Parathyroidectomy For Sporadic Primary Hyperparathyroidism Research Articles

Operative success is achieved regardless of ioPTH criterion used during focused parathyroidectomy for sporadic primary hyperparathyroidism

BackgroundFocused parathyroidectomy (F-PTX) guided by intraoperative parathormone (ioPTH) monitoring may result in higher operative failure rates from missed multiglandular disease (MGD) in patients with sporadic primary hyperparathyroidism (spHPT) when ioPTH levels do not reach normal range. MethodsA retrospective review included 690 patients with spHPT who underwent F-PTX and ioPTH monitoring were divided into 2 groups: >50% ioPTH decrease to normal range, and >50% ioPTH decrease to above normal range. Operative success, recurrence, bilateral/unilateral neck exploration (BNE/UNE), MGD were evaluated. Results533 patients demonstrated >50% ioPTH decrease to normal range, and 157 patients >50% ioPTH decrease to above normal range. There were no differences in operative success 99% vs. 97%, recurrence 2.5% vs. 5%, BNE 12% vs. 11%, UNE 4% vs. 5%, or MGD 4% vs. 4%, (p > 0.05) with 46 months mean follow-up. ConclusionsThere were no differences in operative success, failure, BNE, UNE or MGD regardless of ioPTH criterion used for F-PTX.

The impact of patient age on practice patterns and outcomes for primary hyperparathyroidism

BackgroundManagement of asymptomatic primary hyperparathyroidism (PHPT) in older patients (age >50) is controversial. The 4th International Workshop on the Management of Asymptomatic PHPT recommends surveillance for older patients who lack objective signs of disease, whereas The American Association of Endocrine Surgeons (AAES) guidelines recommend consideration of parathyroidectomy for patients of any age with subjective constitutional, neuropsychiatric, or cognitive symptoms. Therefore, the primary objective of this study was to evaluate the association between patient age and both practice patterns and outcomes in the management of patients with sporadic PHPT. MethodsThe Collaborative Endocrine Surgery Quality Improvement Program (CESQIP) database was queried for all adults (age ≥18) who underwent an index parathyroidectomy for sporadic primary hyperparathyroidism between 2014 and 2020. Associations between patient age (≤50 years vs. >50 years) and both practice patterns and outcomes were evaluated separately using adjusted multivariable logistic and multinomial regression models. ResultsOf 9,938 patients who underwent parathyroidectomy, 8,080 (81.3%) were >50 years old and 1,858 (18.7%) were ≤50. Of this cohort, 17% of older patients and 26% of younger patients presented with only subjective symptoms. Compared to younger patients, older patients were more likely to have an objective indication for parathyroidectomy (aOR = 1.8, 95%CI: 1.6–2.0, p < 0.001). They were also more likely to undergo ≥2 imaging studies pre-operatively (aOR = 1.2, 95%CI: 1.1–1.3, p = 0.003), to undergo bilateral neck exploration (aOR = 1.4, 95%CI: 1.3–1.6, p < 0.001), and to have multi-gland disease (aOR = 1.6, 95%CI: 1.4–1.8, p < 0.001). There was no difference between age groups and parathyroidectomy-related complications including hypocalcemia, vocal cord dysfunction, hematoma requiring evacuation, or reintubation, however, older patients were less likely to have any peri-operative morbidity (aOR = 0.7, 95%CI: 0.6–0.9, p = 0.011). ConclusionsOlder patients were more likely to meet objective criteria prior to undergoing parathyroidectomy by CESQIP participating high-volume endocrine surgeons, however they were less likely to have peri-operative complications compared to younger patients. Given the growing evidence demonstrating improvement of both objective and subjective symptoms after parathyroidectomy for PHPT, additional studies are still needed to fully understand the benefit of surgical referral in older adults for less objective indications.

