Emergency department use after outpatient thyroidectomy across three states.

BACKGROUND: Although outpatient thyroidectomy has become common, few large-scale studies have examined post-thyroidectomy emergency department use, readmission, and encounters not resulting in readmission, known as "treat-and-release" encounters. We evaluated post-outpatient thyroidectomy emergency department use and readmission and characterized associated factors. METHODS: Using the Healthcare Cost and Utilization Project databases, we identified adult outpatient (same-day or <24-hour discharge) thyroidectomies performed in Florida, Maryland, and New York from 2016 to 2017. We identified the procedures linked with emergency department treat-and-release encounters and readmissions within 30 days postoperatively and the factors associated with post-thyroidectomy emergency department use and readmission. RESULTS: Of the 17,046 patients who underwent outpatient thyroidectomy at 374 facilities, 7.5% had emergency department treat-and-release encounters and 2.3% readmissions. The most common reasons for emergency department treat-and-release encounters (9.9%) and readmissions (22.2%) were hypocalcemia-related diagnoses. Greater odds of treat-and-release were associated with identifying as non-Hispanic Black (adjusted odds ratio: 1.5, 95% confidence interval: 1.3-1.8) or Hispanic race/ethnicity (adjusted odds ratio: 1.4, 95% CI: 1.1-1.6), having Medicaid insurance (adjusted odds ratio: 2.7, 95% CI: 2.3-3.2), and living in non-metropolitan areas (adjusted odds ratio: 1.6, 95% CI: 1.1-2.2). We observed no associations between these factors and the odds of readmission. CONCLUSION: Emergency department use after outpatient thyroidectomy is common. Racial, ethnic, socioeconomic, and geographic disparities are associated with treat-and-release encounters but not readmissions. Standardization of perioperative care pathways, focusing on identifying and addressing specific issues in vulnerable populations, could improve care, reduce disparities, and improve patient experience by avoiding unnecessary emergency department visits after outpatient thyroidectomy.

Association between travel distance and overall survival among patients with adrenocortical carcinoma.

BACKGROUND AND OBJECTIVES: Regionalization of care is associated with improved perioperative outcomes after adrenalectomy. However, the relationship between travel distance and treatment of adrenocortical carcinoma (ACC) is unknown. We investigated the association between travel distance, treatment, and overall survival (OS) among patients with ACC. METHODS: Patients diagnosed with ACC between 2004 and 2017 were identified with the National Cancer Database. Long distance was defined as the highest quintile of travel (≥42.2 miles). The likelihood of surgical management and adjuvant chemotherapy (AC) were determined. The association between travel distance, treatment, and OS was evaluated. RESULTS: Of 3492 patients with ACC included, 2337 (66.9%) received surgery. Rural residents were more likely to travel long distances for surgery than metropolitan residents (65.8% vs. 15.5%, p < 0.001), and surgery was associated with improved OS (HR 0.43, 95% CI 0.34-0.54). Overall, 807 (23.1%) patients received AC with rates decreasing approximately 1% per 4-mile travel distance increase. Also, long distance travel was associated with worse OS among surgically treated patients (HR 1.21, 95% CI 1.05-1.40). CONCLUSIONS: Surgery was associated with improved overall survival for patients with ACC. However, increased travel distance was associated with lower likelihood to receive adjuvant chemotherapy and decreased overall survival.

Evaluation and Management of Primary Hyperaldosteronism.

Primary hyperaldosteronism is an important and increasingly prevalent cause of hypertension that is characterized by unregulated aldosterone excess. More than 90% of primary hyperaldosteronism cases are attributable to either idiopathic adrenal hyperplasia or aldosterone-producing adenomas. The approach to the diagnosis of primary hyperaldosteronism should be step-wise, starting with screening of at-risk populations, confirmatory testing for positively screened patients, and subtype classification in order to direct surgical or medical management. Based on current guidelines, subtype classification of primary hyperaldosteronism should be determined with both imaging and adrenal vein sampling (AVS), reserving deferment of AVS for a selective subset of patients.

