Bilateral Parathyroid Exploration Research Articles

Hypercalcemia with a parathyroid hormone level of ≤50 pg/mL: Is this primary hyperparathyroidism?

BackgroundPrimary hyperparathyroidism is characterized by hypercalcemia with inappropriately normal or elevated parathyroid hormone. However, the absolute parathyroid hormone value that is defined as inappropriately normal is unclear. We reviewed our experience with parathyroidectomy in patients with hypercalcemia and parathyroid hormone of ≤50.0 pg/mL (normal range 12.0–88.0 pg/mL). MethodsA total of 2,349 patients underwent parathyroidectomy for primary hyperparathyroidism between 2000 and 2021. Of these, 149 patients had preoperative parathyroid hormone ≤50.0 pg/mL (parathyroid hormone ≤50). The biology and outcomes were compared to patients with parathyroid hormone >50.0 pg/mL (parathyroid hormone >50). ResultsOf the parathyroid hormone ≤50 patients, the median parathyroid hormone was 40.0 pg/mL (range 11.6–50.0 pg/mL). All patients were found to have abnormal hypercellular parathyroid glands with a cure rate of 96.7%. When compared to the parathyroid hormone >50 group, the parathyroid hormone ≤50 group was younger (56 ± 15 vs 60 ± 14 years, P < .001) with a lower body mass index (28.7 ± 7.0 kg/m2 vs 31.2 ± 7.9 kg/m2, P < .001), higher rate of fatigue (73.2% vs 63.0%, P = .033), and higher rate of multiglandular disease (58.9% vs 31.9%, P < .001). There was no difference between the groups with respect to patient demographics, rate of previous parathyroidectomy, surgical cure, or postoperative complications (persistent or recurrent hyperparathyroidism and hypocalcemia). ConclusionPatients with hypercalcemia and parathyroid hormone ≤50 pg/mL have a similar clinical presentation and rate of surgical cure to other primary hyperparathyroidism patients and should be considered for parathyroidectomy. Most of these patients have multiglandular disease and thus should be considered for bilateral parathyroid exploration.

Focused Versus Bilateral Parathyroid Exploration for Primary Hyperparathyroidism: A Systematic Review and Meta-analysis.

Focused exploration (FE) and bilateral parathyroid exploration (BE) are the standard surgical options for patients with primary hyperparathyroidism. However, the relative risk of recurrence, persistence, overall failure, reoperation, and any complications associated with either surgical approach is unclear. This study compared the outcomes and complication rates after FE and BE for patients with primary hyperparathyroidism. PubMed and Embase were searched for studies comparing these outcomes between FE and BE. A meta-analysis was performed using RevMan 5.3 software. Published data were pooled using the DerSimonian random-effect model, and results were presented as odds ratio (OR) or mean difference with 95% confidence interval (CI). A total of 12,743 patients from 19 studies were included in this meta-analysis. In comparison with BE, the FE arm had comparable rates of recurrence (OR1.08; 95% CI 0.59-2.00; p=0.80; n=9 studies), persistence (OR0.89; 95% CI 0.58-1.35; p=0.58; n=13), overall failure (OR0.88; 95% CI 0.58-1.34; p=0.56; n=13), and reoperation (OR1.05; 95% CI 0.25-4.32; p=0.95, n=4). The operative time was significantly shorter (mean difference=-39.86; 95% CI -53.05 to -26.84; p<0.01, n=9), with a lower overall complication rate in the FE arm (OR 0.35; 95% CI 0.15-0.84; p=0.02; n=12). The latter was attributed predominantly to a lower risk of transient hypocalcemia (OR 0.36; 95% CI 0.14-0.90; p=0.03; n=9). There was a significant heterogeneity among these studies for all outcomes except for disease recurrence. Compared with BE, FE has similar recurrence, persistence, and reoperation rates but significantly lower overall complication rates and shorter operative time.

The use of intraoperative parathyroid hormone monitoring in minimally invasive parathyroid surgery.

