THYROID DISEASE:OVERACTIVE MEDICINE

The thyroid, that bowtie shaped gland at the front of the throat, is your body’s metabolic thermostat, regulating your temperature, energy consumption and, in the case of children, growth rate. It accomplishes this with its two hormones, thyroxine, o

Problems with your body metabolism occur anytime these hormone levels or the thermostat itself aren’t on a proper setting. An overactive thyroid usually referred to in medicalese as thyrotoxicosis, or hyperthyroidism means the body is overproducing one or both of the thyroid hormones. This causes you to metabolize too quickly, and results in the racing of many bodily functions. In cases of hypothyroid, when hormones are underproduced, the setting is too slow, and so is mental and physical function. Even the pulse rate slows down.

Although medicine doesn’t know much about why a thyroid goes out of kilter, it is known that most thyroid disease is caused by an autoimmune condition, where the body begins to react to its own tissue. This is true with most causes of hyperthyroid, such as Graves’ disease, where the thyroid glands are infiltrated by white (infection fighting) blood cells, which mystifyingly form antibodies to thyroid cells, eventually causing excessive amounts of thyroxine to be produced. Hashimoto’s disease starts out like Graves’ disease, but then the antibodies begin to inactivate parts of the thyroid, bit by bit, eventually causing an underactive thyroid.

Although medicine regards most thyroid diseases as genetic, a great number of environmental substances appear to be at the heart of thyroid malfunction.

One of the greatest culprits of all is iodized salt, which is promoted as health giving all over the West (see p 1). Iodine, which is present in fish, vegetables, milk and meat, is an essential ingredient of T3 and T4, and adequate amounts of the mineral are necessary for the smooth functioning of both the thyroid and the pituitary. However, in most countries salt is iodized and routinely recommended for use, regardless of whether an area is deficient in the mineral, so that some populations can be exposed to too much iodine over many years. In areas with ample indigenous iodine taking too much extra iodine only a few milligrams per day can cause your thyroid to either over or underproduce (Lancet, 1996; 335: 99-107).

Drugs taken for other conditions can also cause thyroid problems. Lithium, used for manic depressive illness, brings on hypothyroidism in up to a third of long term users (N Eng J Med, 1995; 333: 1688-94), and the heart drug amiodarone (Cordarone in the US) can cause a type of over or underactive thyroid which is difficult to detect clinically after only 18 months (BMJ, 1996; 313: 539-44; Clin Pharm, 1993; 12: 774-9). Long term treatment for hepatitis with interferon alfa can cause either syndrome (South Med J, 1996; 89: 81-3). Even cholesterol lowering drugs have been known to cause hypothyroidism (Arch Mal Coeur Vaiss, 1993; 86: 1761-4).

The thyroid appears especially susceptible to emotional blows, such as bereavement or divorce (Acta Endocronologica, 1993; 128: 293-6). It’s also susceptible to low dose, chronic exposure to radiation or nuclear fall out. Some have made a connection between an increase in hypothyroidism among newborns born as far away as the US and the fallout from the 1986 Chernobyl nuclear accident (Lancet, 1996; 348:476).

There’s some striking evidence that smoking can cause Graves’ disease (Acta Endocrinologica, 1993, 128:156-160) or lowered thyroid function (N Eng J Med, 1995; 33: 964-9).

Virtually all illnesses and surgical procedures will alter the function of the thyroid and pituitary. After surgery of any variety, some doctors often rush in too quickly with thyroid replacement drugs, which can cause a lifetime of dependency. However, new evidence demonstrates that the rapid increase in the T3 thyroid hormone which occurs might have beneficial effects in an emergency, and so it may be better to leave well alone (New Eng J Med, 1995; 333: 1562-3).

It is a tenet of modern medicine that doctors should blast out an overactive thyroid and quickly stabilize hormone levels. There is some value in this, since you run the admittedly small risk of developing a thyroid “storm”, or thyrotoxic crisis, with extremely rapid heart rate, high fever, delirium, marked agitation and dehydration, which can occasionally develop into a life threatening situation.

However, doctors are too quick to get in there early with inexact and extreme solutions that go too far the other way, causing irreversible damage and leaving the thyroid unable to fully function. This is particularly worrisome when you consider that nearly a third of all cases of overactive thyroid will resolve themselves (Clin Endocrinol (Oxford), 1984; 21:163-72).Pregnant women in particular are sometimes given treatments that could damage the fetus, even though thyroid dysfunction tends to disappear as a pregnancy proceeds (Physician’s Desk Reference, 1995).

