Desiccated Thyroid Extract - History

History

The earliest oral treatment for hypothyroidism consisted of thyroid extract. George Redmayne Murray of the United Kingdom first described treatment of myxedema with thyroid extract in 1891, and published a description of long-term successful treatment (28 years) of a patient with myxedema (severe hypothyroidism) in 1920 His treatment was quickly adopted in North America and Europe. The first recorded American use dates to 1891 by a woman who was still taking it 52 years later at 84 years of age

Desiccated thyroid extract is prepared from pig and cow thyroid glands. The glands are dried (desiccated), ground to powder, combined with binder chemicals, and pressed into pills. This was a new use for parts that were previously unwanted slaughterhouse offal, and Armour and Company, the dominant American meatpacker in the 20th century, supplied the best-known brand of thyroid extract.

Replacement by thyroid extract in hypothyroidism was one of the most effective treatments of any disease available to physicians before the middle of the 20th century, and in severe cases afforded dramatic relief of the myriad symptoms. The decision to treat was usually based on the presence of signs and symptoms of hypothyroidism because there were no accurate, readily available laboratory tests of thyroid function. Many less severe cases of hypothyroidism went untreated. Dosage was regulated by improvement of symptoms.

Desiccated Thyroid became a commercial treatment option in 1934 with Westhroid, and has to this day, never been recalled for instability. In the early 1960s, desiccated thyroid hormones (thyroid extract) began to be replaced by levothyroxine (T4), or by combinations of T4 and T3. Replacement occurred faster in the United Kingdom than in North America, but by the 1980s more patients were being prescribed levothyroxine or T4/T3 combinations than desiccated thyroid extract.

Several reasons have been identified as to why prescriptions changed from the previously-effective desiccated thyroid treatment. These factors included a desire for improved effectiveness, medical evidence, scientific theory, cultural fashion, and effective marketing.

• Although thyroid extract was useful and usually effective, some patients continued to complain of fatigue, weight gain, or other symptoms. Dosing until the 1960s was often a matter of prolonged adjustment trials.
• It was known that not all of the iodine content of thyroid extract was in the form of effective T4 and T3 and that actual content of available preparations varied more than the permitted 15%. It was hoped that better dosing precision with levothyroxine alone would increase the proportion of patients effectively treated. In 1980, a widely publicized investigation published in JAMA revealed continued large ranges of hormone content and potency in all of the available thyroid extracts on the American market.
• By the 1960s, it was known that thyroxine was the essential hormone produced by the thyroid gland, and that most T3 was manufactured in other parts of the body by deiodination of thyroxine. It was demonstrated in hypothyroid animals and people that replacement of thyroxine alone corrected the measurable manifestations (laboratory test results) of hypothyroidism. By the 1970s doctors could measure T4, T3, and TSH in human blood with approximate accuracy and confirmed that treatment with thyroxine alone could produce normal blood levels of both T4 and T3, but desiccated thyroid caused supraphysiologic levels of T3. In the majority of patients normalization of these levels eliminated all signs and symptoms of hypothyroidism.
• It was discovered that a healthy person varied the amount of T3 produced from T4 in response to changing needs and conditions and it seemed wiser not to bypass this control system by providing larger amounts of T3 than were naturally produced each day.
• Furthermore, when T3 could be measured, it was discovered that thyroid extract and synthetic combinations of T4 and T3 produced significantly greater fluctuations of T3 throughout the day than occurred in healthy people or hypothyroid people treated with thyroxine alone.
• Endocrinologists found that treatment with thyroxine alone worked as well or better than thyroid extract for the majority of patients, although even thyroxine did not reverse all the symptoms of a minority.
• Cultural fashion and marketing played a role. In the middle of the 20th century, pharmaceutical chemists had been discovering the active molecules in a variety of plant and animal remedies, from aspirin and digitoxin to vitamins, and producing them synthetically with improvements in purity and dosage control. In that cultural context, it was easy to market pure levothyroxine as superior to dried animal glands.
• Synthroid, one of the most successful brand names in pharmaceutical marketing history, became as synonymous with thyroid replacement to generations of American primary care doctors as Kleenex or Xerox became with their respective products.

Thyroid care changed in other ways as well. Accurate T4 and T3 measurements became widely used in the 1970s, and by the late 1980s, TSH measurement had become sensitive enough to detect mild degrees of hyperthyroidism and overtreatment. To no one's surprise, blood levels of thyroid hormones and TSH were found to be the best predictors of objective benefits from thyroid replacement: those with the most severe measurable deficiency enjoyed the most dramatic and sustained benefits. It was also discovered that even mild hyperthyroidism as defined by a suppressed TSH level, whether due to disease or overtreatment, was associated with poorer bone density in women, and with higher rates of atrial fibrillation in elderly patients. Doctors began to trust the TSH measurement more and more as the index of optimal replacement dose.

As more doctors prescribed thyroxine instead of thyroid extract, the use of thyroid extract became associated with those whose medical practices deviated in many ways from standard care. (See complementary and alternative medicine.) This association became a disincentive for using thyroid extract, and those prescribing it were considered to be unscientific and irrational practitioners.