Introduction Surgery is the first-line management option for patients with primary hyperparathyroidism (pHPT). Minimally invasive parathyroidectomy (MIP) is now preferable but few centres offer this service, mainly because of lack of intraoperative parathyroid hormone (IOPTH) testing. The aim of this study was to identify whether the measurement of IOPTH in patients having minimally invasive parathyroidectomy for pHPT alters their management. Methods A retrospective review was carried out of 78 consecutive patients who underwent parathyroid surgery by a single surgeon with a special interest in parathyroid surgery. The clinical impact of IOPTH monitoring was recorded postoperatively in a timely manner. Serum adjusted calcium levels were checked preoperatively (on admission) and one month postoperatively; normalisation was considered a cure. Results In the setting of curative MIP, IOPTH measurement did not influence the management in any of the patients but it could have led to bilateral parathyroid exploration (BPE) in three instances. Similarly, in cases that required lengthening of the MIP incision, IOPTH results did not influence patient management although it could have led to BPE in one case. Conclusion MIP offers an effective cure for patients with hyperparathyroidism. The addition of IOPTH testing adds increased expense, operating time and risk to patients otherwise suitable for MIP.

Surgical exploration for hyperparathyroidism

Traditionally, primary hyperparathyroidism has been managed surgically with 4-gland exploration. Surgical exploration remains the gold standard in parathyroid surgery and remains an important surgical technique despite the popularity of minimally invasive parathyroid surgery. In this article, we describe the indications, technique, and other perioperative considerations in bilateral parathyroid exploration.

Pedicled Parathyroid Autotransposition in Surgical Management of Secondary Hyperparathyroidism

Objectives: In this study, we report a new, less invasive surgical technique in managing preserved parathyroid tissue in patients with secondary hyperparathyroidism who undergo bilateral parathyroid exploration and excision of all 4 parathyroid glands. We report this technique in 4 patients and evaluate their postoperative parathyroid hormone (PTH) levels as a marker to evaluate efficacy. Methods: All 4 glands were first exposed. Superior glands are not possible to transpose and were excised while the inferior glands were mobilized on their pedicles. Once identified, the inferior glands were kept intact until it was determined which gland can be best preserved on its vascular pedicle with adequate length for transposition. This gland was then mobilized through an incision made in the strap muscles, placing it superficial and ventral to the muscles. The majority of the hyperplastic gland was then resected distal to its vascular pedicle. The portion of the gland that was preserved was secured over the strap muscle, making it easily accessible for future exploration and debulking if needed and avoiding a second operative site in the forearm. Results: Rapid intraoperative PTH assay confirmed adequate removal of hypersecreting parathyroids and was indicative of a curative outcome. All patients exhibited a greater than 90% initial reduction in the PTH level from their baseline and a sustained decrease in postoperative PTH levels well below their preoperative baselines at one month. The percentage mean reduction in PTH at longest follow-up was 94.57%. Importantly, none of the patients exhibited postoperative PTH levels indicative of hypoparathyroidism. Conclusions: None provided.

Factors in conversion from minimally invasive parathyroidectomy to bilateral parathyroid exploration for primary hyperparathyroidism

Ongoing experience has documented equivalence of minimally invasive parathyroidectomy (MIP) and standard bilateral parathyroid exploration (BPE) for primary hyperparathyroidism in most patients; however, intraoperative conversion of MIP to BPE is required for multiple indications. This study analyzes the factors, predictors, and cure rates in converted MIP. We retrospectively analyzed a database of 1,002 patients undergoing initial parathyroidectomy for primary hyperparathyroidism from 2008 to 2011 for rate of successful MIP, converted MIP, planned BPE, and factors leading to conversion from MIP to BPE. Of 989 included parathyroidectomies, 647 (65%) were successful MIP, 186 (19%) were converted MIP, and 156 (16%) were planned BPE. The most common indication for conversion included intraoperative parathyroid hormone (IOPTH) criteria not met (46%), localization incorrect (36%), and evidence of multigland disease (17%). Converted MIP had lower preoperative calcium and PTH and lower baseline IOPTH compared with successful MIP. Complication rates were similar; however, rates of persistent hyperparathyroidism were highest in converted MIPs (6%) versus planned BPEs (3%) and successful MIPs (2%; P < .01). Patients requiring conversion of MIP to BPE have lower preoperative serum calcium and PTH levels, a less dramatic decrease in IOPTH, and a greater rate of persistent disease than successful MIP.

