Contemporary surgical treatment of primary hyperparathyroidism without intraoperative parathyroid hormone measurement

Introduction

Primary hyperparathyroidism (pHPT) is usually the result of a single adenoma that can often be accurately located preoperatively and excised by a focused operation. Intraoperative parathyroid hormone (IOPTH) measurement is used occasionally to detect additional abnormal glands. However, it remains controversial as to whether IOPTH monitoring is necessary. This study presents the results of a large series of focused parathyroidectomy without IOPTH measurement.

Methods

Data from 2003 to 2014 were collected on 180 consecutive patients who underwent surgical treatment for pHPT by a single surgeon. Preoperative ultrasonography and sestamibi imaging was performed routinely, with computed tomography (CT) and/or selective venous sampling in selected cases. The preferred procedure for single gland disease was a focused lateral approach guided by on-table surgeon performed ultrasonography. Frozen section was used selectively and surgical cure was defined as normocalcaemia at the six-month follow-up appointment.

Results

Focused surgery was undertaken in 146 patients (81%) and 97% of these cases had concordant results with two imaging modalities. In all cases, an abnormal gland was discovered at the predetermined site. Of the 146 patients, 132 underwent a focused lateral approach (11 of which were converted to a collar incision), 10 required a collar incision and 4 underwent a mini-sternotomy. At 6 months following surgery, 142 patients were normocalcaemic (97% primary cure rate). Three of the four treatment failures had subsequent surgery and are now biochemically cured. There were no complications or cases of persistent hypocalcaemia.

Conclusions

This study provides further evidence that in the presence of concordant preoperative imaging, IOPTH measurement can be safely omitted when performing focused parathyroidectomy for most cases of pHPT.     

Relevance of Bilateral Cervical Thymectomy in Patients with Renal Hyperparathyroidism: Analysis of 161 Patients Undergoing Reoperative Parathyroidectomy

Background

The most frequent location of ectopic or supernumerary inferior parathyroid is the thymus. Bilateral cervical thymectomy has therefore been recommended as an essential part of the initial surgery for renal hyperparathyroidism (rHPT) to avoid persistent or recurrent cervical disease. The aim of this study was to evaluate how often reoperation might have been avoidable if an appropriate cervical thymectomy had been performed during initial surgery.

Methods

A prospective database of patients with rHPT was screened for patients on permanent dialysis who underwent reoperative parathyroidectomy (PTX) between 1976 and 2010. Data were retrospectively analyzed for the performance of bilateral cervical thymectomy during previous surgeries and the presence of ectopic and/or supernumerary intrathymic parathyroid glands during reoperative PTX.

Results

Of 161 patients who underwent reoperative PTX, 95 had neck reexploration. Among them were 29 patients with total PTX and autotransplantation, seven with subtotal PTX (3.5 glands resected), and 59 with incomplete PTX during the initial surgery. Bilateral cervical thymectomy during the initial PTX was performed in only 12 of 95 patients (12.6 %). It was revealed to be incomplete in six of them, inheriting an intrathymic parathyroid gland during reoperative interventions. Reoperative PTX revealed intrathymic parathyroid glands in 27 of 95 patients (28.4 %). The intrathymic parathyroid glands were ectopic in 17 (63.0 %) patients and supernumerary in 8 (29.6 %). Both ectopic and supernumerary intrathymic parathyroid glands were found in two patients (7.4 %).

Conclusions

The risk for persistent and recurrent disease based on intrathymic parathyroid glands is a relevant problem during initial surgery for rHPT. Thus, routine bilateral cervical thymectomy that is as complete as possible is essential during the initial PTX for rHPT.     

Location Frequency of Missed Parathyroid Glands After Parathyroidectomy in Patients with Persistent or Recurrent Secondary Hyperparathyroidism

Background

Reoperative parathyroidectomy (RPTX) because parathyroid glands have been missed is frequently required in patients with secondary hyperparathyroidism (SHPT). The usual locations of these missed glands in patients with SHPT are yet to be fully elucidated.

Methods

We retrospectively investigated the locations of missed glands in 165 patients who underwent RPTX for persistent or recurrent SHPT at our institution from August 1982 to July 2014. At our institution, total parathyroidectomy with forearm autograft is the routine operative procedure for SHPT. We also routinely resect the thymic tongue.

Results

Of 165 patients, 82 underwent initial parathyroidectomy at our institution (Group A), and the remaining 83 underwent initial parathyroidectomy at other institutions (Group B). A total of 239 parathyroid glands were resected (Group A, 93; Group B, 146). Missed glands were most commonly located in the mediastinum (Group A, 22/93) and the thymic tongue (Group B, 31/146).