Normocalcemic hyperparathyroidism: A Collaborative Endocrine Surgery Quality Improvement Program analysis

BackgroundNormocalcemic primary hyperparathyroidism may be more challenging to cure compared with classical primary hyperparathyroidism. The aim of this study was to utilize a multi-institutional database to better characterize this condition. MethodsThe Collaborative Endocrine Surgery Quality Improvement Program database was queried for all patients who underwent parathyroidectomy for sporadic primary hyperparathyroidism. Patient characteristics, operative details, pathology, and outcomes data were compared between patients with normocalcemic primary hyperparathyroidism and those with hypercalcemia. ResultsAmong 7,569 patients, 9.7% (733) were normocalcemic primary hyperparathyroidism. Mean age at surgery and sex were similar for normocalcemic primary hyperparathyroidism and primary hyperparathyroidism with hypercalcemia. The primary hyperparathyroidism with hypercalcemia cohort had a single parathyroid resected more frequently than the normocalcemic primary hyperparathyroidism group (73.3%% vs 47.5%, P < .05). Patients with normocalcemic primary hyperparathyroidism had a higher rate of subtotal (3.5 gland) resection (10.0% vs 4.7%, P < .05). Pathology reported a higher frequency of multigland hyperplasia in the normocalcemic primary hyperparathyroidism cohort (43.1% vs 21.9%, P <.05). In the normocalcemic primary hyperparathyroidism cohort, 47 patients (6.4%) underwent remedial surgery compared with 307 patients (4.5%) with primary hyperparathyroidism with hypercalcemia (P < .05). The rate of clinical concern for persistent hyperparathyroidism was similar between the 2 groups (P = .09) but not reported in 25% overall. ConclusionPatients with normocalcemic primary hyperparathyroidism have higher rates of multigland disease and remedial surgery compared with primary hyperparathyroidism with hypercalcemia.

The Reasons of Eucalcemic Parathyroid Hormone Elevation After Parathyroidectomy for Sporadic Primary Hyperparathyroidism

The success of sporadic primary hyperparathyroidism (SPHPT) treatment is providing normocalcemia independent from parathormone (PTH) levels after parathyroidectomy. However, the PTH levels of 7–40% cases remain elevated. We aimed to determine the timing of the postoperative elevation of PTH, and the relation with type of the operation, preoperative vitamin D levels, and season of the operation. Medical records of 119 SPHPT patients were reviewed retrospectively. For the purpose of the study, 99 patients were appropriate. The study is performed in Izmir, Turkey, and surrounding regions. The patients are grouped as operated on summer-spring and winter-autumn based on the sun exposure. On preoperative, postoperative 1st day, 1st week, 3rd month, 6th month, 12th month PTH levels, calcium, and vitamin D before and a year after the operation were noted. A total of 99 patients with a mean age of 57.88 were included. Low PTH levels in the first day of the operation had significant relation with high PTH levels in the first 6 months (p < 0.05). On the third month, eucalcemic parathyroid hormone elevation (ePTH) reached the top level and declined to 53% and 26% in 6th and 12th month, respectively. There is no significant difference between preoperative vitamin D levels, operation type, and the season of operation time; however, ePTH was more common in patients operated in autumn-winter. Our results showed that ePTH development was unrelated with vitamin D levels, operation type, and operation season. ePTH should not be accepted as an indicator of recurrence on early follow-up of patients having appropriate medical supplementation.

Justified follow-up: a final intraoperative parathyroid hormone (ioPTH) Over 40 pg/mL is associated with an increased risk of persistence and recurrence in primary hyperparathyroidism.

