Patients with Oncocytic Variant Papillary Thyroid Carcinoma Have a Similar Prognosis to Matched Classical Papillary Thyroid Carcinoma Controls.

BACKGROUND: Previous studies have suggested that oncocytic variant papillary thyroid carcinoma (PTC) may be more aggressive, with higher rates of recurrent disease. The aim of this study was to evaluate characteristics and outcomes of patients with oncocytic variant PTC compared to classical PTC. METHODS: Patients with oncocytic variant PTC were retrospectively identified from 519 patients who underwent thyroidectomy for PTC between January 2009 and August 2015. Data collected included patient demographics, laboratory and pathology findings, imaging studies, treatment, and follow-up. Patients were matched 1:1 by age, sex, and TNM stage with patients who underwent total thyroidectomy for classical PTC during the same time period. RESULTS: The cohort included 21 patients, of whom 18 (86%) were female, with a median age of 53 years (range 23-68 years). All patients underwent total thyroidectomy, and 17 (81%) had a central compartment neck dissection (8 [38%] prophylactic). The median tumor size was 2.0 cm (range 0.9-6.5 cm), and four (19%) patients had extrathyroidal extension. There was no significant difference in histopathologic characteristics, including extrathyroidal extension and lymphovascular invasion, between the two groups except for an increased incidence of thyroiditis in oncocytic variant PTC (90.5% vs. 57%; p = 0.01). In oncocytic variant PTC patients who underwent central compartment neck dissection, malignant lymph nodes were found in 12 (57%) patients compared to 13 (62%) classical (p = 0.75). Lateral neck dissection was performed in 5 (24%) oncocytic variant and classical PTC patients, with metastatic lymphadenopathy found in four (a median of four malignant lymph nodes; range 1-6) and five (a median of 2.5 malignant lymph nodes; range 1-9), respectively. Radioactive iodine was administered to 18 (86%) oncocytic variant PTC and 18 (86%) classical PTC patients. At a median follow-up of 51 months (interquartile range 38-61), one oncocytic variant PTC patient had recurrent disease and underwent reoperation at 24 months. In classical PTC patients with a median follow-up time of 77 months (range 56-87 months), two (9.5%) patients had detectable thyroglobulin levels indicating early recurrence, but neither has undergone reoperation. CONCLUSIONS: Oncocytic variant PTC was present in 5% of PTC patients. Most (95%) patients remain disease-free at four years, similar to classical PTC outcomes, suggesting that oncocytic variant may not represent a more aggressive variant.

Delayed Calcium Normalization After Presumed Curative Parathyroidectomy is Not Associated with the Development of Persistent or Recurrent Primary Hyperparathyroidism.

BACKGROUND: Following parathyroidectomy for primary hyperparathyroidism (pHPT), serum calcium levels typically normalize relatively quickly. The purpose of this study was to identify potential factors associated with delayed normalization of calcium levels despite meeting intraoperative parathyroid hormone (IOPTH) criteria and to determine whether this phenomenon is associated with higher rates of persistent pHPT. METHODS: This was a retrospective review of 554 patients who underwent parathyroidectomy for sporadic pHPT from January 2009 to July 2013. Patients who underwent presumed curative parathyroidectomy and had elevated POD0 calcium levels (>10.2 mg/dL) were matched 1:2 for age and gender to control patients with normal POD0 calcium levels. RESULTS: Of the 554 patients, 52 (9 %) had an elevated POD0 Ca (median 10.7, range 10.3-12.2). Compared with the control group, these patients had higher preoperative calcium (12 vs. 11.1, p < 0.001) and PTH (144 vs. 110 pg/mL, p = 0.004) levels and lower 25OH vitamin D levels (26 vs. 31 pg/mL; p = 0.024). Calcium normalization occurred in 64, 90, and 96 % of patients by postoperative days (POD) 1, 14, and 30, respectively. There was no difference in rates of single-gland disease or cure rates between the groups. CONCLUSIONS: After presumed curative parathyroidectomy, nearly 10 % of patients had transiently persistent hypercalcemia. Most of these patients had normal serum calcium levels within the first 2 weeks and did not have increased rates of persistent pHPT. Immediate postoperative calcium levels do not predict the presence of persistent pHPT, and these patients may not require more stringent follow-up.

