Preoperative Calcium and Parathyroid Hormone Values Are Poor Predictors of Gland Volume and Multigland Disease in Primary Hyperparathyroidism: A Review of 2000 Consecutive Patients.

OBJECTIVE: Calcium and parathyroid hormone (PTH) values are believed to have a linear relationship in patients with primary hyperparathyroidism and correlate with parathyroid gland size, with higher values predicting single-gland disease. In this modern series, these preoperative values were correlated with operative findings to determine their utility in predicting the gland involvement at parathyroid exploration. METHODS: Two thousand consecutive patients who underwent initial surgery for sporadic primary hyperparathyroidism from 2000 to 2014 were reviewed. All patients underwent a 4-gland exploration. Relationships between preoperative calcium and PTH values with the total gland volume of each patient were examined and stratified using the number of involved glands: single adenoma (SA), double adenoma (DA), and hyperplasia (H). RESULTS: There were 1274 (64%) SA, 359 (18%) DA, and 367 (18%) H cases. There was a poor correlation between preoperative calcium and PTH values (R = 0.37) and both poorly correlated with the total gland volume (R < 0.40). Similarly, subgroup analysis using the number of involved glands showed poor correlation. The mean total gland volume was similar among all subgroups (SA = 1.28 cm3, DA = 1.43 cm3, and H = 1.27 cm3; P = .52), implying that individual glands were smaller in multigland disease. SA was found in 271 (53%) of patients with calcium levels of ≤10.5 mg/dL and 122 (78%) with levels of ≥12 mg/dL (P < .001). CONCLUSION: This is the largest series correlating preoperative calcium and PTH values with operative findings of gland size and number of diseased glands. Although a lower calcium value predicts somewhat more multigland disease, the overall poor correlation should make the parathyroid surgeon aware that gland size and multigland disease cannot be predicted by preoperative laboratory testing.

A critical analysis of laparoscopic and open approaches to sporadic pancreatic insulinoma resection in the modern era.

BACKGROUND: A single center experience with sporadic pancreatic insulinoma was analyzed to develop an algorithm for modern surgical management. METHODS: Thirty-four patients undergoing surgery from 2001 to 2019 were reviewed. RESULTS: The majority underwent enucleation (10 laparoscopic, 15 open). Laparoscopy was performed in 22 patients with conversion to open in 11, mostly related to the proximity of the tumor to the pancreatic duct (n = 4). Tumors on the anterior and posterior surface of the pancreas in all anatomic locations were completed with laparoscopic enucleation. Overall, the clinically-relevant postoperative pancreatic fistula (CR-POPF) rate was 21%, with no difference between laparoscopic versus open enucleation (10% vs 20%, p = 0.50) or enucleation versus resection (16% vs 33%, p = 0.27). Laparoscopic enucleation had shorter median hospital length of stay (LOS) compared with open (4 vs 7 days, p = 0.02). CONCLUSIONS: Laparoscopic enucleation does not increase the CR-POPF risk and provides an advantage with a shorter hospital LOS in select patients. Tumor location and relationship to the pancreatic duct guide surgical decision-making. These findings highlight tumor-specific criteria that would benefit from a minimally invasive approach.

Use of Preoperative Imaging in Primary Hyperparathyroidism.

