Operative management of primary hyperparathyroidism in Europe.

BACKGROUND: Multicentre studies have previously reported on national outcomes of surgery for primary hyperparathyroidism, but not investigated whether management and outcome are uniform among countries. This study investigated whether there are differences among European countries in operative management and outcome of surgery for primary hyperparathyroidism. METHODS: Using data from Eurocrine®, a pan-European registry for endocrine surgeries, a retrospective observational cross-sectional multicentre study with 99 participating centres in 14 European countries was performed. Data on age, sex, calcium levels, operative strategy, conversion rate and rate of failed exploration were analysed for patients who underwent initial surgery for sporadic primary hyperparathyroidism. Primary outcome measures were intention to perform limited parathyroidectomy and the rate of hypercalcaemia at first follow-up. RESULTS: A total of 9548 patients were registered between 2015 and 2020. There were 7642 (80%, range 74.5-93.2%) females. There was intention to perform limited parathyroidectomy in 7320 of 9548 (76.7%) operations, ranging from 498 of 1007 (49.5%) to 40 of 41 (97.6%) among countries. Hypercalcaemia at first follow-up (median time to follow-up 15 days) was found in 416 of 9548 (4.4%) operations, ranging from 0 of 119 (0%) to 3 of 38 (7.9%) among countries. CONCLUSION: This study demonstrated large differences in the intention to perform limited parathyroidectomy for primary hyperparathyroidism among European countries, as well as differences in the rate of postoperative hypercalcaemia. Future studies are needed to evaluate the impact of these different healthcare practices on patient outcomes.

Risk of Malignant Neoplasm in Patients with Primary Hyperparathyroidism: A Systematic Review and Meta-analysis.

This study aimed to evaluate the prevalence and risk of malignant neoplasm in primary hyperparathyroidism (PHPT) patients. Potentially eligible studies were retrieved from PubMed and Embase databases from inception to November 2023 using search strategy consisting of terms for "Primary hyperparathyroidism" and "Malignant neoplasm". Eligible study must report prevalence of malignant neoplasm among patients with PHPT or compare the risk of malignant neoplasm between patients with PHPT and comparators. Point estimates with standard errors were extracted from each study and combined using the generic inverse variance method.A total of 11,926 articles were identified. After two rounds of systematic review, 50 studies were included. The meta-analysis revealed that pooled prevalence rates of overall cancer was 0.19 (95%CI: 0.13-0.25; I2 94%). The two most prevalent types of malignancy among patients with PHPT ware papillary thyroid cancer (pooled prevalence: 0.07; 95%CI: 0.06-0.08; I2 85%) and breast cancer (pooled prevalence: 0.05; 95%CI: 0.03-0.07; I2 87%). Subgroup analysis of studies focusing on patients undergoing parathyroidectomy reported a fourfold higher prevalence of papillary thyroid cancer than the remaining studies (0.08 versus 0.02). The meta-analysis of cohort studies found a significant association between PHPT and overall cancer with the pooled risk ratio of 1.28 (95%CI: 1.23-1.33; I2 66.9%).We found that the pooled prevalence of malignant neoplasm in PHPT was 19%, with papillary thyroid cancer and breast cancer being the most prevalent types. The meta-analysis of cohort studies showed that patient with PHPT carried an approximately 28% increased risk of malignancy.

Characteristics, management and outcomes of primary hyperparathyroidism from 2009 to 2021: a single centre report from South Africa.

BACKGROUND: There has been a notable shift towards the diagnosis of less severe and asymptomatic primary hyperparathyroidism (PHPT) in developed countries. However, there is a paucity of recent data from sub-Saharan Africa (SSA), and also, no reported data from SSA on the utility of intra-operative parathyroid hormone (IO-PTH) monitoring. In an earlier study from Inkosi Albert Luthuli Central Hospital (IALCH), Durban, South Africa (2003-2009), majority of patients (92.9%) had symptomatic disease. The aim of this study was to evaluate the clinical profile and management outcomes of patients presenting with PHPT at IALCH. METHODS: A retrospective chart review of patients with PHPT attending the Endocrinology clinic at IALCH between July 2009 and December 2021. Clinical presentation, laboratory results, radiologic findings, surgical notes and histology were recorded. RESULTS: Analysis included 110 patients (87% female) with PHPT. Median age at presentation was 57 (44; 67.5) years. Symptomatic disease was present in 62.7% (n:69); 20.9% (n:23) had a history of nephrolithiasis and 7.3% (n:8) presented with previous fragility fractures. Mean serum calcium was 2.87 ± 0.34 mmol/l; median serum-PTH was 23.3 (15.59; 45.38) pmol/l, alkaline phosphatase 117.5 (89; 145.5) U/l and 25-hydroxyvitamin-D 42.9 (33.26; 62.92) nmol/l. Sestamibi scan (n:106 patients) identified an adenoma in 83.02%. Parathyroidectomy was performed on 84 patients with a cure rate of 95.2%. Reasons for conservative management (n:26) included: no current surgical indication (n:7), refusal (n:5) or deferral of surgery (n:5), loss to follow-up (n:5) and assessed as high anaesthetic risk (n:4). IO-PTH measurements performed on 28 patients indicated surgical success in 100%, based on Miami criteria. Histology confirmed adenoma in 88.1%, hyperplasia in 7.1% and carcinoma in 4.8%. Post-operative hypocalcaemia developed in 30 patients (35.7%), of whom, 14 developed hungry bone syndrome (HBS). In multivariate analysis, significant risk factors associated with HBS included male sex (OR 7.01; 95% CI 1.28, 38.39; p 0.025) and elevated pre-operative PTH (OR 1.01; 95% CI 1.00, 1.02; p 0.008). CONCLUSIONS: The proportion of asymptomatic PHPT has increased at this centre over the past decade but symptomatic disease remains the dominant presentation. Parathyroidectomy is curative in the majority of patients. IO-PTH monitoring is valuable in ensuring successful surgery.

