Faculty Bibliography

IMPORTANCE: Adrenal incidentalomas are found in 1% to 5% of abdominal cross-sectional imaging studies. Although the workup and management of unilateral lesions are well established, limited information exists for bilateral incidentalomas. OBJECTIVE: To compare the natural history of patients having bilateral incidentalomas with those having unilateral incidentalomas. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of a prospective database of consecutive patients referred to an academic multidisciplinary adrenal conference. The setting was a tertiary care university hospital among a cohort of 500 patients with adrenal lesions between July 1, 2009, and July 1, 2014. MAIN OUTCOMES AND MEASURES: Prevalence, age, imaging characteristics, biochemical workup, any intervention, and final diagnosis. RESULTS: Twenty-three patients with bilateral incidentalomas and 112 patients with unilateral incidentalomas were identified. The mean age at diagnosis of bilateral lesions was 58.7 years. The mean lesion size was 2.4 cm on the right side and 2.8 cm on the left side. Bilateral incidentalomas were associated with a significantly higher prevalence of subclinical Cushing syndrome (21.7% [5 of 23] vs 6.2% [7 of 112]) (P = .009) and a significantly lower prevalence of pheochromocytoma (4.3% [1 of 23] vs 19.6% [22 of 112]) (P = .003) compared with unilateral lesions, while rates of hyperaldosteronism were similar in both groups (4.3% [1 of 23] vs 5.4% [6 of 112]) (P > .99). Only one patient with bilateral incidentalomas underwent unilateral resection. The mean follow-up was 4 years (range, 1.2-13.0 years). There were no occult adrenocortical carcinomas. CONCLUSIONS AND RELEVANCE: Bilateral incidentalomas are more likely to be associated with subclinical Cushing syndrome and less likely to be pheochromocytomas. Although patients with bilateral incidentalomas undergo a workup similar to that in patients with unilateral lesions, differences in their natural history warrant a greater index of suspicion for subclinical Cushing syndrome.

BACKGROUND:To compare outcomes for patients with recurrent or persistent papillary thyroid cancer (PTC) who had metastatic tumors that were fluorodeoxyglucose-positron emission tomography (FDG-PET) positive or negative, and to determine whether the FDG-PET scan findings changed the outcome of medical and surgical management. METHODS:From a prospective thyroid cancer database, we retrospectively identified patients with recurrent or persistent PTC and reviewed data on demographics, initial stage, location and extent of persistent or recurrent disease, clinical management, disease-free survival and outcome. We further identified subsets of patients who had an FDG-PET scan or an FDG-PET/CT scan and whole-body radioactive iodine scans and categorized them by whether they had one or more FDG-PET-avid (PET-positive) lesions or PET-negative lesions. The medical and surgical treatments and outcome of these patients were compared. RESULTS:Between 1984 and 2008, 41 of 141 patients who had recurrent or persistent PTC underwent FDG-PET (n = 11) or FDG-PET/CT scans (n = 30); 22 patients (54%) had one or more PET-positive lesion(s), 17 (41%) had PET-negative lesions, and two had indeterminate lesions. Most PET-positive lesions were located in the neck (55%). Patients who had a PET-positive lesion had a significantly higher TNM stage (P = 0.01), higher age (P = 0.03), and higher thyroglobulin (P = 0.024). Only patients who had PET-positive lesions died (5/22 vs. 0/17 for PET-negative lesions; P = 0.04). In two of the seven patients who underwent surgical resection of their PET-positive lesions, loco-regional control was obtained without evidence of residual disease. CONCLUSION/CONCLUSIONS:Patients with recurrent or persistent PTC and FDG-PET-positive lesions have a worse prognosis. In some patients loco-regional control can be obtained without evidence of residual disease by reoperation if the lesion is localized in the neck or mediastinum.

