Comedy of errors, Broda O Barnes

In 1954, a group of investigators at the University of California, having become convinced that elevated levels of cholesterol and fats in the blood were a major factor in coronary disease, decided to test the ability of thyroid to reduce these levels below normal. They began with patients in a mental institution who did not have thyroid deficiency. it appeared that about five grains of thyroid were needed.

The error came when the investigators went on to use five grains of thyroid in patients who were nor normal, who had nor only elevated cholesterol and fats bur in many cases coronary heart disease as well. The lesson of thirty years before - that such patients cannot tolerate starting doses of four grains, let alone five -evidently had been overlooked. Angina and heart attacks followed. Once again, thyroid therapy had a black eye because of physician error.

There was too much evidence in the literature implicating thyroid function in atherosclerosis to abandon efforts to try to control the artery disease with thyroid therapy. But instead og using the smaller doses of thyroid that had been found effective in hundres of cases, there was a hunt to find a syntetic derivative of thyroid hormone which might lowerblood cholesterol levels without raising metabolism and causing angina.

When nature produces a compound for use in living organisms, the compound always has the caracteristic of rotating polarized light to the left. When the cemist synthezises a compound in the laboratory, he may obtain equal amounts of two forms of the compound, one rotating polarized light to the left and tha other rotating it to the right - and known as the dextro form - has less physiological activity than the natural or levo form.

Sure enough, when the dextro form of thyroxine, a thyroid hormone, was synthesized, it proved to have only one-tenth to one-twentienth of the metabolic activity of the natural Levo-thyroxine.

Next, attempts to lower blood cholesterol levels with Dextro-thyroxine, or as it is more familiarly known, D-thyroxine, were undertaken. large doses of the compound were neccessary bur the cholesterol did fall some.

And now came another error. The dosage of D-thyroxine recommended by the manufacturer for lowering serum cholesterol was four to eight milligrams a day. But while D-thyroxine had less metabolic activity than L-thyroxine and thyroid extract, four to eight milligrams of it a day would have as much metabolic activity as four to eight grains of thyroid extract a day.

The medical profession was assured by salesmen, by brochures, and by advertising in medical journals, that with such dosage cholesterol could be lowered effectively and safely.

Some of our leading scientists were misled to the point that D-thyroxine was included with other compounds in a national study carried out at a number of medical centers and aimed at lowering cholesterol levels. The study was double-blind, meaning that neither the patients participating nor the physicians would know who was reciving witch compound until the study was over and the secret code was broken. In the study, six milligrams of D-thyroxine were to be used - the equivalent of four and a half grains of dessicated thyroid.

But something went very wrong. Too many patients were dying. The study had to be interrupted and the code broken. It turned out that D-thyroxine was the culprit. it was discarded from the study.

Despite the «comedy of errors» - more appropriately it could be called the tragedy of errors since it has delayed effective use of thyroid therapy for many patients and cost many lives - other investigators have plowed ahead. At least two other serious attempts to use thyroid therapy in proper dosage should be mentioned.

Dr. M. Israel, a New York city clinician, has published several studies in which he has demonstrated repeatedly that thyroid therapy is not only safe but effective in controlling atherosclerosis in patients with demonstrated disease.

In 1971, Dr. James C. Wren reported an extensive five-year study with 347 patients, 173 men and 174 women. He wanted to determine the possible effects of thyroid therapy on the course of atherosclerosis in these patients.

The atherosclerosis was symptomatic in 132 of the patients whose mean age was 64,5 years. Some had experienced a heart attack; some had had stroke; some suffered from angina pectoris. There were others who were suffering difficulties with leg circulation because of atherosclerosis in the leg arteries. Some had electrocardiographic evidence of atherosclerosis of the coronary arteries.

The 215 patients with asymptomatic atherosclerosis had a mean age of 54,7 years and were considered high risks because of the presence of electrocardiographic abnormalities, high blood pressure, diabetes, or high cholesterol levels.

Only 9 percent of the patients - 31 of the total 347 - proved to be hypothyorid by the usual laboratory tests. Nevertheless, all were treated with thyroid and substantial clinical improvement occured in a significant number of patients in both groups. The mean cholesterol levels fell by 22 percent. Of 41 patients who had angina at the start of the study, 29 reported benefits that included increased exercise tolerance, decreased frequency and severity of attacks, and less need for nitroglycerin.

The great majority og the symptomatic patients, 100 of the 132, reported benefits from thyroid treatment in the form of increased sence of well-being, greater alertness, increased ability to be active.

And the death rate was less than was to be expected. Eleven patients died during the study. Their mean age was seventy-five, and ten of the eleven had had a heart attack or other symptomatic episode of atherosclerosis before treatment began. The death rate was less than half - 44 percent - of the expected rate based on U.S. Life Tables.

Atherosclerosis has been looked upon as irreversible. Bur Dr. Wren´s results indicate that administration of thyroid may be of benefit in many cases and some degree og modification or prevention of progression of the artery disease appears possible even after heart attacks or other serious events.

My own experience has been the same. Mine has been a limited experience - fortunately - because so very few of my patients who have been found hypothyroid and have been placed on thyroid therapy have had heart attacks or other serious events.......

Hypothyroidism: The unsuspected illness, Broda O Barnes 1976