Thyroid hormone resistance in two patients with papillary thyroid microcarcinoma and their BRAFV600E mutation status

Abstract

Resistance to thyroid hormone (RTH) is a rare autosomal dominant hereditary disorder. Here in, we report two patients with RTH in whom differentiated thyroid cancer was diagnosed. Two patients were admitted to our clinic and their laboratory results were elevated thyroid hormone levels with unsuppressed TSH. We considered this situation thyroid hormone resistance in the light of laboratory and clinical datas. Thyroid nodule was palpated on physical examination. Thyroid ultrasonography showed multiple nodules in both lobes. Total thyroidectomy was performed. The pathological findings were consistent with papillary thyroid microcarcinoma. BRAFV600E mutation analysis results were negative. RTH is very rare and might be overlooked. There is no consensus on how to overcome the persistently high TSH in patients with RTH and differentiated thyroid cancer (DTC). Further studies are needed to explain the relationship between RTH and DTC which might be helpful for the treatment of these patients.

BRAFV600E mutation contributes papillary thyroid carcinoma and Hashimoto thyroiditis with resistance to thyroid hormone: A case report and literature review

“…An identical BRAF V600E mutation has been identified in solid cell nests in the thyroid and adjacent PTC ( 44 ), indicating that HT and PTC may be initiated by similar stem cell remnants, and may be etiologically related ( 7 ). In studied cases of RTH with PTC, BRAF V600E mutation testing was carried out in two studies ( 17 , 19 ) in the histological section and only one positive mutation was found ( 17 ). To the best of our knowledge, the present case report is the second patient to exhibit BRAF V600E mutation in PTC with RTH.…”

“…In a retrospective study based on 637 medical records, Medenica et al ( 48 ) revealed that patients with increased serum TSH concentrations and/or AITD, exhibited an increased risk of thyroid malignancy. Since RTH is characterized by increased TH concentrations, accompanied by unsuppressed or increased serum TSH levels, whether patients with RTH are at increased risk of thyroid malignancy remains unknown ( 19 ). Owing to the low incidence of RTH and the lack of specific symptoms associated with the disorder, RTH is commonly misdiagnosed as hyperthyroidism or Grave's disease.…”

“…However, in a patient with RTH and thyroidectomy, TSH suppression may not be achieved despite increasing doses of L-T 4 . In the literature review of 14 cases, 3 patients ( 14 , 15 , 19 ) were prescribed T 3 or tri-iodothyroacetic acid (TRIAC), in addition to L-T 4 suppression therapy. Owing to the lack of T 3 or TRIAC, the dosage of L-T 4 was increased in combination with TH tablets and the dopaminergic agent bromocriptine.…”

“…There are a number of studies of adult patients with PTC and HT; however, there are a limited number of studies demonstrating the coexistence of these two diseases in pediatric patients ( 8 , 9 ). In addition, there are a number of case studies that describe RTH with PTC ( 10 – 19 ), which identify the possible association between these diseases. In the present case report, a pediatric patient with newly diagnosed RTH and coexisting PTC and HT is discussed.…”

Update on resistance to thyroid hormone syndromeβ

“…Karakose et al [32] reported two cases of RTH-β combined with papillary thyroid carcinoma that were stable after surgical treatment and replacement therapy. In both cases, the required does of L-T4 was very high, and suppression of TSH to within the goal range was difficult to achieve.…”