The Optimal Surgical Treatment for Primary Hyperparathyroidism in MEN1 Patients: A Systematic Review

Background

The optimal surgical approach for patients with primary hyperparathyroidism (pHPT) and multiple endocrine neoplasia 1 (MEN1) is controversial. We sought to determine the optimal type of surgery for pHPT in MEN1.

Methods

We collected data on clinical presentation, surgery, and follow-up for MEN1 patients with pHPT at the University Medical Center Utrecht and affiliated hospitals between 1967 and 2008. Furthermore, we performed a systematic review of the literature and meta-analysis. Surgical procedures were classified into less than subtotal (Results Fifty-two patients underwent primary surgery for pHPT, of which 29 had Conclusion We believe that SPTX is the best surgical therapy for pHPT in MEN1. MEN1 patients with pHPT should not be treated with 相似文献   

The role of parathyroid hormone measurements after surgery for primary hyperparathyroidism

BACKGROUND: During parathyroidectomy for primary hyperparathyroidism (pHPT), intraoperative parathyroid hormone (IOPTH) levels are used to confirm removal of all hyperfunctioning parathyroid tissue. The phenomenon of elevated parathyroid hormone (PTH) levels with normocalcemia after curative parathyroidectomy, seen in up to 40% of patients, continues to be an unexpected and unexplained finding. We therefore investigated whether postoperative PTH levels are as reliable as IOPTH levels in predicting cure after surgery for pHPT. METHODS: We reviewed our prospective database of consecutive patients undergoing surgery for pHPT between December 1999 and November 2004. Curative parathyroidectomy was defined as normocalcemia 6 months or longer postoperatively. RESULTS: A total of 328 patients who underwent 330 operations for pHPT had IOPTH measurements and serum follow-up calcium levels at 6 months or longer. Surgery was curative in 315 (95.5%) operations. IOPTH levels correctly predicted operative success in 98.2% (positive predictive value [PPV]. Postoperatively, the PPV of a normal PTH level at 1 week, 3 months, and 6 months was 97.1%, 97.3%, and 96.5%, respectively. Of all patients with an elevated postoperative PTH level at 1 week, 3 months, or 6 months, only 13.7%, 14.3%, and 14%, respectively, were not cured. CONCLUSIONS: Normal postoperative PTH levels reliably predict operative success. However, they do not improve upon results predicted by IOPTH levels. Elevated postoperative PTH levels do not predict operative failure in most patients. We propose that PTH measurements after surgery for pHPT may be misleading, costly, and not indicated in normocalcemic patients.     

The Final Intraoperative Parathyroid Hormone Level: How Low Should It Go?

Background

In minimally invasive surgery for primary hyperparathyroidism (HPT), intraoperative parathyroid hormone (IOPTH) monitoring assists in obtaining demonstrably better outcomes, but optimal criteria are controversial.

Methods

The outcomes of 1,108 initial parathyroid operations for sporadic HPT using IOPTH monitoring from 1997 to 2011 were stratified by final post-resection IOPTH level. All patients had adequate follow-up to verify cure.

Results

With mean follow-up of 1.8 years (range 0.5–14.3 years), parathyroidectomy using IOPTH monitoring failed in 1.2 % of cases, with an additional 0.5 % incidence of long-term recurrence at a mean of 3.2 years (range 0.8–6.8 years) postoperatively. Operative success was equally likely with a final IOPTH drop to 41–65 pg/mL vs ≤40 pg/mL (p = 1). In the 76 patients with an elevated baseline IOPTH level that did not drop to ≤65 pg/mL, surgical failure was 43 times more likely than with a drop into normal range (13 vs. 0.3 %; p < 0.001). When the final IOPTH level dropped by >50 % but not into the normal range, surgical failure was 19 times more likely (3.8 vs. 0.2 %; p = 0.015). Long-term recurrence was more likely in patients with a final IOPTH level of 41–65 pg/mL than with a level ≤40 pg/mL (1.2 vs. 0; p = 0.016).

Conclusions

Adjunctive intraoperative PTH monitoring facilitates a high cure rate for initial surgery of sporadic primary hyperparathyroidism. A final IOPTH level that is within the normal range and drops by >50 % from baseline is a strong predictor of operative success. Patients with a final IOPTH level between 41–65 pg/mL should be followed beyond 6 months for long-term recurrence.     

