Thompson, Geoffrey B.

AbstractBackgroundIn patients with persistent (P‐PHPT) or recurrent (R‐PHPT) primary hyperparathyroidism, preoperative localization is important. Selective parathyroid hormone venous sampling (sPVS) is an invasive technique that can be used to regionalize and/or lateralize the source of PHPT when noninvasive imaging studies are nonlocalizing. The aim of the present study was to assess the role of sPVS in the preoperative evaluation of patients with P‐PHPT or R‐PHPT and negative, equivocal, or discordant noninvasive imaging localization.MethodsAfter IRB‐approval a retrospective review of all patients with P‐PHPT or R‐PHPT and nonlocalizing noninvasive imaging that underwent sPVS from 2000 to 2014 was performed. The location of the source of PHPT at sPVS was predicted by a parathyroid hormone (PTH) gradient and compared to the surgical, pathology, and biochemical follow‐up data as the gold standard. Sensitivity and positive predictive value (PPV) were calculated.ResultsOf 30 patients who underwent sPVS, 12 patients did not undergo surgical exploration due to negative or non‐localizing PTH gradient (n = 8) or opted for medical management (n = 4). Of the 18 patients who underwent surgical exploration, 17 (94 %) had a positive PTH gradient and pathologic parathyroid tissue identified at surgery. Sensitivity and PPV of sPVS were 93 and 77 %, respectively, for all surgical cases, 86 and 60.0 % for cervical cases (n = 11), and 100 and 100 % for mediastinal cases (n = 7). Sixteen patients (89 %) were surgically cured.ConclusionsIn patients with P‐PHPT or R‐PHPT and nonlocalizing imaging studies, sPVS is a sensitive test for localizing the source of PHPT when a positive PTH gradient is present.

AbstractIntroductionFocused parathyroidectomy in primary hyperparathyroidism (1°HPT) is possible with accurate preoperative localization and intraoperative PTH monitoring (IOPTH). The added benefit of multimodal imaging techniques for operative success is unknown.MethodPatients with 1°HPT, who underwent parathyroidectomy in 2012–2014 at a single institution, were retrospectively reviewed. Only the patients who underwent the standardized multimodal imaging workup consisting of 123I/99Tc‐sestamibi subtraction scintigraphy, SPECT, and SPECT/CT were assessed.ResultsOf 360 patients who were identified, a curative operation was performed in 96 %, using pre‐operative imaging and IOPTH. Imaging analysis showed that 123I/99Tc‐sestamibi had a sensitivity of 86 % (95 % CI 82–90 %), positive predictive value (PPV) 93 %, and accuracy 81 %, based on correct lateralization. SPECT had a sensitivity of 77 % (95 % CI 72–82 %), PPV 92 % and accuracy 72 %. SPECT/CT had a sensitivity of 75 % (95 % CI 70–80 %), PPV of 94 %, and accuracy 71 %. There were 3 of 45 (7 %) patients with negative sestamibi imaging that had an accurate SPECT and SPECT/CT. Of 312 patients (87 %) with positive uptake on sestamibi (93 % true positive, 7 % false positive), concordant findings were present in 86 % SPECT and 84 % SPECT/CT. In cases where imaging modalities were discordant, but at least one method was true‐positive, 123I/99Tc‐sestamibi was significantly better than both SPECT and SPECT/CT (p < 0.001). The inclusion of SPECT and SPECT/CT in 1°HPT imaging protocol increases patient cost up to 2.4‐fold.Conclusion123I/99Tc‐sestamibi subtraction imaging is highly sensitive for preoperative localization in 1°HPT. SPECT and SPECT/CT are commonly concordant with 123I/99Tc‐sestamibi and rarely increase the sensitivity. Routine inclusion of multimodality imaging technique adds minimal clinical benefit but increases cost to patient in high‐volume setting.

SummaryPatients with multiple endocrine neoplasia type 1 (MEN1) are commonly evaluated for clinical manifestations of this syndrome with the rationale that early diagnosis and adequate treatment will result in improved survival and quality of life. Thymic and bronchial carcinoid tumours are uncommon but important manifestations of MEN1. Current practice guidelines recommend evaluation with computed tomography or magnetic resonance imaging scan of the chest every 1–2 years to detect these neoplasms. However, the certainty that patients will be better off (increased survival or quality of life) as a result of this case detection strategy is based on evidence at moderate–high risk of bias that yields only imprecise results of indirect relevance to these patients. In order to improve the care that patients with MEN1 receive, co‐ordinated efforts from different stakeholders are required so that large, prospective, multicentre studies evaluating patient important outcomes are carried out.

