Do Intraoperative Total Serum and Ionized Calcium Levels, Like Intraoperative Intact PTH Levels, Correlate with Cure of Hyperparathyroidism?

Intraoperative parathyroid hormone (ioPTH) monitoring is useful in the operative management of hyperparathyroidism. Measurement of intraoperative total serum calcium (TSC) and ionized calcium (ICa) levels may be less expensive and more readily available methods of intraoperative guidance during neck dissection than ioPTH levels, the gold standard. We compared the accuracy of monitoring intraoperative TSC and ICa to that of ioPTH for predicting surgical cure during parathyroidectomy. Over a 10-month period, 47 parathyroidectomies were performed, during which ioPTH, TSC, and ICa were measured. Samples were obtained at the start of the operation and 5 and 10 minutes after gland removal. Data were compared and trends analyzed with respect to removal of abnormal parathyroid tissue as confirmed by pathology. The Wilcoxon signed rank test was used to determine if decreases in TSC and ICa were significant. The mean baseline ioPTH level (253 ± 247 pg/ml) dropped by 70% at 5 minutes after removal of the abnormal glands (68 ± 85 pg/ml) and by 83% at 10 minutes (32 ± 25 pg/ml). The mean baseline TSC level (10.1 ± 0.9 mg/dl) dropped by 4% at 5 minutes after removal of the abnormal glands (9.7 ± 0.8 mg/dl) and remained at 4% at 10 minutes (9.6 ± 0.7 mg/dl). The mean baseline ICa level (1.4 ± 0.1 mmol/dl) also dropped by 4% at 5 minutes after removal of the abnormal glands (1.3 ± 0.1 mmol/dl) and remained at 4% at 10 minutes (1.3 ± 0.1 mg/dl). ioPTH dropped by ≥ 50% in 39 patients (83%) at 5 minutes and in 46 patients (98%) at 10 minutes after gland resection. TSC decreased below baseline at 5 minutes and remained below baseline at 10 minutes in only 37 patients (79%). In the remaining 21% of patients, TSC decreased inconsistently, if at all, with respect to baseline at both the 5- and 10-minute time points. ICa decreased below baseline at 5 minutes and remained below baseline at 10 minutes in only 35 patients (77%). In the remaining 23% of patients, ICa, like TSC, changed inconsistently at 5 and 10 minutes after parathyroidectomy with respect to baseline levels. Decreases in TSC and ICa during parathyroidectomy, if present, are thus minimal. Unlike ioPTH levels, TSC and ICa levels do not consistently decrease at 5 and 10 minutes after gland resection. Although inexpensive and readily available, monitoring the intraoperative TSC and ICa is not clinically reliable for confirming removal of hyperfunctioning parathyroid glands.This work was presented at the International Association of Endocrine Surgeons Conference, Uppsala, Sweden, June 2004     

Intraoperative parathyroid hormone measurement in patients with secondary hyperparathyroidism

HYPOTHESIS: Secondary hyperparathyroidism decreases renal clearance of parathyroid hormone (PTH). OBJECTIVE: To determine whether rapid PTH assays can be used to predict the success of a total parathyroidectomy to treat symptomatic secondary hyperparathyroidism. DESIGN: Case series from August 1 to December 31, 2000. SETTING: Tertiary referral center. PARTICIPANTS: Patients with symptomatic secondary hyperparathyroidism (n = 24) who underwent total parathyroidectomy and autotransplantation were included in the study. INTERVENTIONS: Blood samples for rapid PTH analyses were drawn from an indwelling catheter at the induction of anesthesia (baseline) and before (0 minutes), 10 minutes, and 30 minutes after the removal of the last parathyroid gland. Regular intact PTH (iPTH) assays were conducted later. MAIN OUTCOME MEASURE: If a patient's regular iPTH levels were below 65 pg/mL at 1 week or 3 months postoperatively, the operation was considered successful. RESULTS: All 24 patients had successful operations. Rapid PTH and regular iPTH correlated significantly at 0, 10, and 30 minutes. Rapid PTH levels decreased significantly at each time period and were 176 +/- 40.9 pg/mL (mean +/- SE) at 10 minutes. The percentage decrease in rapid PTH levels was 39.5% +/- 12.7% at 0 minutes, 75.1% +/- 6.2% at 10 minutes, and 91.0% +/- 0.1% at 30 minutes (mean +/- SE). A decrease of 60% or more from baseline PTH levels at 10 minutes and/or a decrease of 85% or more at 30 minutes predicted the successful removal of all parathyroid glands. CONCLUSIONS: A drop in PTH levels is delayed until 30 minutes after total parathyroidectomy; however, a rapid PTH assay 10 minutes after the removal of the last parathyroid gland is as accurate as an assay performed at 30 minutes postoperatively. Intraoperative PTH monitoring demonstrates relevant decreases in rapid PTH levels after parathyroidectomy that are similar to those previously documented in patients with primary hyperparathyroidism.     