Surgical Treatment of Patients with Mildly Elevated Parathormone and Calcium Levels

Background

Patients with mildly elevated parathormone (PTH) and calcium levels consistent for primary hyperparathyroidism (pHPT) may present with more underlying multiglandular disease (MGD) and higher operative failure and recurrence rates than those with conventional, or “classic” pHPT. This study compared the clinical characteristics and surgical outcomes of patients with biochemically mild versus conventional pHPT.

Methods

A series of 707 consecutive patients underwent initial targeted parathyroidectomy with intraoperative parathormone monitoring (IPM) at a single institution. Biochemically mild (BM) pHPT was defined as PTH > 65 and <100 pg/ml with serum calcium >10.4 and <11 mg/dl. Conventional pHPT was defined as calcium ≥11 mg/dl and PTH ≥ 100 pg/ml. Prospectively collected data for all patients, including operative indication, preoperative laboratory values, imaging, IPM dynamics, and postoperative laboratory values were retrospectively reviewed. Additional assessments included presence of MGD, bilateral neck exploration (BNE), single-gland volume, and operative failure or success, and recurrence.

Results

Of 60 patients with BM-pHPT, 46 reported preoperative bone pain, kidney stones, fatigue, and/or mental disturbances. The remaining 14 BM-pHPT patients underwent parathyroidectomy based on published asymptomatic guidelines. Patients with BM-pHPT had significantly more kidney stones, MGD, and BNE. Average single-gland volume and postoperative PTH levels were significantly lower in BM-pHPT patients. There were no significant differences between groups regarding preoperative localization accuracy, IPM dynamics, or operative success/failure, recurrence rates.

Conclusions

BM-pHPT patients had more MGD requiring BNE but achieved operative success rates similar to those of patients with conventional disease. IPM successfully identifies MGD in BM-pHPT patients, who should be counseled regarding more extensive operations than limited parathyroidectomy.     

Quality of Life is Modestly Improved in Older Patients with Mild Primary Hyperparathyroidism Postoperatively: Results of a Prospective Multicenter Study

Background

The objectives of this study were to evaluate, in mild primary hyperparathyroidism (pHPT) patients, the quality of life (QoL) using the SF-36 questionnaire before and after parathyroidectomy and to detect preoperatively patients who benefit the most from surgery. Most pHPT patients present a mild pHPT defined by calcemia ≤11.4 mg/dL. For these patients, there is debate about whether they should be managed with surveillance, medical therapy, or surgery.

Methods

A prospective multicenter study investigated QoL (SF-36) in patients with mild pHPT before and after parathyroidectomy in four university hospitals. Laboratory results and SF-36 scores were obtained preoperatively and postoperatively (3, 6, and 12 months).

Results

One hundred sixteen patients were included. After surgery, the biochemical cure rate was 98%. Preoperatively, the mental component summary and the physical component summary (PCS) were 38.69 of 100 and 39.53 of 100, respectively. At 1 year, the MCS and the PCS were 41.29 of 100 and 42.03 of 100. The subgroup analysis showed a more significant improvement in patients < 70 years and with calcemia ≥10.4 mg/dL. Postoperative PCS was correlated with age and preoperative PCS: variation = 32.11 ? 0.21 × age ? 0.4 × preoperative PCS. Men did not improve their MCS postoperatively. Only women with a preoperative MCS <43.6 of 100 showed postoperative improvement.

Conclusions

This study showed, in patients with mild pHPT, an improvement of QoL 1 year after parathyroidectomy. Patients <70 years and with calcemia ≥10.4 mg/dL had a more significant improvement.     

Unilateral Clearance for Primary Hyperparathyroidism in Selected Patients with Multiple Endocrine Neoplasia Type 1

Background

Primary hyperparathyroidism is the most common manifestation of multiple endocrine neoplasia type 1 (MEN1). Guidelines advocate subtotal parathyroidectomy (STP) or total parathyroidectomy with autotransplantation due to high prevalence of multiglandular disease; however, both are associated with a significant risk of permanent hypoparathyroidism. More accurate imaging and use of intraoperative PTH levels may allow a less extensive initial parathyroidectomy (unilateral clearance, removing both parathyroids with cervical thymectomy) in selected MEN1 patients with primary hyperparathyroidism.

