We present a difficult case of pituitary thyroid hormone resistance (PTHR) in a 6 year old girl. She presented at the age of 22 months with chronic cough, diarrhoea, failure to gain weight and gross motor delay. She was also noted to be hyperactive and clumsy with poor co-ordination. Persistent tachycardia was present on examination. Thyroid function tests revealed increased thyroid hormone concentrations with a free T4 of 63.7 pmol/l (925) and a free T3 of 20 pmol/l (3.07.5). Her TSH was 1.9 mU/l (0.56.0). No interference from heterophilic antibodies was noted. Anti-thyroid peroxidase antibodies were negative and anti-TSH receptor antibodies were absent. Her thyroid gland was normal on examination. TSH α-subunit was <0.3 mU/l and an MRI scan of her brain excluded a pituitary adenoma. Her parents had normal thyroid function. DNA sequencing did not reveal a thyroid beta-receptor mutation.
In view of her persistent symptoms she was commenced on 3,5,3′ triiodothyroacetic acid (TRIAC; 0.175 mg (1 tablet) tds). This dose was stepped up over the next 9 months to 2 tablets tds as her tachycardia and diarrhoea did not abate. Carbimazole (CBZ) was added to her treatment a year later as her free T4 remained elevated (fT4 52.7 pmol/l), although her TSH remained within the normal range. On a dose of 2.5 mg three times a day of CBZ, her diarrhoea soon settled allowing her to be toilet trained and her concentration improved. Her most recent results (3 years after addition of CBZ) showed free T4 to be 22.6 pmol/l and TSH 4.75 mU/l. She developed a small soft goitre, but this has not enlarged over the past 2 years.
The majority of patients reported in the literature appear to respond well to TRIAC which is considered to be the most suitable treatment in cases of PTHR. Our patient however had a poor response to TRIAC and this led to the addition of CBZ to her treatment. In view of the potential of CBZ to increase TSH levels and consequently goitre size it is important that TRIAC is continued. We have since achieved good control of her symptoms and her biochemical parameters are near normal, with centrally and peripherally directed therapy.
We would like to report the first known case of pituitary thyroid hormone resistance treated successfully with a combination of TRIAC and CBZ.
05 - 07 Nov 2008
British Society for Paediatric Endocrinology and Diabetes