Factors affecting the rates of incidental parathyroidectomy during thyroidectomy.

BACKGROUND: The most important factors affecting the development of postoperative hypocalcaemia (PH) include intraoperative trauma to the parathyroid glands, incidental parathyroidectomy (IP), and the surgeon's experience. In this study, we aimed to determine the incidence of IP, evaluate its effect on postoperative calcium levels and investigate the effect of surgeon experience and volume on IP incidence and postoperative calcium levels. METHODS: This retrospective study included 645 patients who underwent thyroid surgery at the Department of General Surgery, Kütahya Health Sciences University between September 2016 and March 2020. All patients underwent surgery at a single clinic by general surgeons experienced in thyroid surgery and their residents (3-5 years). RESULTS: Normal parathyroid glands were reported in 58 (8.9%) of 645 patients. In 5 (8.6%) of 58 patients the parathyroid gland was detected in the intrathyroidal region. PH developed in ten patients (17.2%) with incidental removal of the parathyroid glands. A statistically significant difference was found between the number of incidentally removed parathyroid glands and the development of hypocalcaemia (p<0.05). Normal parathyroid glands were reported in the pathology of 37 (7.9%) patients operated on by general surgeons and 22 (12.6%) patients operated on by their residents. PH developed in 39 (8.2%) patients operated on by general surgeons and in 8 (4.5%) patients operated on by their residents. CONCLUSIONS: We found that the complication rate during the resident training process was the same as that of experienced general surgeons. A thyroidectomy can be safely performed by senior residents during residential training.

Stones left unturned: Missed opportunities to diagnose primary hyperparathyroidism in patients with nephrolithiasis.

BACKGROUND: Nephrolithiasis is a sequela of primary hyperparathyroidism and an indication for parathyroidectomy. The prevalence of primary hyperparathyroidism in patients with nephrolithiasis is 3% to 5%; however, recent studies suggest that many hypercalcemic patients with nephrolithiasis never undergo workup for primary hyperparathyroidism. Our goal is to evaluate primary hyperparathyroidism screening rates at a tertiary academic health institution and identify opportunities to increase referral rates in patients presenting with nephrolithiasis. METHODS: We retrospectively reviewed 15,725 patients across an academic health system who presented with nephrolithiasis between 2012 and 2020. Calcium levels measured within 6 months of presentation were identified, and those with hypercalcemia (≥10.3 mg/dL) were reviewed if parathyroid hormone levels were measured. Patients with primary hyperparathyroidism were evaluated to see if they were referred to a specialist for treatment. RESULTS: Of 15,725 patients presenting with nephrolithiasis, 12,420 (79%) had calcium levels measured; 630 patients (4.0%) were hypercalcemic, and 207 (33%) had parathyroid hormone levels measured. Patients were more likely to have parathyroid hormone levels sent if they were older, had higher calcium levels, or presented to an outpatient clinic (P = .028, P = .002, P < .001). We identified 89 patients (0.6%) with primary hyperparathyroidism, of which only 35 (39%) were referred for treatment. CONCLUSION: The proportion of patients presenting with nephrolithiasis ultimately diagnosed with primary hyperparathyroidism was significantly lower than others have reported. Additionally, a substantial number of patients with nephrolithiasis did not have calcium and/or parathyroid hormone levels measured. These missed opportunities for diagnosis are critical as early definitive management of primary hyperparathyroidism can prevent recurrent nephrolithiasis and other primary hyperparathyroidism-related end organ effects.

Recurrence after successful parathyroidectomy-Who should we worry about?

