Endocrine Abstracts (2017) 51 P005 | DOI: 10.1530/endoabs.51.P005

Follicular thyroid carcinoma due to a heterozygous gain of function mutation in thyrotropin receptor (TSHR)

James Blackburn1, Dinesh Giri1, Senthil Seniappan1, Mohammed Didi1, Barbara Ciolka1, Matthew Jones1, George Kokai1, Alison Waghorn2 & Nicole Gossan1


1Alder Hey Children’s Hospital, Liverpool, UK; 2Royal Liverpool Hospital, Liverpool, UK.


Introduction: Activating mutations in thyrotropin receptor (TSHR) have been previously described in the context of non-autoimmune hyperthyroidism (familial or sporadic) and thyroid adenomas. We describe, for the first time, a mutation in TSHR contributing to follicular thyroid carcinoma (FTC) in an adolescent girl.

Case: A 12-year-old girl presented with a right-sided neck swelling, increasing in size over the previous four weeks. Clinical examination revealed a firm, non-tender right sided thyroid nodule with no features of hypo or hyperthyroidism. An ultrasound scan of the thyroid showed a well circumscribed heterogeneous highly vascular mass, measuring 21×17×17 mm, arising from the right lobe. Thyroid function tests showed a suppressed TSH [<0.03 mU/l], normal FT4 [10.1 pmol/l, normal range 9–19] and raised FT3 [9.1 pmol/l, 3.6–6.4]. TPO and TRAB antibodies were negative. A right hemithyroidectomy was performed and the histology of the sample revealed follicular carcinoma with mild to moderate nuclear pleomorphism and evidence of both capsular and vascular invasion (pT1b). A total thyroidectomy was subsequently performed with no histological evidence of residual carcinoma. Sanger sequencing of DNA extracted from the solid tumour tissue revealed a missense somatic mutation (c.1703T>C, p.Ile568Thr) in TSHR. Levothyroxine was commenced post-operatively with normalisation of the thyroid function [TSH 1.7, FT4 9.9 pmol/l]. Corrected calcium [2.38–2.48 mmol/l, normal range 2.15–2.74 mmol/l] and PTH [5.9 pmol/l, normal range 1.1–6.9 pmol/l] were stable during the post-operative period.

Conclusion: Papillary thyroid carcinomas constitute the most common thyroid malignancy in childhood while FTC is exceedingly rare. Follicular carcinoma due to TSHR mutation suggests an underlying, yet to be explored, molecular pathway leading to the development of malignancy. The case is also unique in that the clinic presentation of FTC as a toxic thyroid nodule has not been previously reported in children.