Endocrine Abstracts

A 30 year-old Caucasian male presented for a routine check-up. He was known to have abnormal thyroid function tests since the age of 23 years of unclear nature/aetiology. He reported occasional palpitations and anxiety. There were no other symptoms on systems’ review. He did not take regular medication, was an ex-smoker and consumed alcohol socially. His mother had hypothyroidism and his maternal aunt’s thyroid nodules. He was euthyroid. A palpable isthmic nodule ˜1.5 cm was noted. He had no lymphadenopathy or other findings of note on examination. Free-T4 was 31 pmol/l (NR: 12–22 pmol/l), free-T3 8.4 pmol/l (NR: 3.1–6.8 pmol/l), TSH 1.96 mU/l (0.3–4.2 mU/l).

Thyroid hormone assay interference was excluded.

Pituitary MRI showed a 3 mm right-sided lesion.

The rest of the pituitary profile was normal.

TSH alpha-subunit was normal 0.15 U/l (NR<0.4 U/l).

Genetic analysis for congenital hypothyroidism and thyroid hormone resistance (TRH) sequencing panel with copy number variants (CNV) detection showed heterozygous status for the THRB gene for a variant designated c.1286G>A, predicted to result in the aminoacid substitution p.Arg429Gln. He was negative for CNV within the genomic regions encompassing the genes of this panel. US thyroid revealed a 1.5 cm midline U4 isthmus nodule with no evidence of extracapsular spread/infiltration. In the left lobe a nonspecific 3 mm nodule was also noted along with the 2 cm colloid cyst. FNA showed features of papillary thyroid carcinoma for the isthmic nodule. For the left lobe small nodule, the findings were compatible with Thy2. Genomic PCR analysis revealed BRAFV600E mutation at high-mutant allele frequency, but no other high-risk mutations, such as TERT or TP53. He was diagnosed with Refetoff syndrome (thyroid hormone resistance syndrome), coexistent papillary thyroid carcinoma and pituitary incidentaloma. He underwent total thyroidectomy. Histology showed 1.3 cm papillary thyroid carcinoma in contact with the capsule with no apparent capsular invasion, R0 resection, 0/6 lymph nodes free of neoplasia. Our case offers the opportunity to discuss the challenges in the diagnosis and management of THR. Moreover, coexistence of THR and differentiated thyroid carcinoma is very rare with only a few cases reported. Differentiated thyroid carcinoma in the context of THR is a distinctive model of thyroid cancer, where follow-up likely occurs in the setting of non-suppressed/constantly elevated TSH. We discuss the pitfalls resulting from failure to inhibit TSH secretion, we review the relevant literature and discuss the thresholds for RAI administration post-thyroidectomy in a clinical area lacking consensus for the standardized management of such cases.