What is the thyroid gland?

Structure and Functions

The human body is, to an extraordinary extent, under the metabolic control of chemical secretions called hormones. These molecules are produced by the ductless, or endocrine, glands and carry messages that regulate the rate of production of necessary substances in remote parts of the organism. The endocrine glands in turn are largely controlled by the nervous system, which also uses chemical messengers to manage the multiple and interrelated systems of the body.

The thyroid gland was one of the earliest glands to be studied in detail. It synthesizes, stores, and secretes two principal hormones, thyroxine and triiodothyronine. These substances stimulate carbohydrate metabolism and protein synthesis or breakdown.

The first description of the thyroid that has been accepted as definite was given by Thomas Wharton in 1656; he also named the gland. In his studies of all the glands, he performed animal dissections and human autopsies. Although his written accounts were widely reprinted, it was more than two hundred years later before any serious further work was undertaken.

Nineteenth century clinical studies of goiter (swelling of the thyroid) and hyperthyroidism (the gland’s overproduction of hormones) contributed little to an understanding of the thyroid. An exception is found in the study of the insufficient production of hormone by the thyroid, called hypothyroidism. English and Swiss physicians made discoveries that are considered by some medical historians to be as important as the demonstration that the element iodine is associated with thyroid action.

In the 1870s, the Swiss surgeon Emil Theodor Kocher began to describe the significance of the thyroid gland and its role in goiter formation. He was awarded the 1909 Nobel Prize in Physiology or Medicine for providing a fuller appreciation of the thyroid and associated glands. Kocher was neither a physiologist nor a pathologist by training or disposition, but he recognized that to be an effective surgeon it was essential to understand well the function of the thyroid and its role in the goiters so common in Bern. In this region, 80 to 90 percent of schoolchildren had a malfunctioning thyroid gland and the often-associated goiter. Kocher’s drawings in books and papers show that such enlargements are extremely disfiguring and often interfere with normal breathing and speech.

In Kocher’s day, little was known about any of the endocrine glands, of which the thyroid is the first to have been studied surgically. Such glands deposit chemical regulatory substances called hormones directly into the bloodstream, which carries them to the sites of their activity.

Later clinical observations provided evidence that the thyroid gland produces some material essential for good health. In 1896, Eugen Baumann made the key discovery that the thyroid contains an unusual amount of iodine. He also showed that this excess iodine is present in a protein that he could decompose with water to yield a new substance. During the next twenty-five years, technical progress was made to the point that the hormone thyroxine could be produced in a pure, crystalline form.

With the new tool of radioactive iodine, a powerful method for the study of thyroid functions and malfunctions became available. For example, overactive and underactive thyroid glands can be easily determined through the ingestion of a tiny amount of one of the radioactive isotopes of iodine and the later determination of the amount of the tracer present in the thyroid.

Disorders and Diseases

It is possible for the thyroid to produce either too much (hyperthyroidism) or too little (hypothyroidism) of the hormone thyroxine, which plays a role in controlling metabolism and body growth. If an insufficient quantity of it is produced, the condition called Gull’s disease results. In children, this condition limits both physical and mental growth and is known as congenital hypothyroidism
or cretinism. In Graves’ disease and related conditions, the overactive thyroid gland produces too much hormone. Either of these conditions can produce an enlarged thyroid gland, or goiter. This imbalance existed in many different countries, but physicians designated it by various names, thus causing much misunderstanding and confusion. Emil Kocher’s studies presented the first organization of the field in the form of these basic definitions.

In his first one hundred operations carried out between 1872 and 1883, Kocher completely removed the thyroid gland in thirty-four cases. After a report by his colleague Jacques Louis Reverdin indicating that removal of the thyroid was a causal factor in cretinism, Kocher made as detailed a follow-up of these patients as possible. His conclusion was that if the entire gland was removed, cretinlike symptoms almost always appeared. If at least some of the gland was left, it appeared to regenerate itself and supply the required hormone. He vowed never to remove a thyroid completely again except in the case of malignancy.

Only in the twentieth century did reliable diagnoses and treatments become available for thyroid disorders. Because of the variety of these conditions and their causes, accurate diagnosis is indispensable. Modern approaches that supplement radioactive iodine include ultrasound and the needle biopsy.

The principal difficulty in the treatment of a malfunctioning thyroid gland is the several variations often displayed. Hyperthyroidism can occur in forms that appear quite unrelated to the most common form, Graves’ disease. For example, there may not be a heredity basis, the condition may not spread over the entire gland, the production of antibodies may not be involved, and there may be no progressive failure of the thyroid.

The causes of hypothyroidism are also less than uniform. The age at which the disorder begins is significantly related to its cause. Newborn children with this condition may have never developed the required amount of thyroid tissue. Others may have inherited a defect that prevents the thyroid from producing sufficient hormone. In developing countries, iodine deficiency remains a problem (although an overabundance of that element in the diet of expectant mothers can lead to infants with hypothyroidism and a goiter). Later in life, infection can be the cause of Hashimoto’s disease and the loss of thyroid tissue. Finally, the treatment of an overactive thyroid places a person at risk of later underproduction of hormone.

