Minimally invasive parathyroidectomy without intraoperative parathyroid hormone monitoring in patients with primary hyperparathyroidism

BACKGROUND: Minimally invasive parathyroidectomy (MIP) is the preferred operation for patients with primary hyperparathyroidism (HPT) and positive preoperative imaging. This non-randomized case series assessed the long-term results of MIP performed without the use of intraoperative parathyroid hormone (ioPTH) monitoring. METHODS: The study involved prospective collection of demographic, biochemical and operative details on a consecutive, unselected cohort of 298 patients who underwent surgery for non-familial primary HPT during a 5-year interval. The mean preoperative serum calcium level was 3.00 mmol/l with a mean parathyroid hormone concentration of 25.8 pmol/l. (99m)Tc-labelled sestamibi scanning and neck ultrasonography were performed in 262 patients. RESULTS: Sestamibi scan showed unilateral uptake in 182 patients and a single parathyroid adenoma was confirmed on ultrasonography in 161 patients. MIP was performed in 150 patients. The mean duration of operation was 25 (range 8-65) min. Four patients needed conversion to conventional neck exploration. There was one postoperative haematoma and three cases of temporary recurrent laryngeal nerve neuropraxia. All but four patients were normocalcaemic after MIP. All the parathyroid tumours removed were adenomas, with a mean weight of 1.3 (range 0.1-17.4) g. No patient developed recurrent HPT after a median follow-up of 16 (range 3-48) months. CONCLUSION: The outcome of MIP without ioPTH monitoring was comparable to that reported in series that used ioPTH monitoring.     

Intraoperative parathyroid hormone levels dynamics of cured patients with impaired renal function following parathyroidectomy for primary hyperparathyroidism

BackgroundIntraoperative parathyroid hormones have been used to establish operative success in patients with primary hyperparathyroidism. This study’s aim was to assess the impact of estimated glomerular filtration rate and serum creatinine levels on the fulfillment of >50% drop and normalization of intraoperative parathyroid hormone levels.MethodsPatients successfully treated for primary hyperparathyroidism were analyzed. The samples for parathyroid hormone were collected at baseline, 5-, 10-, and 30-minutes postexcision. The patients were classified as follows: (1) estimated glomerular filtration rate >60 mL/min, (2) estimated glomerular filtration rate <60 mL/min and serum creatinine levels <1.2 mg/dL, and (3) estimated glomerular filtration rate <60 mL/min and serum creatinine levels >1.2 mg/dL. Comparative analysis of patients achieving the >50% parathyroid hormone drop criterion and normalization of intraoperative parathyroid hormone was performed.ResultsOne hundred-fourteen patients were distributed as follows: 88 patients (77.2%), 14 (12.3%), and 12 (10.5%) for groups 1, 2 and 3, respectively. No difference between groups in the proportion of patients fulfilling the >50% parathyroid hormone drop criterion was found. An abnormally elevated intraoperative parathyroid hormone level at 30-minute postexcision was observed in 0, 14.3, and 16.6% in groups 1, 2, and 3, respectively (P ≤ .0001).ConclusionIn the study, >50% parathyroid hormone drop criterion was equally achieved despite normal or reduced estimated glomerular filtration rate. When serum creatinine levels increased >1.2 mg/dL and estimated glomerular filtration rate declined <60 mL/min, the likelihood of reaching normal intraoperative parathyroid hormone levels postexcision was significantly lower.     

Comparison of parathyroid hormone levels from the intact and whole parathyroid hormone assays after parathyroidectomy for primary and secondary hyperparathyroidism

