8507 Misdiagnosis of Graves’ and RAI Treatment in Patient with THRB Gene Mutation
Authors: McBride E , Kennedy R , Davis A N , Healy S J 
Published: October 2024

Abstract
Disclosure: E. McBride: None. R. Kennedy: None. A.N. Davis: None. S.J. Healy: None.
Introduction: Resistance to thyroid hormone (RTH) is an inherited condition in which there is decreased tissue responsiveness to thyroid hormone. Occasionally patients with this condition can be misdiagnosed with hyperthyroidism.Clinical case: A 35 yo female was referred to our clinic for evaluation of postablative hypothyroidism. 6 years prior, the patient was evaluated by endocrinology at our city’s army hospital. The patient had abnormal TFTs during HTN workup but was otherwise asymptomatic. Family history included goiter in paternal aunt and grandmother (s/p thyroidectomy). Labs showed TSH 0.370 mIU/L (0.3-3); FT4 2.01, repeat 1.96 ng/dl (0.6-1.6); FT3 6.10 pg/ml (2.3-4.4); T4 16.2 mcg/dl (4.5-12); alpha subunit 0.32ng/ml; TBG 31 mcg/ml (13-39). On exam patient had thyromegaly. Thyroid US showed normal gland with length 5.6 cm. Subsequent labs showed negative thyroglobulin ab, antithyroid microsomal ab, TBII, and TSI. Resistance to thyroid hormone (RTH) was suspected. Pt underwent RTH mutation analysis. Result was heterozygous for c.715T&gt;A (pTrp239Arg) in exon 7 of the THRB gene, described as variant of unknown significance. Treatment was not recommended. Patient desired pregnancy and was evaluated by our hospital’s MFM clinic for preconception counseling. Per notes, patient had another child who tested negative for the gene.Patient then moved out of state, and 1 year later she underwent ablation for presumed diagnosis of Graves’ disease. The records from that hospital are not available. Patient later moved back to our city and was evaluated in clinic. At that visit, weight was 44 kg and patient was on 200 mcg LT4 daily. Pt endorsed cold intolerance, mood swings, brain fog, some hair loss. Recent thyroid US showed diminutive thyroid, and outside labs showed TSH 7.288, TPO ab &lt;4. Our labs showed TSH 8.6 and FT4 2.05. Pt was still interested in becoming pregnant. She did not recall the prior genetic testing or diagnosis of RTH, and believed that she had Graves’. Patient did not return for follow up visit and later moved out of state.Conclusions: Patient’s labs showed elevated T4 and T3 with normal TSH. Genetic testing revealed a mutation in THRB gene. The normal codon is TGG coding for tryptophan and mutation in this patient is AGG coding for arginine. Other mutations in this same codon result in reduced T3 binding affinity.This patient was later was misdiagnosed as having Graves’ at an outside hospital, presumably due to labs and increased thyroid uptake. Patient underwent unnecessary RAI treatment. It is common for these patients to require higher than expected doses of thyroid hormone.This case illustrates the importance of obtaining outside records and correlating thyroid function tests with imaging studies. It is a reminder that not all cases of increased thyroid uptake are due to Graves’. Management of thyroid hormone can be challenging in patients with RTH who have undergone ablation.
Presentation: 6/3/2024