BACKGROUND: Preventing cervical reoperations is important-especially after parathyroidectomy. We sought to examine early predictors of recurrence of primary hyperparathyroidism after surgical cure. METHODS: Adult patients with sporadic primary hyperparathyroidism treated with parathyroidectomy between September 1, 1997, and September 1, 2019, with confirmed eucalcemia at 6 months postoperatively were identified. Recurrence was defined as hypercalcemia (>10.2 mg/dL) with an elevated or nonsuppressed parathyroid hormone level on subsequent follow-up. RESULTS: Parathyroidectomy was performed in 522 patients (median age, 62.1 years, 77% female) with the majority undergoing planned minimally invasive parathyroidectomy (85.4%, n = 446). After a median follow-up of 30.9 months, 13 patients (2.5%) recurred (median time to recurrence 50.2 months, interquartile range 27.9-66.5), all of whom underwent planned minimally invasive parathyroidectomy (n = 13/446, 2.9%). Recurrence was more common in those with higher (but still normal) 6-month calcium (10.1 vs 9.3 mg/dL, P < .001) or parathyroid hormone values (64 vs 46 pg/mL, P < .01). Multivariate analysis revealed that age >66.5 years, calcium ≥9.8mg/dL and parathyroid hormone ≥80 pg/mL at 6 months were associated with increased risk of recurrence. In addition, the presence of at least 1 preoperative imaging study that conflicted with intraoperative findings among minimally invasive parathyroidectomy patients (n = 446) was associated with increased risk of recurrence (hazard ratio 4.93, 95% confidence interval 1.25-16.53, P = .016). CONCLUSION: Recurrence of sporadic primary hyperparathyroidism after initial surgical cure in the era of minimally invasive parathyroidectomy is 2.5%. Identification of those at risk for recurrence using 6-month serum calcium ≥9.8 mg/dL, parathyroid hormone ≥80 pg/mL, and/or potentially conflicting localization studies may inform surveillance strategies.

Parathyroidectomy for nephrolithiasis in primary hyperparathyroidism: Beneficial but not a panacea.

BACKGROUND: Nephrolithiasis is a classic indication for parathyroidectomy in primary hyperparathyroidism patients; however, the effects of parathyroidectomy on nephrolithiasis recurrence are not well studied. The aim was to determine effect of parathyroidectomy on time to first nephrolithiasis recurrence and recurrence rate per patient-years. METHODS: A retrospective cohort study of patients diagnosed with primary hyperparathyroidism and at least one episode of nephrolithiasis was performed. The patients were divided into observation, presurgery, and postsurgery groups. Endpoints were time to first recurrence of nephrolithiasis and average recurrence rate per patient-years. RESULTS: The cohort was comprised of 1,252 patients. In addition, 334 (27%) patients underwent parathyroidectomy and 918 (73%) were observed. The surgical and nonsurgical groups differed significantly in age, sex, Charlson, calcium, and primary hyperparathyroidism level. Overall recurrence rate was 31.3%. The 5-, 10-, and 15-year recurrence-free survival rates were 74.4%, 56.3%, 49.5%, respectively (presurgery), 82.4%, 70.9%, 62.8%, respectively (postsurgery; P < .0001), and 86.3%, 77.7%, and 70.6%, respectively (observation). The presurgery group had an increased risk of first recurrence compared with the observation group (hazard ratio 1.89; 95% confidence interval, 1.44-2.47). The average recurrence rates among all surgical patients who recurred were 1 event per 4.3 patient-years presurgery versus 1 event per 6.7 patient-years postsurgery (P = .0001). CONCLUSION: Recurrent nephrolithiasis is a significant problem in patients with primary hyperparathyroidism. Parathyroidectomy prolongs the time to first recurrence and decreases the number of re-recurrences over time but does not eliminate recurrences. Observation may also be a reasonable approach in selected patients.

Superior sensitivity of 18F-fluorocholine: PET localization in primary hyperparathyroidism.

BACKGROUND: Preoperative parathyroid imaging guides surgeons during parathyroidectomy. This study evaluates the clinical impact of 18F-fluorocholine positron emission tomography for preoperative parathyroid localization on patients with primary hyperparathyroidism. METHODS: Patients with primary hyperparathyroidism and indications for parathyroidectomy had simultaneous 18F-fluorocholine positron emission tomography imaging/magnetic resonance imaging. In patients who underwent subsequent parathyroidectomy, cure was based on lab values at least 6 months after surgery. Location-based sensitivity and specificity of 18F-fluorocholine positron emission tomography imaging was assessed using 3 anatomic locations (left neck, right neck, and mediastinum), with surgery as the gold standard. RESULTS: In 101 patients, 18F-fluorocholine positron emission tomography localized at least 1 candidate lesion in 93% of patients overall and in 91% of patients with previously negative imaging, leading to a change in preoperative strategy in 60% of patients. Of 76 patients who underwent parathyroidectomy, 58 (77%) had laboratory data at least 6 months postoperatively, with 55/58 patients (95%) demonstrating cure. 18F-fluorocholine positron emission tomography successfully guided curative surgery in 48/58 (83%) patients, compared with 20/57 (35%) based on ultrasound and 13/55 (24%) based on sestamibi. In a location-based analysis, sensitivity of 18F-fluorocholine positron emission tomography (88.9%) outperformed both ultrasound (37.1%) and sestamibi (27.5%), as well as ultrasound and sestamibi combined (47.8%). CONCLUSION: Long-term results in the first cohort in the United States to use 18F-fluorocholine positron emission tomography for parathyroid localization confirm its utility in a challenging cohort, with better sensitivity than ultrasound or sestamibi.

