ESPE Abstracts (2014) 82 P-D-3-1-983

Resistance to Thyroid Hormone Syndrome from Childhood to Adulthood: Variation in Symptoms and Thyroid Function

Aoife Garrahya, Mariana Graceb, Mary Stapletonc, Carla Morand, Krishna Chatterjeed, Matthew Murphya & Susan O’Connelle


aDepartment of Endocrinology and Diabetes, South Infirmary Victoria University Hospital, Cork, Ireland; bDepartment of Paediatrics and Child Health, University College Cork, Cork, Ireland; cDepartment of Clinical Biochemistry, Cork University Hospital, Cork, Ireland; dInstitute of Metabolic Science, University of Cambridge, Cambridge, UK; eDepartment of Paediatrics and Child Health, Cork University Hospital, Cork, Ireland


Introduction: Resistance to thyroid hormone (RTH) is a rare autosomal dominant condition characterised by tissue-specific insensitivity to thyroid hormone. In 85% of cases the disorder is associated with thyroid hormone receptor β (TRβ) gene mutations.

Case report: A 2.6-year-old boy was referred to the Paediatric service with abnormal thyroid function tests (TFTs) (fT4 30.4 pmol/l; RR 12–26, fT3 10.2 pmol/l; RR 3.7–8.5, TSH 2.34 μIU/l; RR 0.73–8.4) and is currently being assessed for behavioural problems. Review of family history revealed the index case’s mother had undergone thyroidectomy. He and two of his three older brothers have subsequently been diagnosed with RTH based on TFTs and genetic testing has confirmed a mutation in the TRβ gene. They have learning problems but are growing normally. The mother was diagnosed with RTH at age 3 (I431T mutation), with abnormal TFTs (fT4 29.7 pmol/L; RR 7.7-21, TSH 1.8 μIU/L; RR 0.6-4.3) and goitre. She was clinically hyperthyroid with tachycardia, diarrhoea and poor concentration. Symptoms improved following beta-blocker and 3,3,5-tri-iodothyroacetic acid treatment. She achieved a final height on the 75 centile, and weight below the 10. Symptoms of hyperthyroidism off treatment abated in her late teens and she was then lost to follow-up. She was re-referred age 28 years with a thyroid nodule and underwent surgery which showed a 22 mm papillary thyroid cancer, follicular variant (pT2(m)).

Conclusions: This family describes the spectrum of RTH presenting across two generations. Clinical features result from tissue-specific resistance to thyroid hormone, with effects on learning and behaviour in childhood, and apparent spontaneous improvement in hyperthyroid symptoms and thyroid function beyond the second decade. In the mother’s case, the condition was complicated by development of papillary thyroid cancer, with congruence of the latter with RTH being extremely rare.

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