Samuel Refetoff

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.{{cite web |url=https://litfl.com/samuel-refetoff/ |title=Samuel Refetoff |website=Life in the Fast Lane (LITFL) |date=11 April 2019 |access-date=2025-04-23}}

At the University of Chicago, Refetoff held appointments including Assistant Professor of Medicine from 1969 to 1973, Associate Professor of Medicine from 1973 to 1977, and 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.{{cite web |url=https://scientificatlas.com/docs/CVs/Samuel%20Refetoff.pdf |title=Samuel Refetoff |website=Scientific Atlas |access-date=2025-04-23}} 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.{{cite web |url=https://www.fulbright.bg/wp-content/uploads/2022/06/fulbright_newsletter_67.pdf |title=Final Nominations for Bulgarian Fulbright Grantees in AY 2012-2013 |website=Bulgarian-American Fulbright Commission |access-date=2025-04-23}}

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 (formerly an estimate of circulating thyroid hormone). They proposed that the condition resulted from target tissue refractoriness to the hormone, which he later demonstrated to be caused by mutations in the thyroid hormone receptor beta (THRB) gene, leading to tissue resistance to the hormone.{{cite journal |last1=Refetoff |first1=S. |last2=DeWind |first2=L.T. |last3=DeGroot |first3=L.J. |title=Familial Syndrome Combining Deaf-Mutism, Stippled Epiphyses, Goiter and Abnormally High PBI: Possible Target Organ Refractoriness to Thyroid Hormone |journal=Journal of Clinical Endocrinology and Metabolism |volume=27 |issue=2 |pages=279–294 |year=1967 |doi=10.1210/jcem-27-2-279 |pmid=4163616 |url=https://academic.oup.com/jcem/article-abstract/27/2/279/2715353 |access-date=2025-04-23|url-access=subscription }}

Refetoff identified mutations in proteins that transport thyroid hormone in blood, namely thyroxine-binding globulin (TBG){{cite journal |last1=Yang |first1=F. |last2=Su |first2=K.P. |last3=Shulman |first3=G.I. |last4=Refetoff |first4=S. |title=A mutation causing reduced biological activity and stability of thyroxine-binding globulin probably as a result of abnormal glycosylation of the molecule |journal=Journal of Clinical Endocrinology & Metabolism |volume=68 |issue=6 |pages=1135–1140 |year=1989 |pmid=2501669 |doi=10.1210/mend-3-3-575}} and albumin, causing familial dysalbuminemic hyperthyroxinemia.{{cite journal |last1=Sunthornthepvarakul |first1=T. |last2=Refetoff |first2=S. |title=An identical missense mutation in the albumin gene results in familial dysalbuminemic hyperthyroxinemia in 8 unrelated families |journal=Journal of Clinical Endocrinology & Metabolism |volume=79 |issue=2 |pages=595–598 |year=1994 |pmid=8048949 |doi=10.1006/bbrc.1994.1998}} He also was first to identify mutations in the gene NKX2.1 that encodes TTF1, resulting in thyroid, brain and lung abnormalities.{{cite journal |last1=Bochukova |first1=E. |last2=Garin |first2=I. |last3=Ferraz-de-Souza |first3=B. |last4=Refetoff |first4=S. |title=The Endocrine Society 2012 Laureate Awards |journal=Endocrine Reviews |volume=38 |issue=3 |pages=179–181 |doi=10.1210/mend.26.8.zmg1468 |year=2012 |pmc=5416988}} 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.{{cite journal |last1=Dumitrescu |first1=A.M. |last2=Refetoff |first2=S. |title=A Novel Syndrome Combining Thyroid and Neurological Abnormalities Is Associated with Mutations in a Monocarboxylate Transporter Gene |journal=American Journal of Human Genetics |volume=80 |issue=3 |pages=483–494 |year=2007 |doi=10.1086/512491 |pmid=17273977|pmc=1821097 }} Along with A.M. Dumitrescu and others, he documented that mutations in the SECISBP2 gene disrupted selenoprotein synthesis, reducing the activity of all three iodothyronine deiodinases and impairing thyroid hormone metabolism, producing a variable clinical phenotype.{{cite journal |last1=Dumitrescu |first1=A.M. |last2=Liao |first2=X.H. |last3=Abdulmessih |first3=N. |last4=Refetoff |first4=S. |title=Mutations in SECISBP2 result in abnormal thyroid hormone metabolism |journal=Nature Genetics |volume=37 |issue=11 |pages=1247–1252 |year=2005 |pmid=16200071 |doi=10.1038/ng1658|pmc=2156108 }} His identification of mutations in the TSH receptor gene in 1995 established a cause for resistance to TSH (RTSH).{{cite journal |last1=Sunthornthepvarakul |first1=T. |last2=Heinrichs |first2=C. |last3=Refetoff |first3=S. |title=Resistance to thyrotropin caused by mutations in the thyrotropin receptor gene |journal=New England Journal of Medicine |volume=332 |issue=3 |pages=157–162 |year=1995 |pmid=7990856 |doi=10.1056/NEJM199501193320303}} Subsequently, in 2005, a new form of dominantly inherited RTSH was uncovered in several families and, although a linkage to a locus located on chromosome 15 was identified, the precise genetic cause eluded further investigation.{{cite journal |last1=Abu-Khudir |first1=R. |last2=Refetoff |first2=S. |title=STR mutations on chromosome 15q cause thyrotropin resistance by activating a primate-specific enhancer of MIR7-2/MIR1179 |journal=Nature Genetics |volume=56 |year=2024 |issue=5 |pages=877–888 |doi=10.1038/s41588-024-01717-7 |pmid=38714869 |pmc=11472772 }}