Surgical Management of Lymph Node Compartments in Papillary Thyroid Cancer.

Although papillary thyroid cancer (PTC) commonly metastasizes to cervical lymph nodes, prophylactic central neck dissection is controversial. The primary treatment for lymph node metastases is surgical resection. Patients diagnosed with PTC should be assessed preoperatively by cervical ultrasound to evaluate central and lateral neck lymph node compartments. Sonographically suspicious lymph nodes in the lateral neck should be biopsied for cytology or thyroglobulin levels. Any compartment (central or lateral) that has definitive proof of nodal metastases should be formally dissected at the time of thyroidectomy.

Improvement in patient-reported physical and mental health after parathyroidectomy for primary hyperparathyroidism.

BACKGROUND: The majority of patients with primary hyperparathyroidism (PHPT) are diagnosed without the classic signs of renal or osseous complications. Vague and subjective symptoms have been attributed to PHPT but have been difficult to measure during the medical encounter. The Patient-Reported Outcomes Measurement Information System (PROMIS) of the National Institutes of Health contains validated measures of physical and mental health that can be administered by the use of computer-adaptive testing (CAT). The objective of this study was to evaluate the feasibility of PROMIS assessment in the clinical setting to measure changes in patient-reported health before and after parathyroidectomy. We hypothesized that patients undergoing parathyroidectomy for PHPT would report greater improvement in mental and physical health compared with control patients. METHODS: Adult PHPT patients scheduled for parathyroidectomy and control patients requiring diagnostic thyroid operation were enrolled prospectively during a 6-month period. Patients were administered clinically relevant PROMIS health domains via CAT at a preoperative visit and 3 weeks after operation. A change in score of 5 or greater for each PROMIS instrument was defined as clinically important. Statistical significance of pre/post-surgery changes in scores was determined using paired t tests. RESULTS: A total of 35 patients with PHPT and 9 control patients completed the study. The mean number of PROMIS items answered during an assessment was 67 (range 51-121, SD 15.4). Median completion time was 8.2 minutes (range 3.4-38.4, SD 4.7). Clinically important improvement after parathyroidectomy in the PHPT group was greater than in the control group in 5 PROMIS domains. The score improvement experienced by PHPT patients was 8.8 in Fatigue, 6.7 in Sleep-Related Impairment, 5.0 in Anxiety, 7.0 in Applied Cognition, and 6.2 in Depression (all P < .05). CONCLUSION: PROMIS is an efficient clinical assessment platform for measuring patient-reported outcomes in PHPT via CAT. Several domains of physical and mental health in patients with PHPT show statistically and clinically important improvement after parathyroidectomy.

Operative treatment of primary hyperparathyroidism: balancing cost-effectiveness with successful outcomes.

Parathyroidectomy is the most cost-effective treatment for hyperparathyroidism. Randomized prospective trials have shown no difference in cure rate between focused parathyroidectomy and bilateral exploration. Costs of the two techniques differ depending on the preoperative and intraoperative localization used, speed of the operation, ability to discharge the patient on the same day as the operation, cure rate, and complications. It may be less costly and more effective to use a policy of routine 4-gland exploration without the use of preoperative or intraoperative localization studies. The potential economic impact and the expected outcome of the various strategies should be formally evaluated.

Denosumab for management of parathyroid carcinoma-mediated hypercalcemia.

CONTEXT: Most of the morbidity and mortality from parathyroid cancer is due to PTH-mediated hypercalcemia. Classically, management mainly consists of surgical resection, chemotherapy, and alleviation of hypercalcemia using bisphosphonates and calcium receptor agonists. The use of denosumab in the treatment of parathyroid cancer-mediated hypercalcemia has not been reported. OBJECTIVE: The aim of this report is to describe the effect of denosumab on parathyroid cancer-induced hypercalcemia. SUBJECT, MEASURES, AND RESULT: The patient is a 39-year-old man with metastatic parathyroid cancer who presented at age 35. His calcium levels initially responded to surgery, bisphosphonates, calcium receptor agonist, and chemotherapy (dacarbazine). However, his disease progressed, and his hypercalcemia became refractory to these measures in the setting of rising PTH levels. The addition of denosumab, a humanized monoclonal antibody inhibiting receptor activator of nuclear factor κB ligand resulted in successful management of his hypercalcemia for an additional 16 months. CONCLUSIONS: Denosumab can be effective in the treatment of refractory hypercalcemia in parathyroid cancer. It may also be of potential use in settings of benign hyperparathyroid-related hypercalcemia such as parathyromatosis, where hypercalcemia is not amenable to surgery or medical therapy with bisphosphonates and calcium receptor agonists.