Conclusions

In patients with persistent or recurrent SHPT, ectopic parathyroid glands are frequently located in the mediastinum and thymic tongue. Therefore, resecting the thymic tongue during the initial operation may reduce the need for RPTX.

     

Ultrasound-Guided Methylene Blue Dye Injection for Parathyroid Localization in the Reoperative Neck

Background

The goal of this study was to review a single institution’s experience using intraoperative ultrasound-guided (ioUSG) methylene blue dye injection for the localization and removal of enlarged parathyroid glands in patients with primary hyperparathyroidism and a history of previous neck surgery.

Methods

We performed a retrospective review of nine consecutive patients who underwent reoperative parathyroidectomy using ioUSG methylene blue dye injection.

Results

All patients had successful resolution of their hyperparathyroidism, with at least a 50 % decrease in intraoperative parathyroid hormone level after resection. One patient had transient recurrent laryngeal nerve paresis. There were no permanent recurrent laryngeal nerve injuries or cases of permanent hypoparathyroidism.

Conclusions

Blue dye injection is a safe and effective method of localizing diseased parathyroid glands in the reoperative neck.     

The value and role of low dose methylene blue in the surgical management of hyperparathyroidism

Introduction

Methylene blue (MB) has been used in the identification of abnormal parathyroid glands in surgery for hyperparathyroidism. Its efficacy and safety profile have been questioned recently and this study sought to demonstrate such aspects in a unit where its use is routine.

Methods

Prospective data collected over six years in a single surgeon’s practice were interrogated to identify factors affecting MB staining, side effects suffered and unusual cases where the dye was invaluable in locating the diseased gland.

Results

A total of 98 patients underwent MB infusion. Of these, 77 cases (78.6%) stained positively with MB and 21 (21.4%) did not. Six patients suffered side effects but there were no cases of neurotoxicity. No positive predictive factors of dye uptake were found. MB was particularly useful in cases of intrathyroidal and ectopic glands as well as improving efficiency in both targeted and open parathyroidectomy.

Conclusions

This series shows that when used correctly, MB is efficacious in locating diseased parathyroid glands, with similar sensitivity rates to preoperative ultrasonography and radionucleotide imaging. Adverse effects were much lower than published previously, which may be attributed to the low dose of MB used (3.5mg/kg).     

A decade of change in the uptake of parathyroidectomy in England and Wales

Introduction

Since the late 1990s, a number of factors have reduced the threshold for parathyroidectomy in patients with primary hyperparathyroidism. This study examined whether this has translated into increased numbers of parathyroid operations over the last decade.

Methods

A retrospective analysis was performed of the Patient Episode Database for Wales and English Hospital Episode Statistics annual data from 2000 to 2010 for parathyroidectomy admissions per 100,000 population. Statistical analysis was by linear regression.

Results

Between 2000 and 2010 there were 24,247 parathyroid operations in England and Wales (0.005% of the population), with 3 times as many women treated as men. Overall, incidence of parathyroidectomy rose from 3.3/100,000 population in 2000 to 5.8/100,000 in 2010 (p<0.0001). In England, it increased from 3.3/100,000 population to 5.8/100,000 and in Wales, it increased from 2.4/100,000 population to 4.6/100,000. Despite similar population demographics, the difference in the rate of change between England and Wales was significant (p<0.05). Uptake also varied according to age; in those aged 0–14 years, incidence of parathyroidectomy remained static whereas in all other age groups, uptake of parathyroidectomy increased significantly from 2000 to 2010. Most notably, surgical intervention in those aged 60–74 and >75 years nearly doubled over the decade (p<0.0001).

Conclusions

The incidence of parathyroidectomy in adults has increased significantly in the last decade in England and Wales. This likely reflects changes in population demography, available guidelines, lower threshold for referral, changing surgical approach and the realisation that surgical morbidity is now infrequent.     

Incremental value and clinical impact of neck sonography for primary hyperparathyroidism: a risk-adjusted analysis

Background

Despite the different preoperative imaging modalities available for parathyroid adenoma localization, there is currently no uniform consensus on the most appropriate preoperative imaging algorithm that should be routinely followed prior to the surgical management of primary hyperparathyroidism (PHPT). We sought to determine the incremental value of adding neck ultrasonography to scintigraphy-based imaging tests.

