Hay, Ian

Abstract Diagnosis and management of thyroid disease benefit substantially from close interactions between clinicians and laboratorians. Clinicians desire reliable tests for diagnosis and management of both hypothyroidism and thyrotoxicosis. Traditionally, multitiered testing has been used, beginning with an index of free thyroxine concentration, which, if abnormal, has been followed by basal thyrotropin (TSH) measurements (for hypothyroidism) or thyrotropin-releasing hormone-stimulated TSH measurements (for thyrotoxicosis). Improvements in analytical methods for TSH have made it practical to use basal TSH measurements in serum as the first-line test for thyroid disease. However, performance guidelines are needed, because not all TSH assays work well in this role. The performance guidelines developed by the American Thyroid Association are reviewed to illustrate how they help to assure consistent analytical testing. Further improvements in TSH assays (third- and fourth-generation assays), which support measurements down to 0.01 mlU/L and 0.001 mIU/L, may provide additional advantages for classifying thyrotoxic patients and monitoring thyroxine-suppressive therapy in patients with thyroid cancer. The potential advantages of these newer assays are illustrated with case examples. Additional analytical performance monitors are proposed to help ensure that these next-generation TSH assays meet the expanded clinical needs.

AbstractBackgroundContemporary guidelines for managing PTC advise an approach wherein primary tumor and regional metastases (RM) are completely resected at first surgery and radioiodine remnant ablation (RRA) is restricted to high‐risk patients, policies our group has long endorsed. To assess our therapeutic efficacy, we studied 190 children and 4242 adults consecutively treated during 1936–2015. Subjects and methodsMean follow‐up durations for children and adults were 26.9 and 15.2 years, respectively. Bilateral lobar resection was performed in 86% of children and 88% of adults, followed by RRA in 30% of children and 29% of adults; neck nodes were excised in 86% of children and 66% of adults. Tumor recurrence (TR) and cause‐specific mortality (CSM) details were taken from a computerized database.ResultsChildren, when compared to adults, had larger primary tumors which more often were grossly invasive and incompletely resected. At presentation, children, as compared to adults, had more RM and distant metastases (DM). Thirty‐year TR rates were no different in children than adults at any site. Thirty‐year CSM rates were lower in children than adults (1.1 vs. 4.9%; p = 0.01). Comparing 1936–1975 (THEN) with 1976–2015 (NOW), 30‐year CSM rates were similar in MACIS <6 children (p = 0.67) and adults (p = 0.08). However, MACIS <6 children and adults in 1976–2015 had significantly higher recurrence at local and regional, but not at distant, sites. MACIS 6+ adults, NOW, compared to THEN, had lower 30‐year CSM rates (30 vs. 47%; p < 0.001), unassociated with decreased TR at any site.ConclusionsChildren, despite presenting with more extensive PTC when compared to adults, have postoperative recurrences at similar frequency, typically coexist with DM and die of PTC less often. Since 1976, both children and adults with MACIS <6 PTC have a <1% chance at 30 years of CSM; adults with higher MACIS scores (6 or more) have a 30‐year CSM rate of 30%.

Background Thyroid cancer ranges from well-differentiated lesions with an excellent prognosis to anaplastic carcinoma, which is almost uniformly fatal. Thus, methods to assess the behavior of thyroid malignancies are necessary to arrive at appropriate treatment decisions. Methods We discuss the factors that affect the prognosis of patients with well-differentiated thyroid malignancies, including papillary, follicular, Hürthle cell, and medullary thyroid carcinomas. We also review the presentation, therapy, and outcome of patients seen at our center over a span of 50 years. These data have identified those prognostic factors that are predictive of survival and recurrence in differentiated thyroid cancer. Results Several classifications with different variables have been developed to define risk-group categories. Three widely used systems, in addition to the TNM staging system, include AGES, AMES, and MACIS. Conclusions A better understanding of independently important prognostic variables will result in improved patient care and treatment.

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.

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.