After parathyroidectomy for sporadic primary hyperparathyroidism (PHPT), overall rates of persistence/recurrence are extremely low. A marker of increased risk for persistence/recurrence is needed. We hypothesized that final intraoperative parathyroid hormone (FioPTH) ≥40pg/mL is indicative of increased risk for disease persistence/recurrence, and can be used to selectively determine the degree of follow-up. A retrospective review of PHPT patients undergoing parathyroidectomy with ioPTH monitoring was performed. An ioPTH decline of 50% was the only criteria for operation termination. Patients were grouped based on FioPTH of <40, 40-59, and >60pg/mL. Between 2001 and 2012, 1,371 patients were included. Mean age was 61±0.4years, and 78°% were female. Overall persistence rate was 1.4°%, with a 2.9°% recurrence rate. Overall, 976 (71°%) patients had FioPTH <40, 228 (16.6°%) had FioPTH 40-59, and 167 (12.2°%) had FioPTH ≥60. Mean follow-up was 21±0.6months. Patients with FioPTH <40 were younger, with lower preoperative serum calcium, PTH, and creatinine (all p≤0.001). Patients with FioPTH <40 had the lowest persistence rate (0.2%) versus patients with FioPTH 40-59 (3.5%) or FioPTH ≥60 (5.4%; p<0.001). Recurrence rate was also lowest in patients with FioPTH <40 (1.3 vs. 5.9 vs. 8.2%, respectively; p<0.001). Disease-free status was greatest in patients with FioPTH <40 at 2years (98.5 vs. 96.8 vs. 90.5%, respectively) and 5years (95.7 vs. 72.3 vs. 74.8%, respectively; p<0.01). Patients with FioPTH <40pg/mL had lower rates of persistence and recurrence, than patients with FioPTH 40-59, or ≥60. Differences became more apparent after 2years of follow-up. Patients with FioPTH ≥40pg/mL warrant close and prolonged follow-up.

Efficacy of localization studies and intraoperative parathormone monitoring in the surgical management of hyperfunctioning ectopic parathyroid glands

Hyperfunctioning ectopic glands remain an operative challenge in patients with sporadic primary hyperparathyroidism. This study examines the incidence of ectopic glands and the utility of sestamibi scans (MIBI), surgeon-performed ultrasonography, and intraoperative parathormone monitoring in such patients undergoing parathyroidectomy. We conducted a retrospective analysis of prospectively collected data from patients who underwent parathyroidectomy from 1980 to 2011 for sporadic primary hyperparathyroidism at a single institution. Demographics, localizing imaging studies, intraoperative parathyroid monitoring dynamics, and surgical outcome for patients with hyperfunctioning ectopic parathyroid glands were studied. Among 1,195 patients who underwent parathyroidectomy for sporadic primary hyperparathyroidism, 120 patients (10%) had hyperfunctioning ectopic glands, which were localized to the neck (n=66) and mediastinum (n = 54). MIBI had a sensitivity of 85%, specificity of 97%, and positive predictive value (PPV) of 91% for ectopic glands in the neck, whereas in the mediastinum there was a sensitivity of 88%, specificity of 95%, and PPV of 86%. Surgeon-performed ultrasonography had a sensitivity of 81%, specificity of 98%, and PPV of 95% for neck ectopic glands. The overall accuracy of surgeon-performed ultrasonography, MIBI, and intraoperative parathyroid monitoring in the neck ormediastinum was 93%. Overall, operative success was 93% with a multiglandular disease rate of5%. A high operative success rate for hyperfunctioning ectopic glands can be achieved using localization studies and intraoperative parathyroid monitoring. Nevertheless, surgeon judgment remains paramount in the operative direction of this patient population.

Factors That Influence Parathyroid Hormone Half-life

Minimally invasive parathyroidectomy using intraoperative parathyroid hormone monitoring remains the standard approach to the majority of patients with primary hyperparathyroidism. This study demonstrates that individual patient characteristics do not affect existing criteria for intraoperative parathyroid hormone monitoring. To identify patient characteristics, such as age, sex, race, body mass index (BMI), and renal function, that may affect existing criteria for intraoperative parathyroid hormone (IOPTH) levels during minimally invasive parathyroidectomy. Retrospective review of a prospectively collected parathyroid database populated from August 2005 to April 2011. Academic medical center. Three hundred six patients with sporadic primary hyperparathyroidism who underwent initial parathyroidectomy between August 2005 and April 2011. All patients underwent minimally invasive parathyroidectomy with complete IOPTH information. Individual IOPTH kinetic profiles were fitted with an exponential decay curve and individual IOPTH half-lives were determined. Univariate and multivariate analyses were performed to determine the association between patient demographics or laboratory data and IOPTH half-life. Mean age of the cohort was 60 years, 78.4% were female, 90.2% were white, and median BMI was 28.3. Overall, median IOPTH half-life was 3 minutes, 9 seconds. On univariate analysis, there was no association between IOPTH half-life and patient age, renal function, or preoperative serum calcium or parathyroid hormone levels. Age, BMI, and an age × BMI interaction were included in the final multivariate median regression analysis; race, sex, and glomerular filtration rate were not predictors of IOPTH half-life. The IOPTH half-life increased with increasing BMI, an effect that diminished with increasing age and was negligible after age 55 years (P = .001). Body mass index, especially in younger patients, may have a role in the IOPTH half-life of patients undergoing parathyroidectomy. However, the differences in half-life are relatively small and the clinical implications are likely not significant. Current IOPTH criteria can continue to be applied to all patients undergoing parathyroidectomy for sporadic primary hyperparathyroidism.

