Co-existence of THRB and TBG gene mutations in a Turkish family

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 449-497-Thyroid Neoplasia & Case Reports
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-461
Alfonso Massimilano Ferrara*1, Mehtap Cakir2, Phillip Harrison Henry1 and Samuel Refetoff1
1University of Chicago, Chicago, IL, 2Konya University Meram School of Medicine
Background. Resistance to thyroid hormone (RTH) is a syndrome characterized by high serum free T4 levels and unsuppressed serum TSH concentration. Thyroxine-binding globulin complete deficiency (TBG-CD) manifests with low serum total T4 and T3 levels and normal serum TSH concentration. Our objective is to describe a family with the co-existence of RTH and TBG-CD.

Clinical case. A 27-year old man presented with mental retardation, hearing loss and recurrent upper respiratory tract infections. At 21 years of age, serum concentration of free T3 was 4.89 pg/ml (n= 2.57-4.43), free T4 was 2.04 ng/dl (n=0.9-1.8), and TSH was 2.38 µU/ml (n=0.23–4.2). On the basis of these laboratory results and the presence of a goiter, the diagnosis of Graves’ disease was made and he was given 10 mCi of 131I. After radioiodide treatment, his TSH rose to levels greater than 100 µU/ml and he was started on 150 µg of L-thyroxine (L-T4). Recent thyroid function tests, on L-T4 replacement, showed high serum levels of TSH (6.8 µU/ml,) and T4 (15.4 µg/dl, n=5-11.6), normal T3 (174 ng/dl, n=90-180), and high TgAb titers. His elder sister presented with normal TSH (2.4 µU/ml) and T3 (176 ng/dl) and high serum T4 levels (14.0 µg/dl). Both patients were found to be heterozygous for the mutation P453A in the THRB gene. One of the proband’s brothers had low serum total T3 (78 ng/dl) and T4 (3.4 µg/dl) and normal TSH concentrations (2.3 µU/ml), without any clinical manifestations. He was hemizygous for the mutation P50fs51X in the TBG gene. The proband’s mother showed slightly elevated TSH (4.1 µU/ml), normal total T3 (152 ng/dl) and T4 (10.8 µg/dl) and elevated titers of TPOAb and TgAb. She was heterozygous for both THRB and TBG genes mutations.

            Conclusion. To our knowledge this is the first report of the co-existence of TBG and THRB gene mutations in the same individual. The case illustrates the difficulty that might be encountered in the interpretation of thyroid function tests when different genetic defects affecting thyroid function coexist.

Disclosure: SR: Consultant, Quest Diagnostics. Nothing to Disclose: AMF, MC, PHH

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Sources of Research Support: NIH