The first method, and one which is gaining in popularity, entails swallowing a capsule of radioactive iodine (usually 131-I), which will accumulate in your thyroid and destroy a proportion of the gland. In two to five months the correct level is assumed to have been reached. In reality, this search and destroy missile isn’t terribly accurate; the actual dose is difficult to calculate for various technical reasons, and ends up destroying too much of the thyroid. After a few years, about half of patients given 131-I turn out to have life long underactive thyroid. If you’re a woman of child bearing age, you also run a special risk if you are unwittingly pregnant. The radioactive iodine can accumulate in the thyroid of the fetus, causing hypothyroidism and cretinism (mental retardation). The use of 131-I also tends to bring on or worsen the bulging eyes often seen in Graves’ disease (N Eng J Med, 1992; 326; 1733-8).

A subtotal thyroidectomy (where part of the thyroid is surgically removed) has better results after the first year than does the radioactive method. But, again, the effects are irreversible, so that any natural trend of the body to normalize its hormone levels ends up leading to an underactive thyroid. The thyroids of at least a fifth of all patients become underactive after surgery (Clin Endocrinol (Oxford), 1984; 21:163-72). In all regards, surgery doesn’t have a terrific success rate; in one eight year follow up study, only 30 per cent had normal thyroid levels. Nineteen per cent were still hyperthyroid and a whopping 41 per cent ended up with underactive thyroid (J Endo-crinol Invest, 1993; 16: 195-9).

The third possibility and the therapy of choice in Europe and Japan is anti thyroid drug treatment. Although more complicated and slower than the other two methods, it offers patients the opportunity of recovering normal thyroid function, being able to stop drug treatment and avoiding the prospect of life long thyroxine replacement therapy.

Many doctors simply use the drugs as an interim measure, managing the patient’s symptoms while waiting for radioactive iodine therapy or surgery. Lowering thyroid levels first through drugs doesn’t seem to do any good in preventing radioiodine caused hypothyroidism (J Assoc Phys India, 1994; 42: 36-8).

The usual anti thyroid drugs of choice are propylthiouracil, methimazole or carbimazole. All three drugs inhibit the synthesis of thyroid hormones, but methimazole is the most potent at least 10 times as strong as propylthiouracil.

However, even this “safer” option comes at terrible cost. The most worrisome side effect is agranulocytosis (sudden decrease in the number of white blood cells), which can result in fever, extreme fatigue and bleeding sores of the rectum, mouth and vagina. It can also cause leukopenia (another type of decrease in white blood cells), thrombocytopenia (reduction of blood platelets) and aplastic anemia (where the bone marrow can no longer make red blood cells). Anyone using this drug must have his bone marrow monitored.

Besides bone marrow problems, this drug can be highly toxic to the liver. Eli Lilly, manufacturer of Tapazole, one version of methimazole, has had reports of fulminant hepatitis and fatal liver disease.

In some instances, doctors end up taking over a patient’s thyroid function with so called “block and replace” therapy, which “turns off” the patient’s thyroid function with high doses of anti thyroid drugs and replaces the missing thyroxine with a synthetic hormonal replacement. The rather dodgy thinking behind block and replace is that by giving the patient’s autoimmune thyroid destroying response a “rest”, it may not start up again.

At one point it seemed as though the combination of drugs might work, but in follow up studies, it didn’t prevent the recurrence of hyperthyroidism (N Eng J Med, 1996; 334: 220-4).

For mild cases of underactive thyroid, doctors again are too quick to prescribe thyroxine replacement hormone, when simple dietary measures would raise thyroid hormone levels adequately (see box p 5). However, if the gland has sustained extensive damage, replacement thyroxine therapy may be the only answer.

Drugs like levothyroxine are synthetic forms of thyroxine. The biggest worry about this drug concerns dosage, since it produces symptoms of hyperthyroidism if too high. There is evidence that patients don’t always get the appropriate dose; one study showed that nearly half of patients receiving thyroxine therapy had TSH values outside the reference ranges of normal (The Lancet, 1991; 337: 171).

The other question concerns the length of therapy. Manufacturers of the drugs advise that replacement therapy is to be taken for life. However, in a variety of studies, up to a quarter of all patients with hypothryoidism treated with thyroxine for more than a year revert to normal thyroid levels once the drug is withdrawn (Lancet, 1996; 335: 99-107). Establishing whether you’re a candidate for remission requires that your doctor reduce your dosage or withdraw the drug, which many doctors are loathe to do unless you specifically request a trial of drug withdrawal yourself.

!ALynne McTaggart and Harald Gaier