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.

Selective parathyroid venous sampling in reoperative parathyroid surgery: A key localization tool when noninvasive tests are unrevealing.

BACKGROUND: Preoperative localization studies are essential for parathyroid re-exploration. When noninvasive studies do not regionalize the abnormal parathyroid gland, selective parathyroid venous sampling may be employed. We studied the utility of parathyroid venous sampling in reoperative parathyroid surgery and the factors that may affect parathyroid venous sampling results. METHODS: Patients with hyperparathyroidism and previous cervical surgery undergoing evaluation for reoperative parathyroidectomy over a 20-year period were identified. Patients with indeterminate or negative noninvasive studies underwent parathyroid venous sampling. Parathyroid hormone values were mapped with a ≥2-fold increase above peripheral signifying positive parathyroid venous sampling. These results were correlated with reoperative findings. RESULTS: Parathyroid venous sampling was positive in 113 of 140 (81%). Re-exploration occurred in 75 (66%). Parathyroid venous sampling correctly detected the region of abnormal glands in 58 (77%). With 1 gradient, 1 abnormal gland was found in 81%. With multiple gradients, 1 abnormal gland was found in 78%, most often at the site with the largest gradient. Eighty percent of patients who underwent reoperative parathyroidectomy were biochemically cured. CONCLUSION: Parathyroid venous sampling can guide parathyroid re-exploration when noninvasive localizing studies are indeterminate. Expectation of 1 versus multiple remaining glands was key in interpreting the results.

Insulinoma: pathophysiology, localization and management.

Insulinoma is a rare neuroendocrine tumor that causes oversecretion of insulin and, as a result, patients present with symptoms of hypoglycemia. Fortunately, insulinomas are usually benign and solitary, and surgical cure rates are highly favorable. Most of these tumors occur sporadically, but they can also be associated with multiple endocrine neoplasia type-1 syndrome. The diagnosis is confirmed by a supervised fast, and early detection is important. Several preoperative and intraoperative techniques with various success rates have been employed in order to localize the lesion. When technically feasible, tumor enucleation is the procedure of choice; however, a more formal resection may be necessary for certain tumors. In the age of laparoscopy, the role of laparoscopic surgery in the management of insulinomas is continuing to attract attention. This review will discuss the historical background, pathogenesis, diagnosis, localization and management of insulinomas.

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.

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.

Endocrine surgery fellowship graduates past, present, and future: 8 years of early job market experiences and what program directors and trainees can expect.

BACKGROUND: Given the increasing number of endocrine surgery fellowship graduates, we investigated if expectations and job opportunities changed over time. METHODS: American Association of Endocrine Surgeons (AAES) fellowship graduates, surgery department chairs, and physician recruiters were surveyed. Univariate analysis was performed with JMP Pro 12 software. RESULTS: We identified 141 graduates from 2008-2015; survey response rate was 72% (n = 101). Compared to earlier graduates, fewer academic opportunities were available for the recent graduates who intended to join them (P = .001). Unlike earlier graduates, recent graduates expected to also perform elective general surgery, which ultimately represented a greater percentage of their practices (both P < .05). Interview offers increased for recent graduates, but job offers decreased. Overall, 84% of graduates matched their intended practice type and 98% reported being satisfied. Reponses from graduates, department chairs, and physician recruiters highlighted opportunities to improve mentor involvement, job search strategies, and online job board utilization. CONCLUSION: The endocrine surgery job market has diversified resulting in more graduates entering nonacademic practices and performing general surgery. This rapid evolution supports future analyses of the job market and opportunities for job creation. Almost every graduate reported job satisfaction, which encourages graduates to consider joining both academic and nonacademic practices equally.

Mapping endocrine surgery: Workforce analysis from the last six decades.

BACKGROUND: We analyzed the demographics of high-volume surgeons (HVS) for endocrine operations. METHODS: We characterized HVS by region, specialty, gender, teaching-affiliation, American Association of Endocrine Surgeons (AAES) membership, and decade they entered practice. Providers were general surgeons (GS) and otolaryngologists (ENT); fellowship trained (FT) or not FT (NFT). RESULTS: We identified 395 HVS in 47 states entering practice between 1958 and 2011. Sixty-eight percent were GS, 35% were FT, and 35% were AAES members. GS, FT surgeons, and endocrine surgery FT surgeons (ES) performed more operations per surgeon. More FT surgeons were in Northeast, West (W), and Midwest than Southeast (SE) and Southwest (SW; P < .0001). More teaching surgeons and AAES members were in the Northeast and Midwest than SE, W, and SW (P < .0001). FT-GS increased over decades (P < .0001) but not FT-ENT (P = .3). Representation of ES, AAES members, and females increased over decades (P < .0001). CONCLUSION: The workforce for endocrine operations displayed increased representation of GS, FT surgeons, and women, correlating with the profile of recent AAES fellowship graduates. More insight is needed to understand why most HVS were not AAES members. Regional disparities can guide the placement of endocrine surgeons into both academic and community practices, increasing trainee exposure and patient access to specialty care.

The endocrine surgery job market: a survey of fellows, department chairs, and surgery recruiters.

