge and his colleagues in Great Britain performed a true population-based survey of the frequency of thyroid disease in one community. They measured thyroid function in every adult living in the small town of Whickham England, a monumental study known as the "Whickham Survey." After 20 years of follow-up, these scientists were able to study the rate of progress of subclinical thyroid failure to overt thyroid failure (i.e., low blood T4 levels and high TSH levels) in individuals who had been recognized 20 years earlier as having mild hypothyroidism, but who had remained untreated. Overall, they found that in approximately 30% of the people with mild thyroid failure, the disease progressed over a 20-year time frame. The greatest rate of progression was in people with the highest initial TSH levels. Having positive antithyroid antibodies also increased the level of progression.

Extending the information from the Whickham survey and the U.S. Census to the Colorado prevalence study, we can estimate that approximately 2.6 million women in the United States will progress to overt thyroid failure over the next 20 years. This projection represents approximately 30% of the 8 million women in the United States who currently have mild hypothyroidism. It is reasonable to assume that many of these individuals with minor symptoms would not be detected unless screening was done.

Five Screening Criteria

Despite this, the role of screening for mild thyroid failure remains controversial because of its costs and uncertain benefits. For a screening program for any medical condition to be acceptable, the following criteria generally apply:

- the condition must be prevalent in the general population - the disease must be associated with significant morbidity and/or mortality - the disease cannot be recognized clinically in its earliest states - the disease needs to be recognized early and treatment can prevent progression - a simple, safe, inexpensive, sensitive, and specific test for the disease exists

Subclinical hypothyroidism fits all the criteria except for the second one: many experts do not believe that mild or subclinical hypothyroidism is associated with significant morbidity: that is, there is no solid proof whether mild thyroid failure is associated with significant symptoms or health problems. However, many other experts argue that preventing progression to overt hypothyroidism is the major rationale that justifies screening. A number of professional organizations have published policies regarding screening for thyroid disease. These run the gamut from recommending screening every five years starting at age 35 (the American Thyroid Association) to not recommending screening at all. (the U.S. Preventative Services Task Force).

The test that meets the fifth criterion - "simple, safe, inexpensive, sensitive and specific" - is of course, the Thyroid Stimulating Hormone or TSH test.

Tertiary Prevention

In the realm of tertiary prevention, the Colorado study also has important lessons. It shows that of the approximately 1500 individuals who were taking thyroid hormone when their thyroid function was tested, only 60% actually had normal thyroid function. Approximately 18% were hypothyroid, indicating that they were taking too little thyroxine, either because the dose was too low or they were not taking their medication as directed by their doctor. Approximately 22% had a low or undetectable TSH, indicating they were mildly hyperthyroid, likely because of being on too much thyroxine.

According to the 1996 U.S. Census, approximately 44 million people in the United States are over age 60. If 6% of these people take thyroid hormone, which was the prevalence of thyroid hormone usage in the Colorado study, it can be calculated that approximately 2.6 million people over the age of 60 are taking thyroid medication in the US. We can infer from the Colorado study that approximately 22% of these people (580,000 people) will have subclinical or overt hyperthyroidism caused by excessive thyroid hormone dosage.

We also know from studies in elderly people (the Framingham study ), that individuals with even mild hyperthyroidism caused by too much thyroid hormone are at higher risk for the development of a serious rhythm disturbance of the heart called atrial fibrillation. In one report, the risk of atrial fibrillation in such people was approximately 28% over 10 years, a value that was approximately three times higher than seen in the general population. If we assume that atrial fibrillation will develop over 10 years in 28% of people over the age of 60 who have mild hyperthyroidism due to thyroid medication, as many as 100,000 people (28% of the 580,000 people who are hyperthyroid due to thyroid hormone) could develop atrial fibrillation (Figure 4). Furthermore, a number of studies have shown that excess thyroid hormone can also lead to low bone mineral density, a risk factor for osteoporosis in postmenopausal women, the group most often affected by mild hypothyroidism. Of course, some patients take higher doses of thyroid hormone under their physicians's supervision because of thyroid cancer, thyroid nodules, and goiters. But, it is likely that most people with a suppressed TSH are simply taking too high a dose of thyroid medication.

The potential negative impact of excessive thyroid hormone dosage on the heart and skeleton emphasizes the importance of monitoring thyroid hormone therapy. It also illustrates how treatment of a seemingly simple disease can become more complicated. Clearly, if mild hypothyroidism is going to be screened for and treated, the treatment needs to be monitored vigilantly. Otherwise, the treatment could end up being worse than the disease, which, after all, is mild to begin with.

The Case for Prevention

In summary, prevention of thyroid disease encompasses a wide range of public health and medical considerations. Since iodine deficiency is probably not a major problem in the United States, primary prevention may not be as releant as it may be in many other countries. But, if campaigns against smoking are successful, there could be a decrease in autoimmune thyroid disease, countered, on the other hand, by an increase in cases of thyroid cancer. Secondary prevention involves screening for subclinical disease. I believe that thyroid screening is justified, especially in women after age 35. I also believe that it is reasonable to screen young women with autoimmune disease or who have a postive family history of thyroid disease, as well as women who wish to become pregnant. There are recent studies suggesting the possibility that even mild maternal hypothyroidism can be associated with a decrease in the intellectual potential of the child.

Tertiary prevention involves monitoring already present disease to detect its progress. It also involves monitoring therapy to assess patient compliance and to detect excess medication dosage. Tertiary prevention is under-utilized in the United States, witnessed by the astonishing 40% of individuals taking thyroid hormone who have abnormal thyroid function tests.

It is my hope that "preventive medicine" in the United States will expand its horizons to include thyroid disease. Until now, prevention of thyroid disease has received too little attention from policymakers and physicians alike.

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