BACKGROUND:Approximately 30% of fine-needle aspiration (FNA) biopsies of thyroid nodules are indeterminate or nondiagnostic. Recent studies suggest microRNA (miRNA, miR) is differentially expressed in malignant tumors and may have a role in carcinogenesis, including thyroid cancer. The authors therefore tested the hypothesis that miRNA expression analysis would identify putative markers that could distinguish benign from malignant thyroid neoplasms that are often indeterminate on FNA biopsy. METHODS:A miRNA array was used to identify differentially expressed genes (5-fold higher or lower) in pooled normal, malignant, and benign thyroid tissue samples. Real-time quantitative polymerase chain reaction was used to confirm miRNA array expression data in 104 tissue samples (7 normal thyroid, 14 hyperplastic nodule, 12 follicular variant of papillary thyroid cancer, 8 papillary thyroid cancer, 15 follicular adenoma, 12 follicular carcinoma, 12 Hurthle cell adenoma, 20 Hurthle cell carcinoma, and 4 anaplastic carcinoma cases), and 125 indeterminate clinical FNA samples. The diagnostic accuracy of differentially expressed genes was determined by analyzing receiver operating characteristics. RESULTS:Ten miRNAs showed >5-fold expression difference between benign and malignant thyroid neoplasms on miRNA array analysis. Four of the 10 miRNAs were validated to be significantly differentially expressed between benign and malignant thyroid neoplasms by quantitative polymerase chain reaction (P < .002): miR-100, miR-125b, miR-138, and miR-768-3p were overexpressed in malignant samples of follicular origin (P < .001), and in Hurthle cell carcinoma samples alone (P < .01). Only miR-125b was significantly overexpressed in follicular carcinoma samples (P < .05). The accuracy for distinguishing benign from malignant thyroid neoplasms was 79% overall, 98% for Hurthle cell neoplasms, and 71% for follicular neoplasms. The miR-138 was overexpressed in the FNA samples (P = .04) that were malignant on final pathology with an accuracy of 75%. CONCLUSIONS:MicroRNA expression differs for normal, benign, and malignant thyroid tissue. Expression analysis of differentially expressed miRNA could help distinguish benign from malignant thyroid neoplasms that are indeterminate on thyroid FNA biopsy.

CONTEXT/BACKGROUND:Parathyroid carcinoma is a rare but ominous cause of primary hyperparathyroidism. OBJECTIVES AND MAIN OUTCOME MEASURES: The objective of the study was to review the outcomes of parathyroid cancer patients and to evaluate the factors associated with mortality. DESIGN, SETTING, AND PATIENTS/METHODS:This was a retrospective review performed on 37 patients with parathyroid cancer treated at a single university tertiary care center between 1966 and 2009. RESULTS:The average age at cancer diagnosis was 53 yr (range 23-75 yr), and 23 patients (62%) were men. Eighteen patients (49%) recurred after their initial cancer operation. The average number of neck dissections done for cancer was three (range 1-11). After initial diagnosis, 22 patients (60%) eventually developed complications, including unilateral (n = 11) or bilateral (n = 3) vocal cord paralysis (38%). Eight patients (22%) had, at some point, an associated benign parathyroid adenoma. Median overall survival was 14.3 yr (range 10.5-25.7 yr) from the date of diagnosis. Factors associated with increased mortality included lymph node or distant metastases, number of recurrences, higher calcium level at recurrence, and a high number of calcium-lowering medications. Factors not associated with mortality included age, race, tumor size, time to first recurrence, and extent of initial operation. Initial operations done at our center had improved survival (P = 0.037) and decreased complication rates (P < 0.001) vs. those done elsewhere. CONCLUSION/CONCLUSIONS:Parathyroid cancer patients typically have a long survival, which often includes multiple reoperations for recurrence and thus a high rate of surgical complications. Patients in whom there is a high index of suspicion for parathyroid cancer should be referred to a dedicated endocrine surgery center for their initial operation.

