Why the History of Thyroid Disease Is Important

Iodine Deficiency, Endemic Goiter, and Cretinism

Iodine deficiency and the subsequent complications, endemic goiter and cretinism, will eventually disappear. In fact, almost no endocrinologist currently practicing in the United States has encountered a cretin in his or her practice unless he/she has worked abroad. So, why should a physician who practices in an iodine-sufficient region take the time to learn about the problem of iodine deficiency and the ensuing consequences?

Iodine deficiency was one of the first disorders of micronutrient malnutrition to be recognized. Thus it set the stage for addressing other disorders related to inadequate intake of trace substances and helped foster the development of strategies for identifying and correcting these problems in a public health setting. By using lessons learned from endemic iodine deficiency, inefficiencies and errors resulting from methods for micronutrient supplementation should now be avoided (2).

Although there is essentially no likelihood of a physician in the United States having a patient with cretinism due to iodine deficiency, there is the possibility of encountering cretinism due to maternal and fetal thyroid hormone deficiency in utero on another basis. The most severe forms of cretinism are uncommon currently, but their features can be discerned from the historical record. This helps guide the physician as to what to expect if they encounter retardation secondary to untreated congenital hypothyroidism. These examples can also provide a standard for researchers working on thyroid hormone dependant neurogenesis to compare with their thyroid hormone deficiency observations. This is important because the human disease cannot be duplicated experimentally.

Physical Examination in Thyroid Disease

Joseph Babinski, a member of the pantheon of physical diagnosticians and for whom the eponymous “toe phenomenon” is named, saw many patients with thyroid disease (3). His descriptions of the neurologic examination of the hyperthyroid patient and procedures for eliciting cerebellar signs that are frequent manifestations of hypothyroidism are so elegant that every doctor can learn from them and use them in their practice (4). Unfortunately the physical examination is neglected in both current practice and in the current clinical literature as the information is not considered novel or important. This has led to the rudimentary skills of current physicians in physical examination compared to that of their predecessors who were more dependent on this for diagnosis and evaluation of disease progression. Indeed, an argument can be made that physical examination can only be adequately regained and learned by studying the historical record. Why bother knowing what Pemberton's sign is and how to elicit it when a thyroid ultrasound can provide much more precise information? Yet, though we love our ultrasounds, there are many times and places in the world where an ultrasound is not available, so having an alternative method to test for a substernal goiter is an important skill to master. This is another example of how descriptions from an earlier era can be useful in an office-based practice.

The Early Treatment of Agranulocytosis from Propylthiouracil

Propylthiouracil (PTU) has been much in the news recently. Edwin B. Astwood introduced the use of PTU for the treatment of hyperthyroidism. He was also the first to describe PTU-induced agranulocytosis (5). In his original description of this complication, Astwood discussed the use of pentnucleotide for the treatment of granuloctyopenia. Pentnucleotide was the accepted therapy for leukopenia from the 1910s until the 1950s (6,7). The drug helped define issues relating to the intellectual property of pharmaceutical products. Moreover, the elucidation of the mechanism of action of pentnucleotide has shed light on innate immunity and alternative strategies for the treatment of granulocytopenia. For someone interested in patent law, immunology, or drug development, there were invaluable lessons to be learned then and now from the history of an obsolete medicine. Similarly, an untapped source for discovering potential thyroid therapeutic agents is the historical record of botanical drugs used in China and India for the treatment of goiter, hyperthyroidism, and hypothyroidism.

Tadpoles and Thyrotropin Receptor α and β

This issue of Thyroid contains an original article describing the effect of hypophysectomy on tadpole metamorphosis and the possible role of the thyroid in this process. To this day, these original observations are used for understanding thyroid hormone receptor biology. Specifically, the appearance of the fore and hind limbs is a sensitive and specific index of thyroid hormone receptor (TR) α activity, while TR β activity is intimately involved in tadpole tail resorption (8,9). Because thyroid receptors are evolutionarily conserved, insights based upon studies using tadpoles are to this day applicable to mammalian physiology. As this example shows, historic observations about the role of the thyroid in the process by which tadpoles become frogs form the basis for current experimental methods to understand the molecular and genomic effects of thyroid hormone (See the Van Meter Prize Award review featured in this issue) (10).

These are just a few of many examples where thyroid history has contributed to our modern day perspective. As the current issue attests to, Thyroid greatly values the importance of this historical perspective on our current understanding of thyroid biology and disease. Indeed, from its inception Thyroid has published a number of important papers with a historic bent (Appendix 1) and this month signals a further series of future papers of historical interest and importance.