The Truth about Double Adenomas: Incidence, Localization, and Intraoperative Parathyroid Hormone.

BACKGROUND: Double adenoma is reported in 3% to 12% of patients with primary hyperparathyroidism. The aim of this study was to determine the true incidence of double adenoma and analyze the use of localization studies and intraoperative parathyroid hormone (IOTPH) assay in these cases. STUDY DESIGN: We conducted a retrospective review of a series of consecutive parathyroid surgical operations from 2010 to 2013. According to the surgical findings, the series was divided into single-gland disease (SGD), double-gland disease (DGD), and multi-gland disease (MGD, more than 2 glands). The sensitivity of ultrasound, technetium 99m-sestamibi, and 4-dimensional CT to correctly lateralize each gland in the DGD group was calculated. Results of the IOPTH assay and how they impacted the extent of surgery were analyzed. RESULTS: Three hundred and forty-seven patients had SGD (69%), 68 patients had DGD (13.5%), and 86 had MGD (17%). In the DGD group, sensitivity of ultrasound, technetium 99m-sestamibi, and 4-dimensional CT to lateralize each adenoma was 42%, 34.5%, and 64%, respectively. Initially, 27 patients (40%) with DGD had been planned for a focal exploration. The conversion to bilateral neck exploration was due to the IOPTH assay in 18 cases (two-thirds of the initially planned focal explorations). At 6-month follow-up, all DGD patients were normocalcemic. CONCLUSIONS: Localization studies in DGD can be misleading by reporting SGD. Four-dimensional CT seems to have the highest sensitivity. In focal explorations, the excision of all hyperfunctioning parathyroid tissue should be verified by IOPTH measurement.

Continuous positive airway pressure with pressure support ventilation is effective in treating acute-onset bilateral recurrent laryngeal nerve palsy.

Acute bilateral recurrent laryngeal nerve injury leading to acute vocal cord paralysis (VCP) is a serious complication of head and neck surgery, often requiring emergent surgical intervention. Although well documented, its presentation may be sudden and unexpected, occurring despite lack of obvious intraoperative nerve injury. There is limited literature on airway management strategies for patients with acute bilateral VCP before attaining a secure airway. We report a case of acute VCP that was successfully treated with continuous positive airway pressure via facemask ventilation. This effective temporizing strategy allowed clinicians to plan and prepare for tracheostomy, minimizing potential complications.

Pediatric thyroidectomy in a high volume thyroid surgery center: Risk factors for postoperative hypocalcemia.

INTRODUCTION: Hypocalcemia is a common complication following thyroid surgery. We seek to report on our experience in pediatric thyroidectomy in a high volume thyroid surgery center and accurately assess the incidence of postoperative hypocalcemia. MATERIALS AND METHODS: A retrospective review of patients aged 18 and younger who underwent thyroid surgery between 1992 and 2013. The primary endpoints were the occurrence of postoperative hypocalcemia as by defined as a nadir calcium <8.0mg/dL and being discharged on oral calcium supplementation, need for intravenous calcium and the occurrence of permanent hypoparathyroidism. RESULTS: 171 patients who underwent 186 thyroid operations were analyzed. The average age was 15.4years with 82.3% female. The most common indications for surgery were nodular disease (74.7%) and hyperthyroidism (12.4%). 24 patients (12.9%) experienced postoperative hypocalcemia with 13 (7.0%) requiring intravenous calcium infusion. One patient (0.9%) experienced permanent hypoparathyroidism. Risk factors for postoperative hypocalcemia included total thyroidectomy (OR 7.39, p<0.01), central and bilateral lateral neck dissection (OR 22.26, p=0.01), Graves' disease (OR 3.99, p=0.02), and malignancy (OR 2.96, p=0.03). CONCLUSIONS: Pediatric patients who undergo total thyroidectomy for underlying malignancy or Graves' disease and those who have more extensive nodal dissections are at increased risk of developing this postoperative hypocalcemia. These patients may benefit from more vigilant preoperative preparation and postoperative calcium and vitamin D supplementation.

Primary hyperparathyroidism after Roux-en-Y gastric bypass.

