Introduction: Thyroid Hormone Resistance (THR) is a rare disorder caused by mutations of Thyroid Hormone Receptor characterised by insensitivity of target tissues to thyroid hormone actions. Patients can present with hyperthyroidism or hypothyroidism symptoms.
Case report: 49 year lady with recurrent thyrotoxicosis with goitre (1989/1994/1998) treated elsewhere with CBZ/PTU and RAI (2001). She developed post-RAI hypothyroidism and at presentation to our OPD (2015) she was on levothyroxine 100 mcg daily. Abnormally raised TSH levels were noted since 2011 despite normal or elevated FT4 levels. Two representative readings are given.
A possibility of THR, TSH-oma or assay interference was considered. Pituitary MRI (15 December 2016) showed no microadenoma. Assay interference was ruled out as there was good agreement between DELFIA and Roche in respect of TSH and FT4. Bloods (21 January 2016): TSH 11.2 mU/l, FT428.5 pmol/l, SHBG 61 nmol/l (32.4128), Alpha subunit peptide 0.8 IU/l (01), TRAB <1.0 U/l (11.8). Levothyroxine dose was gradually reduced and stopped over months. TRH stimulation test organized 6 weeks after stopping levothyroxine (13 April 2017) showed a preserved TSH response with basal TSH of 28 mU/l and peak TSH of >100 mU/l. THR can often be misdiagnosed as Graves disease. THR and Graves can rarely coexist. She was referred to Addenbrookes where in THRB gene sequencing she was heterozygous for THR beta mutation c.1313G>A, p. (Arg438 His) confirming thyroid hormone resistance. Most THR run in families. However, no family history of thyroid illness was noted in our case. As a child, our patient was hyperactive and currently she is having anxiety with depression. We found that there are multiple family members with hyperactivity and anxiety. We lost follow up after the genetic diagnosis was made.
|13 July 2011||20 October 2015|
|TSH||15.7 mU/l||7.9 mU/l||Normal range: 0.274.2|
|FT4||21.4 pmol/l||31.4 pmol/l||Normal range: 1222|
Conclusion: Correct diagnosis of THR, which requires a high index of suspicion, can avoid unnecessary interventions.