Background: Generalised Resistance to Thyroid Hormone (GRTH) is an autosomal dominant condition with impaired tissue responsiveness to thyroid hormones. The majority of patients are asymptomatic and compensate adequately by elevated thyroid hormone production.
Index case: A 47-year-old woman was referred to the thyroid clinic in 2000 when routine thyroid function tests (TFT) showed elevated TSH at 4.9 mU/l and fT4 36 pmol/l. A TSH-oma was excluded by normal levels of SHBG and alpha subunit, normal TSH and prolactin responses to a dopamine antagonist, a marked TSH response to TRH (basal 8.1, peak 44 mU/l) and normal pituitary MRI.
2nd Generation: Her two children then aged 26 and 24 years underwent TFT testing which showed similar results (see Table 1). DNA testing confirmed all three had GRTH (G345S heterozygous mutation).
|Test (reference range)||Index case||Son||Daughter||Grandson|
|TSH (0.353.3 mU/l)||410||2||0.82.0||5.5|
|fT3 (37 pmol/l)||910.7||11.9||8.211.9||15.4|
|fT4 (1025 pmol/l)||3139||41||3150||4567|
|Thyroid peroxidase antibody (0500 U/l)||1563||24||90||5|
3rd Generation: Her daughters second child born in 2004 was found to have a raised TSH and fT4. DNA testing confirmed a diagnosis of GRTH with the same mutation.
All the affected individuals were clinically euthyroid, did not have a significant goitre and were physically and developmentally normal.
Comment: To our knowledge this is the first report of GRTH crossing three generations in the UK. Coexistent autoimmune thyroid disease is challenging to treat and may require high doses of thyroxine to reproduce the initial thyroid profiles. GRTH is a rare cause of discordant TFTs and awareness of the diagnosis in the mother resulted in avoidance of inappropriate treatment and investigation in the infant.
01 - 05 Apr 2006
European Society of Endocrinology