BACKGROUND: Primary hyperparathyroidism (PHPT) in the setting of previous roux-en-Y gastric bypass (RYGBP) is not well described. The diagnosis can be difficult, as secondary hyperparathyroidism (SHPT) commonly occurs in patients after RYGBP due to calcium malabsorption and vitamin D deficiency. METHODS: All patients from 2000 to 2012 who underwent cervical exploration for diagnosis of primary hyperparathyroidism with history of preceding RYGBP were identified and analyzed retrospectively. RESULTS: Ten patients were identified. The average age was 58.4 and all patients were female. Time interval between RYGBP and cervical exploration was 67 months with median follow-up of 19 months. Average preoperative calcium was 10.8 mg/dL, PTH 155 pg/mL, and 25-vitamin-D 32 ng/mL. Eighty percent of patients presented with symptoms and 90% underwent preoperative imaging. Seventy percent underwent initial focused parathyroidectomy with 20% being converted to four-gland exploration. Seventy percent of patients had a single adenoma with two patients having multi-gland disease. Intraoperative PTH was used in seven patients with successful drop to 50% of baseline in all. Ninety percent of patients had greater then 6-month follow-up without evidence of persistent or recurrent PHPT. Average 6-month calcium was 9.3 mg/dL, PTH 73 pg/mL, and 25-vitamin-D 44 ng/ML. Four patients had evidence of persistently elevated PTH despite normalization of calcium. CONCLUSIONS: PHPT after RYGBP is rare but surgery with either a focused approach following successful localization or four-gland exploration is indicated when the biochemical diagnosis holds true. The presence of SHPT can make diagnosis and follow-up difficult and may predispose them to severe post-operative hypocalcemia.

Surgery for Graves' disease: a 25-year perspective.

BACKGROUND: Optimal treatment of Graves' disease (GD) remains controversial. The authors retrospectively reviewed the surgical cases of GD at a single academic tertiary center. METHODS: Demographic, clinical, and surgical data were analyzed for all patients with GD undergoing thyroidectomy over 25 years, in 3 periods: 1985 to 1993 (n = 32), 1994 to 2002 (n = 91), and 2003 to 2010 (n = 177). RESULTS: There were 300 patients with GD (85.7% women; mean age, 39.3 years; median length of follow-up, 24.6 months). Overall, perioperative morbidity occurred in 36 patients (12.0%), and there was no mortality. Thyroidectomy-specific morbidity was very low, and the incidental malignancy rate was 10.3%. CONCLUSIONS: Surgical treatment of GD has a very high safety profile, with low perioperative and thyroidectomy-specific morbidity, even in patients with overt hyperthyroidism. Incidental malignancy in patients with GD is not uncommon.

Recalcitrant hypocalcemia after thyroidectomy in patients with previous Roux-en-Y gastric bypass.

BACKGROUND: Hypocalcemia is a potential complication after thyroidectomy. Patients with previous roux-en-Y gastric bypass (RYGBP) may be at increased risk for recalcitrant symptomatic hypocalcemia after thyroidectomy. This complication is poorly described and there is no current consensus on optimal management in this unique population. METHODS: All patients from 2000 to 2012 who underwent thyroidectomy with history of preceding RYGBP were identified retrospectively. Each of the 19 patients meeting inclusion criteria were matched 2:1 for age, gender, and body mass index (BMI) to a cohort who underwent thyroidectomy without previous RYGBP. The study cohort and matched controls were compared for incidence of symptomatic postoperative hypocalcemia, requirement of intravenous (IV) calcium supplementation, and duration of hospital stay. RESULTS: Age, proportion of female patients, and BMI were equivalent between cases (n = 19) and controls (n = 38). Comparison of primary outcomes demonstrated that the study group had a significantly higher incidence of symptomatic hypocalcemia (42% vs. 0%; P < .01), administration of IV calcium (21% vs. 0%; P < .01), and duration of hospital stay (2.2 vs. 1.2 days, P = .02). CONCLUSION: Patients with previous RYGBP have a greater incidence of recalcitrant symptomatic hypocalcemia after thyroidectomy, resulting in prolonged duration of hospital stay. In this patient population, calcium levels should be closely monitored and early calcium and vitamin D supplementation initiated preemptively.

BRAF V600E status adds incremental value to current risk classification systems in predicting papillary thyroid carcinoma recurrence.

