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Hypothyroid treatments may help, but without resolving symptoms

From the September ACP Observer, copyright © 2007 by the American College of Physicians.

By Deborah Gesensway

TORONTO—It's a common clinical scenario: a depressed, obese woman has come to the doctor complaining of fatigue and mental fogginess. She has mild hypothyroidism with a thyroid stimulating hormone (TSH) level of 5.6 mU/l. The doctor starts her on thyroid hormone therapy.

Nothing improves, however, and the patient gets more and more unhappy.

This patient probably won't be helped by thyroxine therapy but, unfortunately, medicine doesn't have a better alternative to offer her right now, said David S. Cooper, MD, professor of medicine and endocrinology at Johns Hopkins University School of Medicine and head of endocrinology at Sinai Hospital of Baltimore.

"Why do these people continue to feel badly when we have given them the treatment we think is the best and their tests are normal?" he asked a group of attendees at a session during the Endocrine Society's recent annual meeting. In the case of the woman above, it may be that the elevated serum TSH was detected as part of her evaluation but her symptoms had nothing to do with mild hypothyroidism, or, her symptoms are caused by another condition such as Addison's disease, depression, chronic fatigue or pernicious anemia.

Or, perhaps the person's unhappiness stems from the fact that "Now they are labeled with having a disease [mild hypothyroidism] that they never had before," said Dr. Cooper. "There is medicine to take and buy. There are doctors they have to see. There are tests they have to take. They have an altered quality of life."

Thus, there is the conundrum that having a diagnosis potentially makes a person feel sick. Patients may not want to hear it, but study after study has found that thyroid hormone therapy does not improve nonspecific symptoms in people with mild TSH elevations. In addition, he said, there is no evidence that adjusting the thyroxine dose to manipulate serum TSH levels within the range of normal—or substituting T4/T3 combination therapy—helps with symptoms.

At the same time, he said, studies confirm that "hypothyroid individuals have lower quality-of-life than other people despite the fact that they have normal thyroid function tests."

Subclinical hypothyroidism is defined as a condition where serum Free T4 levels are normal while serum TSH levels are mildly elevated, usually between 5 and 10 mU/l. Some experts say the upper limit of normal should be lowered to 3 or even 2.5 mU/l, but this concept has not been accepted by most endocrinologists. Although generally thought to be asymptomatic, some hypothyroid patients complain of multiple symptoms such as mental fogginess and fatigue, but these symptoms are also common in people without thyroid disease.

Dr. Cooper cited a number of studies indicating that although some thyroid diseases clearly affect a person's perception of their own health, the symptoms that people with subclnical hypothyroidism manifest are actually no more prevalent than in the general population. For example, a study published in the Oct. 17, 2006 Annals of Internal Medicine concluded that after controlling for comorbidities and medications, subclinical hypothyroidism was not associated with depression, anxiety or cognitive function in a large population of older individuals. This contrasts with overtly hypothyroid patients, who do have an altered quality of life in most domains, such as function and pain.

Usually, people are identified as having subclinical hypothyroidism through routine screening of thyroid function or in the course of being evaluated for common nonspecific symptoms, or hypercholesterolemia. The worldwide prevalence of subclinical hypothyroidism ranges from 1% to 10% and is most common in women older than age 60, where the frequency may reach 15-20%.

Remaining controversial, however, is whether thyroxine treatment may be useful despite what appears to be its limited value in reversing symptoms of low mood, increased body weight, or cognitive and memory deficits. Regardless of symptoms, thyroxine treatment is advised by many experts if anti-TPO antibodies are positive, since such patients have a high rate of progression to overt hypothyroidism. In addition, thyroxine therapy may improve a patient's lipid profile as well as other nontraditional coronary heart disease risk factors, especially if the serum TSH is above 10 mU/l.

"Some people feel bad," said Dr. Cooper, "but once their serum TSH levels are normal and their symptoms persist, it's our job to say 'It's not your thyroid,' and to refer the patient back to their primary care provider for further evaluation."

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