Institutional experience with lateral neck dissections for thyroid cancer.

INTRODUCTION: Compartment-oriented neck dissection is recommended for patients with evidence of thyroid cancer metastases to lateral compartment lymph nodes. This study reviews the outcomes of patients who underwent lateral neck dissections (LND) at a high-volume institution. METHODS: This is a retrospective review of patients who underwent LND for metastatic thyroid cancer from January 2009 to June 2014. Preoperative evaluation, operative findings, and postoperative outcomes were analyzed. RESULTS: Ninety-six patients underwent 127 LNDs. Fine-needle aspiration (FNA) confirmed metastases in 82 lateral necks (65%). The remaining 45 LNDs (35%) were performed based on clinical suspicion of metastases; 29 (64%) had metastases on final pathology. Twenty patients had 26 complications, which included chyle leak (7 [6%]), spinal accessory nerve dysfunction (7 [6%]), neck seroma requiring drainage (2 [2%]), and surgical site infection (10 [8%]). CONCLUSION: LND is associated with a risk of early postoperative morbidity, but long-term complications are uncommon in the hands of experienced surgeons. In patients with thyroid cancer, a comprehensive preoperative evaluation of the lateral neck with physical examination, ultrasonography, and possible FNA should be performed. For those with suspicion of metastases, LND can be an important therapeutic option, but discussion with the patient regarding potential risks and benefits is essential.

The Effect of Thyroiditis on the Yield of Central Compartment Lymph Nodes in Patients with Papillary Thyroid Cancer.

BACKGROUND: In patients who have undergone thyroidectomy and central compartment neck dissection (CCND) for papillary thyroid cancer (PTC), visualization of enlarged lymph nodes may lead to more extensive CCND. This study sought to determine the effect of patient age and the presence of thyroiditis on the number of malignant and total lymph nodes resected in patients who underwent CCND for PTC. METHODS: This retrospective review examined a prospective database of patients who underwent total thyroidectomy and CCND for PTC between April 2009 and June 2013 and had thyroiditis on the final pathology. The patients were categorized into age groups by decade (18-29, 30-39, 40-49, 50-59, and ≥60 years) and compared with a control group of patients matched by age, gender, and tumor size. RESULTS: Of 74 patients with thyroiditis, 64 (87 %) were women. The median age of the patients was 47.5 years (range 18.2-72.0 years). The patients with thyroiditis had more lymph nodes resected than those without thyroiditis (median 11 vs 7; p < 0.01). However, these patients had fewer malignant lymph nodes (median 0 vs 1.5; p = 0.06), resulting in a lower lymph node ratio (0 vs 0.18; p = 0.02) for the entire cohort, but particularly for the youngest (18-29 years) and oldest (≥60 years) age groups. CONCLUSIONS: Patients with thyroiditis and PTC who underwent CCND had more lymph nodes resected but a had lower proportion of metastatic lymph nodes than those without thyroiditis. Given the relatively low yield of malignant cervical lymphadenopathy, a more judicious approach to CCND might be considered, particularly for the youngest and oldest patients with PTC and thyroiditis.

A single parathyroid hormone level obtained 4 hours after total thyroidectomy predicts the need for postoperative calcium supplementation.