BACKGROUND: Most commercial intact parathyroid hormone (intact PTH) assays cross-react with non-(1-84) PTH (likely 7-84 PTH). Using a whole-molecule PTH (whole PTH) assay that specifically measured only 1-84 PTH, we compared the kinetics of whole PTH and intact PTH after parathyroidectomy in patients with primary hyperparathyroidism (HPT) and secondary HPT. METHODS: This study comprised 74 patients with primary HPT caused by a single adenoma and 18 patients with secondary HPT who underwent parathyroidectomy. Blood samples were drawn after anesthesia, just before excision of a single adenoma in primary HPT, and just before excision of the last parathyroid gland in secondary HPT, and at 5, 10, and 15 minutes after excision. The 7-84 PTH level was calculated by subtracting the whole PTH value from the intact PTH value. RESULTS: There was a difference between the percentage of 7-84 PTH/intact PTH in plasma samples from patients with primary HPT and secondary HPT (28%+/-12% vs 35%+/-9%; P<.05). Plasma whole PTH decreased more rapidly than intact PTH after parathyroidectomy in patients in both the primary HPT (P<.0001) and secondary HPT groups (P<.0001). Decline of intact PTH was slower in patients with secondary HPT than in patients with primary HPT; however, there was no significant difference in the decline of whole PTH between the 2 groups. CONCLUSIONS: The quick intact PTH assay is not used frequently during surgery in patients with secondary HPT; however, our results suggest that a quick whole PTH assay may be a more useful adjunct to parathyroidectomy in both secondary HPT and primary HPT.     

Reassessment of parathyroid hormone monitoring during parathyroidectomy for primary hyperparathyroidism after 2 preoperative localization studies

HYPOTHESIS: For patients with primary hyperparathyroidism and patients with 2 localization studies showing the same single location of parathyroid disease, use of intraoperative parathyroid hormone (IOPTH) measurement does not significantly increase the success of minimally invasive parathyroidectomy. DESIGN: Retrospective cohort study. SETTING: Experience of 2 academic centers over 5 years (at Brigham and Women's Hospital, Boston, Mass) and almost 4 years (at Rhode Island Hospital, Providence). PATIENTS: A total of 569 patients with primary hyperparathyroidism who underwent technetium Tc 99m sestamibi (MIBI) parathyroid imaging and neck ultrasonography (US). MAIN OUTCOME MEASURES: Incidence of correct prediction of location and extent of disease. RESULTS: In 322 patients (57%), MIBI and US imaging identified the same single site of disease. In 319 (99%) of these 322 patients, surgical exploration confirmed a parathyroid adenoma at that site, and the IOPTH levels normalized on removal. In 3 (1%) of the 322 patients, IOPTH measurement identified unsuspected additional disease. In 3 (1%) of the remaining 319 patients, IOPTH-guided removal of a single adenoma failed to correct hypercalcemia. Therefore, the failure rate of surgery in patients with positive MIBI and positive US imaging was 1% with IOPTH measurement and 2% without IOPTH measurement (P = .50). In 201 (35%) of the 569 patients, only 1 of the 2 studies recognized an abnormality or the studies disagreed on location. In these cases, either MIBI imaging or US imaging (if MIBI imaging was negative) failed to predict the correct site or extent of disease in 76 (38%) of the 201 patients (P<.001 vs concordant studies). CONCLUSIONS: In primary hyperparathyroidism, concordant preoperative localization with MIBI and US imaging is highly accurate. Use of IOPTH measurement in these cases adds only marginal benefit. When only 1 of the 2 studies identifies disease or the studies conflict, however, IOPTH measurement remains essential during minimally invasive parathyroidectomy.     

Effects of propofol on intraoperative parathyroid hormone monitoring in patients with primary hyperparathyroidism undergoing parathyroidectomy: a randomized control trial

Purpose

Serial measurements of parathyroid hormone (PTH) serum concentrations aid parathyroidectomy surgery. There are concerns that propofol may increase PTH concentrations and/or interfere with PTH assays. The primary purpose of this study is to determine the effects of propofol on PTH concentrations in patients with primary hyperparathyroidism and to determine its effect on PTH assays.

Methods

Thirty patients with primary hyperparathyroidism were assigned randomly to induction and maintenance with either propofol or sevoflurane. Blood samples for PTH assays were obtained pre-induction, immediately after induction, ten minutes after induction, and after excision of parathyroid adenoma. The primary endpoint was the PTH concentration at ten minutes after induction. This endpoint was compared between groups using analysis of covariance adjusting for pre-induction PTH. An in vitro study was performed with four different pools of PTH concentrations that were spiked with increasing concentrations of propofol. Serum PTH was measured in duplicate in each sample and analyzed using repeated measures analysis of variance.