How to use molecular testing results to guide surgery: a surgeon's perspective.

PURPOSE OF REVIEW: Multiple genetic mutations have been found to be associated with thyroid cancer, and molecular testing of thyroid nodule fine-needle aspiration (FNA) specimens has been proposed as an adjunct to the cytologic diagnosis. The purpose of this review is to examine how molecular testing of FNAs could be used to guide surgical decision-making. RECENT FINDINGS: B-type RAF kinase mutations in papillary thyroid cancer have been found to be associated with extrathyroidal extension, lymph node metastases, and advanced stage in two meta-analyses that are based largely on retrospective data. Testing for a panel of gene mutations has been found to have high specificity and positive predictive value, whereas microarray testing using a commercially available gene-expression classifier has been found to have high sensitivity and negative predictive value for the diagnosis of malignancy in cytologically indeterminate FNAs. Although there is no consensus regarding the use of such tests, they have already started to change clinical practice. SUMMARY: Molecular testing of FNA specimens may help to avoid diagnostic thyroidectomy or may help in deciding the extent of surgery in a patient with an indeterminate FNA biopsy. The use of these tests is currently undergoing review by a task force within the American Thyroid Association.

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.

Cost effectiveness of intraoperative pathology examination during diagnostic hemithyroidectomy for unilateral follicular thyroid neoplasms.

BACKGROUND: The use of intraoperative pathology examination (IPE) during diagnostic hemithyroidectomy for a follicular neoplasm is controversial. Although this service rarely alters intraoperative decision making, it does provide patients with the possibility of avoiding reoperation for completion thyroidectomy if malignancy is detected. We hypothesized diagnostic hemithyroidectomy with IPE for a unilateral follicular thyroid neoplasm diagnosed on fine-needle aspiration is not cost effective compared with diagnostic hemithyroidectomy alone. STUDY DESIGN: Cost-effectiveness analysis with a Markov decision model was performed comparing diagnostic hemithyroidectomy without IPE, diagnostic hemithyroidectomy with IPE, and total thyroidectomy. Treatment outcomes and their probabilities were identified based on literature review. Costs were estimated using data from Medicare, the US Bureau of Labor Statistics, and the Nationwide Inpatient Sample. Sensitivity analysis and a 1,000-iteration Monte Carlo simulation were used to examine the uncertainty of cost, probability, and utility estimates in the model. RESULTS: Diagnostic hemithyroidectomy without IPE had an expected cost of US$7,665 and an effectiveness of 23.95 quality-adjusted life years and dominated both the IPE and total thyroidectomy strategies. Intraoperative pathology examination became cost effective during one-way sensitivity analysis if the sensitivity of IPE increased from 14.3% to 34.4%, the specificity increased from 98.6% to 99.8%, or the pretest probability of malignancy increased from 25% to 43%. Monte Carlo simulation demonstrated that the intraoperative pathology strategy was not cost effective in 92.7% of iterations. CONCLUSIONS: Intraoperative pathology examination is not cost effective in the diagnosis of follicular thyroid neoplasms during diagnostic hemithyroidectomy. Improvements in both the sensitivity and specificity of this service would be needed to justify its use.

Routine on-site evaluation of specimen adequacy during initial ultrasound-guided fine needle aspiration of thyroid nodules: a cost-effectiveness analysis.