Methods

We performed a retrospective cohort study at a high-volume tertiary medical center including patients with MEN1 and primary hyperparathyroidism, who underwent STP or unilateral clearance as their initial surgery from 1995 to 2015. Unilateral clearance was offered to patients who had concordant sestamibi and ultrasound showing a single enlarged parathyroid gland. For both the groups, we compared rates of persistent/recurrent disease and permanent hypoparathyroidism.

Results

Eight patients had unilateral clearance and 16 had STP. Subtotal parathyroidectomy patients were younger (37 vs 52 years). One patient in each group had persistent disease. One (13 %) unilateral clearance and five (31 %) STP patients had recurrent hyperparathyroidism after a mean follow-up of 47 and 68 months (p = 0.62). No unilateral clearance patients and two of 16 SPT patients had permanent hypoparathyroidism (p = 0.54).

Conclusions

Some MEN1 patients with primary hyperparathyroidism who have concordant localizing studies may be selected for unilateral clearance as an alternative to STP. For appropriately selected MEN1 patients, unilateral clearance can achieve similar results as STP and has no risk of permanent hypoparathyroidism, and may facilitate possible future reoperations.

     

Reoperations for primary hyperparathyroidism—improvement of outcome over two decades

Purpose

Reoperations (R-PTX) for primary hyperparathyroidism (pHPT) are challenging, since they are associated with increased failure and morbidity rates. The aim was to evaluate the results of reoperations over two decades, the latter considering the implementation of Tc^99msestamibi-SPECT (Mibi/SPECT), intraoperative parathormone (IOPTH) measurement, and intraoperative neuromonitoring (IONM).

Patients and methods

Data of 1,363 patients who underwent surgery for pHPT were retrospectively analyzed regarding reoperations. Causes of persistent (p) pHPT or recurrent (r) pHPT, preoperative imaging studies, surgical findings, and outcome were analyzed. Data of patients who underwent surgery between 1987 and 1997 (group 1; G1) and between 1998 and 2008 (group 2; G2) with the use of Mibi/SPECT, IOPTH, and IONM were evaluated.

Results

One hundred twenty-five patients with benign ppHPT (n?=?108) or rpHPT (n?=?17) underwent reoperations (R-PTX). Group 1 included 54, group 2 71 patients. Main cause of ppHPT (G1?=?65 % vs. G2?=?53 %) and rpHPT (G1?=?80 % vs. G2?=?60 %) was the failed detection of a solitary adenoma (p?=?0.2). Group 1 patients had significantly less unilateral/focused neck re-explorations (G1?=?23 % vs. G2?=?57 %, p?=?0.0001), and more sternotomies (G1?=?35 vs. G2?=?14 %, p?=?0.01). After a median follow-up of 4 (range 0.9–23.4) years, reversal of hypercalcemia was achieved in 91 % (G1) and in 98.6 % in group 2 (p?=?0.08, OR 7.14 [0.809–63.1]). The rates of permanent recurrent laryngeal nerve palsy (G1?=?G2?=?9 %, p?=?1) and of postoperative permanent hypoparathyroidism (G1?=?9 % vs. G2?=?6 %, p?=?0.5) were not significantly different. Other complications such as wound infection, postoperative bleeding, and pneumonia were significantly lower in group 2 (p?<?0.001).

Conclusion

Nowadays, cure rates of R-PTX are nearly the same as in primary operations for pHPT. These results can be achieved in high-volume centers by routine use of well-established preoperative Mibi/SPECT and US in combination with IOPTH. However, morbidity is still considerably high.     

Primärer Hyperparathyreoidismus

Introduction

Normocalcemic hyperparathyrinemia, i.e. elevated parathyroid hormone (PTH) levels after parathyroidectomy in patients with primary hyperparathyroidism (pHPT) may occur in the course of postoperative recovery without the development of persistence or relapse.

