Does multiple gland disease in primary hyperparathyroidism correlate with age or sex?

Purpose  Paediatric primary hyperparathyroidism (PHPT) patients suffer more often from multiple gland disease (MGD) than adults. The question occurs whether MGD in adult PHPT patients also correlates with age or sex and whether familial PHPT plays a decisive role. This is significant, as it would influence our decision for a focused approach or the bilateral cervical exploration. Materials and methods  We retrospectively analysed 465 consecutive PHPT patients who underwent surgery in our department between September 2001 and December 2008. Results  PHPT patients aged 40 years or younger suffered significantly more often from MGD than older patients (22.9% versus 11.0%). If familial PHPT disorders, which were more common in young patients, were excluded, the divergence between these two groups vanished (12.5% versus 10.0%). There was no statistical significant difference in the frequency of MGD between men (12.2%) and women (12.3%). Conclusions  If familial PHPT can be ruled out, the frequency of MGD in adult PHPT patients does not correlate with age or with sex. Therefore, age and sex do not imply specific surgical approaches in adult PHPT patients. Best of Endocrine Surgery in Europe 2009.     

Is minimally invasive parathyroidectomy reasonable in the nonuniversity setting?

BACKGROUND: Minimally invasive parathyroidectomy (MIPX) hinges on accurate preoperative localization and the intraoperative parathyroid hormone (IOPTH) assay to confirm adequate resection. Our goal was to evaluate the results of this technique when applied in a nonuniversity setting. METHODS: All patients undergoing parathyroidectomy at our institution from August 2000 until June 2005 were retrospectively reviewed. Patients were divided into 2 groups: bilateral cervical exploration versus MIPX based on adequate preoperative localization. RESULTS: There were 271 patients who underwent parathyroidectomy during the study period. Of these cases, 204 patients with primary hyperparathyroidism composed our study group. We observed that 136 patients (67%) had unilaterally positive localization studies (group 1), and MIPX was successfully completed in 52% of cases. CONCLUSIONS: Although nearly all patients with single-gland disease should be candidates for MIPX, we found that adequate preoperative imaging and concurrent thyroid disease limited successful completion of the minimally invasive procedure.     

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.     

Reoperative parathyroidectomy in 228 patients during the era of minimal-access surgery and intraoperative parathyroid hormone monitoring

Background

Reoperative parathyroidectomy (R-PTX) in primary hyperparathyroidism (1HPT) has increased failure rates and morbidity. This study evaluated R-PTX during the era of minimal-access PTX with intraoperative parathyroid hormone (IOPTH) monitoring.

Methods

Two thousand sixty-five patients with 1HPT who underwent PTX were assessed for R-PTX. Preoperative studies, operative findings, and outcomes were evaluated.

Results

Two hundred twenty-eight patients underwent 236 R-PTX procedures. Imaging performed included sestamibi (89%), ultrasound (US; 56%), computed axial tomography/magnetic resonance imaging (5%), and selective venous sampling (1%). Sestamibi was more sensitive than US (84% vs 68%). Curative surgery was performed in 89% of patients. IOPTH was 99% sensitive. There was no relationship between cure and the following parameters: preoperative calcium or PTH levels, persistent or recurrent disease, or use of IOPTH. Solitary gland disease and a single previous operation were associated with increased likelihood of cure (P = .06). Hypoparathyroidism was decreased using IOPTH monitoring (2% vs 9%). One patient had recurrent laryngeal nerve palsy.

Conclusions

R-PTX can be performed effectively with minimal complications. IOPTH is an accurate predictor of cure and may decrease the frequency of permanent hypoparathyroidism.     

Significance of rebounding parathyroid hormone levels during parathyroidectomy

Background

Using minimally invasive parathyroidectomy (MIP), most surgeons require a 50% decline in intraoperative parathyroid hormone (IoPTH) to determine cure, but the significance of IoPTH kinetics occurring after this drop remains unknown. The aim of this study was to determine the impact of IoPTH levels that first meet criteria for cure, but then increase again, or rebound, between 10 and 15 min postexcision.

Methods

We conducted a retrospective review of patients undergoing initial parathyroidectomy for primary hyperparathyroidism at our institution from 2001 to 2011. Rebound IoPTH was defined as an increase in parathyroid hormone ≥5 pg/mL after achieving the 50% drop required for cure. Comparisons were evaluated with the Student t-test, chi-square test, or Fisher exact test where appropriate.