Normocalcemic parathormone elevation after successful parathyroidectomy: Long-term analysis of parathormone variations over 10 years

The long-term significance of normocalcemic parathormone elevation (NPE) after successful parathyroidectomy for sporadic primary hyperparathyroidism remains unclear. Of 239 consecutive patients who underwent targeted parathyroidectomy with intraoperative parathormone monitoring, 96 were followed for ≥ 10 years. NPE was defined as a normal serum calcium level and parathormone (PTH) above the normal reference range ≥ 6 months after successful parathyroidectomy. Recurrence was defined as elevated serum calcium and PTH levels ≥ 6 months after parathyroidectomy. Risk factors for NPE, patterns of postoperative PTH variation, and 10-year outcomes were analyzed. Of 96 patients followed ≥ 10 years, 42 had postoperative NPE. Only male gender (P = .008) was a risk factor for NPE, and NPE did not predict recurrence. Three patterns of postoperative NPE were identified in patients with ≥ 3 PTH measurements over this 10-year period. Group 1 (n = 11): 1 to 2 consecutive PTH elevations; none recurred, and most were explained by physiologic variation. Group 2 (n = 23): multiple PTH fluctuations; 3 recurred, and almost all had physiologic variations. Group 3 (n = 4): PTH always elevated; 2 recurred. Postoperative NPE may be a dynamic, reversible, and transient clinical entity that does not predict recurrence. Nevertheless, patients with postoperative NPE should be monitored and an attempt made to correct any obvious potential causes of PTH elevation.

Recent findings in the use of intraoperative parathyroid hormone monitoring in parathyroid disease

To discuss recent findings and controversies regarding intraoperative parathyroid hormone monitoring (IPM) in guiding parathyroidectomy. IPM is being frequently used in guiding surgeons to complete excision of abnormal glands during parathyroidectomy for sporadic primary hyperparathyroidism (SPHPT). This adjunct is now being used in many centers around the world and has become a standard of care in the treatment of SPHPT. As the use of this technique developed, the understanding of what was necessary to return patients with hyperparathyroidism to a eucalcemic state, namely, excision of all parathyroid tissue secreting high amount of parathyroid hormone, was recognized. Two major controversies have developed during the evolution of IPM guided parathyroidectomy. One is that gland excision based on this modality may not recognize all abnormal glands, which, if not excised, will result in operative failure or recurrent hyperparathyroidism. The second disagreement is a technical one and concerns the best intraoperative protocol to be used. Parathyroidectomy for SPHPT is highly successful regardless of the operative approach used. Despite the controversies summarized in the present review, IPM has been shown to be accurate as an adjunct to guide parathyroidectomy and has changed the operative management of SPHPT.

Long-term Outcome of Patients With Elevated Parathyroid Hormone Levels After Successful Parathyroidectomy for Sporadic Primary Hyperparathyroidism

Long-term Outcome of Patients With Elevated Parathyroid Hormone Levels After Successful Parathyroidectomy for Sporadic Primary Hyperparathyroidism