Racial disparities in the utilization of parathyroidectomy among patients with primary hyperparathyroidism: Evidence from a nationwide analysis of Medicare claims.

BACKGROUND: Among patients with primary hyperparathyroidism, parathyroidectomy offers a chance of cure and mitigation of disease-related complications. The impact of race/ethnicity on referral and utilization of parathyroidectomy has not been fully explored. METHODS: Population-based, retrospective cohort study using 100% Medicare claims from beneficiaries with primary hyperparathyroidism from 2006 to 2016. Associations of race/ethnicity with disease severity, surgeon evaluation, and subsequent parathyroidectomy were analyzed using adjusted multivariable logistic regression models. RESULTS: Among 210,206 beneficiaries with primary hyperparathyroidism, 63,136 (30.0%) underwent parathyroidectomy within 1 year of diagnosis. Black patients were more likely than other races/ethnicities to have stage 3 chronic kidney disease (10.8%) but had lower prevalence of osteoporosis and nephrolithiasis compared to White patients, Black and Hispanic patients were more likely to have been hospitalized for primary hyperparathyroidism-associated conditions (White 4.8%, Black 8.1%, Hispanic 5.8%; P < .001). Patients who were White and met operative criteria were more likely to undergo parathyroidectomy than Black, Hispanic, or Asian patients (White 30.5%, Black 23.0%, Hispanic 21.4%, Asian 18.7%; P < .001). Black and Hispanic patients had lower adjusted odds of being evaluated by a surgeon (odds ratios 0.71 [95% confidence interval 0.69-0.74], 0.68 [95% confidence interval 0.61-0.74], respectively) and undergoing parathyroidectomy if evaluated by a surgeon (odds ratios 0.72 [95% confidence interval 0.68-0.77], 0.82 [95% confidence interval 0.67-0.99]). Asian race was associated with lower adjusted odds of being evaluated by a surgeon (odds ratio 0.64 [95% confidence interval 0.57-0.71]), but no difference in odds of parathyroidectomy. CONCLUSION: Racial/ethnic disparities exist in the management of primary hyperparathyroidism among older adults. Determining the factors that account for this disparity require urgent attention to achieve parity in the management of primary hyperparathyroidism.

Multiple endocrine neoplasia type 1 in children and adolescents: Clinical features and treatment outcomes.

BACKGROUND: Clinical manifestations and treatment outcomes in children and adolescents with multiple endocrine neoplasia type 1 are not well characterized. METHODS: We conducted a retrospective cohort study of 80 patients with multiple endocrine neoplasia type 1 who commenced tumor surveillance at ≤18 years of age. RESULTS: Fifty-six patients (70%) developed an endocrine tumor by age ≤18 years (median age = 14 years, range = 6-18 years). Primary hyperparathyroidism occurred in >80% of patients, with >70% undergoing parathyroidectomy, in which less-than-subtotal (<3-gland) resection resulted in decreased disease-free outcomes versus subtotal (3-3.5-gland) or total (4-gland) parathyroidectomy (median 27 months versus not reached; P = .005). Pancreaticoduodenal neuroendocrine tumors developed in ∼35% of patients, of whom >70% had nonfunctioning tumors, >35% had insulinomas, and <5% had gastrinomas, with ∼15% having metastases and >55% undergoing surgery. Pituitary tumors developed in >30% of patients, and ∼35% were macroprolactinomas. Tumor occurrence in male patients and female patients was not significantly different. Genetic analyses revealed 38 germline MEN1 mutations, of which 3 were novel. CONCLUSION: Seventy percent of children aged ≤18 years with multiple endocrine neoplasia type 1 develop endocrine tumors, which include parathyroid tumors for which less-than-subtotal parathyroidectomy should be avoided; pancreaticoduodenal neuroendocrine tumors that may metastasize; and pituitary macroprolactinomas.

Routine Use of Preoperative Neck Ultrasound in Primary Hyperparathyroidism Identifies Coexisting Thyroid Disease and Improves Parathyroid Localization.