BACKGROUND: Papillary thyroid cancer (PTC) recurrence risk is difficult to predict. No current risk classification system incorporates BRAF mutational status. Here, we assess the incremental value of BRAF mutational status in predicting PTC recurrence relative to existing recurrence risk algorithms. METHODS: Serial data were collected for a historical cohort having undergone total thyroidectomy for papillary thyroid carcinoma (PTC) during a 5-year period. Corresponding BRAF(V600E) testing was performed and Cox proportional hazard regression modeling, with and without BRAF status, was used to evaluate existing recurrence risk algorithms. RESULTS: The 5-year cumulative PTC recurrence incidence within our 356 patient cohort was 15%. A total of 205 (81%) of associated archived specimens were successfully genotyped, and 110 (54%) harbored the BRAF(V600E) mutation. The 5-year cumulative recurrence incidence among BRAF(V600E) patients was 20% versus 8% among BRAF wild type. BRAF(V600E) was significantly associated with time to recurrence when added to the following algorithms: AMES (hazard ratio [HR] 2.43 [confidence interval 1.08-5.49]), MACIS category (HR 2.46 [1.09-5.54]), AJCC-TNM (HR 2.51 [1.11-5.66]), and ATA recurrence-risk category (HR 2.44 [1.08-5.50]), and model discrimination improved (incremental c-index range 0.046-0.109). CONCLUSION: The addition of BRAF mutational status to established risk algorithms improves the discrimination of risk recurrence in patients undergoing total thyroidectomy for PTC.

Diagnostic yield of nondiagnostic thyroid nodules is not altered by timing of repeat biopsy.

BACKGROUND: Guidelines from the National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference recommend a repeat fine-needle aspiration biopsy (FNAB) after 3 months for thyroid nodules with a nondiagnostic (ND) result. Our aims were to assess which factors influenced their clinical management and to determine if the timing of the repeat FNAB affects the diagnostic yield. METHODS: A retrospective institutional review of 298 patients from 1/2006 to 12/2007 with an ND FNAB was performed. The factors influencing the next step in management, including age, gender, history of radiation, presence of Hashimoto's thyroiditis, thyroid-stimulating hormone levels, and ultrasound characteristics, were evaluated. The effect of the time of the repeat FNABs on their diagnostic yield was assessed. RESULTS: Of the 298 patients in our cohort, 9% were referred directly for surgery, 76% had a repeat FNAB, and 15% were observed. Tumor size was the only independent variable correlated with treatment strategy after a ND FNAB. There was not a significant difference in diagnostic yields between repeat FNABs performed earlier than 3 months compared to those preformed later (p=0.58). CONCLUSION: The timing of repeat FNAB for an initial ND FNAB does not affect diagnostic yield of the repeat FNAB.

Preoperative basal calcitonin and tumor stage correlate with postoperative calcitonin normalization in patients undergoing initial surgical management of medullary thyroid carcinoma.

BACKGROUND: The optimal initial operative management of medullary thyroid cancer (MTC) and the use of biomarkers to guide the extent of operation remain controversial. We hypothesized that preoperative serum levels of calcitonin and carcinoembryonic antigen (CEA) correlate with extent of disease and postoperative levels reflect the extent of operation performed. METHODS: We assessed retrospectively clinical and pathologic factors among patients with MTC undergoing at least total thyroidectomy; these factors were correlated with biomarkers using regression analyses. RESULTS: Data were obtained from 104 patients, 28% with hereditary MTC. Preoperative calcitonin correlated with tumor size (P < .001) and postoperative serum calcitonin levels (P = .01) after multivariable adjustment for lymph node positivity, extent of operation, and hereditary MTC. No patient with a preoperative calcitonin level of <53 pg/mL (n = 20) had lymph node metastases. TNM stage (P = .001) and preoperative calcitonin levels (P = .04), but not extent of operation, independently correlated with the failure to normalize postoperative calcitonin. Postoperative CEA correlated with positive margins (adjusted P = 04). Neither preoperative nor postoperative CEA was correlated with lymph node positivity or extent of surgery. CONCLUSION: Preoperative serum calcitonin and TMN stage, but not extent of operation, were independent predictors of postoperative normalization of serum calcitonin levels. Future studies should evaluate preoperative serum calcitonin levels as a determinate of the extent of initial operation.