INTRODUCTION: Fifty endocrine surgery (ES) fellows have completed their training since the American Association of Endocrine Surgeons initiated a formal match process in 2007. This study was designed to better understand the job prospects of current and future endocrine surgeons and to evaluate the evolution of ES practices nationwide. METHODS: Three surveys were conducted of former fellows, surgery department chairs, and surgery recruiters. RESULTS: Of former fellows, 90% are working in academic centers and 10% in private practice. Average number of job interviews was 3.1 and job offers was 2.2. Eighty-eight percent have a practice that attends to ≥50% ES cases, and 45% practice entirely ES. Ninety-eight percent are satisfied with their job. Subjectively, 57% believe that there are not enough job opportunities for young endocrine surgeons, and 50% believe that there are too many ES fellowships. Department chair survey showed that the average number of endocrine surgeons in their department increased from 1.3 to 2.2 in the past decade. A recognized ES section exists in 49% of centers, and 39% of chairs feel that they will need to recruit another endocrine surgeon in the next 2 years. Only 3 of 10 recruiters were familiar with ES, and all had<5 of their hiring institutions asking for endocrine surgeons. CONCLUSIONS: To date, there have been adequate job opportunities to sustain currently trained endocrine surgeons. This contrasts with their subjective belief of limited job prospects. This information can guide the optimal number of fellowship positions and alerts the American Association of Endocrine Surgeons to the opportunity to promote the creation of formal ES sections.

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.

Impact of localization studies and clinical scenario in patients with hyperparathyroidism being evaluated for reoperative neck surgery.

BACKGROUND: Previous studies have focused on the success of localization studies (LSs) in patients undergoing reoperative parathyroid surgery; however, patients who did not undergo reexploration surgery have been excluded from analysis. In addition, the concept of whether clinical scenario (CS) suggests single- vs multiple-gland disease in reoperative strategy is often underemphasized. OBJECTIVE: To evaluate how LSs and CS direct operative strategy in patients being considered for reexploration. DESIGN: Retrospective review of a prospective database. SETTING: Tertiary referral center. PATIENTS: Two hundred three patients with hyperparathyroidism who underwent previous neck surgery. The CS stratified patients as candidates for single- or multiple-site exploration (or unknown). MAIN OUTCOME MEASURE: Ability of CS and LSs to direct successful reexploration. RESULTS: Of 203 patients, 27 were not explored owing to nonlocalizing studies. Of the remaining 176 patients, LSs accurately guided reexploration in 85%. However, when including the 27 nonexplored patients, the success of LSs decreased to 73%. The cure rate in reoperated patients was 96% but was reduced to 83% when including nonexplored patients. Of the reoperated patients, 83% had single-site disease and 17% had multiple-site disease. The positive predictive value of LSs in predicting single- or multiple-site disease was 92% and 73%, respectively. However, when stratified by CS, the positive predictive value increased to 95% for single-site disease and to 100% for multiple-site disease. CONCLUSIONS: Failure to cure patients was 4 times more likely to be due to nonlocalizing studies than to a failed reexploration. Stratification by CS was useful in the interpretation of LSs and in determining the most accurate reoperative approach.

The phenotype of primary hyperparathyroidism with normal parathyroid hormone levels: how low can parathyroid hormone go?

BACKGROUND: While normocalcemic hyperparathyroidism is well recognized in primary hyperparathyroidism (PHP), less is known about patients with high calcium but normal intact parathyroid hormone (iPTH). We aimed to describe this entity and designated it normohormonal primary hyperparathyroidism (NHPHP). METHODS: From a prospectively maintained database of patients undergoing bilateral parathyroid exploration for PHP, we identified and compared those with preoperative iPTH levels below (NHPHP) and above (typical PHP) normal reference peak (60 pg/mL). RESULTS: NHPHP occurred in 46 of 843 patients (5.5%) undergoing initial parathyroidectomy for PHP. All had hypercalcemia (11.1 mg/dL). Regarding preoperative iPTH, 7 patients (15%) had values <40 pg/mL, 19 (41%) had values <60 pg/mL; and 20 (44%) had intermittent values >60 pg/mL. Unlike patients with elevated iPTH, nearly all NHPHP patients had additional testing delaying the operation. Imaging correctly localized NHPHP parathyroid disease in 80%. At the time of operation, 74% of NHPHP patients had single adenomas. Intraoperatively postmobilization, using the same assay that was used preoperatively, 82% had PTH levels >60 pg/mL (mean, 279 pg/mL). During the follow-up period, iPTH levels remained lower among NHPHP patients (21 pg/mL) compared to 41 pg/mL for patients with preoperative iPTH 60 to 100 pg/mL and 56 pg/mL for patients with preoperative iPTH 100 to 200 pg/mL (P < .0001). CONCLUSION: Lower PTH set points may exist in some patients with otherwise typical PHP features. Although high normal iPTH is inappropriate for hypercalcemia and should suggest PHP, this disorder may occur with iPTH levels as low as 5 pg/mL. Awareness of the unusual phenotype of NHPHP may facilitate earlier diagnosis and surgery.