Background: Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in pathophysiology, clinical presentation, and long-term outcomes. Furthermore, therapy that may be recommended for an adult may not be appropriate for a child who is at low risk for death but at higher risk for long-term harm from overly aggressive treatment. For these reasons, unique guidelines for children and adolescents with thyroid tumors are needed. Methods: A task force commissioned by the American Thyroid Association (ATA) developed a series of clinically relevant questions pertaining to the management of children with thyroid nodules and differentiated thyroid cancer (DTC). Using an extensive literature search, primarily focused on studies that included subjects ≤18 years of age, the task force identified and reviewed relevant articles through April 2014. Recommendations were made based upon scientific evidence and expert opinion and were graded using a modified schema from the United States Preventive Services Task Force. Results: These inaugural guidelines provide recommendations for the evaluation and management of thyroid nodules in children and adolescents, including the role and interpretation of ultrasound, fine-needle aspiration cytology, and the management of benign nodules. Recommendations for the evaluation, treatment, and follow-up of children and adolescents with DTC are outlined and include preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed and separate recommendations for papillary and follicular thyroid cancers are provided. Conclusions: In response to our charge as an independent task force appointed by the ATA, we developed recommendations based on scientific evidence and expert opinion for the management of thyroid nodules and DTC in children and adolescents. In our opinion, these represent the current optimal care for children and adolescents with these conditions.

SummaryObjectiveTo report the prevalence of parathyroid carcinoma (PC) in patients with multiple endocrine neoplasia type 1 (MEN1) and review of the literature.BackgroundPrimary hyperparathyroidism (PHP) is the most common manifestation of MEN1. The occurrence of PC in patients with MEN1 is rare and the literature regarding the clinical manifestations – including the prevalence of the disease – is scarce.ContextSingle tertiary care centre experience from 1977 to 2013.DesignElectronic search of the medical records to identify a cohort of patients with MEN1. Literature review based on current case reports.PatientsSingle case of PC in a cohort of 348 patients with MEN1. Ten cases of PC in patients with MEN1 reported in the literature.MeasurementClinical features of PC in patients with MEN1.ResultsThe prevalence of PC in 348 patients with MEN1 was found to be 0·28% (95% CI, 0–1·4%). Based on the current published cases of PC in patients with MEN1, 54·5% were women, mean age at diagnosis was 48·3 years, and the serum PTH concentrations at least four times the upper limit of the reference range in 73% of the cases.ConclusionPC in patients with MEN 1 is rare with a prevalence of 0·28%, and the clinical features are similar to PC in patients without MEN1.

Abstract Context: Hürthle cell cancer (HCC) of the thyroid remains the subject of controversy with respect to natural course, treatment, and follow-up. Objective: The objective of the study was to evaluate the clinical and molecular features associated with outcome in HCC. Design: The study was a review of 173 HCC cases treated at Mayo Clinic over 11 years with a median 5.8-year follow-up. Results: None of the patients with minimally invasive histology had persistent disease, clinical recurrence, or disease-related death. Male gender and TNM stage were independently associated with increased risk of clinical recurrence or death in widely invasive patients. The 5-year cumulative probability of clinical recurrence or death was higher in patients with TNM stage III–IV (females, 74%; males, 91%) compared with patients with TNM stage I–II (females, 0%; males, 17%). Pulmonary metastases were best identified by computed tomography, whereas radioactive iodine scans were positive in only two of 27 cases. Thyroglobulin was detectable in patients with clinical disease, with the notable exception of five patients with distant metastases. The common TERT C228T promoter mutation was detected in both widely invasive and minimally invasive tumors. TERT mRNA was below the limit of detection in all samples. Conclusion: Widely invasive HCC with TNM stage III–IV is aggressive, with low probability of recurrence-free survival. Males have worse outcomes than females. Minimally invasive HCC appears to be considerably less aggressive. Radioactive iodine scan performs poorly in detecting distant disease. Although the TERT gene is mutated in HCC, the role of this mutation remains to be demonstrated.