Accuracy of 4-dimensional computed tomography in poorly localized patients with primary hyperparathyroidism.

BACKGROUND: Four-dimensional computed tomography (4D-CT) utilizes multiplanar images and perfusion characteristics to identify abnormal parathyroid glands. We assessed the role of 4D-CT in patients with inconclusive preoperative ultrasound and sestamibi localization studies. METHODS: Adult patients with primary hyperparathyroidism with negative or discordant standard imaging who underwent both localization with 4D-CT and operative intervention for curative intent were included. Patient characteristics, 4D-CT scan results compared with operative findings, and curative proportion were assessed. RESULTS: Of the 60 patients, 4D-CT accurately lateralized 73% and localized 60% of abnormal glands found at operation. Single candidate lesions (46/60) were confirmed at operation in 70%. When multiple lesions were identified on 4D-CT (14/60), accuracy dropped to 29% (P = .03). The accuracy of 4D-CT was not different between primary and reoperative cases (P = .79). Of the 8 patients with multigland disease diagnosed perioperatively, 5 had multiple candidate lesions noted on 4D-CT. In 94% (48/51) of patients, a >50% drop in intraoperative parathormone (IOPTH) level was achieved after resection and 87% (48/55) had long-term cure with a median follow-up of 221 days. CONCLUSION: 4D-CT identifies the more than half of abnormal parathyroids missed by traditional imaging and should be considered in cases with negative or discordant sestamibi and ultrasound. Bilateral exploration is warranted when multiple candidate lesions are reported on 4D-CT. Multigland disease remains a challenging entity.

Surgical drains can be safely avoided in lateral neck dissections for papillary thyroid cancer.

BACKGROUND: Drains are widely used in lateral neck dissections (LNDs). Our objective was to compare outcomes of LNDs for papillary thyroid cancer (PTC) with and without drains. METHODS: One hundred sixty-five LNDs in 129 patients operated on from July 2001 to October 2008 were analyzed retrospectively. LNDs were divided according to the number of excised lymph nodes as follows: group A < median and group B > median. Further categorization was based on the use of a drain. Main outcome measures were wound complications requiring intervention. RESULTS: One hundred two LNDs were performed with a drain and 63 without. The overall rate of wound complications was 3%. There was no significant difference in complication rate between the drain and the non-drain group (group A: 1.8% vs 0; group B: 2.2% vs 7.9%, respectively). CONCLUSIONS: Significant seromas/hematomas are rare complications of LNDs. Patients who undergo LND for PTC without a drain show no significantly increased rate of these complications.

Clinical and cytological features predictive of malignancy in thyroid follicular neoplasms.

BACKGROUND: The preoperative diagnosis of malignancy in nodules suspicious for a follicular neoplasm remains challenging. A number of clinical and cytological parameters have been previously studied; however, none have significantly impacted clinical practice. The aim of this study was to determine predictive characteristics of follicular neoplasms useful for clinical application. METHODS: Four clinical (age, sex, nodule size, solitary nodule) and 17 cytological variables were retrospectively reviewed for 144 patients with a nodule suspicious for follicular neoplasm, diagnosed preoperatively by fine-needle aspiration (FNA), from a single institution over a 2-year period (January 2006 to December 2007). The FNAs were examined by a single, blinded pathologist and compared with final surgical pathology. Significance of clinical and cytological variables was determined by univariate analysis and backward stepwise logistic regression. Odds ratios (ORs) for malignancy, a receiver operating characteristic curve, and predicted probabilities of combined features were determined. RESULTS: There was an 11% incidence of malignancy (16/144). On univariate analysis, nodule size >OR=4.0 cm nears significance (p = 0.054) and 9 of 17 cytological features examined were significantly associated with malignancy. Three variables stay in the final model after performing backward stepwise selection in logistic regression: nodule size (OR = 0.25, p = 0.05), presence of a transgressing vessel (OR = 23, p < 0.0001), and nuclear grooves (OR = 4.3, p = 0.03). The predicted probability of malignancy was 88.4% with the presence of all three variables on preoperative FNA. When the two papillary carcinomas were excluded from the analysis, the presence of nuclear grooves was no longer significant, and anisokaryosis (OR = 12.74, p = 0.005) and presence of nucleolus (OR = 0.11, p = 0.04) were significantly associated with malignancy. Excluding the two papillary thyroid carcinomas, a nodule size >or=4 cm, with a transgressing vessel and anisokaryosis and lacking a nucleolus, has a predicted probability of malignancy of 96.5%. CONCLUSIONS: A combination of larger nodule size, transgressing vessels, and specific nuclear features are predictive of malignancy in patients with follicular neoplasms. These findings enhance our current limited predictive armamentarium and can be used to guide surgical decision making. Further study may result in the inclusion of these variables to the systematic evaluation of follicular neoplasms.