BACKGROUND:Medullary thyroid cancer (MTC) commonly presents with lymph node (LN) metastases, and has a worse prognosis than papillary thyroid cancer (PTC). Tumor size and LN involvement have been shown to affect stage of disease; however, to our knowledge, ours is the first study that attempts to correlate anterior neck pain on presentation with the extent of disease. METHODS:We performed a retrospective review of patients with MTC who underwent an operation from February 1998 through December 2008. We compared the symptom of anterior neck pain with the pathologic extent of disease. Our control group comprised patients who underwent an operation for PTC. Analysis was performed using the Fisher's exact test and the Mann-Whitney test. RESULTS:Of the 109 patients with MTC, 50 (46%) met our inclusion criteria. Of the 50 patients with MTC, 11 presented with neck pain, compared to 3 of the 50 patients with PTC (p = 0.041). Of those 11 patients, 9 (82%) had LN involvement on final pathology, as compared with 14 (36%) of the 39 without neck pain (p = 0.014). Of patients with neck pain, 18% were diagnosed at stage I to II and 82% at stage III to IV, compared to 64% at stage I to II and 36% at stage III to IV (p = 0.014). CONCLUSIONS:Our study demonstrates that more patients with MTC present with anterior neck pain than do patients with PTC and that patients with MTC and neck pain have an increased risk of LN metastases. The results of this study suggest that MTC patients, who present with concomitant neck pain, should undergo a total thyroidectomy, prophylactic bilateral central neck dissection, and ipsilateral lateral neck dissection.

INTRODUCTION/BACKGROUND:Intraoperative aspiration of a nodule and parathyroid hormone (PTH) assay has been shown to accurately confirm parathyroid tissue. However, the reported aspiration technique varies in the literature. We sought to determine if the number of passes affected the accuracy of PTH analysis. METHODS:A prospective analysis was performed on 25 consecutive patients who underwent a parathyroidectomy for primary hyperparathyroidism. The excised parathyroid gland was aspirated using 1, 3, and 5 passes. The data were analyzed using the Wilcoxon rank, chi-square, and Fisher exact tests to calculate the 2-tailed P value. RESULTS:Of the 26 glands aspirated, the mean PTH value varied with the number of passes, 2,073 pg/mL for 1 pass, 2,347 for 3 passes, and 2,695 for 5 passes (P = .02). Accuracy was dependent on the number of passes, with 5 passes (P = .018) having less PTH variation than 1 or 3 passes. CONCLUSIONS:Aspiration of nodules to determine the PTH level helps confirm the presence of parathyroid tissue. The number of needle passes affects the accuracy of the PTH level, with 5 passes being the optimal number of passes to attain no false-negative results.

BACKGROUND:The role of routine prophylactic central-neck lymph node dissection (CLND) for papillary thyroid cancer (PTC) remains controversial. We perform CLND for PTC only in patients with enlarged nodes as determined by preoperative ultrasound and intraoperative inspection and palpation. METHODS:We identified all patients with PTC who underwent CLND during thyroidectomy (group 1) at our institution, and then we identified an equivalent number of demographically matched patients who underwent thyroidectomy without CLND (group 2) and compared the outcomes of the 2 groups. RESULTS:In all, 191 patients were identified for each group; 49/191 (26%) patients in group 1 developed locoregional nodal recurrence (12% central neck and 21% lateral neck), compared with 11/191 (6%) patients in group 2 (3% central neck and 3% lateral neck; P < .05). Overall, 161/191 (84%) patients in group 1 were disease free at last survey, compared with 180/191 (94%) patients in group 2 (P < .05). Transient hypocalcemia was significantly greater in group 1. No difference was found in disease-specific mortality. CONCLUSION/CONCLUSIONS:Surgeon assessment of the central neck compartment is an accurate predictor of which patients with PTC will benefit from CLND. Patients with nonenlarged central neck nodes who undergo total thyroidectomy without CLND have a low risk of developing recurrence.