CONTEXT: Preoperative imaging is performed routinely to guide surgical management in primary hyperparathyroidism, but the optimal imaging modalities are debated. OBJECTIVE: Our objectives were to evaluate which imaging modalities are associated with improved cure rate and higher concordance rates with intraoperative findings. A secondary aim was to determine whether additive imaging is associated with higher cure rate. DESIGN, SETTING, AND PATIENTS: This is a retrospective cohort review of 1485 adult patients during a 14-year period (2004-2017) at an academic tertiary referral center that presented for initial parathyroidectomy for de novo primary hyperparathyroidism. MAIN OUTCOME MEASURES: Surgical cure rate, concordance of imaging with operative findings, and imaging performance. RESULTS: The overall cure rate was 94.1% (95% confidence interval, 0.93-0.95). Cure rate was significantly improved if sestamibi/single-photon emission computed tomography (SPECT) was concordant with operative findings (95.9% vs. 92.5%, P = 0.010). Adding a third imaging modality did not improve cure rate (1 imaging type 91.8% vs. 2 imaging types 94.4% vs. 3 imaging types 87.2%, P = 0.59). Despite having a low number of cases (n = 28), 4-dimensional (4D) CT scan outperformed (higher sensitivity, specificity, positive predictive value, negative predictive value) all imaging modalities in multiglandular disease and double adenomas, and sestamibi/SPECT in single adenomas. CONCLUSIONS: Preoperative ultrasound combined with sestamibi/SPECT were associated with the highest cure and concordance rates. If pathology was not found on ultrasound and sestamibi/SPECT, additional imaging did not improve the cure rate or concordance. 4D CT scan outperformed all imaging modalities in multiglandular disease and double adenomas, and sestamibi/SPECT in single adenomas, but these findings were underpowered.

Recognition of primary hyperparathyroidism: Delayed time course from hypercalcemia to surgery.

BACKGROUND: Under recognition of primary hyperparathyroidism can lead to delays in diagnosis and surgical management. We aimed to establish a time course for primary hyperparathyroidism from initial hypercalcemia to surgery and evaluate the impact of guidelines for surgical referral on this time course. METHODS: A retrospective review was conducted on all patients undergoing parathyroidectomy for primary hyperparathyroidism in 2013 at the Cleveland Clinic. Patients were stratified by adherence to 2008 indications for surgery guidelines, age, calcium values, osteoporosis, history of nephrolithiasis, 24-hour urinary calcium values, and estimated glomerular filtration rate. RESULTS: 219 patients with sporadic primary hyperparathyroidism underwent initial surgery. Twenty-three (10.5%) normocalcemic patients were excluded. Time course from initial hypercalcemia to surgery was 3.9 years for 137 (70%) patients who met objective guideline criteria versus 3.8 years for 59 (30%) patients who did not meet objective guideline criteria (P = .87). Stratification by age <50 years and calcium value >11.5 mg/dL revealed earlier times to surgery. However, osteoporosis, nephrolithiasis, 24-hour urinary calcium values, and estimated glomerular filtration rate had no impact. CONCLUSION: There is a delayed time course for patients with sporadic primary hyperparathyroidism from initial hypercalcemia to surgery. Despite published objective criteria, one third of the patients who underwent surgery did not meet criteria, signifying the importance of clinician and patient decision making. Furthermore, patients with osteoporosis and nephrolithiasis who can significantly benefit from surgical cure have no apparent impact on the time to surgery. Overall, the objective guideline criteria have no effect in referral patterns suggesting a call for revision.

RECEIVER OPERATING CHARACTERISTIC ANALYSIS OF INTRAOPERATIVE PARATHYROID HORMONE MONITORING TO DETERMINE OPTIMUM SENSITIVITY AND SPECIFICITY: ANALYSIS OF 896 CASES.