Thyroid surgery in octogenarians is associated with higher complication rates.

BACKGROUND: The incidence of thyroid nodules increases with age and little information is available regarding the risks of thyroid surgery in elderly patients. The aim of this study was to determine whether thyroid surgery in patients > or =80 is associated with higher complication rates. METHODS: Out of 3,568 patients undergoing thyroid surgery between July 2001 and October 2007 at a single institution, the records of 90 consecutive patients > or =80 years were reviewed retrospectively and compared with a cohort of 242 randomly selected patients aged 18-79, who underwent thyroid surgery during the same time period. Clinical variables included age, gender, pre-operative diagnosis, substernal component, previous surgery, final pathology, length of stay, comorbidities, American Society of Anesthesiologists (ASA) score, body mass index, postoperative complications, and mortality. RESULTS: Preoperative indications for surgery included benign disease in 51% vs 39%, suspected malignancy in 19% vs 26%, and suspected follicular neoplasms in 30% vs 35% in the octogenarian patient group (> or =80 years old) vs the younger patient cohort (P = NS). Octogenarians had 20% significant malignancy on final pathology vs 27% in the younger cohort (P = NS). The overall complication rate in the octogenarian group was 24% vs 9% in the younger cohort (P < .001). Male gender and ASA > or =3 were found to be independent risk factors for perioperative complications after thyroid surgery, while age alone was not. CONCLUSION: Age > or =80 is associated with higher morbidity after thyroid surgery, although not independently. Earlier operative intervention may be advised in those at high risk for disease progression, whereas follow-up strategies without operation may be advised for others.

Predictors of an accurate preoperative sestamibi scan for single-gland parathyroid adenomas.

OBJECTIVE: To investigate why some patients with single parathyroid adenomas have negative preoperative sestamibi scans. DESIGN: Retrospective review. SETTING: Tertiary care center. PATIENTS: Twenty-one patients with false-negative (FN) scans were compared with 22 patients with true-positive (TP) scans. All patients had single parathyroid adenomas. INTERVENTIONS: Neck exploration and removal of parathyroid adenomas. MAIN OUTCOME MEASURES: Age; sex; preoperative serum calcium and parathyroid hormone levels; gland weight; location; and pathologic features. RESULTS: There was no significant difference in age or preoperative serum calcium or parathyroid hormone levels. Gland weight was greater in the TP group compared with the FN group (mean +/- SD, 1336 +/- 1603 mg vs 475 +/- 365 mg; P = .04); 13 (62%) of the 21 glands in the FN group were located in the upper position, compared with 6 (27%) of the 22 glands in the TP group (P = .03). Ten of the 22 glands in the TP group consisted predominantly of oxyphil cells, compared with 2 of the 21 glands in the FN group (P = .02). A multivariate logistic regression model yielded the following factors that predicted an accurate scan: higher percentage of oxyphil cells (P = .03), heavier gland (P = .03), female sex (P = .04), and gland location in the lower position (P = .04). CONCLUSIONS: Smaller-volume parathyroid adenomas and those in the upper position are less likely to be localized with sestamibi scans. A TP scan correlates with oxyphil cell predominance, supporting a role for the mitochondrial-rich cell in sestamibi uptake and retention.

Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma.