Intraoperative monitoring of kinetic total serum calcium levels in primary hyperparathyroidism surgery

BACKGROUND: In the setting of minimal approach Sestamibi-guided parathyroid surgery for primary hyperparathyroidism we evaluated if total serum calcium level monitoring is as valuable as intraoperative parathyroid hormone (iPTH) monitoring. STUDY DESIGN: Prospective open single-blinded efficacy trial of two intraoperative diagnostic monitoring methods (iPTH and total serum calcium level) on a cohort of surgical patients. All patients (n = 35) were undergoing parathyroid surgery at the Department of General Surgery at B Cruces' Hospital, Vizcaya, Spain, between October 1999 and March 2001. Kinetics of serum levels of Ca and iPTH during surgery and time of prediction of cure for each method (measured in the clinic, admission, and intraoperatively, such as induction of anesthesia, and every 5 minutes after removal of adenoma) were analyzed. RESULTS: Hypercalcemia and iPTH levels became corrected in 34 patients. Average serum calcium levels dropped from pathologic 11.07 +/- 0.41 mg/dL (mean +/- standard deviation) to normal values 9.7 +/- 0.82 mg/dL during the first intraoperative determination (minute 5), but mean iPTH decreased from pathologic (192 +/- 98 pg/mL) to normal values (39.93 +/- 25.12 pg/mL) during the third intraoperative determination (minute 15). Serum calcium level at 5 minutes after removal decreased by 100% in 34 patients, but iPTH only showed a similar drop during the third determination at 15 minutes. Frozen sections were conclusive for parathyroid tissue (20.56 +/- 10.3 minutes after removal). CONCLUSIONS: Intraoperative measurement of total calcium level might be an easier and less expensive method than iPTH measurement in the prediction of cure during surgery for primary hyperparathyroidism resulting from adenoma.     

Role of cyclase activating parathyroid hormone (1-84 PTH) measurements during parathyroid surgery: potential improvement of intraoperative PTH assay

SUMMARY BACKGROUND DATA: Quick intraoperative parathyroid hormone assays are widely used as a guide to the adequacy of resection during parathyroid surgery. However, some authors have reported a 15% error rate of these assays because of the presence of false-positive and false-negative results. Recently the authors have found that most commercial intact PTH (iPTH) assays cross-react with non-(1-84) PTH (likely 7-84 PTH) and that the proportional levels of non-(1-84) PTH in patients were variable in a much wider range, accounting mostly for 20% to 60% of the immunoreactivity in samples obtained from hyperparathyroid patients. A cyclase activating PTH (CAP) measured by a novel immunoradiometric assay was shown to measure specifically 1-84 PTH. Using a CAP assay, the authors studied the rate of decline of CAP after parathyroidectomy and compared it with iPTH as measured by the Nichols intact PTH immunoradiometric assay. METHODS: This study comprised 29 patients with primary hyperparathyroidism (pHPT) caused by a single adenoma and 7 patients with secondary hyperparathyroidism (secondary HPT) who underwent parathyroidectomy. Blood samples were drawn after anesthesia, before excision of one enlarged parathyroid gland in pHPT and of the last gland in secondary HPT, and at 5, 10, and 15 minutes after excision. The 7-84 PTH level was calculated by subtracting the CAP value from the iPTH value. RESULTS: The percentage of 7-84 PTH in iPTH in plasma samples was 27.5 +/- 14.4% in pHPT and 39.6 +/- 15.1% in secondary HPT. In pHPT patients the plasma CAP and iPTH value decreased to 23.4 +/- 10.8 and 32.0 +/- 11.3% of the preexcision level at 5 minutes, 10.6 +/- 7.7 and 21.1 +/- 8.8% at 10 minutes, and 8.5 +/- 4.9 and 16.1 +/- 6.8% at 15 minutes after removal of the enlarged gland, respectively. At 5 minutes, CAP levels of all 29 pHPT patients had decreased to less than 40% of the preparathyroidectomy level; however, 7 (24%) patients still had an iPTH level of more than 40%. In secondary HPT patients, CAP and iPTH values had dropped to 43.3 +/- 20.2 and 66.1 +/- 19.7% at 5 minutes, 28.6 +/- 16.6 and 53.6 +/- 18.1% at 10 minutes, and 14.2 +/- 9.0 and 41.0 +/- 12.9% at 15 minutes after removal of the last enlarged gland, respectively. At 10 minutes, CAP levels of all seven secondary HPT patients had decreased to less than 50% of the preexcision level; however, three (43%) patients still had an iPTH level of more than 50%. In pHPT and secondary HPT, the 7-84 PTH level had dropped to 57.4 +/- 85.9 and 62.1 +/- 84.9%, respectively, of the preexcision value 15 minutes after removal of the enlarged gland or glands. CONCLUSIONS: The percentage of 7-84 PTH in iPTH in plasma samples varies substantially between patients with HPT. In both pHPT and secondary HPT, the plasma CAP value decreased more rapidly than iPTH after parathyroidectomy, depending on the amount of 7-84 PTH in circulation. These results suggest that the CAP assay may be a more useful adjunct to parathyroidectomy than the currently used iPTH assay.     

