Endocrine Abstracts

Resistance to thyroid hormone (THR) is a rare genetic condition affecting the nuclear thyroid hormone receptor, and inherited in a dominant negative pattern. It is often diagnosed in patients with discordant thyroid function. Patients have a ‘pituitary resistance’ to the elevated circulating levels of thyroid hormone, resulting in the failure of TSH suppression. While this consequent TSH drive has been associated with follicular thyroid cancer, it is thought that coexisting papillary thyroid cancers (PTC) occur at a similar rate to the general population and are not more common in this patient group. This results in marked challenges in intermediate and high risk PTC as the need for TSH suppression is challenging to achieve without unacceptable cardiovascular risk.

Case history: We present a 40 year old woman, diagnosed with resistance to thyroid hormone 16 years previously, following investigations for goitre and discordant thyroid function tests. She was confirmed to have a NM_000461.4:c.1357C>T p.(Pro453Ser) heterozygous, missense THRB mutation. Baseline investigations were normal, with the exception of bone densitometry which confirmed osteopaenia.

Investigations: Serial ultrasounds were performed of her multinodular goitre. In June 2019 a single suspicious nodule was identified. Fine needle aspiration demonstrated a Thy 5 papillary thyroid carcinoma. She underwent total thyroidectomy in Italy and returned to the UK for post-operative care. Histology confirmed a 1.5 cm PTC with pT1bN0R0 resection. Dynamic risk stratification recommended the need for post-operative radioiodine ablation, low-normal TSH suppression and serial monitoring of thyroglobulin levels.

Results and treatment: Pre-operatively her thyroid function was: TSH 2.17 mIU/l (0.27–4.2), free T4 36.9 pmol/l (12–22) and free T3 9.3 pmol/l (3.1–6.8). Post-operatively she was started on 100 mcg and 125 mcg of levothyroxine on alternate days, resulting in: TSH 58.5 mIU/l, free T4 26.6 pmol/l. Her levothyroxine was incrementally increased in response to her thyroid function. She is presently on 200 mcg, resulting in: TSH 9.9 mIU/l, free T4 48.8 pmol/l. This is a challenging clinical situation, and future measures may include the use of beta blockers to limit her cardiovascular side effects. Radioiodine has not yet been administered due to patient reluctance; this is still being considered.

Conclusion and points for discussion: Supraphysiological doses of levothyroxine are likely to be needed to achieve TSH suppression in patients with THR after total thyroidectomy for thyroid cancer. Accurate dynamic risk stratification of PTC patients with THR is important to determine the TSH target following thyroidectomy. Managing these patients is challenging due to the associated cardiovascular risks.