I have a patient who has had evidence of thyroid hormone resistance.Â He has had a thyroidectomy for a fib.Â He is now well but feels hyper at TSH of 3-5. I now keep his TSH about 5 with beta blockade this is tolerable for him. His mother and sister also had thyrotoxicosis treated as Gravesâ disease in past.Â His pituitary is normal.
I had RTH mutation testing done through Quest:Â He was negative for THRB gene but hadÂ 2 abnormalities that individually have not been associated with resistance, but I wonder if the compounded effect is of actual clinical relevance:
C.735 C>T in exon 7 of THRB gene, andÂ also has c.1114+9 G>A polymorphism in intron 9.
Please let me know your thoughts on this.
Beatriz Olson, MD, FACP
Both findings represent known polymorphisms and have no clinical relevance. The C>T (phe>phe) in exon 7 occurs in 20% of the normal population, and the G>A in intron 9 occurs in 16% of the normal population. However, 15% of patient with proven RTH have no mutation in the THRB gene and the inheritance can be dominant. However proof of RTH requires detailed clinical testing with L-T3 administration and cosegregation (linkage) analysis. What were the FT4 and FT3 values in the patient, mother and sister when their TSH levels were between 1 and 5 mU/L?
Hope this helps,
Samuel Refetoff, MD