Samuel Refetoff is a Bulgarian-American endocrinologist and an academic. He is the Frederick H. Rawson Professor in Medicine and director of the Endocrinology Laboratories at The University of Chicago.
Refetoff is known for discovering resistance to thyroid hormone (RTH), also known as Refetoff syndrome and its genetic and molecular basis, along with resistance to thyrotropin (RTSH) and a hereditary thyroid hormone metabolism defect caused by SECISBP2 gene mutations.
Education.
Refetoff completed his baccalaureate at the Lycée in Antwerp in 1955. He earned his B.Sc. (Hon.) in Biochemistry, from the University of Montreal in 1959 and obtained his M.D., C.M. from McGill University in 1963. During his postdoctoral training, he completed an Internship at Notre Dame Hospital from 1964 to 1965, followed by Residencies in Internal Medicine at the Hospital of the Good Samaritan in Los Angeles from 1964 to 1965 and at the Lahey Clinic, Boston, Massachusetts, from 1965 to 1966.
Refetoff trained in Endocrinology as an Assistant in Medicine at Peter Bent Brigham Hospital and as a Research Fellow in Medicine at Harvard Medical School from 1966 to 1968.
Career.
At the University of Chicago, Refetoff held appointments including Director of the Thyroid Function Laboratory from 1973 to 1994. In 1977, he also assumed the position of Professor of Medicine, which he held until 2000, and since 2001, he has held the title of The Frederick H. Rawson Professor in Medicine. Since 1983, he has also been a Professor of Pediatrics and, since 2001, a member of the Committee on Genetics there. Additionally, he served as Director of the Endocrinology Training Program during two separate periods, from 1978 to 1983 and from 1999 to 2004. He has been the Director of the Endocrinology Laboratories since 1994. He was the Head of the Thyroid Study Unit from 2005 to 2022 and visited the Medical University of Sofia as a Fulbright Senior Specialist in 2011.
Research.
Refetoff has worked in endocrinology, with research interests in congenital and genetic defects affecting thyroid hormone synthesis, transport, and action. Together with DeWind and DeGroot, he characterized a familial syndrome linking deaf-mutism, stippled epiphyses, goiter, and elevated PBI.
Refetoff identified mutations in proteins that transport thyroid hormone in blood, namely thyroxine-binding globulin (TBG) and albumin, causing familial dysalbuminemic hyperthyroxinemia. He identified mutations in the gene NKX2.1 that encodes TTF1, resulting in thyroid, brain and lung abnormalities. His laboratory uncovered mutations of the SLC16A2 gene, encoding the thyroid hormone cell membrane transporter MCT8, which cause severe thyroid hormone deprivation in the brain, resulting in psychoneuromotor abnormalities formerly described by Allan, Herndon, and Dudley. Along with A.M. Dumitrescu and others, he documented that mutations in the SECISBP2 gene disrupted selenoprotein synthesis, impairing thyroid hormone metabolism.