BACKGROUND: In Jan 2018, we began routinely obtaining neck ultrasound (US) with 123I/99Tc-sestamibi (MIBI) for parathyroid gland localization and to identify thyroid pathology in the setting of primary hyperparathyroidism (1HPT). The aim of this study is to assess if routine neck US is a useful adjunct to 123I/99Tc-MIBI in 1HPT. METHODS: Patients undergoing surgery for 1HPT with both 123I/99Tc-MIBI and US at our institution after implementation of routine US were reviewed. Biopsy and surgical management of thyroid pathology was evaluated. 123I/99Tc-MIBI and US results were compared to intraoperative findings to determine sensitivity and positive predictive value (PPV) for parathyroid localization. RESULTS: From January 2018 to September 2019, there were 423 patients (mean, 61 years) that met inclusion criteria (80% women). Thyroid nodules were found on US in 57%, mean size 1.3 + 0.8 cm. Fine needle aspiration (FNA) was performed in 87 patients with nodules (36%). 35 patients (8.5%) required total or partial thyroidectomy for diagnoses/treatment. Papillary thyroid cancer (PTC) was found in 3.5% of the cohort with micro-PTC 53% and PTC 1-2 cm 40%. A successful parathyroid operation for 1HPT was achieved in 98.6% of patients. Positive predictive value for localization of abnormal parathyroid glands was 97% when US and 123I/99Tc-MIBI had concordant findings. DISCUSSION: Routine use of US in 1HPT commonly identifies nodules that are benign or low-risk PTC. Ultrasound is less sensitive for parathyroid localization but when used with 123I/99Tc-MIBI, concordant imaging has a high PPV.

How and when is multiglandular disease diagnosed in sporadic primary hyperparathyroidism?

BACKGROUND: In total, ∼15% of patients with sporadic primary hyperparathyroidism have multiglandular disease, which may be suspected preoperatively but can only be confirmed intra or postoperatively. The study aim is to determine how and when patients are diagnosed with multiglandular disease and to what extent different modalities contribute. METHODS: Consecutive cases of sporadic primary hyperparathyroidism (2013-2019) undergoing initial exploration were reviewed from a single-institution prospective database. Preoperative single-photon emission tomography/computed tomography and neck ultrasound were routinely performed to help direct either bilateral or unilateral exploration guided by intraoperative parathyroid hormone monitoring using the dual criteria. Multiglandular disease was defined as either resection of >1 enlarged parathyroid or hypercalcemia at ≥6 months after single gland resection. RESULTS: Of 1,890 patients with sporadic primary hyperparathyroidism, multiglandular disease was identified in 254 (13.4%); 244 (96.1%) were diagnosed intraoperatively and 10 (3.9%) postoperatively. In these multiglandular disease patients, single gland disease was suggested on single-photon emission tomography/computed tomography in 54.0%, ultrasound in 49.2%, and both were concordant for single gland disease in 29.4%. Intraoperative multiglandular disease diagnosis was prompted by an inadequate intraoperative parathyroid hormone monitoring drop in 38.5%, by surgeon interpretation of imaging in 38.1%, by observing ipsilateral gland enlargement in 11.0%, by finding an initial gland <200 mg in 10.3%, and 2.0% had unexpected multiglandular disease during thyroidectomy. Multiglandular disease was diagnosed by postoperative hypercalcemia in 10 of 254 patients (4.9%). CONCLUSION: To avoid failure at parathyroidectomy for primary hyperparathyroidism, expert surgeons use multiple approaches to diagnose and manage multiglandular disease. Preoperative localization studies alone are insufficient, missing multiglandular disease in at least 30% of cases. All examined adjuncts are informative, including intraoperative parathyroid hormone monitoring, imaging, and intraoperative visual cues.

Correlation of Preoperative Imaging Findings and Parathyroidectomy Outcomes Support NICE 2019 Guidance.

CONTEXT: Preoperative localization studies are standard practice in patients undergoing parathyroidectomy for primary hyperparathyroidism (pHPT). The most common modalities are neck ultrasound (US) and sestamibi scanning. However, the nature of pHPT is changing, with imaging increasingly yielding negative results. Numerous studies suggest unlocalized disease is associated with poor outcomes, calling into question whether such patients are best treated conservatively. OBJECTIVE: This study aims to correlate parathyroidectomy outcomes with preoperative imaging in a single, high-volume institution. METHODS: Data from a prospectively maintained departmental database of operations performed from 2017 to 2019 were analyzed. All patients undergoing first-time surgery for sporadic pHPT were included. Data collected included patient demographics, preoperative imaging, surgical strategy, and postoperative outcomes. RESULTS: A total of 609 consecutive parathyroidectomies were included, with a median age of 59 years (range 20-87 years). The all-comer cure rate was 97.5%; this was 97.9% in dual localized patients (those with positive US and sestamibi), compared to 95.8% in the dual unlocalized group (those with negative US and sestamibi) (P = 0.33). Unilateral neck exploration was the chosen approach in 59.9% of patients with double-positive imaging and 5.7% of patients with double-negative imaging (otherwise, bilateral parathyroid visualization was performed). There was no significant difference in postoperative complications between patients undergoing unilateral or bilateral neck exploration. CONCLUSIONS: Patients with negative preoperative imaging who undergo parathyroidectomy are cured in almost 96% of cases, compared to 98% when the disease is localized. This difference does not reach statistical or clinical significance. These findings therefore support current recommendations that all patients with pHPT who are likely to benefit from operative intervention should be considered for parathyroidectomy, irrespective of preoperative imaging findings.