Materials, methods and results

Intraoperative and long-term (7 year) postoperative PTH and calcium levels after curative parathyroidectomy are demonstrated on the basis of a case report of a 62-year-old female patient with severe pHPT and pronounced osseous and renal manifestations. The intraoperative PTH gradient displayed a decrease from 1072 pg/ml to 13 pg/ml (normal range 11–67 pg/ml) followed by an increase of up to 287pg/ml. The hyperparathyoid values decline to subnormal levels on administration of calcium and vitamin D and increase again after tapering these medications. The inverse calcium/PTH correlation in the course of the 7-year observation period suggests an intact feed-back mechanism. Preoperative PTH screening was performed in 316 consecutive normocalcemic thyroid patients to evaluate the rate of incidental hyperparathyroidism in patients with normal serum calcium levels. Of these patients 31 (9.8%) with normocalcemia (average 2.28 mmol/l, normal range 2.1–2.7 mmol/l) exhibited increased PTH levels averaging 84.2 pg/ml. A parathyroid adenoma was found intraoperatively as the cause for normocalcemic pHPT in only 1 of these 31 patients.

Discussion and conclusions

A review of the literature revealed that late postoperative elevated parathyroid hormone levels after successful pHPT surgery occur in 21.5%. Multiple causes are discussed, e.g. reactive hyperparathyroidism in cases of relative hypocalcemia, hungry bone syndrome, vitamin D deficiency, renal dysfunction and ethnic or lifestyle differences. In mild cases of postoperative hyperparathyrinemia observation of the patient may be sufficient. In cases of reactive hyperparathyroidism due to hypocalcemia, administration of calcium is indicated, in symptomatic patients, additional administration of vitamin D or calcitriol is necessary. Vitamin D deficiency per se needs adequate substitution. In cases of ongoing hyperparathyrinemia an interdisciplinary diagnostic and therapeutic approach is required.     

Bilateral Neck Exploration Decreases Operative Time Compared to Minimally Invasive Parathyroidectomy in Patients with Discordant Imaging

Background

Unilateral parathyroidectomy for primary hyperparathyroidism (PHPT) has a high success rate in patients with concordant imaging by sestamibi and ultrasound. However, the optimal procedure when imaging is discordant remains controversial; therefore we compared unilateral exploration with intraoperative parathyroid hormone (IOPTH) monitoring to bilateral neck exploration without IOPTH monitoring in patients with discordant localization studies.

Methods

We conducted a retrospective study of 324 consecutive patients with PHPT treated at our institution from October 2005 to September 2009. We collected information regarding imaging, localization site, procedure performed, operative time, and calcium/PTH measurements.

Results

Of the 324 patients in the study, 79 (24 %) had discordant imaging by sestamibi and ultrasound. Of these, 62 patients (78 %) underwent bilateral neck exploration without IOPTH monitoring, and 14 patients (18 %) had unilateral exploration with IOPTH monitoring. IOPTH monitoring during unilateral exploration correctly predicted removal of single adenomas in 10/14 patients (71 %) and altered operative management in 4/14 cases (29 %), resulting in conversion to bilateral neck exploration. Operative time for unilateral exploration with IOPTH [median time: 96 min (range: 51–153 min)] was significantly increased relative to bilateral exploration [median time: 52 min (range: 28–149 min)]; p = 0.0027. We identified single-gland disease in 53/76 patients (70 %), double adenomas in 13/76 patients (17 %), and multiglandular hyperplasia in 10/76 patients (13 %). There was no difference in cure rate between these two surgical approaches (p = 1.0)

Conclusions

In contrast with prior studies, we found that operative time for unilateral exploration with IOPTH was significantly increased compared to bilateral neck exploration. In patients with discordant imaging, IOPTH is a useful adjunct in limiting exploration to a single side despite a high false negative rate.     

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.     

4D Parathyroid CT as the Initial Localization Study for Patients with De Novo Primary Hyperparathyroidism

Background

Preoperative localization of parathyroid tumors of primary hyperparathyroidism (pHPT) is required for minimally invasive parathyroidectomy (MIP). Parathyroid four-dimensional computed tomography (4DCT) has mainly been used as an adjunct to other imaging modalities in the remedial setting. 4DCT was evaluated as the initial localization study in de novo patients with pHPT.

Materials and Methods

A total of 87 consecutive patients underwent parathyroidectomy for pHPT from August 2008 to November 2009. 4DCT was introduced as the preferred imaging modality instead of sestamibi with SPECT (SeS) in April 2009. Results of the imaging studies [4DCT, SeS, and ultrasonography (US)], operative and, pathologic findings, and biochemical measurements were evaluated.