Objective: While intraoperative parathyroid hormone (IOPTH) monitoring with a ≥50% drop commonly guides the extent of exploration for primary hyperparathyroidism (pHPT), receiver operating characteristic (ROC) analysis has not been performed to determine whether other criteria yield better sensitivity and specificity. The aim of this study was to identify the optimum percent change of IOPTH following removal of the abnormal parathyroid pathology, in order to predict biochemical cure. Secondary aims were to identify patient subgroups with increased area under the ROC curve (AUC) and the need for moderated criteria. Methods: A retrospective review was performed on patients undergoing primary parathyroid surgery for sporadic pHPT between 1999 and 2010 at a tertiary center for endocrine surgery. Eight hundred and ninety-six patients with primary hyperparathyroidism were included. Multigland disease (MGD) was defined as the intraoperative detection of more than 1 enlarged hypercellular gland or persistent disease after single gland excision. ROC analysis was used to determine the value with the best performance at predicting MGD, following bilateral exploration. Results: MGD was diagnosed in 174 patients (19.4%). ROC analysis demonstrated an AUC of 0.69. An IOPTH drop of 72% was the point of optimal discrimination with a sensitivity of 55% and specificity of 76% for predicting MGD. Subgroup analysis by preoperative calcium, preoperative PTH, localization studies, or pre- and post-excision IOPTH, did not identify any factors associated with an improved AUC. Conclusion: To our knowledge, this is the first study to use ROC analysis in a large patient cohort. An IOPTH drop of 72% was found to have optimal discriminating ability. We failed to identify a subset of patients for whom there was substantial improvement in the AUC, sensitivity, or specificity. Abbreviations: AUC = area under the ROC curve; BE = bilateral neck exploration; FE = focal parathyroid exploration; IOPTH = intraoperative parathyroid hormone; MGD = multigland disease; MIBI = Tc99m-sestamibi I-123 subtraction single-photon emission computed tomography/computed tomography; pHPT = primary hyperparathyroidism; ROC = receiver operating characteristic; SGD = single gland disease; US = surgeon-performed neck ultrasound.

Importance of surgeon-performed ultrasound in the preoperative nodal assessment of patients with potential thyroid malignancy.

INTRODUCTION: A comprehensive cervical ultrasound evaluation is essential in the operative planning of patients with thyroid disease. Reliance on radiographic reports alone may result in incomplete operative management as pathologic lymph nodes are often not palpable and evaluation of the lateral neck is not routine. This study examined the role of surgeon-performed ultrasound in the evaluation of patients who underwent lateral neck dissection for thyroid cancer. METHODS: We conducted a retrospective review of a prospectively maintained database of patients who underwent therapeutic lymph node dissection for thyroid cancer between 2001 and 2016 at our tertiary referral center. All patients had surgeon-performed ultrasound preoperatively by 1 of 7 endocrine surgeons. These findings were compared with prereferral imaging studies to determine the value of surgeon-performed ultrasound to their overall treatment. RESULTS: Of 92 patients who underwent thyroidectomy with lateral neck dissection, 97% had prereferral imaging of the neck (ultrasonography, computed tomography, positron emission tomography). Of these patients, nodal disease was suggested by computed tomography scanning in 70.8% and by ultrasonography in 54%. Of all patients, 45% had positive lateral neck nodes detected only on surgeon-performed ultrasound despite prior neck imaging. Nodal disease was identified in 50% of patients with only 1 study and 50% of patients with greater than 1 study before surgeon-performed ultrasound. Of patients with nodes detected by surgeon-performed ultrasound, only 67% had a prereferral diagnosis of thyroid cancer. CONCLUSIONS: Our data demonstrate that reliance on standard preoperative imaging alone would have led to an incorrect initial operation in 45% of our patients. Awareness of the limitations of prereferral imaging is important for surgeons treating patients with thyroid and parathyroid disease. Surgeon-performed ultrasound is a useful tool in the diagnosis and accurate staging of patients.

Pattern of calcium and parathyroid hormone normalization at 12-months follow-up after parathyroid operation.

BACKGROUND: At 12 months after a parathyroid operation, we expect cured patients to have biochemical profiles similar to those of healthy individuals. The aim of the current study was to compare the biochemical characteristics patients at 12 months after parathyroidectomy for primary sporadic hyperparathyroidism with those of healthy controls. METHODS: A total of 547 patients who underwent parathyroid neck operation for primary sporadic hyperparathyroidism from 2000-2014 were analyzed. A control group consisted of 74 healthy subjects. Calcium and parathyroid hormone were collected perioperatively. Graphic plots of the relationship between calcium versus parathyroid hormone (95% confidence intervals) were used to compare the biochemical profiles of patients after parathyroid operation and controls. RESULTS: Preoperatively, patients with primary sporadic hyperparathyroidism had a calcium level of 10.9 ± 0.5 mg/dL and parathyroid hormone level of 124.4 ± 68.5 pg/dL vs controls' values of 9.2 ± 0.3 mg/dL and 34.4 ± 13.4 pg/dL, respectively. Before operation, all primary sporadic hyperparathyroidism patients had calcium versus parathyroid hormone values outside the normal zone. At 12 months after operation, 335 (69%) patients showed normalization of the chemical profile; 13 (2.7%) had absolute elevation of calcium and parathyroid hormone, reflecting persistent disease; 2 (0.4%) patients had hypoparathyroidism after subtotal parathyroidectomy; and 149 (31%) had calcium and parathyroid hormone values outside the normal zone, not fitting into the above categories. There were no marked differences between patients with simple adenoma those with multiple-gland disease. CONCLUSION: Longer follow-up might be needed for patients after parathyroid operation to confirm stabilization of biochemical profiles.