Refetoff's father, a banker, contributed to the establishment of the University of Ruse. His first wife, Gunvor Thomsen, was Danish. Following her death in 1978 at the age of 42, he raised their three children with Heather Bendall from Hampshire, England, whom he married in 1980.{{cite journal |last=Ross |first=D.S. |title=A Conversation with Samuel Refetoff, MD: How Treating One Family Stimulated a Lifelong Series of Major Discoveries in Thyroid Physiology and Disease |journal=Thyroid |volume=34 |issue=3 |pages=223–226 |year=2024 |pmid=39163036 |doi=10.1089/thy.2024.0246}}

• 1989 – Doctor Honoris Causa, Free University of Brussels, Belgium
• 1989–1999 – MERIT Award, National Institutes of Health (USA)
• 1990 – Doctor Honoris Causa, University of Cagliari, Italy
• 1991 – Paul Starr Award and Lectureship, The American Thyroid Association
• 1996 – Sidney H. Ingbar Distinguished Lectureship Award, The American Thyroid Association{{cite web |url=https://www.thyroid.org/about-american-thyroid-association/events-awards-lectures/sidney-h-ingbar-distinguished-lectureship/ |title=Sidney H. Ingbar Distinguished Lectureship Award |website=American Thyroid Association |access-date=2025-04-23}}
• 1999 – The Shizume Lecture Prize, Japan Thyroid Association
• 2001 – Elected Corresponding Member, Belgian Royal Academy of Medicine
• 2004 – Honorary Fellow, Royal College of Physicians of Ireland{{cite web |url=https://chronicle.uchicago.edu/040819/accolades-bsd.shtml |title=Accolades go to faculty, clinical staff in biological sciences |website=UChicago News |access-date=2025-04-23}}
• 2005 – Thyroid Pathophysiology Award Medal, The American Thyroid Association
• 2006–2016 – MERIT Award, National Institutes of Health (USA)
• 2011 – The Rosalind Pitt-Rivers Medal and Lectureship, The British Thyroid Association
• 2012 – Fred Conrad Koch Medal, Endocrine Society{{cite web |url=https://www.endocrine.org/awards/laureate-awards/koch-award |title=Fred Conrad Koch Lifetime Achievement Award |website=Endocrine Society |access-date=2025-04-23}}
• 2013 – Honorary Member, European Thyroid Association{{cite web |url=https://www.eurothyroid.com/membership/honorary_members.html |title=Honorary Members – European Thyroid Association |website=European Thyroid Association |access-date=2025-04-23}}
• 2014 – Doctor Honoris Causa, University of Ruse, Bulgaria{{cite web |url=https://bnr.bg/en/post/100460856/honors-for-professor-samuel-refetov-nominated-for-the-nobel-prize-also-in-bulgaria |title=World-renowned scholar Samuel Refetoff nominated for the Nobel Prize also in Bulgaria |website=Bulgarian National Radio |access-date=2025-04-23}}
• 2018 – Honorary Member, Bulgarian Thyroid and Parathyroid Association
• 2019 – The Lissitzky Medal, European Thyroid Association{{cite web |url=https://www.eurothyroid.com/news/prize-winners-2019.html |title=ETA prize winners 2019 |website=European Thyroid Association |access-date=2025-04-23}}

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Category:Bulgarian academics

Category:Canadian endocrinologists

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Category:1937 births