BACKGROUND: On-site evaluation (OSE) of specimen adequacy during fine needle aspiration (FNA) of thyroid nodules reduces unsatisfactory results but adds cost. We hypothesized that the addition of routine OSE to initial ultrasound-guided FNA of thyroid nodules is not cost-effective. METHODS: Formal cost-effectiveness analysis was performed using a decision model to compare strategies of routine initial OSE versus restriction of OSE to cases of prior inadequate FNA. Adequacy rates for FNA without OSE and detriment to quality-adjusted life expectancy (QALE) for undergoing repeat FNA were estimated on the basis of literature review and institutional experience. Costs were estimated using Medicare limiting charges and Bureau of Labor Statistics wage rates. Sensitivity analysis was used to examine the uncertainty of the model variable estimates. RESULTS: The routine OSE strategy produced a gain of 0.00007 quality-adjusted life-years (QALYs) at an additional cost of $43.75 for an incremental cost-effectiveness ratio of $639,143/QALY when compared to restriction of OSE to cases with prior inadequate results. During sensitivity analysis, routine OSE became cost-effective if FNA adequacy rate without OSE decreased from 90 to 85 %, cost of OSE decreased from $116 to $75, cost of FNA increased from $366 to $735, hourly wage increased from $23 to $123, or QALE detriment for repeat FNA increased from 0.25 to 1.6 days. CONCLUSIONS: OSE for initial ultrasound-guided FNA of thyroid nodules is not cost-effective unless the adequacy rate without OSE is less than 85 %. When operator performance exceeds this rate, OSE should be reserved for cases with previous inadequate results.

Routine prophylactic central neck dissection for low-risk papillary thyroid cancer: a cost-effectiveness analysis.

BACKGROUND: Routine prophylactic central neck dissection (pCND) after total thyroidectomy (TTX) for low-risk papillary thyroid cancer (PTC) offers the potential to decrease disease recurrence but may increase operative complications. We hypothesized that routine pCND is not cost-effective in low-risk PTC. METHODS: A Markov transition-state model was constructed to compare TTX with and without pCND. Outcome probabilities, utilities, and costs were estimated on the basis of literature review. The threshold for cost-effectiveness was $100,000 per quality-adjusted life year. Sensitivity analysis was used to examine model uncertainty. RESULTS: pCND cost $10,315 and produced an effectiveness of 23.785 quality-adjusted life years. This strategy was more costly and less effective than TTX without pCND and was therefore dominated. pCND became cost-effective when the probability of recurrence increased from 6% to 10.3%, cost of reoperation for recurrence increased from $8,900 to $26,120, or added probabilities of recurrent laryngeal nerve injury and hypoparathyroidism due to pCND were less than 0.20% and 0.18% during 2-way sensitivity analysis. Monte Carlo simulation showed that pCND was not cost-effective in 97.3% of iterations. CONCLUSION: Routine pCND for low-risk PTC is not cost-effective unless the recurrence rate is greater than 10.3%. Application of pCND should be individualized based on risk of recurrence and added complications.

Primary hyperaldosteronism: challenges in subtype classification.

BACKGROUND: Primary hyperaldosteronism (PA) is a serious and potentially debilitating disease. Detailed guidelines have been written to guide endocrinologists in establishing the diagnosis of PA as well as in subtype classification of PA. The objective of this case report is to present a case where subtype classification of PA was challenging and repeated imaging of the adrenal glands helped establish the diagnosis in a patient with initial normal adrenal glands on CT and MRI images. CASE PRESENTATION: We report a case of a 29-year-old woman with an established diagnosis of PA, but unclear subtype, who presented to us for further management. She initially presented for medical evaluation of uncontrolled hypertension and spontaneous hypokalemia 4 years prior. In the investigation of secondary causes of hypertension, plasma aldosterone-to-plasma renin activity ratio was elevated on two separate occasions, and primary hyperaldosteronism was confirmed by saline infusion test. Also during this time, she had adrenal venous sampling done 3 times at multiple institutions yielding confusing results. Initially, imaging by CT and MRI showed normal adrenal glands. To help establish the subtype of PA, we reimaged this patient's adrenal glands one year later revealing a 2 cm left adrenal adenoma. Laparoscopic left adrenalectomy improved her hypertension and was curative of her hypokalemia. CONCLUSION: This case presents an unusual case where reimaging of the adrenal glands led to the discovery of a single adenoma, initially not observed on imaging studies.