Methods

In a single institution, surgically naive patients with PHPT underwent the following localization studies before parathyroidectomy: 1) Tc-99m sestamibi imaging with single photon emission computed tomography/computed tomography (SPECT/CT) or Tc-99m sestamibi imaging with SPECT alone, or 2) ultrasonography in addition to those tests. We retrospectively collected data and performed a multivariate analysis comparing group I (single study) to group II (addition of ultrasonography) and risk of bilateral (BNE) compared with unilateral (UNE) neck exploration.

Results

Our study included 208 patients. Group II had 0.45 times the odds of BNE versus UNE compared with group I (unadjusted odds ratio [OR] 0.45, 95% confidence interval [CI] 0.25–0.81, p = 0.008). When adjusting for patient age, sex, preoperative calcium level, use of intraoperative PTH monitoring, preoperative PTH level, adenoma size, and number of abnormal parathyroid glands, Group II had 0.48 times the odds of BNE versus UNE compared with group I (adjusted OR 0.48, 95% CI 0.23–1.03, p = 0.06). In a subgroup analysis, only the addition of ultrasonography to SPECT decreased the risk of undergoing BNE compared with SPECT alone (unadjusted OR 0.40, 95% CI 0.19–0.84, p = 0.015; adjusted OR 0.38, 95% CI 0.15–0.96, p = 0.043).

Conclusion

The addition of ultrasonography to SPECT, but not to SPECT/CT, has incremental value in decreasing the extent of surgery during parathyroidectomy, even after adjusting for multiple confounding factors.     

The impact of surgeon-based ultrasonography for parathyroid disease on a British endocrine surgical practice

INTRODUCTION

Surgeon-based ultrasonography (SUS) for parathyroid disease has not been widely adopted by British endocrine surgeons despite reports worldwide of accuracy in parathyroid localisation equivalent or superior to radiology-based ultrasonography (RUS). The aim of this study was to determine whether SUS might benefit parathyroid surgical practice in a British endocrine unit.

METHODS

Following an audit to establish the accuracy of RUS and technetium sestamibi (MIBI) in 54 patients, the accuracy of parathyroid localisation by SUS and RUS was compared prospectively with operative findings in 65 patients undergoing surgery for primary hyperparathyroidism (pHPT).

RESULTS

The sensitivity of RUS (40%) was below and MIBI (57%) was within the range of published results in the audit phase. The sensitivity (64%), negative predictive value (86%) and accuracy (86%) of SUS were significantly greater than RUS (37%, 77% and 78% respectively). SUS significantly increased the concordance of parathyroid localisation with MIBI (58% versus 32% with RUS).

CONCLUSIONS

SUS improves parathyroid localisation in a British endocrine surgical practice. It is a useful adjunct to parathyroid practice, particularly in centres without a dedicated parathyroid radiologist, and enables more patients with pHPT to benefit from minimally invasive surgery.     

Limitations of Tc99m-MIBI-SPECT Imaging Scans in Persistent Primary Hyperparathyroidism

Background  

In primary hyperparathyroidism (PHPT) the predictive value of technetium 99m sestamibi single emission computed tomography (Tc99m-MIBI-SPECT) for localizing pathological parathyroid glands before a first parathyroidectomy (PTx) is 83–100%. Data are scarce in patients undergoing reoperative parathyroidectomy for persistent hyperparathyroidism. The aim of the present study was to determine the value of Tc99m-MIBI-SPECT in localizing residual hyperactive parathyroid tissue in patients with persistent primary hyperparathyroidism (PHPT) after initial excision of one or more pathological glands.     

Role of cervical ultrasound in detecting thyroid pathology in primary hyperparathyroidism

Background

Minimally invasive parathyroidectomy for primary hyperparathyroidism is made possible with accurate preoperative imaging. In addition to the detection of parathyroid adenomas, cervical ultrasound also provides concomitant assessment of the thyroid gland, and many surgeons believe that it is essential. However, the incidental identification of thyroid nodules may then subject patients to further workup and potentially invasive thyroid procedures. We sought to determine the long-term consequence of omitting preoperative ultrasound on the development of thyroid pathology and cancer.

Methods

At our institution, 222 patients with primary hyperparathyroidism underwent parathyroidectomy without preoperative cervical ultrasound from 1990–2001. Thyroid pathology discovered by follow-up after parathyroidectomy, subsequent biopsy, and surgical interventions were analyzed.

Results

Of the 222 patients who underwent parathyroidectomy, the mean age was 55 ± 1 y and 149 were female (67%). In the course of their follow-up after parathyroidectomy, 13 patients (6%) received a cervical ultrasound, and seven of 13 (3%) underwent fine needle aspiration of a thyroid nodule. Only one of seven (0.4% of all patients) was ultimately diagnosed with thyroid cancer. Four additional patients were discovered to have thyroid malignancies as a result of intraoperative decision making. All five patients are currently alive with an average follow-up time of 14.9 ± 1.6 y. No patients in this series had an unnecessary thyroid intervention.

