Background: Thyroglobulin (Tg) measurement in patients with positive antithyroglobulin antibodies (anti-TgAbs) is not reliable. Tg measurement using liquid chromatography–tandem mass spectrometry (LC/MS) may be useful in this setting. Methods: This is a retrospective study with the objective of determining the accuracy of Tg-LC/MS in patients with thyroid cancer with anti-TgAbs. All patients with follicular cell-derived thyroid cancer (TC) who had thyroglobulin measured using LC/MS assay from November 1, 2013, to November 7, 2014, were evaluated. The frequency of detectable Tg-LC/MS was evaluated, with a functional sensitivity (FS) of 0.5 ng/mL in patients with structural disease. Then performance of Tg-LC/MS versus Tg immunometric assay (IMA) was compared using either Immulite assay (Tg-1) with a FS of 0.9 ng/mL or Beckman assay (Tg-B) with a FS of 0.1 ng/mL in detecting structural disease in patients with positive anti-TgAbs. Results: A total of 154 consecutive patients were included in this evaluation. Of these, 116 (75%) patients were positive for anti-TgAbs. In patients with structural disease and positive anti-TgAbs, Tg-LC/MS was undetectable in 43.7% of patients. Then the diagnostic accuracy for structural disease of Tg-LC/MS was compared with each Tg-IMA assay separately. In the 26 patients with positive anti-TgAbs where a Tg-I assay was used, the sensitivity and specificity for detecting structural disease were 33.3% and 88.2%, respectively, for the Tg-I assay, and 44.4% and 94.1%, respectively, for the Tg-LC/MS assay. In the 74 patients with positive anti-TgAbs where Tg-B was used, the sensitivity and specificity for detection of structural disease were 72.7% and 71.4%, respectively, for the Tg-B assay, and 62.6% and 93.7%, respectively, for the Tg-LC/MS assay. Conclusion: In patients with thyroid cancer with positive anti-TgAbs, Tg-LC/MS was frequently undetectable and was less sensitive for detecting disease than a Tg assay was with a functional sensitivity of 0.1 ng/mL. For patients with detectable Tg-LC/MS and anti-TgAbs, use of the assay for monitoring requires further prospective studies.

Objective. Thyroid disease has been reported among the endocrinopathies that can occur after treatment with ipilimumab. Graves’ disease, however, has been rarely reported with this medication. Here we report a case of Graves’ disease diagnosed after initiation of ipilimumab in a patient with melanoma.Methods. We present the clinical presentation and management course of this patient followed by a related literature review.Results. A 67-year-old male with metastatic melanoma was started on ipilimumab. He developed hyperthyroidism after two doses of ipilimumab. The cause of hyperthyroidism was determined to be Graves’ disease. Ipilimumab was held and the patient was started on methimazole with return to euthyroid status. Ipilimumab was resumed and the patient continued methimazole during the course of ipilimumab therapy, with controlled hyperthyroidism. Restaging studies following four cycles of ipilimumab showed complete response in the lungs, with residual melanoma in the neck. The patient then underwent total thyroidectomy and left neck dissection as a definitive treatment for both hyperthyroidism and residual melanoma.Conclusion. Graves’ disease can develop after starting ipilimumab and methimazole can be an effective treatment. For patients whose hyperthyroidism is well-controlled on methimazole, ipilimumab may be resumed with close monitoring.

Background: Papillary thyroid cancer (PTC) is reported to be highly heritable in epidemiological studies. Genome-wide association studies (GWAS) have uncovered several variants associated with PTC predisposition. It remains unknown whether these variants might contribute to better clinical stratification of PTC patients. Methods: In order to assess the usefulness of germline genetic analyses in the management of PTC patients, the genotypes of five variants (rs965513, rs944289, rs116909374, rs2439302, and rs966423) were determined in 1216 PTC patients and 1416 controls. Additionally, the expression of seven genes located close to GWAS variants ( PTCSC3 , MBIP , NKX2-1 , FOXE1 , DIRC3 , PTCSC2 , and NRG1 ) were measured in 73 PTC paired tumor/normal tissues, respectively. Next, the association was analyzed between the genotypes of the germline variants and the levels of gene expression with clinical/pathological features such as age, sex, TNM staging, multifocality status, extrathyroidal expansion, and MACIS score. Results: The risk allele of rs965513 was associated with larger tumor size ( p = 0.025) and extrathyroidal expansion (odd ratio [OR] = 1.29, p = 0.045). The variant rs2439302 showed association with lymph node metastasis (OR = 1.24, p = 0.016), and multifocality status of the tumor (OR = 1.24, p = 0.012). The expression of MBIP was associated with T stage ( p = 0.010). MBIP and PTCSC3 displayed lower expression in PTC tissue in males than in females ( p = 0.025 and p = 0.036, respectively). NKX2-1 displayed lower expression in patients with N1 stage ( p = 0.040). Conclusions: The studied germline risk alleles predisposing to PTC were associated with a more aggressive course of the disease reflected by larger tumor diameter, higher multifocality rate, and more advanced N stage at the time of diagnosis. These results show that germline variants not only predispose to PTC but also might impact its clinical course. However, these associations were only moderate, and further large multi-ethnic studies are required to evaluate the usefulness of these germline variants in the clinical stratification of PTC patients.

Usually the episodes occurred between 3:00 and 7:30 p.m. The symptoms occurred without regard to meals and were relieved with food or juice. Her most severe witnessed episode, which occurred while she was at college, happened a few days before the consultation, while K.D. was working, 2 hours postprandially. Observers reported that she appeared confused, agitated, and diaphoretic. Her glucose via fingerstick by paramedics was 35 mg/dl. She received intravenous dextrose, and subsequently her glucose rose to 217 mg/dl with resolution of her symptoms. She had several episodes with neuroglycopenic symptoms and glucose levels of 35-45 mg/dl.

Immune check point inhibitor (ICI) therapy can be a potentially effective salvage treatment for anaplastic thyroid cancer (ATC) with progression despite standard of care therapies. We report a case of unresectable treatment‐naïve ATC showing a dramatic and durable response to first‐line pembrolizumab therapy. A 69‐year‐old male presented with a large, right‐sided neck mass associated with compressive symptoms. A neck ultrasound showed a large, right‐sided, and highly suspicious thyroid nodule. A fine needle aspiration (FNA) biopsy revealed tumor cells consistent with ATC that were positive for PD‐L1, with an expression score of >95% and negative for the BRAF V600E mutation. Imaging studies were negative for distant metastases. The disease was declared surgically inoperable, and the patient declined chemotherapy/radiation therapy (XRT), but agreed to ICI therapy with intravenous pembrolizumab 200 mg every three weeks. The patient has received 25 doses of pembrolizumab to date, with rapid resolution of symptoms and a significant reduction in tumor size. He remains alive without disease progression 18 months since initial diagnosis.