The most common symptoms associated with thyroid problems are a too rapid or too slow heartbeat, nervousness or a tired and run-down feeling, frequent bowel movements or constipation, and weight loss or weight gain. An excess of the hormones that direct the use of food and the production of energy might reasonably be expected to produce the first of each pair of contrasting observations, while a deficiency would lead to the opposite effects.

The treatment of Graves’ disease falls into three distinct classes, and in modified application these techniques are employed with the other forms of hyperthyroidism. Since the early 1940s, a series of antithyroid drugs have been synthesized. They function by preventing the gland from making hormone, and the symptoms lessen in a short time. Unfortunately, only about 30 percent of patients remain well when the medication is stopped after six to twelve months.

If antithyroid drugs fail to control the overactive thyroid, a radioactive isotope of iodine is often successful. Since the iodine goes directly to the thyroid and remains there for a period of time, it is able to irradiate and destroy a portion of the tissue. It is a demanding task to calculate the proper amount of iodine to administer, but a surprising 80 percent of patients find their condition under control after a single treatment.

Surgical treatment of Graves’ disease and related hyperthyroid conditions became practical with Kocher’s efforts, and it remains the method of choice in many cases. Kocher began his Nobel Prize lecture by describing the crucial importance of the work of Louis Pasteur, Joseph Lister, and others in making surgery on internal organs possible, and he suggested the future of thyroid research when he examined the effective use of extracts and the search for chemical means of providing substitutes for the gland’s secretions.

The standard treatment of hypothyroidism is oral thyroid hormone tablets. Typically, a synthetic form of thyroxine, called Levothyroxine, is given to compensate for low thyroid hormone levels. As is the case with Graves’ disease, good follow-up is essential because the prescribed dosage will likely change with the patient’s age. The administration of too much thyroxine can lead to hyperthyroidism.

Two notes should be made in concluding this discussion of malfunctions of the thyroid. First, there is a tendency to believe that iodine prevents and cures goiter. Statements to that effect, found in many general reference books, are both misleading and dangerous. Second, publications for laypersons tend to minimize the importance of thyroid blood tests, which is a serious disservice. Regular and complete physical examinations are essential in maintaining good health.

Perspective and Prospects

Historians of medical history have attributed knowledge of the thyroid gland and the treatment of goiter to many significant figures. The works of Galen, Paracelsus, ancient Chinese writers, and other classical Roman and Greek authors, as well as medieval manuscripts, have been studied. In the twentieth century, the study of the thyroid and goiter illustrates central themes in the evolution of medical practice; these are shown clearly in the career of Emil Kocher. His being chosen as an early Nobel laureate is prophetic—first for his role in creating modern surgery, with its total reliance on a germ-free environment and its demand for detail, and second for successful synthesis of the roles of clinician and research scientist. He both possessed the necessary surgical skill to develop such a delicate procedure as thyroidectomy (removal of the thyroid gland) and appreciated the importance of understanding the role played by the thyroid in controlling distant and seemingly unrelated functions. Finally, Kocher kept abreast of any new discovery that might, in any way, be of significance to his surgical goals.

The study of the thyroid in many ways unlocked the secrets of other endocrine glands. As in many areas of scientific research, new medical knowledge follows quickly after the discovery of materials and techniques. At the same time, the search for knowledge provides both motivation and information driving the discovery of materials and techniques.

The identification of iodine as an elemental substance by the French chemist Bernard Courtois in 1811 rapidly led to its indiscriminate use as a treatment for goiter, along with a wide variety of related conditions. Important work in the mid-nineteenth century by A. Chatin demonstrated the high correlation between goiter and low levels of iodine in the food and water supplies throughout central Europe. In the 1930s, with the creation of radioactive isotopes, including those of iodine, a vital and productive new phase of thyroid research began.

A similar pattern is seen during World War II, when four independent research groups showed that sulfa drugs were capable of exerting a strong influence on the behavior of the thyroid. All these studies were conducted within a two-year period, and it was less than a year later that the therapeutic use of sulfa drugs was demonstrated.

While much knowledge and technical skill concerning the thyroid has been gained, the number of conferences and publications devoted to endocrinology attests to the continued importance of that general field of study. For example, while malignant tumors are rare in the thyroid, benign lumps or nodules are common. The reasons for this pattern and the role of endocrine glands in the development and spread of cancerous cells warrant detailed and continuing study.

In 2013, researchers analyzing data from the U.S. National Health and Nutrition Examination Survey linked exposure to perfluorinated chemicals (PFCs) to changes in thyroid function. PFCs are often found in fabrics, cosmetics, and carpets.

Bibliography

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