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

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

Prospective Study in 3,000 Consecutive Parathyroid Operations Demonstrates 18 Objective Factors that Influence the Decision for Unilateral versus Bilateral Surgical Approach

Although localizing studies are well-known predictors of which patients are candidates for unilateral versus bilateral parathyroid exploration, there are a number of other factors that have positive or negative influence preoperatively and intraoperatively. A prospective study was conducted during 20 months on 3,000 consecutive patients undergoing surgery for primary hyperparathyroidism to determine which factors caused the surgeons to explore bilaterally or, in contrast, influenced a unilateral approach. Seventeen preoperative and 5 intraoperative objective points were documented on all patients to see how decisions were made. Parathyroidectomy was unilateral in 32% and bilateral in 68%. Preoperative factors that had a positive predictive value in dictating a unilateral approach were (in decreasing frequency): positive sestamibi, previous parathyroid/thyroid surgery, age older than 80 years, anticoagulation medications, morbid obesity, and presence of large goiter (all p < 0.001). Preoperative parameters dictating a bilateral approach included negative sestamibi, more than one focus on sestamibi, contralateral thyroid disease, family history, lithium use, history of radiation, MEN, age younger than 20 years, and pregnancy (all p < 0.001). Intraoperative parameters influencing conversion of unilateral to bilateral were false-positive sestamibi, hormone measures not meeting sufficient levels, abnormal ipsilateral gland, and contralateral thyroid pathology identified (all p < 0.001). Factors that had no effect were gender, degree of calcium, and/or parathyroid hormone elevation, and age between 20 and 80 years. Cure rates were 99.9% for bilateral and 99.0% for unilateral (p = 0.057). High-volume surgeons use a number of identifiable objective factors to determine the best candidates for unilateral versus bilateral parathyroid exploration. Localizing studies such as sestamibi scans ultimately play a minor role in determining how many parathyroid glands are evaluated.

Bilateral parathyroid exploration for hyperparathyroidism

In recent years, there has been considerable interest in unilateral parathyroid surgery with the goals of achieving high cure rates of hyperparathyroidism but accomplishing this with perhaps shorter operative times, fewer complications, and better cosmesis than associated with traditional bilateral exploration. Although limited parathyroid exploration has had demonstrated success in selected patients, clear indications still exist for evaluating all 4 parathyroids by bilateral neck exploration. This article describes our technique and the pre- and intraoperative contexts warranting bilateral parathyroid exploration.

Para-Hyoid Ectopic Parathyroid Adenoma Localized by Tc-99m MIBI SPECT

A 64-year-old woman with a history of I-131 ablation for Graves hyperthyroidism and bilateral parathyroid exploration with resection of a left inferior parathyroid adenoma presented 2 years after surgery with marked fatigue, irritability, and joint pain. Laboratory testing revealed an elevated calcium and parathyroid hormone levels suspicious for hyperparathyroidism. The ultrasound indicated no evidence of a parathyroid adenoma. Tc-99m-MIBI SPECT demonstrated a focus of uptake posteroinferior to the right submandibular gland, suspicious for a parathyroid adenoma. Repeat ultrasound and CT confirmed the presence of a para-hyoid adenoma inferior to the right submandibular gland.

Intra-Operative Parathyroid Identification Using Methylene Blue in Parathyroid Surgery

The objective of this study was to determine the value of intra-operative methylene blue (MB) during parathyroid surgery. We did a retrospective study of 473 patients after initial exploration for previously untreated symptomatic primary hyperparathyroidism. Procedural and post procedural data were collected on four groups of patients: minimally invasive parathyroidectomy with MB (n = 147), and without MB (n = 205), bilateral parathyroid exploration with intra-operative parathormone assay with MB (n = 56), and without MB (n = 65). Length of surgery was shorter for patients explored with MB (P = 0.026). For the minimally invasive parathyroidectomy group, the difference between the MB and non-MB groups was seven minutes. Twelve minutes was the difference between the MB and non-MB intra-operative parathormone assay groups. Length of stay, local complications, and correction of hypercalcemia after parathyroidectomy were not significantly affected by the use of MB. Systemic complications were lower in the MB groups. Aside from a statistically significant, but quantitatively minimal decrease in the length of surgery, no consistent benefit was identified with the use of MB for intra-operative parathyroid identification.

The Negative Sestamibi Scan: Is a Minimally Invasive Parathyroidectomy Still Possible?