Results

In this study, 84% of patients (73 of 87) underwent an US, 59.8% (52 of 87) a SeS, and 38.0% (33 of 87) had a 4DCT. 4DCT had improved sensitivity (85.7%) over SeS (40.4%) and US (48.0%) to localize parathyroid tumors to the correct quadrant of the neck (P < 0.005) as well as to localize (lateralize) the parathyroid lesions to one side of the neck (93.9% for 4DCT vs. 71.2% for US and 61.5% for SeS; P < 0.005). 4DCT correctly predicted multiglandular disease (MGD) in 85.7% (6 of 7) patients, whereas US and SeS were unable to detect MGD in any case. All patients achieved cure based on intraoperative parathyroid hormone (PTH) measurements and normalization of intact PTH and S-Ca during follow-up.

Conclusions

4DCT provides significantly greater sensitivity than SeS and US for precise localization of parathyroid tumors of pHPT. Additionally, it correctly predicted MGD in a majority of patients.     

Vitamin D3 Deficiency is Associated with Late-Onset Hypocalcemia After Minimally Invasive Parathyroidectomy in a Vitamin D Borderline Area

Background

Concurrent vitamin D₃ deficiency is common in primary hyperparathyroidism (pHPT). We aimed to examine the clinicopathologic features and short-term outcomes of vitamin D₃-deficient patients after minimally invasive parathyroidectomy (MIP).

Methods

Over 2-year period, 80 consecutive MIP patients had preoperative-fasting 25-hydroxyvitamin D₃ (25OHD₃) checked. Forty-five patients had a 25OHD₃ level <20 ng/ml and were defined as deficient. Intraoperative parathyroid hormone (IOPTH) assay was used for all MIP. Postoperative adjusted calcium (Ca) was checked at 6, 16 (with intact PTH), and 24 h. Oral calcium and vitamin D supplements were given if hypocalcemic symptoms developed or Ca < 2.00 mmol/l. Late-onset hypocalcemia (LOH) was defined as symptoms developed after 24 h.

Results

Both deficient and nondeficient groups had similar demographic data and bone density scores. The deficient group had significantly higher PTH (190 vs. 121 pg/ml, p = 0.015). Although IOPTH in the deficient group were higher at induction and 0 min after excision, the percentage drop from induction to 10 min after excision was similar. Ca was similar at 6 and 16 h in the two groups but was significantly lower in the deficient group at 24 h (2.10 vs. 2.45 mmol/l, p = 0.033). At 1 week, the proportion of LOH was significantly higher in the deficient group (12/42 vs. 3/34, p = 0.043) and in those with preoperative PTH > 100 pg/ml (15/57 vs. 0/19, p = 0.013).

Conclusions

Vitamin D₃ deficiency was associated with a higher preoperative PTH level and a greater risk of LOH after MIP. However, the likely cause of LOH remains unclear as both low preoperative vitamin D₃ and high PTH levels could be responsible.     

Operative Failure in Minimally Invasive Parathyroidectomy Utilizing an Intraoperative Parathyroid Hormone Assay

Background

Minimally invasive parathyroidectomy (MIP) is a targeted operation to cure primary hyperparathyroidism utilizing intraoperative parathyroid hormone monitoring (IOPTH). The purpose of this study was to quantify the operative failure of MIP.

Methods

Utilizing institutional parathyroid surgery database, demographic, operative, and biochemical data were analyzed for successful and failed MIP. Operative failure was defined as <6 months of eucalcemia after operation.

Results

Five hundred thirty-eight patients (96.6 %) had successful MIP with mean follow-up of 13 months, and 19 (3.4 %) had operative failure. The major cause of operative failure (11 of 19) was the result of surgeons’ inability to identify all abnormal parathyroid glands. The remaining eight operative failures were the result of falsely positive IOPTH results. Eleven of 19 patients whose MIP had failed underwent a second parathyroid surgery. All but one of these patients achieved operative success, and 9 patients had missed multigland disease. Only 46 (8.3 %) of 557 patients had conversion to bilateral cervical exploration (BCE). Eighty percent of patients had more than 70 % IOPTH decrease, and all had successful operations. Patients with a marginal IOPTH decrease (50–59 %) had a treatment failure rate of 20 %.

