Endocrine Abstracts

: A family with generalised resistance to thyroid hormone secondary to a missense point mutation in thyroid hormone receptor β (TR-β) gene corresponding to substitution of arginine to histidine at amino acid 438 (R438H) is described in three successive generations.

Case 1: (Index case) A 43 year old lady presented with thyrotoxicosis and was initially treated with carbimazole followed by radio-iodine ablation of the thyroid. Thyroxine was commenced 8 weeks after treatment. Despite thyroxine replacement TSH remained inappropriately raised. The patient was further investigated to exclude an underlying TSH secreting pituitary adenoma or GRTH. CT scan of pituitary revealed gland enlargement suggesting an underlying TSHoma. Pituitary hormone profile was otherwise normal. Further investigations however revealed normal α subunit with preserved TSH response to TRH stimulation suggesting the diagnosis of GRTH confirmed on genetic analysis to be secondary to point mutation R438H in TR-β. Supra-physiological doses of thyroxine led to resolution of pituitary enlargement after 22 months. Family thyroid function test screening detected transmission of GRTH in three successive generations.

Case 2: Daughter of index case also had inappropriately high TSH with high FT₄ levels. She didn’t require treatment. She was informed of the possibility of transmission of the same mutation to her children and the possibility of temporary hypothyroidism in new born if she became pregnant.

Case 3: A 2 year old child (grand-daughter of the index case) was also shown to have inappropriately raised TSH and FT₄. The child is under follow up with the paediatric endocrinologist but has no evidence of stunted growth or mental retardation. This case series report illustrates the importance of family screening to prevent inappropriate therapy following detection of abnormal TFT.