Limited role for intraoperative intact PTH measurement in parathyroid surgery.

Primary hyperparathyroidism may be cured surgically by complete excision of abnormal parathyroid tissue. Reoperation for persistent hypercalcaemia due to residual abnormal parathyroid tissue may be associated with a high complication rate. It is possible to assay intact parathormone (iPTH) intraoperatively and as iPTH has a relatively short half-life, its measurement intraoperatively may be used to predict successful parathyroidectomy. We have studied intraoperative iPTH levels in a consecutive series of 33 patients undergoing surgery for primary hyperparathyroidism. We found that iPTH levels fell significantly (P < 0.05) from a median pre-excision level of 122 pg/ml to a median level of 36 pg/ml 20 min after excision. However, in 3/31 successful parathyroidectomies, the intraoperative iPTH levels either remained unchanged or had risen. Reliance on intraoperative iPTH levels in these patients may have resulted in unnecessary re-exploration. We conclude that intraoperative iPTH measurement has limited usefulness as a predictor of successful parathyroidectomy for primary hyperparathyroidism.     

Intraoperative monitoring of intact parathyroid hormone during surgery for primary hyperparathyroidism

The aim of the present study was to evaluate a new immunometric assay for intraoperative parathyroid hormone monitoring. The test was applied in 70 patients who underwent surgery for primary hyperthyroidism (pHPT) between 6/1999 and 6/2001. Among these patients, 61 showed a solitary adenoma, eight a hyperplasia and one a double adenoma. Intraoperative iPTH samples were taken at the beginning of the operation and 5, 10 and 15 min after removal of the parathyroid gland. Criterion for a successful operation were a decrease of iPTH levels of more than 50 % within 5 min and of more than 60 % within 15 min after parathyroidectomy. Following the removal of a solitary adenoma, iPTH levels decreased by 63 % (+/- 13 %) after 5 min and by 76 % (+/- 10 %) after 15 min respectively. In case of hyperplasia, a significant decrease of iPTH levels was not observed until a subtotal parathyroidectomy had been carried out. In the present study there were 2 false negative and one false positive results corresponding with a sensitivity of 97 % and a specificity of 89 % for prediction of a solitary adenoma. In our opinion, intraoperative iPTH monitoring using this new assay allows the safe distinction between adenoma and multiglandular disease. It represents a valuable adjunct to surgical skill as it permits minimally invasive operations for solitary adenomas, and in case of recurrent surgery helps to detect the region of interest by selective venous sampling for parathyroid hormone.     

Normalization of intraoperative parathyroid hormone does not predict normal postoperative parathyroid hormone levels

BACKGROUND: Intraoperative intact parathyroid hormone (iPTH) is being used to confirm complete excision of hyperfunctioning parathyroid tissue. It is uncertain whether normalization of intraoperative iPTH levels accurately predicts long-term postoperative iPTH values. METHODS: Fifty-two consecutive patients with primary or secondary hyperparathyroidism underwent parathyroidectomy with measurement of intraoperative iPTH. Ten patients were excluded due to incomplete laboratory follow-up. Follow-up serum calcium and iPTH levels were measured at 1- and 3-month intervals. RESULTS: Before operation, the mean serum iPTH level was 249 pg/mL (SD=208) and mean serum calcium level was 11.4 +/- 0.9 mg/dL (+/- SD). In all but 4 patients, final intraoperative iPTH levels normalized to less than 67 +/- 41 pg/mL (mean, 35 pg/mL). One week after operation, serum calcium levels had returned to normal (mean, 9.4 +/- 1.1 pg/mL), which directly correlated with the final intraoperative serum iPTH values (Pearson correlation, r = -.434; P <.01). By 1 month, all but 2 patients were normocalcemic (mean, 9.4 +/- 0.9 pg/mL) with a mean iPTH level of 74.8 +/- 82 pg/mL. There was no correlation between final intraoperative and postoperative serum iPTH values (r =.099; P <.533). Both patients with persistent hypercalcemia at 1 month had appropriate intraoperative decreases in iPTH values. CONCLUSIONS: Intraoperative serum iPTH levels significantly correlate with postoperative serum calcium levels but not with postoperative serum iPTH levels. There was a 4.8% failure rate in the correction of postoperative serum calcium levels and a 29% failure rate in the normalization of postoperative serum iPTH levels.     