Appreciation Of Osteoporosis Among Men With Hyperparathyroidism

To define the scope of bone disease among men referred for parathyroidectomy and to document bone density screening trends in this high-risk population. Clinical data were analyzed from a prospectively maintained database of 1000 patients undergoing parathyroidectomy for sporadic primary hyperparathyroidism at the Cleveland Clinic between 2000 and 2006. Information collected included demographics, reason for referral, body mass index, intraoperative findings, preoperative and postoperative laboratory values (serum calcium, phosphorus, parathyroid hormone, 25-hydroxyvitamin D, and 24-hour urinary calcium excretion), and preoperative and postoperative dual-energy x-ray absorptiometry (DXA) findings. Of the 1000 patients, 243 (24%) were men. As with women, bone health-related issues were the most common reason for referral (32%). In 2000, only 12% of men had preoperative DXA scans; this rose to 42% by 2005. The frequency of prereferral DXA screening increased throughout the study, but even by 2006, referring physicians did not screen most of their male patients. In 2000, the prevalence of bone disease (osteoporosis or osteopenia) in men was 8%, but with improved screening, this increased to 26%, approaching the 34% rate in women. Preoperative and postoperative levels of calcium, parathyroid hormone, phosphorus, 24-hour urinary calcium, and 25-hydroxyvitamin D were the same among men with and without bone disease. Analysis of postoperative DXA scans revealed that gains in postparathyroidectomy bone density were significantly greater in men than in women at all anatomic testing sites. In men, lowest T scores improved by a mean +/- SEM of +0.35 +/- 0.09 compared with +0.098 +/- 0.035 in women (P = .009). Men were 4 times less likely than women to have continued bone loss after parathyroidectomy. Clinical and laboratory parameters cannot identify men with hyperparathyroidism who have bone loss, illustrating the need for routine DXA screening. Despite this, DXA remains underused. Improved screening practices will favorably effect men's health.

Long-term Outcome of Patients With Elevated Parathyroid Hormone Levels After Successful Parathyroidectomy for Sporadic Primary Hyperparathyroidism

Untreated long-term elevated parathyroid hormone (PTH) levels after successful parathyroidectomy may predict recurrent hyperparathyroidism (HPT). Although elevated PTH levels have been reported in eucalcemic patients after parathyroidectomy for sporadic primary HPT, the long-term clinical significance of this finding remains unclear. Retrospective case series. Tertiary referral center. Five hundred seventy-six consecutive patients with HPT. Parathyroidectomy guided by intraoperative monitoring of PTH levels. Overall incidence of elevated PTH levels (measurements of >or= 70 pg/mL at any time during follow-up) and recurrent HPT (hypercalcemia and elevated PTH levels more than 6 months after parathyroidectomy). Of the 505 patients who underwent successful parathyroidectomy in this series and were followed up for more than 6 months, 337 (66.7%) consistently had PTH levels within the reference range, and 168 (33.3%) had elevated PTH levels. Of the 168 patients with elevated PTH levels, only 8 (4.8%) developed recurrent disease. The earliest recurrence occurred 2 years postoperatively. Factors associated with elevated PTH levels included advanced age, higher preoperative PTH levels, and mild postoperative renal insufficiency. Although one-third of the patients had elevated PTH levels after successful parathyroidectomy, most of these patients with elevated PTH levels (95%) will achieve long-term eucalcemia.

Surgeon Performed Ultrasound Facilitates Minimally Invasive Parathyroidectomy by the Focused Lateral Mini‐incision Approach

Minimally invasive parathyroidectomy (MIP) is now widely accepted where a single adenoma can be localized preoperatively. In our unit, MIP is offered once a parathyroid adenoma is localized with a sestamibi (MIBI) scan, with or without a concordant neck ultrasound. The aim of this study was to compare the accuracy of surgeon performed ultrasound (SUS) with radiologist performed ultrasound (RUS) in the localization of a parathyroid adenoma in MIBI-positive primary hyperparathyroidism (PHPT). This is a prospective study of patients undergoing parathyroidectomy for sporadic primary hyperparathyroidism (PHPT) from April 2005 to October 2006 at the University of Sydney Endocrine Surgical Unit. Patients were then divided into those who underwent preoperative RUS or SUS. Two-hundred eighteen patients formed the study group. One hundred forty-eight (66%) patients had RUS and 87 (39%) had SUS. Overall, RUS correctly localized the parathyroid adenomas in 121 of 148 (82%) patients. Surgeon performed ultrasound correctly localized the abnormal parathyroid adenoma in 72 of 87 (83%) of cases. There was no significant difference in the proportion of patients with single gland disease, double adenomas, or hyperplasia correctly localized by SUS or RUS. Incorrect interpretation of ultrasound imaging was due to cystic degeneration in thyroid nodules, lymph nodes, retro-esophageal location of adenomas and ectopic and small parathyroid glands. Surgeon performed ultrasound is a useful adjunctive tool to MIBI localization for facilitating MIP and when performed by experienced parathyroid surgeons, it can achieve accuracy rates equivalent to that of a dedicated parathyroid radiologist.

