A number of seemingly healthy patients were referred to our office with elevated FT3 and normal or high TSH. Our objective was to find the cause of this laboratory and clinical discrepancy.
We assessed FT3 levels on a smaller and a larger sample. Smaller sample were 10 outpatients referred to us. Larger sample consisted of 1048 outpatient FT3 and TSH results conducted between January and June 2018. Larger sample was not routinely seen by our service and consisted of test results requested by any provider. FT3 and TSH were measured by immunoassay using Beckman Coulter DXI (Beckman Coulter Inc.,Brea,CA) with manufacturer supplied references, FT3: 2.5-3.9pg/mL, TSH: 0.34-5.60µIU/ml.
10 patients with elevated FT3 and normal or high TSH were seen. Repeat thyroid function tests, anti-thyroid antibodies and thyroid ultrasound showed no evidence of thyroid disease. Larger sample showed 139 elevated FT3 with low TSH, 682 normal FT3 and TSH, 81 low FT3 and high TSH, and all were classified as appropriate. 3 had low FT3 and low TSH, 12 low FT3 and normal TSH and were also classified as appropriate. 121 had elevated free T3 with normal TSH, 10 elevated free T3 and high TSH and were classified as inappropriate. 131 out of 1048 samples(12.5%) were inappropriate. We re-evaluated our data by adjusting the upper limit of reference range from another laboratory using the same immunoassay for FT3. When using the upper reference from Mayo Clinic of 4.4pg/mL, the abnormal finding of high FT3 and high or normal TSH was reduced to 41 samples(3.9%).
High FT3 with normal or high TSH can be seen in thyroid hormone resistance and central hyperthyroidism. They are rare and unlikely to explain our finding of 12.5% of samples with high FT3 and normal or high TSH. We discovered there was a formulation change with Beckman Coulter FT3 kits in 2015 with an upward shift in FT3 that was expected to be maintained for all future lots. Our lab tested 20 reference samples per EP28-A3c guideline to verify the manufacturer suggested FT3 reference range in use prior to the formulation change and concluded that no adjustment of the reference was required. We do not know how Mayo Clinic selected the 4.4pg/mL as the upper limit of normal range, however, it reduced our abnormally elevated free T3 results to a acceptable level.
We demonstrate that adjusting the reference range would result in fewer discordant results. This would likely reduce unnecessary visits and tests, loss of resources and patient anxiety over abnormal results. In our opinion, analysis of 20 samples of healthy qualified individuals as per EP28-A3c guideline is not adequate to verify a previously used reference range.
Christopher Barnes– Fellow, Division of Endocrinology and Metabolism, Arnot-Ogden Medical Center, Lake Erie College of Osteopathic Medicine, Horseheads, New York
Jimmie Mar– Internal Medicine Resident, DO, PGY-2, Department of Internal Medicine, Arnot Ogden Medical Center, Horseheads, New York
Tahir Haytoglu– Endocrinologist, Arnot Health, Horseheads, New York
Ahmet Can– Program Director and Faculty, Arnot-Ogden Medical Center, Lake Erie School of Osteopathic Medicine, Horseheads, New York
Division of Endocrinology and Metabolism, Arnot-Ogden Medical Center, Lake Erie College of Osteopathic Medicine
Horseheads, New York
Dr. Barnes graduated from Lake Erie College of Osteopathic Medicine in 2014. He completed residency in Internal Medicine at the Arnot Ogden Medical Center and remains there for fellowship in Endocrinology.
Internal Medicine Resident, DO, PGY-2
Department of Internal Medicine, Arnot Ogden Medical Center
Horseheads, New York
Jimmie Mar, DO went to Medical School at Touro University College of Osteopathic Medicine and graduated in 2017. He is currently completing his internal medicine residency at Arnot Ogden Medical Center.
Horseheads, New York
Graduated 1996 HACETTEPE University School of Medicine in ANKARA, TURKEY
Internal Medicine Residency:
1997 – 2000 St. Barnabas Hospital (Affiliated with Cornell Medical School) in BRONX, NY
200 -2002 University of California, Davis, Medical Center in SACRAMENTO, CA
Preventive Cardiology Fellowship:
2002-2003 VA Boston Healthcare System / Brigham and Women’s Hospital (Affiliated with Harvard Medical School) in Boston, MA
09/2003 – 06/2018 American Hospital of Istanbul, Turkey. Practicing Endocrinologist and served as Vice Chief and Chief of the Endocrinology Division
07/2018 – Current ARNOT HEALTH Endocrinologist
ABIM Board Certified in Endocrinology and Internal Medicine in 2002 and 2000 and re-certified from both in 2017.
Program Director and Faculty
Arnot-Ogden Medical Center, Lake Erie School of Osteopathic Medicine
Horseheads, New York
Ahmet Selcuk Can, MD went to medical school in Istanbul Faculty of Medicine and graduated in 1989. He did his internship and residency in internal medicine in Cabrini Medical Center affiliated with New York Medical College, in New York City between 1994 and 1996. He completed his Endocrinology Fellowship in Weill Cornell Medicine and Memorial Sloan-Kettering Cancer Center combined program. During his fellowship, he worked in inborn errors of steroid metabolism and published a paper about molecular genetics of 5 alpha reductase deficiency. After fellowship, he worked in various Hospitals and Universities in Turkey. He published about prevalence of the metabolic syndrome and on the sensitivity and specificity of the thyroid fine needle aspiration biopsies. Before joining to Arnot-Ogden Medical Center in Elmira, New York, he worked in a private practice and had affiliations in the Community Medical Center, in Toms River and Ocean Medical Center in Brick, New Jersey and after that worked as a Professor of Medicine in Termal Vocational School in Yalova, Turkey. He has 20 publications in peer-reviewed journals. He serves as the Program Director for Endocrinology, Diabetes and Metabolism Fellowship at Arnot-Ogden Medical Center in Elmira, NY, affiliated with Lake Erie School of Osteopathic Medicine.