BACKGROUND: Parathyroid hormone (PTH) levels after total thyroidectomy have been shown to predict the development of symptomatic hypocalcemia and the need for calcium supplementation. This study aimed to determine whether a PTH level drawn 4 hours postoperatively is as effective as a level drawn on postoperative day 1 (POD1) in predicting this need. STUDY DESIGN: This is a single-institution retrospective review of 4-hour and POD1 PTH levels in patients who underwent total thyroidectomy from January 2012 to September 2012. If POD1 PTH was ≥10 pg/mL, patients did not routinely receive supplementation; if PTH was <10 pg/mL, patients received oral calcium with or without calcitriol. RESULTS: Of 77 patients, 20 (26%) had a 4-hour PTH <10 pg/mL; 18 (90%) of these patients had a POD1 PTH <10 pg/mL. No patient with a 4-hour PTH ≥10 pg/mL had a POD1 PTH <10 pg/mL. All 18 patients with POD1 PTH <10 pg/mL received calcium supplementation. Three additional patients received supplementation due to reported symptoms or surgeon preference. A 4-hour PTH ≥10 pg/mL compared with a POD1 PTH had a similar ability to predict which patients would not need calcium supplementation; sensitivity was 98% vs 98%, specificity was 90% vs 86%, and and negative predictive value was 95% vs 95%. Of 21 patients who received supplementation, 13 (62%) also received calcitriol, including 9 patients (69%) with a 4-hour PTH <6 pg/mL. CONCLUSIONS: A single PTH level obtained 4 hours after total thyroidectomy that is ≥10 pg/mL accurately identifies patients who do not need calcium supplementation or additional monitoring of serum calcium levels. Same-day discharge, if deemed safe, can be accomplished with or without calcium supplementation based on the 4-hour PTH level. Greater consideration should be given to calcitriol supplementation in patients with a 4-hour PTH <6 pg/mL.

Effect of prophylactic central compartment neck dissection on serum thyroglobulin and recommendations for adjuvant radioactive iodine in patients with differentiated thyroid cancer.

BACKGROUND: Controversy exists in the management of patients with differentiated thyroid cancer (DTC). The purpose of this study was to examine the effect of prophylactic central compartment neck dissection (CCND) on serum thyroglobulin (Tg) levels and recommendations for adjuvant radioactive iodine (RAI). METHODS: The records of 103 patients who underwent completion/total thyroidectomy for DTC between January 2009 and November 2010 were reviewed. Prophylactic CCND was defined as removal of central compartment lymph nodes with no preoperative or intraoperative evidence of lymphadenopathy. Institutional protocol included a diagnostic whole-body scan before RAI; patients with a negative scan and Tg < 2.0 did not receive adjuvant RAI. RESULTS: Among the 103 patients, therapeutic CCND was performed in 17 (17 %) and prophylactic CCND in 49 (48 %). Of the 49 patients, 20 (41 %) had positive cervical lymph nodes. Positive lymph nodes changed American Joint Committee on Cancer tumor, node, metastasis staging in 17 patients and recommendations for RAI in 14. At a median follow-up of 21 months, there was no difference in Tg level based on the application of CCND; however, 92 % of patients with M0 disease had an undetectable Tg. One patient had recurrent DTC based on serum Tg only. CONCLUSIONS: Prophylactic CCND resulted in detection of unsuspected metastatic lymphadenopathy in 20 (41 %) of 49 patients and changed RAI recommendations in 14 (33 %). To date, most patients have an undetectable Tg. Longer follow-up is needed to detect potential differences in recurrent disease based on the use of CCND or long-term effects of RAI.

Systemic chemotherapy for adrenocortical carcinoma: comparative responses to conventional first-line therapies.

The objective of this study was to evaluate and compare the efficacies of conventional first-line chemotherapies for adrenocortical carcinoma. We reviewed the records of adult patients (> or =17 years) who had received first-line systemic chemotherapy with serial pretreatment and posttreatment radiologic staging studies in our institution between 1980 and 2000. Overall survival (OS) and time to progression (TTP) for different treatment groups were determined using the Kaplan-Meier method and were compared using the log-rank test. Univariate and multivariate models were fitted to different subsets of patients for OS and TTP and used to calculate hazard ratios (HRs) with 95% confidence intervals. We identified 224 patients with a diagnosis of adrenocortical carcinoma, 57 of whom met the inclusion criteria for further study. Chemotherapy groups included: mitotane (n=12), platinum and etoposide (n=16), mitotane with platinum and etoposide (n=11), mitotane and other cytotoxics (n=5), platinum and etoposide with other cytotoxics (n=3), and other miscellaneous cytotoxics (n=10). No statistically significant differences in OS (P=0.31) were noted among the treatment groups, but there was a statistically significant difference in TTP (P=0.02) favoring mitotane alone (TTP=6.24 months; 95% confidence interval, 3.58-32.13). Multivariate analysis was most notable for a significantly greater OS (HR=0.49, P=0.04) and TTP (HR=0.3, P=0.01) associated with peritoneal metastases. Our analysis revealed no clear advantage for any single agent or combination over any of the other conventional frontline chemotherapeutic choices for adrenocortical carcinoma. Novel agents are thus sorely needed in the treatment of this aggressive cancer.