Use of Calcium and Parathyroid Hormone Nomogram to Distinguish Between Atypical Primary Hyperparathyroidism and Normal Patients.

BACKGROUND: The diagnosis of primary hyperparathyroidism (1°HP) has become more complex, as fewer patients present with classic phenotype of concomitant elevation of calcium and parathyroid hormone (PTH). In addition, the distinction between normal versus abnormal patients is challenging, with an increasing number of patients with 1°HP, who have calcium and/or PTH values within the "reference" range. Patients with "inappropriately" elevated PTH values relative to their serum calcium are considered to have 1°HP. METHODS: The study population consisted of 1753 patients with pathologically proven 1°HP and 74 healthy control patients. Nomograms were created by plotting PTH versus calcium of the two groups. The 95 % confidence zone of calcium and PTH for normal individuals was plotted and compared to patients with 1°HP. RESULTS: The comparison of control and disease groups showed a clear demarcation zone on the plots of calcium versus PTH. In the group of 1°HP, 70 % had classic 1°HP presentation with the concomitant elevation of both calcium (≥10.5 mg/dL) and PTH (≥65 pg/dL). 21 % had "normocalcemic" HP with calcium ≤10.5 mg/dL and PTH ≥65 pg/dL. 6 % had "normohormonal" HP with calcium ≥10.5 mg/dL and PTH ≤65 pg/dL. 3 % had both calcium and PTH within the reference range. 68.5 % of patients had single adenoma, 16 % double adenoma, and 15.5 % hyperplasia. CONCLUSION: This nomogram serves as a diagnostic tool to distinguish normal patients from those with 1°HP, particularly those with atypical presentations. This recognition would permit previously observed patients to benefit from curative surgery.

Value of Prophylactic Cervical Thymectomy in Parathyroid Hyperplasia.

BACKGROUND: In parathyroid hyperplasia (HPT), parathyroid glands within the cervical thymus are a cause for recurrence. As a result of differences in pathophysiology, variable practice patterns exist regarding performing bilateral cervical thymectomy (BCT) in primary hyperplasia versus hyperplasia from renal failure or familial disease. The objective of this study was to capture patients where thymic tissue was found with subtotal parathyroidectomy (PTX) and intended BCT, identify number of thymic supernumerary glands (SNGs), and determine overall cure rate. METHODS: Retrospective review of patients with four-gland exploration and intended BCT for HPT from 2000 to 2013 was performed. Identification of thymic tissue and SNGs were determined by operative/pathology reports. Univariate analysis identified differences in cure rate for patients undergoing subtotal PTX with or without BCT. RESULTS: Thymic tissue was found in 52 % of 328 primary HPT (19 % unilateral, 33 % bilateral), 77 % of 128 renal HPT (28 % unilateral, 49 % bilateral), and 100 % of familial HPT (24 % unilateral, 76 % bilateral) patients. Nine percent of primary, 18 % of renal, and 10 % of familial HPT patients had SNGs within thymectomy specimens. Cure rates of primary HPT patients with BCT were 99 % compared to 94 % in subtotal PTX alone. Renal HPT cure rates were 94 % with BCT compared to 89 % without BCT. CONCLUSIONS: Renal HPT patients benefited most in cure when thymectomy was performed. Although the rate of SNGs found in primary HPT was lower than renal HPT, the cure rate mimicked the pattern in renal disease. Furthermore, the incidences of SNGs in primary and familial HPT were similar. On the basis of these data, we advocate that BCT be considered in primary HPT when thymic tissue is readily identified.