Intraoperative parathyroid hormone monitoring fails to detect double parathyroid adenomas: a 2-institution experience.

BACKGROUND: We hypothesized that intraoperative parathyroid hormone monitoring (IOPTH) reliably would detect double parathyroid adenomas. METHODS: This was a retrospective study of 20 patients undergoing conventional parathyroidectomy with resection of exactly 2 abnormal glands. Full exploration was performed regardless of IOPTH values, which were measured after anesthetic induction and 5 and 10 minutes following removal of the first abnormal parathyroid gland. Failure to fall below 50% of baseline value by 10 minutes following resection of the first gland indicated the presence of multiglandular disease. RESULTS: All patients were cured. All excised glands were hypercellular on histology. Mean IOPTH values in 9 of the 20 patients with true negative results (noncurative decrease, another gland present) were 66% +/- 7% at 5 minutes and 83% +/- 15% at 10 minutes. The IOPTH values in 11 of the 20 patients with false positive results (curative decrease, another gland present) were 28% +/- 4% at 5 minutes and 18% +/- 2% at 10 minutes. The false positive rate of IOPTH was 55%. CONCLUSIONS: We found that IOPTH failed to reliably detect the presence of double parathyroid adenomas. These data suggest that caution should be exercised when terminating limited parathyroid exploration based on a curative fall in IOPTH values.     

Parathyroid graft function after presternal subcutaneous autotransplantation for renal hyperparathyroidism

HYPOTHESIS: Presternal subcutaneous autotransplantation of parathyroid tissue after total parathyroidectomy for renal hyperparathyroidism could be at least as effective as intramuscular grafting, without its complications. DESIGN: Prospective study of a postoperative diagnostic method of monitoring intact parathyroid hormone (iPTH) levels among a cohort of surgical patients, without loss to follow-up. SETTING: Hemodialysis unit in a university hospital. PATIENTS: Twenty-five patients (17 women and 8 men) underwent total parathyroidectomy and presternal subcutaneous autotransplantation for renal hyperparathyroidism at Donostia Hospital, San Sebastián, Spain, between January 1, 2002, and June 30, 2004. MAIN OUTCOME MEASURES: Evaluation of parathyroid graft function by measurement of serum iPTH levels at admission and 24 hours and 1, 3, 5, 15, 30, and 60 weeks after surgery. RESULTS: The mean +/- SD preoperative serum iPTH level was 1302 +/- 425 pg/mL; the iPTH level was undetectable in all patients 24 hours after surgery. Subsequent mean +/- SD iPTH levels obtained were 14 +/- 10 pg/mL after 1 week, 54 +/- 1 pg/mL after 5 weeks, 64 +/- 9 pg/mL after 15 weeks, 77 +/- 8 pg/mL after 30 weeks, and 106 +/- 21 pg/mL after 60 weeks. Autotransplanted parathyroid tissue appears to be adequately functional at week 5 (criterion level of adequate functioning, 50 pg/mL). CONCLUSIONS: Presternal subcutaneous autotransplantation after total parathyroidectomy for renal hyperparathyroidism may be an alternative to avoid musculus brachialis grafting and its complications. Our functional results compare favorably with the published data on other surgical techniques for the treatment of renal hyperparathyroidism. Long-term follow-up of this series is planned.     

Minimally invasive video-assisted parathyroidectomy and intraoperative parathyroid hormone monitoring. The first 36 cases and some pitfalls

Background: The success of parathyroid surgery depends on the identification and removal of all hyperactive parathyroid tissue. At this writing, bilateral cervical exploration and identification of all parathyroid glands represent the operative standard for primary hyperparathyroidism (pHPT). However, improved preoperative localization techniques and the availability of intraoperative parathyroid hormone monitoring prepare the way for minimally invasive procedures. Methods: Patients with pHPT and one unequivocally enlarged parathyroid gland on preoperative ultrasound and 99mTc-SestaMIBI scintigraphy underwent minimally invasive video-assisted parathyroidectomy by an anterior approach. Intraoperatively, a rapid chemiluminescense immunoassay was used to measure intact parathyroid hormone (iPTH) levels shortly before and then 5, 10, and 15 min after excision of the adenoma. The operation was considered successful when more than a 50% decrease in preexcision iPTH levels was observed after 5 min. Results: Between October 1999 and November 2001, 36 of 82 patients with pHPT were eligible for a minimally invasive approach. A conversion to open surgery became necessary in five patients because of technical problems. In three cases, intraoperative iPTH monitoring showed no sufficient decrease in iPTH values. In these cases, subsequent cervical exploration showed one double adenoma and two hyperplasias, respectively. In two patients we had difficulty interpreting intraoperative iPTH values, resulting in persistent pHPT. Conclusions: Despite the use of high-resolution ultrasound and 99mTc-SestaMIBI scintigraphy, the presence of multiple glandular disease cannot be ruled out completely. Intraoperative iPTH monitoring to ensure operative success is indispensible for a minimally invasive approach. Despite our problems with iPTH monitoring in two patients, we believe that in selected cases, minimally invasive parathyroidectomy represents an attractive alternative to conventional surgery.     