Results

At ten minutes after induction, PTH concentrations did not differ significantly between groups (least square mean difference ?7.0 pg·mL^?1; 95% confidence interval, ?34.2 to +20.2). The PTH level in vitro did not change significantly with increasing propofol concentrations.

Discussion

Parathyroid hormone concentrations in patients with primary hyperparathyroidism were not affected by the type of anesthesia (propofol vs sevoflurane). Furthermore, propofol was found not to interfere with PTH assays at clinically relevant concentrations. There is no evidence to support the avoidance of a propofol anesthetic for parathyroid surgery.     

Successful minimally invasive parathyroidectomy for primary hyperparathyroidism without using intraoperative parathyroid hormone assays

BACKGROUND: The need for intraoperative parathyroid hormone (iPTH) assays in minimally invasive parathyroidectomy (MIP) remains controversial. We report the results of MIP performed without the use of iPTH assays. METHODS: This was a single-institution retrospective review of patients with primary hyperparathyroidism treated with MIP between October 1, 1998, and December 31, 2002. RESULTS: Seventy-seven patients were studied. The mean preoperative calcium level was 11.4 mg/dL. All patients had a normal calcium level postoperatively (range, 7.4-10.2 mg/dL, mean, 9.1 mg/dL). Three patients (4%) required re-exploration for various reasons including the development of a second adenoma, secondary hyperparathyroidism, and discordant pathology. All 3 patients initially were eucalcemic. CONCLUSIONS: Our success rate of 96% using a combination of preoperative sestamibi scans, intraoperative gamma probe localization, and selective frozen pathology is consistent with the published success rates using iPTH assays of 95% to 100%. We conclude that MIP can be performed successfully without using iPTH assays.     

Intact parathyroid hormone in primary hyperparathyroidism

In 49 patients with primary hyperparathyroidism, intact parathyroid hormone (PTH) was measured with a recently developed immunoradiometric assay, and midregional PTH fragments (sequence 44-68) were measured with an established radioimmunoassay technique. In 47 normal subjects, the concentration of intact PTH ranged from 2.0 to 6.8 pmol/l, and in 49 patients with primary hyperparathyroidism it ranged from 6.4 to 80.0 pmol/l. In contrast, midregional PTH fragments were normal in seven of 49 patients with primary hyperparathyroidism. In five healthy controls and in 12 patients with surgically confirmed primary hyperparathyroidism and serum calcium levels below 3.0 mmol/l, a rapid calcium loading test was performed. In healthy controls, intact PTH was in the low normal to subnormal range within 2.5-5.0 min, and had recovered within 15 min of calcium infusion. In patients with primary hyperparathyroidism, the calcium infusion also led to a 30-50 per cent decrease in intact PTH levels within 5.0-7.5 min after injection, with a slow recovery after 10-15 min. In six of the patients with only slightly elevated basal intact PTH, a suppression to the normal range was observed. In 24 patients (16 patients with a solitary adenoma and eight patients with four-gland hyperplasia) the intact PTH levels were followed intraoperatively during parathyroidectomy, revealing a significantly different rate of decline for single adenomas compared with hyperplasia during the first 15 min after removal of the primary enlarged gland. Intact PTH values remained constantly elevated in one patient with primary hyperparathyroidism and an unsuccessful neck exploration. These results confirm that (a) the measurement of intact PTH in patients with primary hyperparathyroidism is superior to the measurement of midregional fragments; (b) PTH secretion in primary hyperparathyroidism is not totally autonomous; and (c) intraoperative monitoring of intact PTH values could be used to monitor the success of surgery.     

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

Background

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

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.     

Decrease in serum uric acid level following parathyroidectomy in patients with primary hyperparathyroidism

Serum uric acid levels in 101 patients with surgically treated hyperparathyroidism were studied retrospectively. Twenty-five patients had preoperative hyperuricemia and 8 patients had a history of gout. Preoperatively the serum uric acid level correlated positively with the blood urea nitrogen and serum creatinine levels, but not with serum immunoreactive parathyroid hormone or calcium levels. Following parathyroidectomy the serum uric acid level decreased from a preoperative level of 6.55±0.18 mg/100 ml (mean±S.E.) to 6.05±0.21 mg/100 ml at 1 week to 1 month postoperatively, and the uric acid level remained decreased at 6–18 months postoperatively (5.22±0.31 mg/100 ml). Patients with the highest serum uric acid level seemed to improve most.