Conclusions

The most common cause of operative failure in MIP utilizing IOPTH was the result of surgeons’ failure to identify all abnormal parathyroid glands. Falsely positive IOPTH is rare, and a targeted MIP utilizing IOPTH can achieve an excellent operative success rate without routine BCE. Selective BCE on patients with marginal IOPTH decrease may improve surgical outcome.     

Results of a Fifteen-Year Follow-up Program in Patients Operated with Unilateral Neck Exploration for Primary Hyperparathyroidism

Background

Since the introduction of unilateral parathyroidectomy for primary hyperparathyroidism (pHPT) it has been debated wherever this approach is associated with greater long-term risk for recurrence compared to bilateral neck exploration.

Methods

This is a prospective study based on a structured 15-year follow-up program in patients with non-hereditary, sporadic pHPT, undergoing first time surgery with unilateral or focused neck exploration (unilateral procedures), with the use of intraoperative PTH (iOPTH) between 1989 and 2010.

Results

292 patients were analyzed. The median age of the patients was 66 years [interquartile range (IQR) 57–75], and 234 (80.4 %) were female. The median preoperative level of total calcium was 2.74 mmol/L (IQR 2.63–2.85 mmol/L) and the median PTH level was 10 pmol/L (IQR 7.4–14 pmol/L). The median follow-up time was 5 years (IQR 1–10 years). Some 275 patients were followed for 1 year (94.2 %/275 person-years/5 patients deceased), 164 for 5 years (56.2 %/820 person-years/31 patients deceased), 70 for 10 years (24.0 %/700 patient-years/57 patients deceased) and 51 (17.5 %/765 patient-years/69 patients deceased) for 15 years after surgery. Three patients (1.1 %) had signs of persistent disease. One patient recurred in pHPT at 5 years postoperatively during 15 years of follow-up. Histopathology indicated solitary parathyroid adenoma at primary surgery.

Conclusion

Patients with pHPT operated with unilateral procedures and iOPTH, had a low risk for long-term recurrence during a 15 years follow-up program.

     

Feasibility of video-assisted bilateral neck exploration for patients with primary hyperparathyroidism and failed or discordant localization studies

Purpose

Minimally invasive video-assisted parathyroidectomy (MIVAP) is generally adopted for patients affected by primary hyperparathyroidism (pHPT) with clear preoperative localization. Standard bilateral neck exploration (BNE) is considered the obligate surgery for patients with unlocalized glands. We reviewed our experience of minimally invasive video-assisted BNE in patients with pHPT and negative or discordant localization studies.

Methods

From a prospective series of 576 MIVAP for pHPT, 107 patients (19 males, 88 females; mean age 58 years) with failed localization studies underwent BNE using the video-assisted technique. Operative time, complications, conversions to standard cervical exploration, and cure rate were analyzed.

Results

MIVAP with BNE was successfully completed in 99 (93 %) patients with 8 conversions. Mean operative time was 57?±?37 min (range 20–180 min). Permanent recurrent laryngeal nerve palsy occurred in one patient. Biochemical cure was achieved in 104 patients (97 %). Five patients required a reoperation in the immediate postoperative period, which achieved cure in four. Two patients remained with persistent disease; one developed recurrence disease 3 years after the first exploration.

Conclusion

In experienced hands, video-assisted BNE for pHPT is feasible and safe and provides results equivalent to the conventional open technique.     

Prediction of Permanent Hypoparathyroidism after Total Thyroidectomy

Background

Hypoparathyroidism is a common complication with thyroid surgery. The ability to predict a high risk of permanent hypoparathyroidism is important for individual prognosis and follow-up.

Methods

Permanent hypoparathyroidism, defined as continuing need for vitamin D medication at 1-year post-operatively, was investigated in patients after total thyroidectomy. Blood levels of calcium and parathyroid hormone (PTH) were measured intra-operatively, the day after surgery and at 1 month post-operatively. Logistic regression analysis was performed to investigate the risk of vitamin D treatment at last follow-up, calculated as odds ratios (ORs) with 95 % confidence intervals (CIs). Patients were followed until cessation of vitamin D and/or calcium medication, until death, loss to follow-up, or end of follow-up, whichever came first.

