Playing With Fire

Doctors often prescribe hormone therapy for elderly patients with listless thyroid glands. However, such treatments could shorten the lives of those with mild thyroid deficiencies, new results suggest.

When the thyroid gland falters, metabolism slows, chilling the body and possibly spurring cardiovascular disease and dementia. To stave off these problems, doctors commonly prescribe thyroid hormone therapy to patients--even those with thyroid activity on the low end of the normal range. Yet two new studies suggest that restoring hormone quantities could bring an unwelcome consequence: shortened life.

Thyroid hormone helps pace metabolism throughout the body. But in many older people--including 20% of women over 60--thyroid activity flags. In some cases, thyroid hormone quantities plummet, a condition known as clinical hypothyroidism; individuals with this affliction suffer from low energy, heart problems, and fading memory.

In other people, thyroid hormone concentrations dip less dramatically, remaining within the normal range. The change is so subtle that doctors can diagnose the problem only by looking for high concentrations of thyroid stimulating hormone (TSH), which the pituitary produces when it senses that thyroid hormone quantities have waned. Such people don't typically develop pronounced symptoms of clinical hypothyroidism.

But if patients complaining of fatigue have a sluggish thyroid, physicians often prescribe thyroid hormone therapy. "Doctors say, 'It's perfectly harmless, let's go ahead and treat,' " says endocrinologist David Cooper of Johns Hopkins University School of Medicine in Baltimore, Maryland. The treatment is so common that two years ago, the Institute of Medicine (IOM) debated whether Medicare should pony up for routine TSH screening in the elderly.

But the lack of conclusive and complete data prompted the IOM panel to declare that Medicare shouldn't do so. Researchers have never conducted a controlled clinical trial of thyroid hormone for the treatment of mild hypothyroidism. So, no solid data exist on whether thyroid hormone therapy is beneficial. And studies probing whether a slight decline in thyroid activity hampers health have generated ambiguous results. The wisdom of dosing patients with mild hypothyroidism "is a major controversy in thyroidology," says Cooper.

To understand how thyroid activity influences health in the elderly, epidemiologist Rudi Westendorp of Leiden University in the Netherlands and colleagues quantified thyroid hormone and TSH in nearly 600 85-year-olds and assessed their mental status. Signs of depression and memory problems were as rare in individuals with low but normal thyroid activity as they were in those with higher thyroid output, the researchers reported in the Journal of the American Medical Association last month. That finding suggests, contrary to common belief, that dampened thyroid output might not be detrimental to brain function in the elderly.

What's more, participants with low thyroid activity were the least likely to die within 4 years of the initial exam, the researchers found. And those with high thyroid function had the highest mortality rate. Together, the findings indicate that declining thyroid function doesn't impair thinking and might bolster longevity--which suggests that giving thyroid hormone to elderly patients with mild hypothyroidism could shorten their lives without providing substantial benefits. The study "calls into question the wisdom of treating these patients," says Cooper.

"There's no doubt that at a young age, patients with hypothyroidism feel better [with thyroid hormone treatment]," says Westendorp. "Now, if you transpose this knowledge to old age, you expect to see the same benefit. But these data suggest otherwise." The healthiest degree of thyroid activity for an older person might not be the same as that for a younger person, he says, "and we need to figure out what the optimal set point is."

However, endocrinologist Anthony Toft of the Royal Infirmary of Edinburgh in Scotland cautions against overinterpreting these results. Toft notes that too much thyroid hormone can spur cancer or irregular heartbeat. Thus the patients with overactive thyroids might have died prematurely because of illness--making it seem as though those with lazy thyroids were living longer.

At the same time, a second study in mice supports the idea that thyroid hormone can shorten life. Certain lines of dwarf mice have defective pituitaries and live longer than their standard-sized peers. Some work has suggested that a dearth of growth hormone and insulin-like growth factor 1 might be the cause (see "Growing Pains"). But the animals also produce little thyroid hormone.

To investigate whether a lack of thyroid hormone might help enhance life span, pathologist Richard Miller of the University of Michigan, Ann Arbor, and colleagues injected dwarf mice with thyroid hormone and growth hormone for 11 weeks during puberty and adolescence--from 4 to 15 weeks of age. After this period, some of the animals also received thyroid hormone in their food until they died.

The researchers found that animals that received only the 11-week treatment lived as long as untreated dwarfs. But the rodents that received thyroid hormone throughout their lives died earlier. It's uncertain whether the thyroid treatment accelerated aging or was simply toxic, says Miller, but the finding supports the idea that a shortage of thyroid hormone contributes to the exceptional longevity of these diminutive rodents. Moreover, because animals that received thyroid hormone only until 15 weeks of age lived as long as untreated dwarfs, the results suggest that ditching thyroid hormone in adulthood is the key to long life. Additional experiments revealed that untreated long-lived dwarfs are protected from certain kinds of age-related tissue damage: They suffer fewer cataracts and less kidney damage than normal.

"It's a rich data set," says Westendorp of Miller's study. Physiologist Andrzej Bartke of Southern Illinois University in Springfield adds, "These papers really bring up the importance of the thyroid in longevity."

However, Cooper says that flagging thyroid function is unlikely to have been an adaptive mechanism that humans fostered to live longer. The most common cause of thyroid snafus is an autoimmune syndrome in which the body's own antibodies attack the gland. "This isn't the natural aging process. It's truly a disease," Cooper says. But researchers hope further studies will clarify whether older people and their doctors should warm up to vanishing thyroid hormone.

R. John Davenport is associate editor of SAGE Crossroads' sister site, SAGE KE. He'd like to know which hormone to jettison to get more hours in the day.