Adrenocortical cancer update.

Although preoperative clinical, biochemical, and radiologic features can aid in the diagnosis of adrenocortical cancer (ACC), uncertainty often remains. This diagnostic ambiguity and the subsequent potential for an inadequate surgical resection have likely contributed to the currently dismal disease-free survival, although unsettlingly high rates of locoregional recurrences still persist even in the setting of a supposedly R0 resection. Refinements in both diagnostic criteria and surgical techniques, as well as the increasing use and study of novel multimodality therapies for ACC, have provided advances in the treatment of these patients, and renewed hope for meaningful improvements in patient outcomes.

Line-associated thrombosis as the major cause of hospital-acquired deep vein thromboses: an analysis from National Surgical Quality Improvement Program data and a call to reassess prophylaxis strategies.

BACKGROUND: Quality improvement has mitigated the occurrence of postoperative deep vein thromboses (DVTs); however, despite adherence to protocols, they continue to occur. This study aimed to characterize their rate and distribution at our institution, and appropriate use of thromboprophylaxis. METHODS: Local American College of Surgeons National Surgical Quality Improvement Program data were queried for general surgery cases complicated by DVT from 2009 to 2011. Medical records were evaluated to ascertain the following: classify DVTs by site, ascertain if appropriate prophylactic measures were instituted, evaluate treatment instituted, evaluate the occurrence of a PE if the DVT was line-associated, and if so, the indication for the central line. RESULTS: Of 1,857 patients, 39 had postoperative DVTs (2.1%). Fourteen lower-extremity (35.9%) DVTs, 4 central (10%) DVTs, and 21 upper-extremity (53.8%) DVTs (UEDVTs) were captured. All but 2 had appropriate thromboprophylaxis. All but one UEDVT was line-associated. Diagnoses were prompted by symptoms in 72% of the patients. Pulmonary emboli developed in 3 of 39 patients. CONCLUSIONS: An unexpected finding was that line-associated UEDVTs comprised over half of all DVTs, mostly in patients without cancer. This analysis highlights the need for more selective central-line use; choosing peripheral access may reduce DVT rates further. Improved pharmacoprophylaxis protocols would likely benefit this population.

A multi-institutional international study of risk factors for hematoma after thyroidectomy.

BACKGROUND: Cervical hematoma can be a potentially fatal complication after thyroidectomy, but its risk factors and timing remain poorly understood. METHODS: We conducted a retrospective, case-control study identifying 207 patients from 15 institutions in 3 countries who developed a hematoma requiring return to the operating room (OR) after thyroidectomy. RESULTS: Forty-seven percent of hematoma patients returned to the OR within 6 hours and 79% within 24 hours of their thyroidectomy. On univariate analysis, hematoma patients were older, more likely to be male, smokers, on active antiplatelet/anticoagulation medications, have Graves' disease, a bilateral thyroidectomy, a drain placed, a concurrent parathyroidectomy, and benign pathology. Hematoma patients also had more blood loss, larger thyroids, lower temperatures, and higher blood pressures postoperatively. On multivariate analysis, independent associations with hematoma were use of a drain (odds ratio, 2.79), Graves' disease (odds ratio, 2.43), benign pathology (odds ratio, 2.22), antiplatelet/anticoagulation medications (odds ratio, 2.12), use of a hemostatic agent (odds ratio, 1.97), and increased thyroid mass (odds ratio, 1.01). CONCLUSION: A significant number of patients with a postoperative hematoma present >6 hours after thyroidectomy. Hematoma is associated with patients who have a drain or hemostatic agent, have Graves' disease, are actively using antiplatelet/anticoagulation medications or have large thyroids. Surgeons should consider these factors when individualizing patient disposition after thyroidectomy.

Trends and disparities in education between specialties in thyroid and parathyroid surgery: An analysis of 55,402 NSQIP patients.

