Background. Recent revision significantly changed the American Joint Committee on Cancer (AJCC) staging criteria for differentiated thyroid cancer (DTC). To quantitatively evaluate resulting changes in patient stage distribution and the associated disease-specific survival (DSS) incorporating diverse populations, we performed a meta-analysis of studies comparing the AJCC 7th edition (AJCC-7) with 8th edition (AJCC-8) staging for DTC. Materials and Methods. After PROSPERO registration (#CRD42019123657), publications in English reporting DSS of DTC with AJCC-7 and AJCC-8 from inception to June 2019 were identified by search of MEDLINE and PubMed. Random-effects meta-analyses were conducted to compare differences in survival between AJCC-7 and AJCC-8. Pooled hazard ratios, 10-year DSS, and corresponding interval estimates were calculated for AJCC subgroups. Differences in survival between editions were assessed using subgroup analysis with nonoverlapping confidence intervals indicating statistical significance. Results. Final analysis included six studies with 10,850 subjects and median follow-up from 55 to 148 months. Use of AJCC-8 shifted classification to earlier stages: stage I, from 60% to 81%; stage II, from 5% to 13%; stage III, from 21% to 2%; stage IV, from 10% to 3%. Ten-year DSS was significantly lower in AJCC-8 versus AJCC-7 in patients with stage II (88.6%, 95% confidence interval [CI] 82.7-94.6% vs. 98.1%, 95% CI 96.6-99.6%, respectively) and stage III disease (70.5%, 95% CI 59.1-83.9% vs. 96.8%, 95% CI 94.1-99.64%, respectively). Conclusion. Meta-analysis of revised AJCC staging for DTC, incorporating diverse populations, demonstrates redistribution of patients toward earlier clinical stages and better stratification of disease-specific mortality risk, specifically among patients now classified with stage II and III disease.

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Cushing's disease, due to pituitary adrenocorticotropic hormone (ACTH) hypersecretion, is the most common etiology of spontaneous excess cortisol production. The majority of pituitary tumors causing Cushing's disease measure 1 cm and the excess morbidity associated with these tumors is mostly due to the effects of elevated, nonsuppressible, ACTH levels leading to adrenal steroid hypersecretion. Elevated circulating cortisol levels lead to abnormal fat deposition, hypertension, diabetes, coronary artery disease, osteoporosis, muscle weakness and psychological disturbances. At experienced centers, initial surgical remission rate via transnasal, transphenoidal resection approaches 80% for tumors less than 1 cm, but may be as low as 30% for larger lesions and long-term recurrence in all groups approaches 25%. Residual disease may be managed with more radical surgery, pituitary-directed radiation, bilateral adrenalectomy, or medical therapy. This paper addresses current and novel therapies in various stages of development for Cushing's disease.

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Subclinical hyperthyroidism is a laboratory diagnosis defined by a serum thyroid stimulating hormone (TSH) concentration below the reference range (< 0.4 mU/L in most assays), and a free thyroxine (FT4) and triiodothyronine levels (FT3) in the reference range. Many patients diagnosed with subclinical hyperthyroidism will be clinically euthyroid while others may present with manifestations characteristic of thyroid hormone excess, such as tachycardia, tremor, intolerance to heat, bone density loss, or weight loss. In addition to the laboratory abnormalities, patient factors such as age, symptoms, underlying heart and bone disease, are used to stratify patients for the risk of adverse outcomes and determine the appropriate treatment. Evaluation should include repeat thyroid function tests to document persistent TSH suppression, investigation of the underlying cause, as well as evaluation of the patient’s risk of adverse outcomes in the setting of a subnormal TSH. Persistent subclinical hyperthyroidism has been associated with an increased risk of a range of adverse events, including, cardiovascular events such as atrial fibrillation and heart failure, bone loss and fracture, and in some studies, cognitive decline. Despite the consistent association of these adverse events with subclinical hyperthyroidism, prospective studies showing improved outcomes with treatment remain limited. Management options include observation without active therapy, radioactive iodine ablation of the thyroid, antithyroid medication, thyroid surgery, or radiofrequency ablation, as appropriate for the patient and clinical setting. The choice of therapy should be guided by the underlying etiology of disease, patient factors, and the risks and benefits of each treatment option. (248 words)