Perioperative cardiac investigations for chest pain after parathyroidectomy rarely yield a cardiac diagnosis.

BACKGROUND: The incidence of adverse perioperative cardiac complications after parathyroidectomy has not been well described. This study aimed to evaluate the incidence of perioperative chest pain and cardiac complications after parathyroidectomy and to evaluate risk factors that may identify patients who are more likely to benefit from a cardiac workup. METHODS: We performed a retrospective study of all patients undergoing parathyroidectomy for primary hyperparathyroidism by a single endocrine surgeon at a tertiary endocrine centre between 2011 and 2018. Patient demographics, clinicopathologic variables, operative and postoperative details (reported chest pain, performance of a cardiac workup and new postoperative cardiac diagnosis) were reviewed. Patients with chest pain were compared to those without chest pain using the Fisher exact test and Student t test. RESULTS: Fourteen of 295 patients (4.7%) reported chest pain in the immediate postoperative period. Most patients were investigated with a 12-lead electrocardiogram and troponin (n = 12/14), yet none were diagnosed with a cardiac event. When comparing patients with and without chest pain, there was no significant difference in age, gender, body mass index, presence of cardiovascular risk factors, American Society of Anesthesiologists score or length of surgery. CONCLUSION: Postoperative chest pain after parathyroidectomy is not an uncommon event and leads to a cardiac workup in most cases; however, the risk of significant postoperative cardiac events is minimal. In the "choosing wisely" era, one should evaluate each patient's pretest probability of such events and avoid extensive workup in low-risk patients to avoid unnecessary costs to the health care system.

Multidisciplinary team efforts to improve the pregnancy outcome of pregnancy complicated with primary hyperparathyroidism: case series from a single hospital.

BACKGROUND: There is no consensus or management algorithm for primary hyperparathyroidism (PHPT) in pregnancy. METHODS: This study comprises a retrospective case series. From August 2014 to December 2020, 9 cases of PHPT in pregnancy were diagnosed by a multidisciplinary team (MDT) consultation center of obstetrics in our hospital. Their clinical manifestations, treatment strategies, and maternal and infant outcomes were analyzed. RESULTS: The median onset age of the patients was 32 (25 ~ 38) years. PHPT was diagnosed in two cases before pregnancy, in six cases during pregnancy and in one case postpartum. The main clinical manifestations were nausea, vomiting, and other nonspecific symptoms, with anemia as the most common maternal complication. Hypercalcemia crisis was developed in one case. The median levels of preoperative serum calcium and parathyroid hormone (PTH) were 3.08 (2.77 ~ 4.21) mmol/L and 300.40 (108.80 ~ 2603.60) pg/ml, respectively. The parathyroid ultrasonography tests were positive in eight cases and negative in one patient who had an ectopic lesion localized by 99mTc-MIBI. Parathyroidectomy was conducted in 7 cases during the 2nd trimester, including 2 patients diagnosed before pregnancy who refused surgery, 1 patient during the 1st trimester, and 1 patient postpartum, with a significant reduction in serum concentrations of calcium and PTH. A management algorithm was developed. CONCLUSION: This case series suggests that pregnant women with PHPT should be managed by MDT according to the algorithm. If PHPT is confirmed in fertile women before pregnancy, parathyroidectomy should be strongly suggested and performed. If PHPT is diagnosed during pregnancy, even in its mild form, surgical treatment, optimally during the 2nd trimester, is effective and safe for pregnancy and neonatal outcome.

Use and disparities in parathyroidectomy for symptomatic primary hyperparathyroidism in the Medicare population.

