Multiple Hürthle cell adenomas in a patient with thyroid hormone resistance

Abstract

SummaryBackground: Thyroid hormone resistance (RTH) is a rare cause of thyroid dysfunction. High TSH levels, as described in RTH syndrome, are known to be associated with an increased risk of developing thyroid nodules with subsequent growth and malignancy.Patient findings: In 2006, a 29-year-old Caucasian man presented with a palpable mass in the neck. Increased free thyroxine and triiodothyronine levels were found in the context of unsuppressed TSH levels, despite no signs or symptoms of hyperthyroidism. Ultrasonography revealed a multinodular and enlarged goitre, and fine-needle aspiration cytology revealed suspicious features of malignancy. After excluding pituitary tumour and levothyroxine (l-T4) treatment, the patient was diagnosed with generalized RTH. Screening for all the known mutations in thyroid hormone receptor-β (TR β (THRB)) was negative. Thyroidectomy disclosed five Hürthle adenomas and three hyperplasic nodules. Euthyroidism was achieved after surgery with 6.1 μg/kg per day of l-T4.Conclusion: RTH may be a risk factor that predisposes to the development of multiple Hürthle cell adenomas. To our knowledge, this is the first case of multiple Hürthle cell adenomas in a patient with RTH.Learning points High TSH levels, as described in RTH syndrome, are known to be associated with an increased risk of developing thyroid nodules, with subsequent growth and malignancy.The exact role of TR β mutants in thyroid carcinogenesis is still undefined.We report the first case of multiple Hürthle cell adenomas associated with RTH.

Synergistic Signaling of KRAS and Thyroid Hormone Receptor β Mutants Promotes Undifferentiated Thyroid Cancer through MYC Up-Regulation

“…These findings suggest that cross talks of the activated KRAS pathway with the activated PI3K-AKT and β-catenin signaling mediated by TRβPV induced dedifferentiated thyroid cancer. THRB gene mutations are rare, but case studies have reported patients with thyroid cancer [29] , [30] , [31] , [32] , [33] , [34] . Thousands of rare mutations have been identified in the human genome.…”

“…However, our data could explain the in vivo findings that the Pax8 mRNA level was less than that in WT mice, Kras G12D mice, and Thrb PV/PV mice ( Figure 5 D ). While mutations of the THRβ gene are rare in human thyroid cancer [29] , [30] , [31] , [32] , [33] , [34] , [40] , the collaboration of MYC with TRβ mutants to suppress the expression of the Pax8 gene has yet to be uncovered. However, our findings exemplified how MYC could collaborate with other transcription factors and oncogenes to suppress the expression of the Pax8 gene and thereby could participate in the induction of the dedifferentiation process.…”