Results

Of the 1386 patients who met selection criteria, 86 (6.2%) patients exhibited rebound IoPTH. The mean magnitude of rebound was 13.8 ± 3.6 pg/mL. Compared with those not displaying rebound, more patients with rebound IoPTH were treated with open parathyroidectomy rather than MIP (10.8% versus 4.5%, P < 0.01). The recurrence rate among those with rebound IoPTH was more than double that of the patients without rebound IoPTH (5.8% versus 2.2%, P = 0.03). Magnitude of rebound, however, did not correlate with recurrence. The rate of persistent disease was not different between those with and without rebound IoPTH. Rebound was a much better indicator of recurrence than patients whose final IoPTH levels were not within the normal range.

Conclusions

Rebound IoPTH is more common in patients who develop recurrent hyperparathyroidism. Therefore, surgeons should closely monitor patients with rebound IoPTH for disease recurrence.     

Minimally invasive endoscopic-assisted parathyroidectomy for primary hyperparathyroidism

Background: Minimally invasive surgery for primary hyperparathyroidism (pHPT) depends on both an accurate preoperative localization and the availability of intraoperative parathyroid hormone monitoring. Methods: Patients with sporadic pHPT and one unequivocally enlarged parathyroid gland on preoperative imaging underwent endoscopic-assisted parathyroidectomy. Intraoperative rapid parathyroid hormone (quick PTH) monitoring was performed, and surgical success was confirmed when there was a >50% decrease in quick PTH level 10 min after excision as compared with the baseline level at induction. The surgical outcome and the use of preoperative localization, together with the role played by quick PTH assay in enhancing the operative success, were evaluated. Results: From 1999 to 2002, 66 of 107 patients (62%) were selected for this approach. The accuracy of ^99mTc-Sestamibi scintigraphy and ultrasonography was 97% and 70%, respectively. Conversion was required in four cases due to technical problems, and four additional patients failed to show a significant decline in quick PTH levels postexcision. Two patients underwent cervical exploration without the finding of any additional pathology, and another two patients had a delayed drop in quick PTH that was confirmed 30 min postexcision. All patients had a solitary adenoma and were cured of hypercalcemia during a median follow-up of 9 months. Conclusions: Minimally invasive endoscopic-assisted parathyroidectomy can be performed expeditiously in a select group of patients based on ^99mTc-Sestamibi scintigraphy. The use of quick PTH assay can ensure surgical success, but careful interpretation of the results is mandatory.     

Relationship between parathyroid gland size and responsiveness to maxacalcitol therapy in patients with secondary hyperparathyroidism.

BACKGROUND: Although vitamin D has been reported to be useful in the treatment of patients with secondary hyperparathyroidism, it is not effective in some of them. The goal of this study was to see whether a relationship could be found between maxacalcitol responsiveness and parathyroid gland size. METHODS: Parathyroid gland size was measured by ultrasonography in 25 patients with secondary hyperparathyroidism [serum intact parathyroid hormone (PTH) >300 pg/ml, 58.1 +/- 2.8 years old, 15 males and 10 females], who were treated with maxacalcitol. Patients were divided into two groups according to the mean value of the maximum diameter of the glands: group S with a diameter <11.0 mm and group L with a diameter >or =11.0 mm. Between the two groups there were no significant differences in serum intact PTH, calcium or phosphate level or duration of haemodialysis. RESULTS: Mean (+/- SE) maximal diameter of detectable parathyroid glands was 11.0 +/- 0.7 mm before treatment. At 4-24 weeks after administration of maxacalcitol, intact PTH concentrations decreased significantly in group S (from 546 +/- 39 to 266 +/- 34 pg/ml at 24 weeks; P < 0.01), but did not significantly change in group L (from 481 +/- 39 to 403 +/- 49 pg/ml at 24 weeks). At 24 weeks after maxacalcitol administration, the number of detectable parathyroid glands was significantly decreased in group S (from 2.2 +/- 0.3 to 1.8 +/- 0.4; P < 0.05), but not in group L. Serum calcium increased significantly in group L (from 9.6 +/- 0.2 to 10.2 +/- 0.3 mg/dl; P < 0.05), but not in group S. There was a significant correlation between reduction in PTH and parathyroid gland size (r = -0.42, P < 0.05). CONCLUSIONS: These results indicate that the responsiveness to maxacalcitol therapy of secondary hyperparathyroidism is dependent on parathyroid gland size and that the simple measurement of maximum parathyroid gland diameter by ultrasonography may be useful for predicting responsiveness to maxacalcitol treatment.     