BACKGROUND: We looked for mutations of the HRPT2 gene, which encodes the parafibromin protein, in sporadic parathyroid carcinoma because germ-line inactivating HRPT2 mutations have been found in a type of familial hyperparathyroidism--hyperparathyroidism-jaw tumor (HPT-JT) syndrome--that carries an increased risk of parathyroid cancer. METHODS: We directly sequenced the full coding and flanking splice-junctional regions of the HRPT2 gene in 21 parathyroid carcinomas from 15 patients who had no known family history of primary hyperparathyroidism or the HPT-JT syndrome at presentation. We also sought to confirm the somatic nature of the identified mutations and tested the carcinomas for tumor-specific loss of heterozygosity at HRPT2. RESULTS: Parathyroid carcinomas from 10 of the 15 patients had HRPT2 mutations, all of which were predicted to inactivate the encoded parafibromin protein. Two distinct HRPT2 mutations were found in tumors from five patients, and biallelic inactivation as a result of a mutation and loss of heterozygosity was found in one tumor. At least one HRPT2 mutation was demonstrably somatic in carcinomas from six patients. Unexpectedly, HRPT2 mutations in the parathyroid carcinomas of three patients were identified as germ-line mutations. CONCLUSIONS: Sporadic parathyroid carcinomas frequently have HRPT2 mutations that are likely to be of pathogenetic importance. Certain patients with apparently sporadic parathyroid carcinoma carry germ-line mutations in HRPT2 and may have the HPT-JT syndrome or a phenotypic variant.

Mutational analyses of RB and BRCA2 as candidate tumour suppressor genes in parathyroid carcinoma.

OBJECTIVE: Strong evidence indicates that at least one key tumour suppressor gene important for the development of malignant parathyroid tumours is located on chromosome 13, but the critical target gene remains unknown. Importantly, the region of acquired DNA loss includes two established tumour suppressor genes, the retinoblastoma gene, RB (RB1) and BRCA2. Resolution of whether RB or BRCA2 is the critical 13q tumour suppressor gene in parathyroid cancer requires analysis of these genes' sequences for intragenic inactivating mutations. Therefore, RB and BRCA2 were analysed in a group of parathyroid carcinomas in which mutations of these genes should be most readily detectable. PATIENTS AND DESIGN: Six parathyroid carcinomas from four patients which showed loss of heterozygosity (LOH) at the RB locus and/or 13q loss by comparative genomic hybridazation (CGH) were selected from a CGH/LOH-screened panel of 16 carcinoma specimens from 10 patients. These tumours were examined for mutations by direct sequencing of the complete 27-exon coding region, intron-exon boundaries and promoter of RB. The 26 coding exons and intron-exon boundaries of BRCA2 were also directly sequenced in seven parathyroid carcinomas with loss in the BRCA2 region. RESULTS: No microdeletions, insertions, or point mutations were detected in either RB or BRCA2 in any of the carcinomas. CONCLUSION: The absence of tumour-specific somatic mutations in RB and BRCA2 suggests that they are unlikely to act as classic tumour suppressor genes in the pathogenesis of parathyroid carcinomas. While decreased expression of these genes might contribute to parathyroid carcinomatosis in a secondary fashion and 13q loss warrants further study as a diagnostic marker for parathyroid carcinoma, the putative 13q tumour suppressor awaits identification.

The effect of surgery and radiotherapy on outcome of anaplastic thyroid carcinoma.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is an aggressive rare tumor. We analyzed our experience for prognosis and the effect of surgery and radiotherapy on patients with ATC. METHODS: We conducted a retrospective review of all patients (n = 67) with ATC treated at a tertiary care center from 1969 to 1999. Survivor median follow-up was 51 months. Tumor and patient characteristics and therapy were assessed for effect on survival by multivariate analysis. RESULTS: Patients presented with a neck mass (99%), change of voice (51%), dysphagia (33%), and dyspnea (28%). Surgery was performed in 44 of 67 patients, with 12 complete resections. The 6-month and 1- and 3-year survival rates were 92%, 92%, and 83% after complete resection; 53%, 35%, and 0% after debulking; and 22%, 4%, and 0% after no resection, respectively (P < .0001). A radiation dose of >45 Gy improved survival as compared with a lower dose (P = .02). Multivariate analysis showed that age < or = 70 years, absence of dyspnea or dysphagia at presentation, a tumor size < or = 5 cm, and any surgical resection improved survival (P < .05). CONCLUSIONS: Candidates for surgery with curative intent for ATC are patients < or = 70 years, tumors < or = 5 cm, and no distant disease. Radiotherapy >45 Gy improves outcome.