Tc-99-sestamibi scanning is utilized to determine whether patients with primary hyperparathyroidism (HPT) are candidates for minimally invasive parathyroidectomy (MIP). However, if the result of this scan is negative, many surgeons recommend bilateral parathyroid exploration because of possible multi-gland disease. The objectives of this study were to determine whether patients with primary HPT and negative sestamibi scans can benefit from additional imaging studies and are still potential candidates for MIP. Between March 2001 and April 2006, 578 consecutive patients with HPT underwent parathyroidectomy by a single surgeon. Pre-operative sestamibi scans had been done in 458 (79%) of these patients, 90 (20%) of which had negative results. These patients formed our study cohort. Of the 90 patients, 60 (67%) had a single adenoma, 17 (19%) double adenomas and 13 (14%) 3- to 4-gland hyperplasias. In 74 (82%) patients, localization was further investigated with one or more studies including thallium subtraction scans (n = 30), ultrasound (n = 15) and intra-operative internal jugular venous sampling (n = 49). Additionally, the use of radio-guided techniques intra-operatively facilitated minimally invasive techniques. Of these 90 patients, 47 had positive results from preoperative studies, including 12 positive thallium, 5 positive ultrasound and 13 positive internal jugular sampling results. In addition, positive results were observed for 17 patients using radio-probe techniques in the operating room. Accordingly, minimally invasive techniques were attempted in these 47 patients; 42 (89%) had single adenomas and in 5 the technique was converted to bilateral exploration for double adenoma/hyperplasia. In the setting of a negative sestamibi, the sensitivities of thallium scans and ultrasound were 30% and 27%, respectively. The overall cure rate in the 90 patients with negative sestamibi scans was 99%. In patients with primary HPT and a negative sestamibi scan, most patients (67%) will have a single adenoma. These patients benefitted from additional localization tests, which yielded a positive result in 52% of patients. Therefore, even in the setting of a negative sestamibi scan, the majority of patients with primary HPT are still candidates for MIP.

Sestamibi Scans and Intraoperative Parathyroid Hormone Measurement in the Treatment of Primary Hyperparathyroidism

To assess the value of preoperative sestamibi scanning and intraoperative parathyroid hormone (IOPTH) measurement in the treatment of patients with primary hyperparathyroidism due to multiple gland disease (MGD). Retrospective medical record review. Tertiary care academic medical center. The study population comprised 383 consecutive patients who underwent surgery for primary hyperparathyroidism at Long Island Jewish Medical Center, New Hyde Park, NY, between June 1, 1999, and January 31, 2002. Sestamibi scanning, IOPTH measurement, bilateral parathyroid exploration, and minimally invasive parathyroid surgery. Rate of postoperative persistent hyperparathyroidism. A total of 376 patients met the requirements for inclusion in the study. There were 275 women (73%) and 101 men (27%). Of the patients, 325 (86%) had single adenomas, 28 (7%) had double adenomas, 16 (4%) had 3 or more abnormal glands, and 1 had parathyroid cancer. There were 9 cases (2%) of persistent or recurrent hypercalcemia after surgery. Duration of follow-up ranged from 1 to 37 (median, 7) months. The sensitivity of sestamibi scanning for detecting MGD was 23%, and the positive predictive value was 63%. Using the requirement that the IOPTH level fall by 50% from the first baseline and into the normal range, MGD was distinguished from solitary adenoma in 36 (88%) of 41 cases. The combination of preoperative sestamibi scanning and IOPTH measurement is effective in identifying cases of MGD and allows successful minimally invasive parathyroidectomy in most patients.

Incision length for standard thyroidectomy and parathyroidectomy: when is it minimally invasive?