Intraoperative parathyroid hormone monitoring during parathyroidectomy for hyperparathyroidism in waiting list and kidney transplant patients

This report describes the use of the intraoperative parathyroid hormone (ioPTH) assay during parathyroidectomy in waiting list and transplanted patients. ioPTH levels were determined in 40 patients on the waiting list for kidney transplantation with secondary hyperparathyroidism who underwent subtotal parathyroidectomy and 9 transplanted patients with tertiary hyperparathyroidism who underwent removal of hyperplasic glands. Rapid PTH levels decreased significantly at each time period; the percentage decrease in rapid PTH levels was 61.3% among patients with IPT II and 70.2% in patients with IPT III at 10 minutes and 86.5% in patients with IPT II and 91% in patients with IPT III at 15 minutes after excision of hypersecreting parathyroid tissue. A decrease of 50% or more from baseline PTH levels at 10 minutes and/or a decrease of 85% or more at 15 minutes predicted successful removal of abnormal parathyroid glands. The application of this technique during subtotal parathyroidectomy has proved useful for correct excision of parathyroid glands among waiting list patients with IPT II, while in kidney transplant patients with IPT III it allowed removal of only the pathological glands with a limited surgical approach.     

Intraoperative Monitoring of Intact PTH in Surgery for Renal Hyperparathyroidism as an Indicator of Complete Parathyroid Removal

In the setting of total parathyroidectomy and autotransplantation surgery (TPT × AS) as treatment for secondary hyperparathyroidism (SHPT), we evaluated whether intraoperative parathyroid hormone (iPTH) monitoring is useful as a reference for total parathyroid removal. We conducted a prospective, open, single value measurement efficacy study of the intraoperative (i.o.) diagnostic monitoring of iPTH in a cohort of surgical patients. All patients (n = 25) underwent TPT × AS at the Department of Surgery, Donostia Hospital from January 2002 to October 2004. The primary outcome measures were kinetics of serum levels of iPTH during surgery and prediction time of the of descent of PTH levels (measured in the clinic on the day of admission and intraoperatively during induction of anesthesia, every 5 and 10 minutes after removal of the adenoma, and again 24 hours thereafter). iPTH levels returned to normal in all 25 patients, decreasing from pathological levels at the beginning of the operation (1302.24 + 424.9 pg/ml) to half (50%) values at the third intraoperative determination, minute 10 (614.8 ± 196.62), becoming undetectable at 24 hours. Frozen sections were conclusive for parathyroid tissue (20.56 + 10.3 minutes after removal). Intraoperative measurement of iPTH is useful in the prediction complete removal of all parathyroid tissue prior to autotransplantation, thus avoiding persistence of disease because of incomplete surgery.     

Intraoperatives Monitoring des intakten Parathormons (iPTH) in der Chirurgie des primären Hyperparathyreoidismus mit einem neuen Schnelltest

OBJECTIVES: Intraoperative differentiation between adenoma and hyperplasia during surgery for primary hyperparathyroidism (pHPT) is sometimes difficult, but essential for good results. The aim of our study was to evaluate a new highly sensitive electrochemiluminescence immunoassay (ECLIA) for intraoperative monitoring of intact parathyroid hormone (iPTH) following parathyroidectomy as an adjunct for identification of solitary adenoma in patients with pHPT. METHODS: Thirty consecutive patients with pHPT (2 with recurrent pHPT) were examined following a standardized protocol: Immediately before and 5, 10 and 15 min following parathyroidectomy of the enlarged gland, iPTH was measured with a new ECLIA (Roche-Diagnostics, Mannheim, Germany). The results were available within 15-20 min. Besides 20 conventional bilateral neck explorations, parathyroidectomy was carried out in a minimally invasive video-assisted technique (MI-VAP) in 10 patients. RESULTS: Among the 30 patients we found 24 with solitary adenoma (80%), 5 with hyperplasia (17%) and one with a double adenoma (3%). Five minutes after removal of a solitary adenoma the level of iPTH had decreased by 65 (12)% [mean (+/- SD)], after 10 min by 76 (8)% and after 15 min by 81 (8)%. All patients with multiple gland disease could be clearly identified, as iPTH after 15 min did not fall below 50% of basal value. Only after removal of all hyperplastic glands did iPTH decrease to the normal range. Sensitivity and specificity for prediction of a solitary adenoma were 92% and 100% (decline of iPTH more than 50% from baseline value 5 min after parathyroidectomy). In one patient with recurrent pHPT intraoperative sampling from different sites in both internal jugular veins could predict the quadrant of the enlarged gland. Correlation (r) between the results of the quick and the conventional assay, which requires 24 h of incubation, was 0.955. All patients had normal or low calcium levels postoperatively. CONCLUSIONS: (1) Intraoperative monitoring of iPTH with this new quick assay allows safe identification of patients with solitary adenoma during surgery for pHPT. (2) It represents a valuable adjunct to surgical skill not only in primary operations for pHPT but especially in cases of recurrent surgery for pHPT. (3) With this test available minimally invasive techniques for parathyroidectomy may be employed in cases of preoperatively localized adenoma (ultrasound, sesta-mibi scan), avoiding bilateral neck exploration with its higher potential for complications.     