BACKGROUND: Few studies assess use of parathyroidectomy among older adults with symptomatic primary hyperparathyroidism. Our objective was to determine national usage and disparities in parathyroidectomy for symptomatic primary hyperparathyroidism among insured older adults. METHODS: We identified older adult patients with symptomatic primary hyperparathyroidism using Medicare claims (2006-2017). Primary study variables were race/ethnicity, rurality, and zip-code socioeconomic status. We calculated cumulative incidence of parathyroidectomy and used multivariable Cox proportional hazards regression models to assess the adjusted association of our study variables with parathyroidectomy. RESULTS: We included 94,803 patients. The median age at primary hyperparathyroidism diagnosis was 76 years (interquartile range 71-82). The majority of patients were female (72%), non-Hispanic White (82%), from metropolitan areas (82%), and had a Charlson Comorbidity score ≥3 (62%). Nine percent of patients (n = 8,251) underwent parathyroidectomy during follow-up. After adjustment, non-Hispanic Black patients, compared to non-Hispanic White (hazard ratio 0.80; 95% confidence interval 0.74, 0.87), and living in a low socioeconomic status neighborhood (low socioeconomic status vs highest socioeconomic status hazard ratio 0.89; 95% confidence interval 0.83, 0.95) were both associated with lower incidences of parathyroidectomy. Patients from non-metropolitan areas were more likely to undergo parathyroidectomy. CONCLUSION: Parathyroidectomy is underused for symptomatic primary hyperparathyroidism in older adults. Quality improvement efforts, rooted in equitable care, should be undertaken to increase access to parathyroidectomy for this disease.

Higher prevalence of Concomitant Hyperparathyroidism in African American Patients Undergoing Thyroid Surgery.

BACKGROUND: Hyperparathyroidism (HPT) occurs in about 1% of the general population. Previous studies have suggested that the incidence is higher in those patients with thyroid disease who are undergoing thyroid surgery. The study purpose was to examine the incidence of concomitant HPT in patients already undergoing a thyroid procedure and to identify risk factors. MATERIALS AND METHODS: A prospective database of all patients who had thyroidectomy by the endocrine surgery team was reviewed between August 2012 and April 2020. Per institutional protocol, all patients having thyroid surgery were screened for concomitant hyperparathyroidism. ANOVA/T-Test and Chi-square were conducted to compare those with and without hyperparathyroidism. RESULTS: The median age was 43 and 79% were female. Of the 481 patients undergoing thyroidectomy, 31 (6%) had HPT. The mean preoperative calcium and parathyroid hormone levels were 10 ± 0 mg/dL and 67 ± 5 pg/mL, respectively. When comparing the groups, patients with concomitant HPT were older (53 ± 4 versus 42 ± 1 y, P = 0.005). African American race was a significant risk factor for concomitant HPT. While African Americans represented only 29% of those undergoing surgery, 58% of those with concomitant HPT were African American (P = 0.007). CONCLUSION: In patients having thyroid surgery, concomitant HPT was present in 6% of the population, higher than estimated general population prevalence. While we understand that primary HPT incidence increases with age, to our knowledge, this is the first report to document that African Americans are at a higher risk for concomitant HPT with thyroid disease. Thus, routine screening for hyperparathyroidism in patients undergoing thyroid surgery, especially in vulnerable populations, such as the older and African American population, is beneficial.

An Institutional experience with primary hyperparathyroidism in the elderly over two decades.

BACKGROUND: Parathyroidectomy is the only curative treatment for primary hyperparathyroidism (pHPT) and is associated with low morbidity. This study examined the severity of disease and outcomes of parathyroidectomy based on patient age at a high-volume institution. METHODS: This is a retrospective review of sporadic pHPT patients who underwent initial parathyroidectomy. To study disease severity over time, patients were divided into timeframes: 1999-2007, 2007-2012, and 2013-2018. Elderly was defined as age ≥75 years. RESULTS: Over time, the elderly had progressively lower preoperative calcium (11.0, 10.7, 10.7; p = 0.05) and PTH (150.4, 111.9, 107.9; p < 0.001) levels. By age, there was no difference in preoperative calcium (10.8, 10.9; p = 0.91) or in rates of recurrent laryngeal nerve injury, hypoparathyroidism, or persistent/recurrent pHPT. CONCLUSIONS: Over the 3 time periods of the study, elderly patients had progressively lower calcium and PTH levels. There was no difference in endocrine-specific complications between the age groups, suggesting that parathyroidectomy in the elderly is safe and therefore, age-associated morbidity should not preclude parathyroidectomy.

Sestamibi Single-Positron Emission Computed Tomography/Diagnostic-quality Computed Tomography for the localization of abnormal parathyroid glands in patients with primary hyperparathyroidism: What clinicopathologic factors affect its accuracy?

