Much has happened since then. Kendall discovered thyroxine in 1914. Dietary iodine supplementation followed Marine and Kimball’s work on the role of iodine in the treatment of goiter in 1920. Harrington worked out the structure of thyroxine (T4) and synthesized it in 1926. A second and more potent thyroid hormone, triiodothyronine (T3), was discovered and synthesized by Gross and Pitt-Rivers in 1952. Utiger and Odell developed the first thyroid stimulating hormone (TSH) assays in the 1960s. In 1970, Braverman, Ingbar, and Sterling demonstrated that most T3 was produced by the extra thyroidal conversion of T3 from T4. By the mid 1970s, congenital hypothyroidism screening programs were implemented, virtually eliminating congenital hypothyroidism in developed parts of the world.

Since then, more sophisticated serum assays have enabled us to diagnosis mild or early hypothyroidism, termed ‘subclinical hypothyroidism’. Reliable thyroid hormone preparations have enabled clinicians to precisely and safely treat hypothyroidism, whatever its degree.Thus, after about a century of clinical milestones and triumphs in thyroidology, clinical practice has shifted considerably. Most patients now have subclinical or mild hypothyroidism rather than disease that is quite evident clinically.

The recent shift in clinical focus has led to a number of newer questions and issues which I will touch briefly on, and, perhaps to the chagrin of the reader, as well as the author, not offer many definitive answers. My comments will generally pertain to ambulatory patients without acute or major chronic illness, who are not being treated with medications known to alter thyroid hormone economy, and whose clinical circumstances allows them to have confirmatory laboratory determinations at least three or so weeks apart.