Results

A total of 519 patients were included. The median (range) follow-up in patients unable to cease vitamin D was 2.7 (1.2–10.3) years. The rate of permanent hypoparathyroidism was 10/519, 1.9 %. Parathyroid auto-transplantation was performed in 90/519 (17.3 %) patients. None of these developed permanent hypoparathyroidism, nor did any patient with normal PTH day 1 (>1.6 pmol/l or 15 pg/ml). The adjusted risk (OR, 95 % CI) for permanent hypoparathyroidism for log PTH on day 1 was 0.25 (0.13–0.50). In patients not auto-transplanted and with unmeasurable PTH day 1 (<0.7 pmol/l or 6.6 pg/ml), 8/42 (19.2 %) developed permanent hypoparathyroidism.

Conclusions

Auto-transplantation protects against permanent hypoparathyroidism, whereas low PTH day 1 is associated with high risk.     

Initial Surgery for Benign Primary Hyperparathyroidism: An Analysis of 1,300 Patients in a Teaching Hospital

Background

Success rates of initial surgery for primary hyperparathyroidism (pHPT) are greater than 95 % in specialized centers, mostly referring to single-surgeon experiences. The present study was performed to identify changes in clinical manifestations, diagnostic procedures, surgical strategies, and outcome of initial parathyroid interventions in a teaching hospital during the past 25 years with special regard to the surgical expertise.

Methods

Clinical data of patients who underwent an initial neck exploration for benign pHPT between 1985 and 2010 at the University hospital Marburg were retrospectively evaluated. All data were analyzed particularly with regard to the implementation of additional pre- and intraoperative procedures and to the particular surgical strategy. In addition, operative results were furthermore analyzed with regard to the experience of the responsible surgeons.

Results

An initial neck exploration for benign pHPT was performed in 1,300 patients. Of these, 1,035 patients had a bilateral cervical exploration (BCE) and 265 patients had a focused, minimally invasive parathyroidectomy (MIP). Cure rates did not differ between focused surgeries and BCE (98.9 vs. 98.3 %, p = 0.596) after a mean follow-up of 33.4 (± 44.3) months. Postoperative transient hypoparathyroidism was significantly lower in the MIP group (11 vs. 47 %, p < 0.0001). The rate of permanent recurrent laryngeal nerve palsies (0.4 vs. 2 %, p = 0.064) and nonsurgical complications (0 vs. 1.4 %, p = 0.0875) tended to be lower in the MIP group. Success and complication rates of chief surgeons (n = 2), attending surgeons (n = 20), and residents (56 < 3 years, 30 > 3 years) were similar, despite a significantly shorter operating time in the chief surgeon group (p < 0.01).

Conclusions

Despite the implementation of several diagnostic procedures and significant changes concerning the surgical strategy, high success rates of primary interventions for pHPT did not change over the past three decades. High success rates also can be achieved in a teaching hospital, provided that surgery is supervised by an experienced endocrine surgeon. MIP is the treatment of choice in patients with benign sporadic pHPT and positive preoperative localization studies.     

Cure Predictability During Parathyroidectomy

Background

A mathematical model for primary hyperparathyroidism (1°HPTH) was developed and embedded in software to yield intraoperative predictability curves.

Methods

A total of 1,754 consecutive 1°HPTH operative cases were screened to select 617 [554 single adenoma (SA), 63 multigland] patients with complete preoperative, intraoperative (pre-exploration, time 0, every 5 min post-resection), and postoperative parathyroid hormone (PTH) and calcium data. Data transformations and models were hypothesized and tested, including inverse functions, differences, half-lives, differences from projected half-lives, second-order kinetics, second-order derivatives, and time-dependent ratios. Sub-models of ratios were developed for time-dependent and initial-value combinations. For each time segment the log odds were modeled using multiple logistic stepwise regression. An idealized model was selected, embedded in software, and installed in a laptop computer to enable intraoperative decision analyses, PTH curve plotting, and storage and transmission of data. A subsequent cohort of 100 consecutive unselected patients [81 SAs, 19 multigland (13 hyperplasia, 2 MEN1, 1 lithium, 3 double adenomas)] inclusive of seven remedial cervical explorations were tested.