Conclusions

In patients who underwent parathyroidectomy without a preoperative ultrasound, only a small number (0.4%) were subsequently diagnosed with thyroid cancer. Furthermore, omission of ultrasound during the localization of parathyroid glands does not have a negative impact on the diagnosis of thyroid pathology as all patients who had thyroid cancer had good outcomes, and in fact, may prevent unnecessary thyroid interventions. Therefore, the use of cervical ultrasound for parathyroid localization should be considered optional rather than essential.     

The changing face of reoperative parathyroidectomy: a single-centre comparison of 147 parathyroid reoperations

IntroductionReoperative parathyroidectomy for persistent and recurrent primary hyperparathyroidism is dependent on radiology. This study aimed to compare outcomes in reoperative parathyroidectomy at a single centre using a combination of traditional and newer imaging studies.Materials and methodsRetrospective case note review of all reoperative parathyroidectomies for persistent and recurrent primary hyperparathyroidism over five years (June 2014 to June 2019; group A). Imaging modalities used and their positive predictive value, complications and cure rates were compared with a published dataset spanning the preceding nine years (group B).ResultsFrom over 2000 parathyroidectomies, 147 were reoperations (101 in group A and 46 in group B). Age and sex ratios were similar (56 vs 62 years; 77% vs 72% female). Ultrasound use remains high and shows better positive predictive value (76% vs 57 %). 99mTc-sestamibi use has declined (79% vs 91%) but the positive predictive value has improved (74% vs 53%). 4DCT use has almost doubled (61% vs 37%) with better positive predictive value (88% vs 75%). 18F-fluorocholine positron emission tomography-computed tomography and ultrasound-guided fine-needle aspiration for parathyroid hormone are novel modalities only available for group A. Both carried a positive predictive value of 100%. Venous sampling with or without angiography use has decreased (35% vs 39%) but maintains a high positive predictive value (86% vs 91%). Cure rates were similar (96% vs 100%). Group A had 5% permanent hypoparathyroidism, 1% permanent vocal cord palsy and 1% haematoma requiring reoperation. No complications for group B.ConclusionOptimal imaging is key to good cure rates in reoperative parathyroidectomy. High-quality, non-interventional imaging techniques have produced a shift in the preoperative algorithm without compromising outcomes.     

Successful parathyroidectomy guided by intraoperative parathyroid hormone monitoring for primary hyperparathyroidism is preserved in mild and moderate renal insufficiency

Background

The effect of altered parathyroid hormone metabolism in renal insufficiency on intraoperative parathyroid hormone monitoring during parathyroidectomy is not well known. This study evaluates operative outcomes in patients undergoing parathyroidectomy guided by intraoperative parathyroid hormone monitoring for primary hyperparathyroidism with mild and moderate renal insufficiency.

Acute Suppression of Bone Turnover With Calcium Infusion in Persons With Spinal Cord Injury

Background:

Some people with chronic spinal cord injury (SCI) have low vitamin D levels and secondary hyperparathyroidism.

Objective:

To determine whether, and to what extent, an acute calcium infusion decreased levels of N-telopeptide (NTx), a marker of osteoclastic activity, in individuals with chronic SCI.

Study Design:

Case series.

Subjects:

Eight men with chronic SCI. A relatively low serum 25 hydroxyvitamin D concentration (25[OH]D ≤20 ng/mL) and/or a high parathyroid hormone (PTH) (>55 pg/mL) was a prerequisite for study inclusion.

Methods:

Calcium gluconate bolus 0.025 mmol elemental calcium/kg over 20 minutes followed by a constant infusion of 0.025 mmol/kg per hour for 6 hours was infused; blood samples were collected every 2 hours for measurement of serum total calcium, creatinine, NTx, and PTH.

Results:

All results are expressed as means (± SDs). Baseline serum 25-hydroxyvitamin D level was 14.5 ± 3.5 ng/mL (range: 10.2–19.6 ng/mL); PTH, 70 ± 25 pg/mL (range: 37–100 pg/mL); and NTx, 21 ± 7 nM bone collagen equivalents (BCE) (range: 14–34 nM). At 2, 4, and 6 hours after the calcium infusion, serum calcium rose from 9.3 ± 0.2 to 10.8 ± 0.9, 10.5 ± 0.8, and 10.6 ± 0.6 mg/d; PTH was suppressed from 70 ± 25 pg/mL to 18 ± 12, 16 ± 9, and 15 ± 9 pg/mL, respectively; NTx fell from 21 ± 8 nM BCE to 17 ± 5, 12 ± 4, and 12 ± 3 nM BCE, respectively.