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Resumen La asociación entre la hiperuricemia y el hiperparatiroidismo ha sido observada por muchos investigadores desde su descripción original en 1961 por Mainz. Sinembargo, la causa de la hiperuricemia en pacientes hiperparatiroideos, y si los niveles séricos de ácido úrico mejoran después de una paratiroidectomía exitosa, siguen siendo motivo de controversia. Los niveles séricos de ácido urico en 101 pacientes con hiperparatiroidismo tratado quirùrgicamente fueron estudiados en forma retrospectiva. Veinticinco pacientes presentaban hiperuricemia preoperatoria y 8 tenían historia de gota. Preoperatoriamente se observé correlación entre el nivel de ácido úrico y los niveles de nitrógeno ureico sanguíneo y de creatinina, pero no con los nivelés de hormona paratiroidea inmunorreactiva o de calcio. Después de la paratiroidectomía el nivel de ácido urico sérico decreció de un valor preoperatorio de 6.55±0.18 mg/100 ml (promedio±DE) a 6.05±0.21 mg/100 ml entre 1 semana y 1 mes postoperatorios, y el nivel disminuído de ácido úrico se mantuvo a los 6 y a los 18 meses postoperatorios (5.22 ±0.31 mg/100 ml). Los pacientes con los más elevados nivelés de ácido urico aparentemente son los que mayormente se benefician.

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Résumé Les taux d'acide urique dans le sérum ont été étudiés rétrospectivement chez 101 malades qui avaient été traités pour hyperparathyroïdisme. Vingt-cinq d'entre eux présentaient une hyperuricémie préopératoire et 8 des antécédents de goutte. Avant l'intervention existait une corrélation entre le taux d'acide urique sérique et ceux de l'urée sanguine et de la créatinine sérique mais la corrélation faisait défaut avec le taux de l'hormone parathyroïdienne et le calcium. Après la parathyroïdectomie le taux de l'acide urique s'est abaissé de 6.55±0.18 mg/100 ml (moyenne±S.E.) à 6.05±0.21 mg/100 ml de une semaine à un mois après l'intervention puis il est resté bas de 6 à 18 mois après l'intervention (5.22±0.31 mg/100 ml). Les malades qui ont le taux d'acide urique sérique le plus élevé semblent les plus améliorés après l'intervention.

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Presented at the International Association of Endocrine Surgeons in Paris, September 1985.

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Supported in part by the Medical Research Service of the Veterans Administration Medical Center.     

Parathyroid carcinoma arising on transplanted parathyroid tissue after total parathyroidectomy for renal hyperparathyroidism

Parathyroid carcinoma usually develops in association with primary hyperparathyroidism. Only 18 cases have been reported in patients with secondary or tertiary renal hyperparathyroidism. We present a case of parathyroid carcinoma arising on transplanted parathyroid tissue after total parathyroidectomy for renal hyperparathyroidism.     

Muscle strength is improved after parathyroidectomy in patients with primary hyperparathyroidism.

Fatigue and muscular weakness are prevalent symptoms in patients with primary hyperparathyroidism. This study examined muscular strength before and after operation in a group of eight patients with hyperparathyroidism and in a control group of seven patients with benign thyroid lesions. The maximum power grip, pronation and supination, and endurance for the same muscular movements, were studied by means of a computer program. Patients with hyperparathyroidism had impaired muscular strength compared with the controls but 12 months after operation a significant improvement of all muscular performance was observed. No such improvement was detectable among the controls. There was no correlation between the levels of serum calcium and parathyroid hormone and the measurements recorded before and after operation. Muscular impairment in hyperparathyroidism is measurable by an objective technique. Improvement occurs after surgery.     