PURPOSE: To determine practice patterns/outcomes and educational opportunities in endocrine surgery by resident involvement in general surgery (GS) and otolaryngology (ENT). METHODS: We queried the American College of Surgeon National Surgical Quality Improvement Program for thyroid/parathyroid operations. Resident involvement was categorized by postgraduate year (PGY) and specialty. RESULTS: Of 38,257 thyroid patients, attendings alone performed 28% in GS versus 65% in ENT, and of 17,145 parathyroid patients, 22.1% vs 66.5%. Of GS cases done with housestaff, the percentages with junior residents (PGY1-3), senior residents (PGY4,5), and fellows were 42%, 50%, and 7%, respectively, whereas for ENT operations, the percentages were 35%, 46%, and 16%. For parathyroidectomies, the percentages were 41.1%/46.8%/12.1% vs 38.7%/45.9%/15.5%. Operative time was less for GS (115 minutes) versus ENT (123 minutes). Time in the operating room increased with increasing PGY in ENT, but not in GS. Case complexity and outcomes were similar. Duration of hospital stay was greater in ENT. CONCLUSION: No differences exist in case complexity between specialties. More thyroid/parathyroid operations are performed with residents in GS; junior residents in GS perform a large percentage of these cases (∼40%), indicating early exposure to endocrine surgery and balanced experience between resident levels with minimal effect of fellows. Although junior residents receive exposure in ENT, a greater proportion is performed by fellows. Outcomes were similar by resident level, except operative time, which was greater for ENT at all levels. Ultimately, equal outcomes but lesser operating times and durations of hospital stay are seen with GS residents than their ENT counterparts.

Complementary use of resection and radiofrequency ablation for the treatment of colorectal liver metastases: an analysis of 395 patients.

BACKGROUND: Liver resection and radiofrequency ablation (RFA) are two surgical options in the treatment of patients with colorectal liver metastases (CLM). The aim of this study was to analyze patient characteristics and outcomes after resection and RFA for CLM from a single center. METHODS: Between 2000 and 2010, 395 patients with CLM undergoing RFA (n = 295), liver resection (n = 94) or both (n = 6) were identified from a prospective IRB-approved database. Demographic, clinical and survival data were analyzed using univariate and multivariate analyses. RESULTS: RFA patients had more comorbidities, number of liver tumors and a higher incidence of extrahepatic disease compared to the Resection patients. The 5-year overall actual survival was 17 % in the RFA, 58 % in the Resection group (p = 0.001). On multivariate analysis, multiple liver tumors, dominant lesion >3 cm, and CEA >10 ng/ml were independent predictors of overall survival. Patients were followed for a median of 20 ± 1 months. Liver and extrahepatic recurrences were seen in 69 %, and 29 % of the patients in the RFA, and 40 %, and 19 % of the patients in the Resection group, respectively. CONCLUSIONS: In this large surgical series, we described the characteristics and oncologic outcomes of patients undergoing resection or RFA for CLM. By having both options available, we were able to surgically treat a large number of patients presenting with different degrees of liver tumor burden and co-morbidities, and also manage liver recurrences in follow-up.

Falsely low parathyroid hormone secondary to biotin interference: a case series.

OBJECTIVE: To present a case series on biotin interference in parathyroid hormone (PTH) level measurement. METHODS: We review the presentation and management of patients at our institution evaluated for unexpectedly low PTH levels while taking biotin supplements in the setting of high or normal serum calcium. RESULTS: Two patients presented with surprising low parathyroid levels--one during preoperative evaluation for hyperparathyroidism and another during postoperative follow-up after subtotal parathyroidectomy. The patients were found to be taking 1,500 mcg and 5,000 mcg of biotin per day, respectively. The role of biotin interference was confirmed in one of the patients when she was retested off biotin, and PTH levels responded appropriately. Biotin supplements remain as unbound molecules in the serum, thus interfering with PTH enzyme-linked immunosorbent assay (ELISA) results and falsely depressing the PTH level. CONCLUSION: Biotin supplement use has expanded over the years, ranging from medically endorsed therapies to home remedies. Review of the 2 ELISA systems used at our institution demonstrates that free biotin mimics the biotinylated antibody used in the detection process. Screening for biotin use prior to PTH measurement and automatic biotin levels for clinically aberrant PTH levels provide the clinician with a true PTH level--lowering the disease burden of untreated hyperparathyroidism while avoiding unnecessary work-ups for other processes.