Conclusions:

Serum NTx is a marker for bone collagen catabolism, and its reduction suggests that bone turnover was decreased. A relative deficiency of vitamin D associated with chronically elevated levels of PTH would be expected to increase bone turnover and to worsen the bone loss associated with immobilization.     

Influence of morbid obesity on parathyroidectomy outcomes in primary hyperparathyroidism

Background

We sought to evaluate the influence of morbid obesity in patients undergoing parathyroidectomy for primary hyperparathyroidism (pHPT).

Methods

All patients with pHPT who underwent parathyroidectomy at a single institution between July 2002 and October 2008 were included. Body mass index (BMI), laboratorie vlaues, operative findings, and outcomes were examined.

Results

Two hundred thirteen of the 776 patients identified (28%) were morbidly obese (BMI ≥35 kg/m²). When compared with nonmorbidly obese patients, the morbidly obese patients were younger, had higher preoperative intact parathyroid hormone (iPTH) levels, heavier parathyroids, and required overnight stay more often (P <.05 for all). However, the rates of complications, eucalcemia, and recurrence were similar for all patients.

Conclusion

In this study, more than a quarter of the patients who underwent parathyroidectomy for pHPT were morbidly obese and had significantly higher preoperative iPTH levels, heavier parathyroids, and longer hospital stay but similar rates of complications and operative success.     

Total parathyroidectomy without autotransplantation in dialysis patients and renal transplant recipients, long-term follow-up evaluation

Background

Persistent secondary hyperparathyroidism not responding to medication is treated successfully with surgical excision of parathyroid glands (total parathyroidectomy [PTX]). PTX without autotransplantation of parathyroid glands excludes the risk for recurrence of hyperparathyroidism.

Methods

During the years 2002 to 2005, 36 total parathyroidectomies were performed in 33 patients: 21 dialysis patients because of end-stage renal disease and 12 renal transplant recipients.

Results

PTX without autotransplantation was performed successfully in 33 patients, whereas 3 patients were reoperated for remaining parathyroid glands. Immediate improvement of clinical symptoms and a decrease of serum calcium and parathormone levels were observed after surgical procedures. Oral replacement treatment with vitamin D (1a-calcidiol) and calcium was commenced and long-term follow-up evaluation (23.5 ± 7.6 mo) showed that calcium homeostasis was controlled adequately.

Conclusions

PTX without autotransplantation is a safe and effective surgical procedure for the treatment of resistant secondary hyperparathyroidism with immediate response of clinical symptoms. Replacement treatment with vitamin D and calcium provides satisfactory coverage of individual needs.     

Outcomes of a Third Bariatric Procedure for Inadequate Weight Loss

Background and Objectives:

The robust volume of bariatric surgical procedures has led to significant numbers of patients requiring reoperative surgery because of undesirable results from primary operations. The aim of this study was to assess the feasibility, safety, and outcomes of the third bariatric procedure after previous attempts resulted in inadequate results.

Methods:

We retrospectively identified patients who underwent a third bariatric procedure for inadequate weight loss or significant weight regain after the second operation. Data were analyzed to establish patient demographic characteristics, perioperative parameters, and postoperative outcomes.

Results:

A total of 12 patients were identified. Before the first, second, and third procedures, patients had a mean body mass index of 67.1 ± 29.3 kg/m², 60.9 ± 28.3 kg/m², and 49.4 ± 19.8 kg/m², respectively. The third operations (laparoscopic in 10 and open in 2) included Roux-en-Y gastric bypass (n = 5), revision of pouch and/or stoma of Roux-en-Y gastric bypass (n = 3), limb lengthening after Roux-en-Y gastric bypass (n = 3), and sleeve gastrectomy (n = 1). We encountered 5 early complications in 4 patients, and early reoperative intervention was needed in 2 patients. At 1-year follow-up, the excess weight loss of the cohort was 49.4% ± 33.8%. After a mean follow-up time of 43.0 ± 28.6 months, the body mass index of the cohort reached 39.9 ± 20.8 kg/m², which corresponded to a mean excess weight loss of 54.4% ± 44.0% from the third operation. At the latest follow-up, 64% of patients had excess weight loss >50% and 45% had excess weight loss >80%.

Conclusion:

Reoperative bariatric surgery can be carried out successfully (often laparoscopically), even after 2 previous weight loss procedures.