Diagnostic challenges in adrenocortical carcinoma: recommendations for surveillance after surgical resection of selected adrenal nodules.

OBJECTIVE: To discuss challenges in the diagnosis of adrenocortical carcinoma and to suggest surveillance measures after removal of selected adrenal nodules. METHODS: We present the case of a 65-year-old man with worsening hypertension and new-onset hypokalemia attributed to primary hyperaldosteronism due to a 3-cm right adrenal nodule. RESULTS: A laparoscopic right adrenalectomy was performed, and the histologic diagnosis was a benign adenoma. The patient's hypertension and hypokalemia improved postoperatively but recurred 8 months later, and florid Cushing's syndrome developed. Magnetic resonance imaging showed an 8-cm mass in the right adrenal bed and multiple hepatic metastatic lesions. Fine-needle biopsy confirmed the presence of adrenocortical carcinoma. CONCLUSION: Despite a comprehensive biochemical, radiologic, and histologic assessment, the diagnosis of adrenocortical carcinoma can be missed. Particularly, we caution against undue reliance on the initial tumor size. We recommend that abdominal imaging be performed every 3 months for the first year and every 6 months for the second year after surgical removal of selected adrenal nodules.

Hypercortisolemia and infection.

Hypercortisolemia is a condition involving a prolonged excess of serum levels of cortisol that can develop as a result of disregulatory abnormalities in the hypothalamic-pituitary-adrenal axis or from exogenous-source steroids. Hypercortisolemia induces a state of immunocompromise that predisposes the patient to various bacterial, viral, fungal, and parasitic infections. To ensure optimal management of hypercortisolemia, the primary clinician must be cognizant of its different causes and aware of the different infections associated with cortisol excess. In the hypercortisolemic patient, it is necessary to restore normal cortisol levels to reduce the risk of infection or to improve the control and cure of established infection.

Regression of acanthosis nigricans correlates with disappearance of anti-insulin receptor autoantibodies and achievement of euglycemia in type B insulin resistance syndrome.

Autoantibodies directed against specific epitopes in the insulin receptor are rarely the cause of either recurrent hypoglycemia or a severe form of insulin resistance (type B insulin resistance). Type B insulin resistance occurs more commonly in women of African heritage and is frequently associated with a history of other autoimmune diseases. We present the unusual case of a 61-year-old African American woman with a background of autoimmune hypothyroidism and autoimmune hepatitis who developed type 2 diabetes mellitus and marked facial acanthosis nigricans (AN) over a period of weeks. Despite treatment with multiple oral antidiabetic agents, she rapidly developed severe, recalcitrant hyperglycemia and ketoacidosis, requiring hospitalization and intravenous insulin administration for 4 weeks at rates of up to 180 U/h. Immunologic testing revealed a high titer of anti-insulin receptor autoantibodies of both immunoglobulin G and immunoglobulin A classes. After a recurrence of diabetic ketoacidosis despite aggressive management, the patient was treated with a short course of cyclophosphamide; within 10 weeks, she experienced striking improvement of her hyperglycemia as well as marked regression of the AN lesions. Subsequently, the patient also experienced episodes of fasting hypoglycemia, which resolved with a brief course of glucocorticoids. She has since remained euglycemic with no therapy for 5 years. We have documented, for the first time, regression of AN in temporal association with disappearance of circulating anti-insulin receptor autoantibodies and achievement of euglycemia in a patient with type B insulin resistance.