The prevalence of undiagnosed and unrecognized primary hyperparathyroidism: a population-based analysis from the electronic medical record.

BACKGROUND: The electronic medical record (EMR) of a large, tertiary referral center was examined to study the prevalence of undiagnosed and unrecognized primary hyperparathyroidism (PHPT). METHODS: The EMR was queried for outpatient serum calcium >10.5 mg/dL over a 2-year period. RESULTS: Of 2.7 million patients, 54,198 (2%) had hypercalcemia (>10.5 mg/dL). In a 2-year sample of 7,269 patients, 1.3% (95 patients) had a recorded diagnosis of PHPT, and 0.3% (16 patients) had parathyroidectomy. Of the remaining patients, parathyroid hormone (PTH) values were recorded in 32% (2,337 patients). Of patients with PTH measured, 71% (1,662 patients) had PHPT (PTH > 30 pg/mL). Patients with calcium of 11.1­11.5 mg/dL were most likely to have PHPT (55%). Patients with calcium >12 mg/dL were most likely to have PTH measured (52%). Of hypercalcemic patients, 67% never had PTH obtained, 28% of whom were likely to have PHPT. It is estimated that 43% of hypercalcemic patients are likely to have PHPT. The estimated prevalence of PHPT in the general population is 0.86%. CONCLUSION: PHPT is a more common disorder than previously documented. It is crucial to evaluate even mild hypercalcemia, because 43% of these patients have PHPT. PHPT is underdiagnosed and undertreated.

Should patients with Cowden syndrome undergo prophylactic thyroidectomy?

BACKGROUND: Cowden syndrome (CS) is dominantly inherited and predisposes patients to tumors in multiple organs. We characterized CS-associated malignant and benign thyroid disease. METHODS: Of data from 3,477 prospectively recruited CS patients with known genetic analysis, we analyzed 225 PTEN mutation+ patients whose treatment occurred at our center (n = 25) or other hospitals nationwide (n = 200). RESULTS: A total of 32 of 225 PTEN mutation+ patients (14%) had thyroid cancer: 52% papillary, 28% follicular-variant papillary, 14% follicular, and 6% anaplastic. Median age at diagnosis was 35 years compared with 49 years for Surveillance Epidemiology and End Results population data. Initial thyroid ultrasonography in 16 of 25 patients revealed thyroiditis/goiters in all >13 years age, leading to FNA in 7 (64%), thyroidectomy in 3 (27%), and new cancer diagnosis in 2 (18%). Three with severe autism required intraoperative sedation for ultrasonography. A total of 9 of 25 patients were monitored after multiple partial thyroidectomies for goiters by age 42 (n = 5), thyroiditis, or cancer detected by age 36 (n = 3). CONCLUSION: PTEN mutation+ patients with CS have an enormous prevalence of thyroid disease. Earlier screening may be advisable because thyroiditis and nodules are seen by the time patients reach adolescence, and cancer diagnosis occurs on average 14 years earlier than expected. Furthermore, the risks observed may justify prophylactic total thyroidectomy in select, if not all, patients, particularly those with developmental disorders.

Calculating an individual maxPTH to aid diagnosis of normocalemic primary hyperparathyroidism.