Parathyroidectomy for primary hyperparathyroidism: A retrospective analysis of localization,surgical characteristics,and treatment outcomes

ObjectiveTo evaluate parathyroidectomy for primary hyperparathyroidism (PHPT) regarding localization, surgical characteristics, and treatment outcomes.MethodsSeventy-eight patients who underwent parathyroidectomy for PHPT were retrospectively reviewed. The results were analyzed according to intraoperative localization technique (IOLT), intraoperative parathyroid hormone (IOPTH) monitoring, and intraoperative nerve monitoring (IONM). The localization accuracy of ultrasonography (US), computed tomography (CT), and single-photon emission computed tomography (SPECT)-CT with sestamibi Tc99m was evaluated.ResultsParathyroidectomy was successfully completed in all 78 patients, achieving 100% surgical cure. For 60 patients with IOPTH monitoring, 10-min IOPTH decreased >50% from baseline in 57 (95.0%), and they achieved surgical cure. In the remaining three (5.0%) patients with ≤50% decrease in 10-min IOPTH, 20-min IOPTH decreased >50% from baseline in two (3.3%) patients, achieving surgical cure without additional neck exploration. There were no differences in surgical cure and complications as a function of IOLT use or IOPTH monitoring. Operating time was significantly shorter with IOLT and IOPTH monitoring than without (IOLT: 70.9 min vs. 88.0 min, p = 0.013; IOPTH: 74.9 min vs. 91.9 min, p = 0.037). All 78 patients had adenoma including one patient with a double adenoma. Vocal cord paralysis was not observed in our series, regardless of IONM. US, CT, and SPECT-CT localized the pathological parathyroid gland accurately in 88.1%, 85.5%, and 86.8% of patients, respectively (p = 0.894).ConclusionThe surgical outcomes of parathyroidectomy for PHPT were excellent regardless of IOLT and IOPTH monitoring. However, these techniques can maximize the performance of parathyroid surgery by reducing operating time and rescuing challenging cases.     

Benefits of surgeon-performed ultrasound for primary hyperparathyroidism

Background  Focused, minimally invasive parathyroidectomy (MIP) is widely accepted when preoperative imaging localizes a single parathyroid adenoma. Many surgeons use ^99mTc-sestamibi scintigraphy (MIBI) +/−, a cervical ultrasound for preoperative localization. We propose that surgeon-performed ultrasound (SUS) is the only imaging modality required in most patients with primary hyperparathyroidism (pHPT), resulting in patient convenience and reduced cost. Materials and methods  Since July 2006, patients with pHPT underwent MIP based solely on a positive SUS. Intraoperative parathyroid hormone assay was used to determine the extent of operation. A retrospective review from July 2006 through December 2008 identified 160 patients who underwent parathyroidectomy after SUS on their initial office visit. Results  SUS correctly identified an enlarged parathyroid gland in 119/160 (74%) patients. In 41 patients, SUS was the only localizing study. MIBI was done in 119 patients. In 54 patients, SUS confirmed the MIBI, and in 28 patients with a negative MIBI, SUS was positive. In the 41 patients with a negative SUS, an MIBI was positive in ten. Ninety-eight patients had MIP. Theoretically, 85 MIBIs were unnecessary because of a positive SUS corresponding to a potential cost savings of at least $90,000. Conclusion  SUS to localize parathyroid adenomas is accurate and facilitates MIP. It provides substantial cost savings and patient convenience and should be the first diagnostic procedure performed for patients suspected to have pHPT. MIBI can be reserved for those patients in whom ultrasound has failed to localize a parathyroid gland. Best of endocrine surgery in Europe 2009.     

Effect of parathyroid hormone on serum magnesium levels: the neglected relationship in hemodialysis patients with secondary hyperparathyroidism