Impact of hypercalcemia and parathyroid hormone level on the sensitivity of preoperative sestamibi scanning for primary hyperparathyroidism

Technetium 99m sestamibi scanning (MIBI) can direct unilateral parathyroidectomy. However, the clinical application remains variable with sensitivities ranging from 55 to 100 per cent. We examined whether patient factors including serum calcium (Ca) and parathyroid hormone (PTH) levels impact the sensitivity of MIBI. We completed a retrospective review of 102 patients with primary hyperparathyroidism and mild hypercalcemia who underwent preoperative MIBI. All patients underwent bilateral neck explorations with abnormalities confirmed by histopathology. MIBI sensitivity was correlated with preoperative Ca and PTH levels using univariate and logistic regression analysis. The mean preoperative Ca was 11.0 mg/dL and the mean PTH was 158 pg/mL. More than 95 per cent of patients with Ca greater than 11.3 mg/dL had a positive scan as compared with 60 per cent of those with lesser values (P = 0.0024). Similarly a serum PTH level greater than 160 pg/mL correlated with positive scans in 93 per cent as opposed to 57 per cent in those with lower levels (P = 0.006). Using a scan-directed approach 65 of 74 patients would have undergone unilateral exploration; this would yield a 7.7 per cent operative failure rate because of contralateral multigland disease. Lower Ca and PTH levels seem to correlate with reduced sensitivity of MIBI. Increasing acceptance of surgery for hyperparathyroidism with minimal hypercalcemia may make MIBI less attractive without ancillary diagnostic measures such as rapid parathormone assays.     

Normocalcemia with elevated parathyroid hormone levels after surgical treatment of primary hyperparathyroidism

BACKGROUND: Thirty percent of patients who undergo successful parathyroidectomy for primary hyperparathyroidism show unexplained elevated postoperative serum parathyroid hormone (PTH) levels despite normocalcemia. METHODS: PTH levels were measured monthly in 97 patients for 6 months after parathyroidectomy. Renal function, 25-OH-vitamin D levels, serum alkaline phosphatase levels, osteocalcin, and bone densitometry were evaluated before and 6 months after surgery. PTH reactivity to calcium loading was tested at the sixth month. RESULTS: Thirty patients had elevated PTH levels despite normocalcemia after parathyroidectomy. Before surgery, these 30 patients had higher PTH and creatinine levels, lower vitamin D levels, and more extensive bone involvement than those with normal postoperative PTH levels. In patients with normal renal function and normal vitamin D levels, postoperative PTH values correlated with preoperative PTH levels but not with bone disease. CONCLUSION: In most cases, elevated PTH levels after surgery is an adaptive reaction to renal dysfunction or vitamin D deficiency. If no adaptive cause can be found, persistent hyperparathyroidism must be suspected.     

Prospective study of parathyroid graft function in patients with renal hyperparathyroidism after total parathyroidectomy and heterotopic autotransplantation by measurement of the intact parathyroid hormone concentrations in both antecubital veins.

OBJECTIVE: Evaluation of the value of gradients for intact parathyroid hormone after total parathyroidectomy and heterotopic autotransplantation for renal hyperparathyroidism. DESIGN: Prospective long-term follow-up study. SETTING: Teaching hospital, Germany. SUBJECTS: A total of 115 patients operated on for renal hyperparathyroidism between 1 August 1987 to 15 August 1997. INTERVENTIONS: 100/115 had total parathyroidectomy with autotransplantation. MAIN OUTCOME MEASURES: Analyses of serum calcium, alkaline phosphatase, and intact parathormone in serum 1, 4, 8, 12, 18 and 24 months postoperatively and annually thereafter. Parathormone gradients were calculated as the ratio of the parathormone concentrations in the antecubital venous blood of the grafted and the non-grafted arm. RESULTS: During follow-up (mean 32 months, range 1 month to 9 years), 111 of the 115 patients had one to 10 re-examinations (mean: 4) and in the patients who had had total parathyroidectomy with autotransplantation a total of 437 gradients could be calculated, 91% of which were < or =20. Postoperative hypocalcaemia caused by calcium deficiency of the skeleton led to an increase in parathormone secretion and gradients. Increasing parathormone gradients during follow-up as a result of excessive parathormone secretion in the grafted-arm indicated graft-dependent recurrence. In 6 of the 9 patients with graft-dependent recurrences the gradients exceeded 20. CONCLUSION: The combined sequential assessment of gradients for intact parathyroid hormone and of serum calcium concentrations permits objective evaluation of parathyroid graft function.