BACKGROUND: We aimed to validate a nomogram for diagnosing primary hyperparathyroidism (PHP), particularly when normocalcemic PHP and vitamin D (VitD25) deficiency coexist. METHODS: The nomogram calculates maximal upper limit of normal PTH unique for each person by maxPTH = 120 - [6*calcium] - [½*VitD25] + [»*age]. PHP is suspected when serum PTH exceeds maxPTH. Normocalcemic PHP (NCPHP) was defined as always normal serum calcium (8.5-10.5 mg/dL) with PTH >60 pg/mL preoperatively and VitD25 deficiency as <31 ng/mL. RESULTS: A total of 477 patients had operatively and histologically proven PHP. Overall and including those with classical presentation (high serum levels of calcium and PTH), the nomogram predicted PHP in 97% patients. A total of 66 had NCPHP: 47 with low VitD25 levels (20 ± 0.4 ng/mL) made initial PHP diagnosis challenging; 19 had normal VitD25 status. Although the level of serum calcium concentrations were equivalent in these 2 groups (10.1 ± 0.4 mg/dL), PTH was greater in patients with concurrent VitD25 deficiency (129 vs 97 pg/mL, P = .04). However, when used to calculate maxPTH, the nomogram predicted PHP correctly in all 66 NCPHP patients (100%). CONCLUSION: The maxPTH nomogram functions as expected to classify patients with PHP and may aid in the diagnosis of NCPHP regardless of vitamin D status and repletion, reassuring primary providers and surgeons alike to embark on appropriate and timely PHP management.

A new classification of positive sestamibi and ultrasound scans in parathyroid localization.

BACKGROUND: Ultrasound (US) and sestamibi (MIBI) are traditionally considered positive or negative. The purpose of this study was to define and test a new scoring system for MIBI and US and to determine whether this can improve their accuracy for primary hyperparathyroidism. METHODS: This is a prospective study of 200 consecutive patients with primary hyperparathyroidism who had a single uptake on MIBI scans before bilateral neck exploration at a tertiary academic center between 2007 and 2008. These patients also had surgeon-performed neck US in the office, which was scored as "typical" or "atypical" based on how characteristic the image resembled a parathyroid gland. The MIBI uptake was scored by the nuclear medicine specialist as "weak," "moderate," or "strong" compared with the signal intensity of the thyroid. US and MIBI scoring was done preoperatively and their findings were compared with operative data. RESULTS: Of 200 patients, 71 % had a single adenoma, 12 % had double adenomas, and 17 % had four-gland hyperplasia. A weak, moderate, and strong signal on MIBI had an accuracy of 23, 47, and 72 %, respectively, in demonstrating single-gland disease. An atypical versus typical US appearance was accurate in 55 and 74 % of the time, in identifying single-gland disease. CONCLUSIONS: An appraisal of US and MIBI positivity in relation to image characteristics affects the reliability of both studies. This information should be kept in mind when selecting patients for focal neck exploration.

Robotic transaxillary endocrine surgery: a comparison with conventional open technique.

BACKGROUND: Robotic transaxillary (RT) endocrine surgery may improve cosmetic outcomes. We report our initial experience in RT thyroid and parathyroid surgery and the associated learning curve, and compare early surgical outcomes to those of open thyroidectomy (OT) and focal parathyroidectomy (FP). METHODS: A prospective database review identified patients who had undergone RT endocrine surgery. A case-matched group who underwent OT or FP was also identified. Demographics, histopathology, operative outcomes, and follow-up data were collected. Groups were compared using Student's t test and the χ(2) test. RESULTS: Fifteen RT procedures were performed: 11 RT thyroidectomies (6 total, 5 lobectomies) and 4 RT parathyroidectomies (2 focal, 2 unilateral), representing 5.9% and 2.2% of thyroidectomies and parathyroidectomies performed. The OT group contained 16 patients (13 totals, 3 lobectomies). The FP group contained 12 patients. There was no significant difference in age, gender, BMI, pathology, or complications between the groups. Mean operating time was significantly longer in the RT group (232 vs. 109 min, P = 0.0002) as was mean incision length (6 vs. 3.6 cm, P < 0.0001). No RT procedures were converted and no major complications occurred. Operating time decreased significantly over consecutive cases demonstrating a learning curve. CONCLUSIONS: RT thyroidectomy and parathyroidectomy can be performed safely by specialist endocrine surgeons, early in their learning curve, without an increased complication rate, albeit with significantly longer operating times.