Abstract #1406483: Thyroid Hormone Resistance Diagnostic and Therapeutic Challenges

Resistance to thyroid hormone (RTH) is a clinical syndrome defined by impaired sensitivity (TH). We present the challenges in diagnosing and treating 24-year-old male who presented with mixed picture of hypothyroidism hyperthyroidism elevated TSH, upper normal free T4, T3 was found have mutation THRβ gene. A referred for second opinion post-ablative T3, suspicion pituitary microadenoma. He complained fatigue, weight gain, tremors heat cold intolerance. Family history Graves’ disease his mother's status post partial thyroidectomy due salivary tumor. Initially, 2020, he diagnosed negative antibody Grave’s disease. Labs were TSH 0.86 mIU/L, T4 1.99 ng/dl (0.89-1.76), 4.66 pg/ml (2.3-4.2). ultrasound showed mild thyromegaly. uptake scan 24-hour 36.7%. Thyroid antibodies including thyroglobulin, TPO, receptor, stimulating immunoglobulin negative. treated radioactive iodine ablation (I-131). Afterward, His increased gradually along T3. Free normal. The patient remained symptomatic, not on any replacement therapy. repeat an increase 36% at 24 hrs. During our evaluation, 54.05 mIU/l, 1.3 ng/dl, 4.3 pg/ml, equilibrium dialysis 4.0. magnetic resonance imaging head no definitive focal enhancing lesion. Pituitary axis hormones normal, alpha subunit 0.73 (high); however, alpha-glycoprotein /TSH molar ratio 0.135 sex binding globulin 5.8 nmol/l (low), macro detected. These findings raised THRB mutation; hence genetic studies obtained. PCR amplification gene exons 10, 9, 8, followed sequencing, heterozygous missense C >G located exon 10. caused change receptor beta protein amino acid 453 proline alanine, P453A started levothyroxine 25 mg PO daily but soon after, it stopped palpitations; blocker liothyronine 5 every other day 50 day. tolerated regimen significant improvement symptoms. RTH rather uncommon; important be able recognize avoid unnecessary invasive treatment. There specific therapy currently available fully correct TRβ defect. goal treatment based patient's symptoms instead aiming normalize levels. Thyroidectomy result lifelong RTHβ persistently high serum TSH. Levothyroxine challenging, supraphysiologic doses are often needed maintain lowest tolerable level.