Intraoperative measurement of intact parathyroid hormone in renal hyperparathyroidism by an inexpensive routine assay

Although the kinetics of intraoperative intact parathyroid hormone (iPTH) are well characterised in primary hyperparathyroidism, no data are available for patients with renal hyperparathyroidism and renal insufficiency, partially because of the high costs of intraoperative quick iPTH measurement. Therefore we evaluated an inexpensive laboratory test with a duration of 18 min for intraoperative use and measured iPTH intraoperatively in 34 patients with renal hyperparathyroidism. Samples were taken before and 5 min and 15 min after parathyroid resection. Blood samples were put on ice immediately and sent to the hospital central laboratory via a pneumatic tube system. The first 76 probes were measured in parallel using three assays: the Nichols Quick PTH, the Roche Elecsys and the Biermann Immulite assay. The subsequent samples were only measured using the Elecsys assay. Determination of iPTH from 76 samples showed a correlation coefficient of 0.997 between the Immulite and Elecsys assay and a correlation coefficient of 0.987 for the Nichols Quick PTH and the Elecsys test. In renal hyperparathyroidism the mean iPTH was 26+/-2% of the starting value 5 min after subtotal parathyroidectomy and 18+/-2% after 15 min. Renal function influenced absolute iPTH values in patients with renal hyperparathyroidism but not relative changes. In patients with terminal renal insufficiency iPTH decreased from 615+/-57 pg/m before preparation to 109+/-13 pg/ml 15 min after subtotal resection. In contrast in patients after kidney transplantation iPTH decreased from a lower starting value of 341+/-94 pg/ml to 58+/-9 pg/ml after 15 min. The iPTH kinetics showed a biphasic clearance of iPTH with an initial dominant half-life of 3.2 min and a terminal half-life of 29.2 min. Half-life did not correlate with renal function. All operations were successful as indicated by an adequate drop in PTH (from 709+/-92 pg/ml preoperatively to 22+/-6 pg/ml at discharge) and calcium (from 2.57+/-0.04 mmol/l to 2.32+/-0.04 mmol/l). In conclusion, intraoperative measurement of iPTH is also reliable in patients with renal hyperparathyroidism. Elimination kinetics are similar to that in patients with primary disease. However, the half-life was not influenced by renal function. The availability of a quick, inexpensive, routine iPTH test might expand its use to renal hyperparathyroidism, specifically for surgical decisions in problem cases.     

Minimally Invasive Radio-guided Surgery for Primary Hyperparathyroidism

Background Minimally invasive parathyroidectomy can reduce operative morbidity and operative time.1,2 Radio-guided parathyroidectomy utilizing Tc-99m Sestamibi is one approach to minimally invasive parathyroidectomy.3,4 Here, we report a multimedia case study of minimally invasive radio-guided parathyroidectomy. Methods A 60-year-old African American female was found to have total calcium of 11.1 mg/dl, intact parathyroid hormone (iPTH) of 175 pg/ml, and a 24-h urine calcium of 620 mg/24 h. A Tc-99 Sestamibi scan (23.5 mCi of Tc-99 Sestamibi injected i.v.) and ultrasound localized a candidate adenoma to the right upper position. The patient was injected with 5.3 mCi Tc-99m Sestamibi 3 h before incision. Results A gamma probe (C-Trak Automatic System, Care Wise Medical Products) recorded in vivo counts of the right upper parathyroid (3,465) that were 160% of the background. Background counts were recorded from the resected tumor bed (2,224). A 1.4-g adenoma was identified in this location; ex vivo counts (3,226) were 150% of the background.5 Intra-operative iPTH baseline values were 176 pg/ml and 148 pg/ml, and 5- and 10-min post-resection levels were 17 pg/ml (90% drop) and 18 pg/ml (90% drop), respectively. The patient’s recovery was uncomplicated. At 1 week postoperatively, total calcium was 8.9 mg/dl and iPTH was 16 pg/ml. At 1 year, the calcium and iPTH levels were 8.7 mg/dl and 53 pg/ml, respectively. Conclusions Radio-guided minimally invasive parathyroidectomy using Tc-99 Sestamibi localization is an effective approach to hyperparathyroidism. For patients without localization, exposure of all four parathyroid glands is preferable.6,7 Surgeons should be familiar with both techniques. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734, solely to indicate this fact.     