Cost-effectiveness analysis of repeat fine-needle aspiration for thyroid biopsies read as atypia of undetermined significance.

BACKGROUND: The 2007 National Cancer Institute (NCI) conference on Thyroid Fine-Needle Aspiration (FNA) introduced the category atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS). Repeat FNA in 3 to 6 months was recommended for low-risk patients. Compliance with these recommendations has been suboptimal. We hypothesized that repeat FNA would be more effective than diagnostic lobectomy, with decreased costs and improved rates of cancer detection. METHODS: Cost-effectiveness analysis was performed in which we compared diagnostic lobectomy with repeat FNA. A Markov model was developed. Outcomes and probabilities were identified from literature review. Third-party payer costs were estimated in 2010 US dollars. Outcomes were weighted by use of the quality-of-life utility factors, yielding quality-adjusted life years (QALYs). Monte Carlo simulation and sensitivity analysis were used to examine the uncertainty of probability, cost, and utility estimates. RESULTS: The diagnostic lobectomy strategy cost $8,057 and produced 23.99 QALYs. Repeat FNA cost $2,462 and produced 24.05 QALYs. Repeat FNA was dominant until the cost of FNA increased to $6,091. Dominance of the repeat FNA strategy was not sensitive to the cost of operation or the complication rate. CONCLUSION: The NCI recommendations for repeat FNA regarding follow-up of AUS/FLUS results are cost-effective. Improving compliance with these guidelines should lead to less overall costs, greater quality of life, and fewer unnecessary operations.

Is subtotal thyroidectomy a cost-effective treatment for Graves disease? A cost-effectiveness analysis of the medical and surgical treatment options.

BACKGROUND: The 3 treatment options for Graves disease (GD) are antithyroid drugs (ATDs), radioactive iodine (RAI), and thyroid surgery. We hypothesized that thyroid surgery is cost-effective for Graves disease when compared to RAI or ATD. METHODS: Cost-effectiveness analysis was performed to compare operative strategies to medical treatment strategies for GD. The decision model, based on a reference case, included treatment outcomes, probabilities, and costs derived from literature review. Outcomes were weighted using quality of life utility factors, yielding quality-adjusted life years (QALYs). The uncertainty of costs, probabilities, and utility estimates in the model were examined by univariate and multivariate sensitivity analysis and Monte Carlo simulation. RESULTS: The subtotal thyroidectomy strategy produced the greatest QALYs, 25.783, with an incremental cost-effectiveness ratio of $26,602 per QALY, reflecting a gain of 0.091 QALYs at an additional cost of $2416 compared to RAI. Surgery was cost-effective when the initial postoperative euthyroid rate was greater than 49.5% and the total cost was less than $7391. Monte Carlo simulation showed the subtotal thyroidectomy strategy to be optimal in 826 of 1000 cases. CONCLUSION: This study demonstrates that subtotal thyroidectomy can be a cost-effective treatment for GD. However, a 49.5% initial postoperative euthyroid rate was a necessary condition for cost-effective surgical management of GD.

Influence of lymph node metastases on survival in pediatric medullary thyroid cancer.

PURPOSE: Lymph node metastases (LNM) from medullary thyroid cancer (MTC) are common in adults and are a poor prognostic factor. Less is known about LNM in children, who often have hereditary forms of MTC. Guidelines recommend prophylactic thyroidectomy in early childhood, but randomized prospective trials are not feasible. We hypothesized that LNM is associated with poor prognosis in children. METHODS: Patients with MTC 21 years or younger from the National Cancer Data Base from 1985 to 2007 were studied. Multivariable logistic regression was used to identify factors associated with lymph node evaluation. Survival was estimated using the Kaplan-Meier method. RESULTS: Of 430 patients, 276 (64.2%) had nodal evaluation with LNM present in 121 (28.1%). Older patients, those with tumors larger than 2 cm, and those with involved margins were more likely to have LNM (all P < .05). Patients undergoing total thyroidectomy, those with involved margins, and older patients were more likely to undergo lymph node evaluation after controlling for patient, tumor, and hospital factors (all P < .05). Over time an increasing number of patients with MTC have undergone total thyroidectomy. Patients 16 to 21 years of age had lower 10-year overall survival compared to patients 0 to 15 years old (88.7% vs 98.1%, P = .005). Lymph node metastases were also associated with decreased 10-year overall survival (84.4% vs 100%, P < .001). CONCLUSIONS: In pediatric MTC, LNM predict poorer overall survival. Adequate lymph node assessment can provide valuable prognostic information for the pediatric MTC patient. Lymph node assessment should be considered for older pediatric patients undergoing surgery for hereditary MTC or biopsy confirmed MTC.