Results

The model predicted an overall curative resection in 95 % of patients. In SA patients, cure was predicted in 78/81 patients with a mean probability of 99.3 % at 11.8 ± 10.4 min post-resection. In three cured patients, the software failed to suggest cure, because of a low baseline PTH or delayed clearance. The model also correctly predicted residual hyperfunctioning tissue in all tested multigland patients. All multigland patients underwent additional exploration with resection of residual disease resulting in a mean predicted cure rate of 97.9 % at 10.6 ± 7.3 min post-resection completion in 17 patients. In two patients, the software predicted a mean cure rate of 22 % due to either a low PTH baseline or delayed clearance. Overall, the software accurately predicted cure in 95 of 100 cured cases.

Conclusions

This intraoperative prediction software expedites termination of surgery with a high level of curative confidence. Alternatively, the model accurately predicts residual disease prompting additional exploration. Because the model is based on a large set of multivariate regression curves, PTH values obtained at any post-resection sampling interval generate prediction data with far greater accuracy than existing algorithms. The software is designed for convenient operative use and can print, store, and electronically transmit probability analyses and PTH curves in real-time.     

Presentation, Management, and Outcomes of Hyperparathyroidism in Octogenarians and Nonagenarians

Background

Various elective surgical procedures are routinely performed on patients ≥80 years of age. With primary hyperparathyroidism (PHPT), surgical management is the only treatment. The goal of this study was to compare presentation and outcome of patients ≥80 to that of those <80 years of age.

Methods

Retrospective review of a prospectively collected database of all parathyroidectomies for PHPT performed at a university hospital. Patients ≥80 years at the time of surgery compared with patients <80 years.

Results

Over 13 years, 1,826 patients underwent parathyroidectomy for PHPT. A total of 154 patients were ≥80 years at the time of surgery (8.4 %), ranging from 80 to 91 years. Patients ≥80 years had higher serum PTH, creatinine and vitamin D levels and lower T scores. Calcium levels were similar. Patients ≥80 years had a greater history of hypertension, coronary artery disease, congestive heart failure, and stroke. Psychiatric disease was less common. Patients ≥80 years had the procedure under local anesthesia only more often. Use of a unilateral approach was equivalent. Rates of adenoma, double adenoma, and hyperplasia were comparable. Patients ≥80 years were observed overnight more frequently. Stays >24 h and disease recurrence and persistence, as well as morbidity rates, were all equivalent.

Conclusion

Disease presentation of PHPT in patients ≥80 is similar to <80. Despite increased comorbidities, parathyroidectomy is a safe procedure in this patient population with a noted equivalent complication rate to younger patients. Operative management remains the only treatment. Patient age should not be a deterrent to offer curative surgical intervention.     

Undiagnosed Primary Hyperparathyroidism and Recurrent Miscarriage: The First Prospective Pilot Study

Background

Primary hyperparathyroidism (pHPT) in pregnancy is reported to be associated with significant maternal and foetal complications and an up to threefold increase in the risk of miscarriage. However, the true incidence of pHPT in pregnancy, complete and miscarried, is unknown and there are no data on the prevalence of undiagnosed pHPT in recurrent miscarriage (RM) (≥3 consecutive miscarriages under 24-week gestation). This is the first prospective study aiming to establish the prevalence of undiagnosed pHPT in RM.

Methods

Following UK National ethics committee approval, women who had experienced 3 or more consecutive miscarriages were recruited from a nationwide RM clinic. Serum corrected calcium, phosphate, PTH and vitamin D were evaluated. Patients with raised serum calcium and/or PTH were recalled for confirmatory tests. Power calculations suggested that a minimum of 272 patients were required to demonstrate a clinically significant incidence of pHPT.

Results

Three hundred women were recruited, median age 35 years (range 19–42). Eleven patients had incomplete data, leaving 289 patients suitable for analysis; 50/289 patients (17%) with abnormal tests were recalled. The prevalence of vitamin D deficiency (<25 nmol/l) and insufficiency (25–75 nmol/l) was 8.7 and 67.8%, respectively. One patient was diagnosed with pHPT (0.34%) and underwent successful parathyroidectomy.

Conclusions

The prevalence of undiagnosed pHPT (0.34%) in RM in this study appears to be many times greater than the 0.05% expected in this age group. The findings of this pilot study merit follow-up with a larger-scale study. Routine serum calcium estimation is not currently undertaken in RM and should be considered.