PURPOSE: Sestamibi Single-Positron Emission Computed Tomography/Diagnostic-quality Computed Tomography (MIBI-SPECT/CT) is a common technology used for primary hyperparathyroidism (PHPT) localization in clinical practice. However, the clinicopathologic factors affecting the accuracy of MIBI-SPECT/CT and the potential limitations remain unclear. METHODS: Retrospectively enrolled PHPT patients (n = 280) were analyzed from August 2017 to December 2019. RESULTS: Of 96 patients with PHPT (mean age, 54 years; 63 females), 17 had discordance between MIBI-SPECT/CT and intraoperative findings. Among the 17 patients with discordance, 58.8% had major discordance, which occurred in most patients with multigland disease (MGD). Compared with concordant patients, discordant patients exhibited increased frequencies of autoimmune thyroid disease (29.4% vs 10.1%, p = 0.035), MDG (41.2% vs 3.8%, p = 0.035), higher PTH (296 pg/mL vs 146 pg/mL; p = 0.012),and lower phosphorus levels (0.77 mmol/L vs 0.90 mmol/L; p = 0.024). MDG (odds ratio [OR], 16.95; 95% CI 2.10-142.86), parathyroid lesion size of 12 mm or less (OR, 6.93; 95% CI 1.41-34.10), and a PTH level higher than 192.5 pg/mL (OR, 12.66; 95% CI 2.17-71.43) were independently associated with discordant MIBI-SPECT/CT results. CONCLUSION: MGD was most strongly associated with discordance between MIBI-SPECT/CT and intraoperative findings followed by a PTH level higher than 192.5 pg/mL and parathyroid lesion size of 12 mm or less. Surgeons should recognize these potential limitations, which may improve the preoperative procedure by encouraging further localization imaging and promptly facilitate intraoperative troubleshooting.

Patient Factors Associated With Parathyroidectomy in Older Adults With Primary Hyperparathyroidism.

Importance: Parathyroidectomy provides definitive management for primary hyperparathyroidism (PHPT), reducing the risk of subsequent fracture, nephrolithiasis, and chronic kidney disease (CKD), but its use among older adults in the US is unknown. Objective: To identify patient characteristics associated with the use of parathyroidectomy for the management of PHPT in older adults. Design, Setting, and Participants: This population-based, retrospective cohort study used 100% Medicare claims from beneficiaries with an initial diagnosis of PHPT from January 1, 2006, to December 31, 2016. Patients were considered to meet consensus guideline criteria for parathyroidectomy based on diagnosis codes indicating osteoporosis, nephrolithiasis, or stage 3 CKD. Multivariable logistic regression was used to identify patient characteristics associated with parathyroidectomy. Data were analyzed from February 11, 2020, to October 8, 2020. Main Outcomes and Measures: The primary outcome was parathyroidectomy within 1 year of diagnosis. Results: Among 210 206 beneficiaries with an incident diagnosis of PHPT (78.8% women; mean [SD] age, 75.3 [6.8] years), 63 136 (30.0%) underwent parathyroidectomy within 1 year of diagnosis. Among the subset of patients who met consensus guideline criteria for operative management (n = 131 723), 38 983 (29.6%) were treated with parathyroidectomy. Patients treated operatively were younger (mean [SD] age, 73.5 [5.7] vs 76.0 [7.1] years) and more likely to be White (90.1% vs 86.0%), to be robust or prefrail (92.1% vs 85.7%), and to have fewer comorbidities (Charlson Comorbidity Index score of 0 or 1, 54.6% vs 44.1%), in addition to being more likely to live in socioeconomically disadvantaged (46.9% vs 40.3%) and rural (18.1% vs 13.6%) areas (all P < .001). On multivariable analysis, increasing age had a strong inverse association with parathyroidectomy among patients aged 76 to 85 years (unadjusted rate, 25.9%; odds ratio [OR], 0.68 [95% CI, 0.67-0.70]) and older than 85 years (unadjusted rate, 11.2%; OR, 0.27 [95% CI, 0.26-0.29]) compared with those aged 66 to 75 years (unadjusted rate, 35.6%), as did patients with moderate to severe frailty (unadjusted rate, 18.9%; OR, 0.60 [95% CI, 0.56-0.64]) compared with robust patients (unadjusted rate, 36.1%) and those with a Charlson Comorbidity Index score of 2 or greater (unadjusted rate, 25.9%; OR, 0.77 [95% CI, 0.75-0.79]) compared with a Charlson Comorbidity Index score of 0 (unadjusted rate, 37.0%). With regard to operative guidelines, a history of nephrolithiasis increased the odds of parathyroidectomy (OR, 1.43 [95% CI, 1.39-1.47]); stage 3 CKD decreased the odds of parathyroidectomy (OR, 0.71 [95% CI, 0.68-0.74]); and osteoporosis showed no association (OR, 1.01 [95% CI, 0.99-1.03]). Conclusions and Relevance: In this cohort study, most older adults with PHPT did not receive definitive treatment with parathyroidectomy. Older age, frailty, and multimorbidity were associated with nonoperative management, and guideline recommendations had minimal effect on treatment decisions. Further research is needed to identify barriers to surgical care and develop tools to target parathyroidectomy to older adults most likely to benefit.