Prior head and neck radiation exposure is not a contraindication to minimally invasive parathyroidectomy.

BACKGROUND: Most patients with primary hyperparathyroidism can have a minimally invasive parathyroidectomy based on localization studies showing single-gland disease. In patients with a history of head and neck irradiation, due to the increased risk of multigland disease and risk of concurrent thyroid cancer, minimally invasive parathyroidectomy is considered by some to be a contraindication. We postulated that previous history of head and neck irradiation should not be a contraindication for minimally invasive parathyroidectomy and tested this hypothesis in a prospective cohort of patients undergoing parathyroidectomy for primary hyperparathyroidism. STUDY DESIGN: We performed a retrospective analysis of a prospective database of 491 consecutive parathyroidectomies performed between May 2005 and May 2007 at a tertiary referral medical center. RESULTS: Fifty-two (12.6%) patients had a history of head and neck irradiation and 360 (87.4%) had no exposure to radiation. The 2 groups had no significant difference in terms of gender or ethnicity. The radiation group was older, with an average age of 65.1 years versus 58.1 years (p < 0.0009). There was no significant difference in concurrent benign thyroid neoplasm, thyroid cancer, and type of parathyroid disease (single vs multigland) in the 2 groups. There was no significant difference in the operative approach used between the 2 groups (focused vs unilateral or bilateral). CONCLUSIONS: Head and neck irradiation should not be a contraindication for minimally invasive parathyroidectomy in patients with primary hyperparathyroidism in the setting of preoperative localization studies showing single-gland disease and no concurrent thyroid neoplasm. Furthermore, history of head and neck irradiation is associated with a later age of presentation for parathyroidectomy.

Are additional localization studies and referral indicated for patients with primary hyperparathyroidism who have negative sestamibi scan results?

HYPOTHESIS: Additional imaging studies are useful to select patients who are candidates for minimally invasive parathyroidectomy, and referral is not indicated when results from a preoperative sestamibi scan are negative. DESIGN, SETTING, AND PATIENTS: Prospective analysis of 492 operations for primary hyperparathyroidism from May 2005 to May 2007 at a tertiary care center. MAIN OUTCOME MEASURES: Accuracy of imaging studies, pathologic findings, and biochemical cure. RESULTS: Among the patients, 96% were cured. Of the sestamibi scan results, 91% were positive and 82% were true-positive. Ultrasonography results were positive in 51% of patients with negative sestamibi scan results, and 43% were true-positive. Patients with positive sestamibi scan results compared with those with negative sestamibi scan results had a higher rate of single-gland disease (87% vs 63%, respectively) and lower rates of double adenoma (6% vs 22%, respectively) and asymmetric hyperplasia (7% vs 15%, respectively) (P<.001). In patients with positive sestamibi scan results compared with those with negative sestamibi scan results, there was no significant difference in the rate of ectopic parathyroid glands (18% vs 12%, respectively) but there was a significant difference in cure rate (97% vs 89%, respectively) (P=.008). CONCLUSIONS: Additional imaging with neck ultrasonography is helpful for selecting minimally invasive parathyroidectomy in most patients with primary hyperparathyroidism who have negative sestamibi scan results. Referral for parathyroidectomy may be considered in patients with negative sestamibi scan results because these results are associated with multigland disease and lower cure rates.