Quick PTH assay cannot predict incomplete parathyroidectomy in patients with renal hyperparathyroidism

BACKGROUND: Contradictory reports on the value of intraoperative quick parathyroid hormone (PTH) monitoring in renal hyperparathyroidism have been published. METHODS: Thirty-five consecutive patients underwent total parathyroidectomy, central neck dissection, bilateral thymectomy, and immediate autotransplantation. PTH levels were measured by PTH assay at induction of anesthesia (baseline level) and in 5-minute intervals after excision of the last parathyroid gland. Parathyroidectomy was considered "total" in patients with PTH levels <10 pg/mL (subgroup 1), "subtotal" between 10 and 65 pg/mL (subgroup 2) and "insufficient" at >65 pg/mL (subgroup 3) within the first postoperative week. RESULTS: Fifteen minutes after excision of the last gland, PTH levels dropped to 19.4 +/- 15.7% (subgroup 1), 14.9 +/- 5.9% (subgroup 2), and 18 +/- 6.7% (subgroup 3) from baseline among 22 patients on hemodialysis, to 22.1 +/- 18.7% and 17.5% in 9 patients (subgroups 1 and 2) after successful kidney transplantation, and to 10.7% and 17.5% (subgroup 1) and 12.8% and 31.4% (subgroup 2) in 4 patients with reduced renal function after kidney transplantation. CONCLUSIONS: Currently available QPTH assays are not useful to predict insufficient resection of hyperfunctioning parathyroid tissue.     

The role of intraoperative parathyroid hormone testing in patients with tertiary hyperparathyroidism after renal transplantation

BACKGROUND: Intraoperative parathyroid hormone (PTH) testing has been shown to accurately define adequacy of parathyroid resection in patients with primary hyperparathyroidism (HPT) and alters the operative management in 10% to 15% of cases. However, the benefit of this technique in patients with tertiary HPT after renal transplantation undergoing parathyroidectomy is unclear. METHODS: Intraoperative PTH was measured in 32 consecutive patients undergoing parathyroidectomy for tertiary HPT after renal transplantation between March 2001 and November 2004 by using the Elecsys assay at baseline and, subsequently, 5, 10, and 15 minutes after curative resection. The outcomes of these patients were evaluated. RESULTS: All patients were cured after surgery. Of the 32 patients, 29 were found to have parathyroid hyperplasia, while 1 had a single adenoma and 2 had double adenomas. The average drop in intraoperative PTH levels after curative resection was 69 +/- 3.5% at 5 min., 77 +/- 2.3% at 10 minutes, and 83 +/- 3.4% at 15 minutes. PTH testing changed the intraoperative management in 5 (16%) patients. One patient with a single adenoma and 2 patients with double adenomas had a >50% drop at 10 minutes. after excision; therefore, the operation was terminated without further resection. Two patients did not have a >50% drop at 10 minutes after 3.5 gland resection. These patients were explored further, and additional supernumerary parathyroid glands were identified and resected. After resection of these additional glands, the PTH fell by >50%, indicating cure. CONCLUSIONS: In patients undergoing parathyroidectomy for tertiary HPT after renal transplantation, a decrease in intraoperative PTH levels >50% at 10 minutes after completion of the operation indicated adequate resection. Furthermore, intraoperative PTH testing altered the operative management in 16% of patients. Therefore, similar to its role in patients with primary HPT, intraoperative PTH testing appears to play an equally important role in the management of patients with tertiary HPT undergoing parathyroidectomy.     

Significance of monitoring Bio-Intact PTH (1-84) during parathyroidectomy for secondary hyperparathyroidism

