Horm Metab Res 2018; 50(11): 827-831
DOI: 10.1055/a-0751-0498
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Levothyroxine Therapy Achieves Physiological FT3/FT4 Ratios at Higher than Normal TSH Levels: A Novel Justification for T3 Supplementation?

David Strich*
1  Pediatric Specialist Clinic, Clalit Health Services, Jerusalem District, Jerusalem, Israel
2  Department of Pediatrics, Shaare Zedek Medical Center, Jerusalem, Israel
Cherut Chay*
3  Medical Students, Faculty of medicine, Technion, Haifa, Israel
Gilad Karavani
4  Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Shalom Edri
5  Health Information Center, Clalit Health Services, Jerusalem, Israel
David Gillis
6  Department of Pediatrics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
› Author Affiliations
Further Information

Publication History

received 12 July 2018

accepted 19 September 2018

Publication Date:
05 November 2018 (online)


In euthyroidism, as thyroid Stimulating hormone (TSH) levels increase, the free triiodothyronine (FT3) to free thyroxine (FT4) ratio increases. The aim of this study was to assess if beyond the euthyroid range of TSH levels FT3/FT4 ratio continues to increase and if levothyroxine treatment reduces this ratio, possibly through TSH suppression. This cross sectional retrospective study included a total of 77 832 patients [age 22.76±15.17 years (4 days to 112 years)] evaluated and treated in community clinics between January 2009 and September 2013. Blood samples drawn in community clinics for which TSH, FT4, FT3, age, and gender were available were included. Tests with TSH below 0.5 IU/l were excluded as were samples taken during pregnancy. The FT3/FT4 ratio continued to increase significantly even with TSH above 50 mIU/l (p for trend<0.001) with an increase of more than 50% over the entire TSH range. With increasing age and female gender, the phenomenon was less prominent (p<0.001). Levothyroxine treated patients had significantly lower FT3/FT4 ratios in comparison to untreated patients up to TSH levels of 5.0 mIU/l. In conclusion, increasing TSH increases FT3/FT4 ratio even with severe hypothyroidism, less so with aging. With levothyroxine therapy, a ratio similar to untreated patients is achieved at TSH of above 5.0 mIU/l. Since T3 suppresses TSH better than T4, administration of T3 would likely normalize the FT3/FT4 ratio at a lower, ostensibly more physiological, TSH level. This could be seen as a rationale for add-on T3 therapy.

* Equal contribution first authors. Cherut Chay’s contribution to this study was performed as part of the research requirements for the M.D. degree at the Technion Medical School, Haifa, Israel