Current techniques for open conventional thyroidectomy or parathyroidectomy have evolved to enable a shorter incision (main proposition), and the length of the incision is influenced by objective factors. Case series. University referral center. Retrospective study of the most recent 200 primary consecutive routine thyroid and parathyroid operations (excluding neck dissections). The length of incision was routinely measured with a ruler before the incision. Univariate and multivariate analysis was performed to distinguish variables affecting length of incision. Mean length of the incision was 5.5 cm for total thyroidectomy, 4.6 cm for lobectomy, and 3.5 cm for parathyroidectomy (P<.001). It was 4.1 cm for bilateral parathyroid exploration, but was reduced to 3.2 and 2.8 cm for unilateral (P<.001) and focal (P<.001) explorations, respectively. By multiple regression analysis, thyroid specimen volume and patient body mass index were independent predictors of incision length in thyroidectomy. Extent of exploration and resident training level were independent predictors of incision length in parathyroidectomy. Current techniques for open conventional thyroidectomy or parathyroidectomy have evolved to enable a shorter incision. Thyroid volume, patient body mass index, extent of the planned parathyroid exploration, and the resident clinical training stage are important variables for incision length in open operation and should be taken into account when minimally invasive thyroidectomy and parathyroidectomy are evaluated.

Differing histologic findings after bilateral and focused parathyroidectomy.

Minimally invasive parathyroid surgery with intraoperative parathyroid hormone testing has been reported to be as successful as a bilateral operation. This study aimed to determine whether the histologic findings and outcomes differ in patients with primary sporadic hyperparathyroidism treated by a focal or a bilateral parathyroid exploration with intraoperative parathyroid hormone testing. To make the two groups comparable all patients had a solitary parathyroid adenoma identified preoperatively. Eighty unselected patients with primary hyperparathyroidism and a single abnormal parathyroid gland identified preoperatively by sestamibi scanning or ultrasonography were included in this study. All patients had intraoperative parathyroid hormone testing. Forty-five patients had standard bilateral neck explorations and 35 patients had focal neck explorations. In the bilateral neck exploration group a single adenoma was found in 38 patients (84%), a double adenoma in 3 patients (7%), hyperplasia in 3 patients (7%), and carcinoma in 1 patient (2%). In contrast, a single adenoma was identified in all patients in the focal neck exploration group. Sestamibi scanning and intraoperative parathyroid hormone assay were accurate in 87% and 84%, respectively, in the bilateral neck exploration group and in 96.9% and 94.3%, respectively, in the focal neck exploration group. All patients were normocalcemic (mean followup 17 months). Patients with primary hyperparathyroidism having a bilateral exploration had about a 15% higher rate of multiple parathyroid tumors than did patient having a focal approach. Despite this observation all patients were normocalcemic postoperatively. This suggests that either some histologically abnormal parathyroid glands do not function or there will be recurrences in patients treated by a focused approach. Longterm followup will be necessary to determine whether patients treated by focal neck exploration will develop recurrent primary hyperparathyroidism.

Primary hyperparathyroidism in the 1990s. Choice of surgical procedures for this disease.

Many advances have occurred in recent years in the diagnosis, localization, and treatment of primary hyperparathyroidism. Several different operative choices for primary hyperparathyroidism also have been proposed--a unilateral approach versus the standard bilateral parathyroid exploration. The unilateral approach is based on the concept that if an enlarged parathyroid gland and a normal gland are found on the first side of the neck that is explored, then this is an adenoma and the second side should not be explored. Only if both glands on the initial side are recognized to be abnormal is the second side explored. The theoretical advantages of this unilateral approach are a decrease in operative morbidity rates--hypoparathyroidism and nerve injuries--and a decrease in operative time. Furthermore, proponents argue that if persistent hyperparathyroidism occurs, the second side can be easily explored because it was previously untouched. In the hands of several expert parathyroid surgeons, excellent results have been achieved. However, the unilateral approach has a number of disadvantages. It places considerable pressure on the surgeon and pathologist, for they have only one parathyroid gland other than the large one to examine. There is a significant potential risk of missing double adenomas or asymmetric hyperplasia because the second, ipsilateral parathyroid gland may appear normal or near normal in these conditions. This could lead to an increased incidence of persistent or recurrent hyperparathyroidism. Furthermore, a significant reduction of operative time may be questioned, especially when the time for performing special fat stains, which often are performed with unilateral explorations, is added. Finally, even if the intent is to perform a unilateral exploration, a bilateral exploration will be necessary about half of the time. The authors strongly recommend a bilateral parathyroid exploration for all patients undergoing an initial parathyroid operation. In cases of adenoma, bilateral visualization of normal parathyroid glands and careful biopsy of only one of them will minimize hypoparathyroidism. This operative approach will lead to better results, especially for the less experienced parathyroid surgeon.