Impact of 25-Hydroxyvitamin D Deficiency on Perioperative Parathyroid Hormone Kinetics and Results in Patients with Primary Hyperparathyroidism

Successful parathyroidectomy for sporadic primary hyperparathyroidism (pHPT) is predicted by a 50% drop in PTH intra-operatively. Vitamin D is a known inhibitor of PTH secretion and is associated with secondary HPT following adenoma resection. This study examined the impact of 25-hydroxyvitamin D (25OHD) deficiency on perioperative PTH kinetics and outcomes following parathyroidectomy. Patients undergoing adenoma resection for pHPT (n=93) had PTH levels recorded at six perioperative time points. Preoperative 25OHD levels were examined retrospectively. Patients were considered 25OHD deficient if the level was <25 ng/mL (n=47) and adequate if the level was >or=25 ng/mL (n=46). Patients with 25OHD-deficiency had significantly higher preoperative calcium, alkaline phosphatase, and PTH levels. PTH levels were significantly higher in 25OHD-deficient patients at incision, at 1 week postop and 1-3 months postop. Average drop in PTH level five minutes post resection was 79+/-14% in the deficient group and 72+/-22% in the non-deficient group (P=.03). 25OHD levels inversely correlated with adenoma weight (P=.03) and postoperative PTH measurements (P=.008). Sporadic pHPT patients with 25OHD deficiency have higher baseline and postoperative PTH levels compared to non-deficient patients but do not have altered intraoperative PTH kinetics. Vitamin D deficiency is associated with postoperative elevation of PTH.

Recurrent disease after limited parathyroidectomy for sporadic primary hyperparathyroidism

Limited parathyroidectomy guided by intraoperative parathyroid hormone (PTH) assay (QPTH) is highly successful (97% to 99%) in predicting postoperative eucalcemia, usually with less extensive dissection when compared with bilateral neck exploration. Because fewer glands are excised when resection is guided by QPTH as opposed to resection guided by gland size, a higher recurrence rate may occur. Recurrence rate after bilateral neck exploration is 0.4% to 5%, but frequency of recurrence after limited parathyroidectomy is unknown. This study reports outcomes of this operative approach in sporadic primary hyperparathyroidism. Four-hundred twenty-three patients with sporadic primary hyperparathyroidism undergoing limited parathyroidectomy, followed 6 months or more or considered operative failures, were studied. In most patients, calcium and PTH levels were measured immediately after operation, and then at 2 and 6 months and yearly intervals. Operative failure is defined as hypercalcemia and high PTH within 6 months after operation, and recurrent hyperparathyroidism is hypercalcemia and elevated PTH occurring after a successful parathyroidectomy. Recurrence distributions were estimated using Kaplan-Meier analysis. The success rate of limited parathyroidectomy is 97% (412/423). Four-hundred six patients were eucalcemic over an average of 34 months (median 27, range 6 to 118 months) of followup and recurrent hyperparathyroidism developed in 6 of 412 (1.5%). Estimated 5 years recurrence-free rate was 97% (95% confidence interval, 91% to 99%). Earliest and latest recurrences were diagnosed at 24 and 83 months, respectively. QPTH results did not predict any recurrence. Overall success rate was achieved, with multiple gland resections performed in only 3% of patients. Recurrence rate after limited parathyroidectomy is similar to rates reported after bilateral neck exploration. Parathyroidectomy guided by QPTH is successful not only in resolving hypercalcemia in the short term, but also in providing longterm eucalcemia.