Abstract
An asymptomatic male was found on screening to have a low serum TSH and total T
. The diagnosis of Graves' disease was made with positive thyroid stimulating immunoglobulin (TSI) and elevated free T
in the presence of complete TBG deficiency (TBG-CD). Genetic testing of the patient and family members revealed a novel frameshift mutation in the
(
) gene resulting in a complete deficiency of the protein.
The laboratory testing included total T
, free T
by analog method and direct dialysis and TBG measurements. Sequencing of genomic DNA was performed from peripheral blood.
A 35-year-old East Indian male was referred to endocrinology because of abnormal thyroid function tests (TFTs): TSH 0.01 mIU/L (0.4-3.6), total T
3.0 µg/dl (5.5-10.5) done as part of a "routine office visit". Upon further testing, the serum free T
2.0 ng/dl (0.8-1.8) and TSI 355% (<140% baseline) were elevated and the diagnosis of Graves' disease was made. TBG deficiency was suspected because the total T
concentration was inconsistent with hyperthyroidism and further testing confirmed TBG was undetectable. Sequencing of the
gene revealed a novel hemizygous frameshift mutation: p.Ala64Pro
Ter106, TBG-CD Mia (numbering excludes 20 a.a. signal peptide) associated with the complete deficiency of TBG in a patient with Graves' disease.
Patients with Graves' disease harboring a
mutation have conflicting TFTs. If a clinically hyperthyroid patient presents with normal or low total T
, serum TBG should be measured to identify an abnormality and prevent unnecessary testing.