Chronic kidney disease–mineral and bone disorder (CKD–MBD) is an important complication in patients with end-stage renal disease. Since recent studies have shown that magnesium (Mg) disturbance plays an important role in CKD–MBD and cardiovascular mortality, the interest on magnesium has grown recently. Although much concern focused on the effect of Mg on parathyroid hormone (PTH) levels, however, the influence of PTH on serum Mg levels is nearly unexplored. To evaluate the effect of PTH on serum Mg levels, we first described the relationship between serum Mg and PTH in secondary hyperparathyroidism. Besides, we also monitored the changes of serum Mg concentration after parathyroidectomy (PTX) in 23 patients. In our study, we found that hypermagnesemia (>2.5?mg/dL) occurred in up to 44% of cases and hypomagnesemia did not present. No statistically signi?cant correlations were found between serum Mg levels and PTH (r?=??0.143, p?=?0.134). Correlation analysis and regression analysis suggested that the derangement of magnesium homeostasis was consistent with the derangement of calcium/phosphorus homeostasis. However, after PTX, serum magnesium levels dropped immediately after the surgery, minimally at the first day and gradually restored from the third day. The changes of serum Mg after surgery was positive correlated with the changes of serum phosphate (r?=?0.558, p?=?0.003). Taken altogether, our data suggested that the therapeutic strategies to achieve optimum serum magnesium levels in CKD-MBD should take into account the varying stages of disease development since PTH could also influence magnesium metabolism and this problem might be important in severe secondary hyperparathyroidism.     

Intraoperative total serum calcium levels,unlike intraoperative intact PTH levels,do not correlate with cure of hyperparathyroidism

BACKGROUND: Intraoperative intact parathyroid hormone (iPTH) monitoring is useful in the operative management of hyperparathyroidism. Recent studies suggest that measurement of intraoperative total serum calcium (TSC) levels may be a more cost effective and readily available method of intraoperative guidance during neck dissection than iPTH levels, the gold standard. We compared the accuracy of intraoperative TSC to iPTH in predicting surgical cure during parathyroidectomy. PATIENTS AND METHODS: From September 1, 2001 to October 31, 2002, 88 parathyroidectomies were performed. iPTH and TSC were measured at the start of the operation, and at 5 and 10 min after gland removal. Data were compared, and trends were analyzed with respect to removal of abnormal parathyroid tissue as confirmed by pathology. One-way analysis of variance was used to determine if decreases in TSC were significant. RESULTS: The mean baseline iPTH level (418 +/- 610 pg/ml) dropped by 70% 5 min after removal of the abnormal glands (86 +/- 102 pg/ml) and by 85% at 10 min (39 +/- 39 pg/ml). The mean baseline TSC level (10.0 +/- 0.8 mg/dl) dropped by 4% at 5 min after removal of the abnormal glands (9.6 +/- 0.9 mg/dl) and remained at 4% at 10 min (9.6 +/- 0.8 mg/dl). iPTH dropped by > or =50% in 73 patients (83%) at 5 min and in 87 patients (99%) at 10 min after gland resection. TSC decreased below baseline at 5 min and remained below baseline at 10 min in only 47 patients (54%). In the remaining patients, intraoperative TSC changes were less predictable and did not respond consistently to resection of abnormal glands. CONCLUSIONS: The decreases in TSC during parathyroidectomy, if present, are minimal. Unlike iPTH levels, TSC levels do not consistently decrease at 5 and 10 min after gland resection. While attractive in terms of cost and availability, intraoperative TSC levels are not clinically reliable in confirming removal of abnormal parathyroid tissue.     

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.     

Surgery for patients with primary hyperparathyroidism and negative sestamibi scintigraphy—a feasibility study

Background  We report the surgical treatment of a consecutive series of scan negative patients with the intention of unilateral parathyroid exploration with the aid of intraoperative quick PTH (qPTH). Materials and methods  The study included 35 consecutive sestamibi scan negative patients (27 women, eight men) with sporadic pHPT subjected to first time surgery. Median age was 70 years and median preoperative calcium level 2.8 mmol/L. Results  Thirty-three patients had a histological diagnosis of a parathyroid adenoma (median weight 0.48 g [range 0.12 g–2.5 g]). Nineteen patients were explored bilaterally and 16 patients (46%) were operated unilaterally. The median operation time was 40 min in the unilateral group and 95 min in the bilateral group (p < 0.001). Three patients were treated for postoperative hypocalcemia after bilateral exploration versus none in the unilateral group (p = 0.23). With a minimum of 12 months of follow-up, 33 patients (94.3%) were cured. One case of recurrent HPT presented after bilateral exploration with visualization of four glands. One case of persistent HPT was observed after unilateral exploration. qPTH was predictive of operative failure in both patients. Conclusion  Forty-six percent of the patients in our study could be operated unilaterally with a total cure rate of 94%. Patients in the unilateral group had a significant shorter operation time and a lower incidence of postoperative hypocalcemia. In conclusion our investigation shows that limited parathyroid exploration can safely be performed on patients with negative sestamibi scintigraphy by the aid of qPTH. Best of Endocrine Surgery in Europe 2009