BACKGROUND: The Bio-Intact PTH (1-84) assay has recently been developed to specifically measure the intact PTH (1-84) molecule, and in this study we used it to investigate sequential changes in serum Bio-Intact PTH (1-84) levels during parathyroidectomy for secondary HPT. MATERIAL AND METHODS: The subjects of this study were 70 patients (41 women, 29 men) who underwent parathyroidectomy between April 2002 and March 2005. Ethylene diamine tetraacetic acid serum samples were drawn via a peripheral venous catheter after induction of anesthesia (basal), and at 5, 10, and 30 min after diseased glands excision. Serum active PTH (1-84) was measured by the Bio-Intact PTH (1-84) assay, which is a two-site chemiluminometric assay. RESULTS: When 4 or more diseased parathyroid glands were removed, the basal of Bio-Intact PTH (1-84) level in patients without persistent HPT (52 cases) was 539 +/- 355 pg/mL. The level of the Bio-Intact PTH (1-84) at 30 min after sufficient parathyroidectomy had decreased to less than 45 pg/mL, whereas the Bio-Intact PTH (1-84) level in patients with persistent HPT at 30 min was greater than 45 pg/mL (3 cases). After removal of three or fewer diseased parathyroid glands (15 cases), the Bio-Intact PTH (1-84) at 30 min in patients without persistent HPT (13 cases) was less than 45 pg/mL. The 2 patients whose the Bio-Intact PTH (1-84) at 30 min was greater than 45 pg/mL underwent reoperation, and residual enlarged parathyroid gland in the neck was removed. CONCLUSIONS: The Bio-Intact PTH (1-84) level at 30 min after parathyroidectomy seems to be useful for judging whether the parathyroidectomy is complete irrespective of the number of glands removed from patients with secondary HPT. When only three diseased parathyroid glands are removed, the surgeon can decide whether to continue or stop neck exploration according to the level of Bio-Intact PTH (1-84) at 30 min.     

Minimally invasive video-assisted parathyroidectomy

BACKGROUND: The standard surgical procedure for parathyroidectomy consists of bilateral cervical exploration and the visualization of all four parathyroid glands. However, improved preoperative localization techniques and the availability of intraoperative intact parathyroid hormone (iPTH) monitoring now allow single adenomas to be treated with minimally invasive techniques. METHODS: Patients with primary hyperthyroidism (pHPT), who were found to have one unequivocally enlarged parathyroid gland on preoperative ultrasound and 99mTc-SestaMIBI scintigraphy underwent minimally invasive video-assisted parathyroidectomy by an anterior approach. Intraoperatively, rapid electrochemiluminescense immunoassay was used to measure iPTH levels shortly before and 5, 10, and 15 mins after excision of the adenoma. The operation was considered successful when a >50% decrease in preexcision iPTH levels was observed after 5 min. RESULTS: Between November 1999 and May 2000, 10 of 22 patients with pHPT were deemed eligible for the minimally invasive approach. In all cases, the adenoma was removed successfully. However, in two cases, intraoperative iPTH monitoring did not show a sufficient decrease in iPTH values. Subsequent cervical exploration revealed a double adenoma in one case and hyperplasia in the other. CONCLUSIONS: Even when high-resolution ultrasound and 99mTc-SestaMIBI scintigraphy are used, the presence of multiple glandular desease cannot be ruled out entirely. When the minimally invasive approach is contemplated, intraoperative iPTH monitoring is indispensible to ensure operative success. However, in selected cases, minimally invasive parathyroidectomy represents an excellent alternative to the conventional technique.     

Experienced radio-guided surgery teams can successfully perform minimally invasive radio-guided parathyroidectomy without intraoperative parathyroid hormone assays

Minimally invasive parathyroidectomy is an accepted treatment option for primary hyperparathyroidism. The need for intraoperative parathyroid hormone assays (iPTH) to confirm adenoma removal remains controversial. We studied minimally invasive radio-guided parathyroidectomy (MIRP) performed using preoperative sestamibi localization studies, intraoperative gamma detection probe, and the selective use of frozen section pathology without the use of iPTH. This is a single institution review of patients with primary hyperparathyroidism treated with MIRP by surgeons experienced in radio-guided surgery between October 1, 1998 and July 15, 2005. Information was obtained by reviewing computer medical records as well as contacting primary care physicians. Factors evaluated included laboratory values, pathology results, and evidence of recurrence. One hundred forty patients were included with a median preoperative calcium level of 11.3 mg/dL (range, 9.6-17) and a PTH level of 147 pg/mL (range, 19-5042). The median postoperative calcium level was 9.3 mg/dL. All patients were initially eucalcemic postoperatively except for one who had normal parathyroid levels. However, five (4%) patients required re-exploration for various reasons. Of the failures, one was secondary to the development of secondary hyperparathyroidism, and therefore would not have benefited from iPTH, one had thyroid tissue removed at the first operation, and three developed evidence of a second adenoma. One of these three patients had a drop in PTH level from 1558 pg/mL preoperatively to 64 pg/mL on postoperative Day 1, indicating that iPTH would not have prevented this failure. Thus, only three (2.1%) patients could have potentially benefited from the use of iPTH. MIRP was successful in 96 per cent of patients using a combination of preoperative sestamibi scans, intraoperative localization with a gamma probe, and the selective use of frozen pathology. This correlates with reported success rates of 95 per cent to 100 per cent using iPTH. We conclude that minimally invasive parathyroidectomy can be successfully performed without using iPTH assays.