Less-than-subtotal parathyroidectomy increases the risk of persistent/recurrent hyperparathyroidism after parathyroidectomy in tertiary hyperparathyroidism after renal transplantation.

BACKGROUND: The optimal surgical approach for tertiary hyperparathyroidism (HPT) after kidney transplantation is unknown. Existing studies are limited by small sample size, lack of adjustment for kidney function, and no long-term follow-up. METHODS: We retrospectively analyzed 74 patients with tertiary HPT who underwent parathyroidectomy at two centers since 1978. Persistent HPT was defined as parathyroid hormone (PTH) concentrations in excess of the K/DOQI target range for the corresponding estimated creatinine clearance (eCrCl). RESULTS: Seventy-four patients had 83 operations (72 subtotal and 11 less-than-subtotal parathyroidectomies). Mean follow-up time was 5.4 +/- 4.7 years. Calcium concentrations decreased significantly after parathyroidectomy (2.83 vs 2.28 mmol/L, P < 0.001), as did eCrCl (54.5 vs 44.9 mL/min, P < 0.001) and PTH (382 vs 132 pg/mL, P < 0.001). In the multivariable regression analysis, only the type of operation and postoperative eCrCl were significantly correlated with PTH at follow-up. A limited parathyroidectomy was associated with a fivefold increase in risk of persistent or recurrent hyperparathyroidism. CONCLUSIONS: The use of limited parathyroidectomy for tertiary HPT after kidney transplantation has a higher risk of persistent/recurrent HPT. Subtotal parathyroidectomy is recommended for patients with tertiary HPT.

Long-term results of less than total parathyroidectomy for hyperparathyroidism in multiple endocrine neoplasia type 1.

BACKGROUND: Our aim was to assess long-term results after less than total parathyroidectomy for hyperparathyroidism in multiple endocrine neoplasia type 1. METHODS: Of 1888 patients undergoing operation at our institution for primary hyperparathyroidism between 1972 and 2001, 83 (4.4%) had multiple endocrine neoplasia type 1. Outcome data were available for 79; 66 underwent subtotal parathyroidectomy, 55 (83%) of these with bilateral thymectomy. In 13 patients, only grossly enlarged glands were resected (mean 1.1 per patient) as the syndrome of multiple endocrine neoplasia type 1 was not yet evident or the initial exploration was performed elsewhere. RESULTS: Follow-up has been 48 +/- 51 months (mean + SD). Intraoperative serum PTH assay decay in 20 patients was suggestive of cure in 18 patients, none of whom required reoperation. Nine patients (11%) required reoperation (3 required reoperation twice) after a mean interval of 77 +/- 53 months. Subtotal parathyroidectomy resulted in a lesser reoperation rate than resection of grossly enlarged glands (7% vs 30%, P =.02). At the time of review, 63 patients (80%) were normocalcemic, 10 (13%) hypocalcemic (2 after unsuccessful delayed autograft), and 7% hypercalcemic (none after reoperation). By Kaplan-Meier analysis, the rate of surgical cure (patients who are nonhypercalcemic) is 60% and 51% at 10 and 15 years, respectively. CONCLUSION: Subtotal parathyroidectomy reduces the need for reoperation. Selective reoperation leads to long-lasting biochemic cure.

Accuracy of intra-operative PTH measurement during subtotal parathyroidectomy for tertiary hyperparathyroidism after renal transplantation.

BACKGROUND AND AIMS: Intra-operative parathyroid hormone (IOPTH) results are not known in the setting of tertiary hyperparathyroidism (HPT) after renal transplantation. MATERIALS AND METHODS: A retrospective analysis of 35 tertiary HPT patients who all underwent subtotal parathyroidectomy and IOPTH monitoring was conducted. RESULTS: The mean follow-up time was 2.2+/-1.4 years. Thirty-four patients were cured; one patient (2.8%) had a persistent disease and was cured after reoperation. Median parathyroid hormone (PTH) (median percent decrease from highest) at baseline and at 5, 10, 20, and 30 min were 244, 78 (69%), 63 (75%), 53 (79%), and 49 pg/ml (83%), respectively. Four patients who were cured had a decrease of <50% at 5 min and two of them had a decrease of <50% at 10 min. The patient with persistent disease had a decrease of >50% at 10 min. The sensitivity of the test was 94% at 10 min using the Miami criteria. CONCLUSION: This study shows that IOPTH in tertiary hyperparathyroidism has a high sensitivity. However, because of the low risk of persistent hyperparathyroidism when a subtotal parathyroidectomy is performed, its potential impact on the overall success rate is very small. We therefore do not recommend the routine use of IOPTH in tertiary hyperparathyroidism.

Is surgery beneficial for MEN1 patients with small (< or = 2 cm), nonfunctioning pancreaticoduodenal endocrine tumor? An analysis of 65 patients from the GTE.

BACKGROUND: The management of small, nonfunctioning pancreaticoduodenal endocrine tumors (NFPET) in multiple endocrine neoplasia type 1 (MEN1) patients is still controversial. We therefore investigated the effect of surgery on survival and tumor progression in MEN1 patients with NFPET < or = 2 cm by analyzing data from the Groupe des Tumeurs Endocrines (GTE) registry. MATERIALS AND METHODS: Among 579 MEN1 patients in the registry, 65 had NFPET < or = 2 cm. Fifteen (23%) underwent pancreatectomy, 9 at least segmental pancreatectomies and 6 biopsies or enucleations (the surgery group), and 50 (77%) were followed conservatively (the no surgery group). Age at MEN1 and NFPET diagnosis was similar in both groups, as was size of the primary tumor. Seven (10.8%) patients had metastases. Five metastases were synchronous, and 2 (one in each group) were metachronous. Tumor size was similar in patients with or without metastasis. RESULTS: There was no perioperative mortality. The average follow-up time after NFPET diagnosis was 6.7 years in the surgery group and 3.3 years in the no surgery group. Three (4.6%) patients died during follow-up, 2 due to NFPET and 1 due to thymus tumor. The 2 patients who died of NFPET had undergone pancreatic surgery at the time of NFPET diagnosis. The 2 groups did not differ significantly with respect to tumor progression [5/15 (33%) vs 6/38 (16%), P = 0.16]. Overall life expectancy of patients with NFPET < or = 2 cm was not different than that of the 229 MEN1 patients in the registry without any pancreaticoduodenal tumor (P = 0.33). CONCLUSIONS: This study suggests that surgery may not be beneficial for MEN1 patients with NFPET < or = 2 cm.

Epidemiology data on 108 MEN 1 patients from the GTE with isolated nonfunctioning tumors of the pancreas.

OBJECTIVE: To analyze the penetrance and clinical course of isolated nonfunctioning tumors of the pancreas (NFTP) in MEN 1 patients, and to propose a strategy for managing them. SUMMARY BACKGROUND DATA: Pancreaticoduodenal tumors develop in a majority of MEN 1 patients and are a major cause of death. The natural history of NFTP is poorly defined, and no clear-cut guidelines have been widely accepted regarding treatment. METHODS: Data on 108 patients with isolated NFTP among 579 MEN 1 patients from the French Endocrine Tumor Study Group (GTE) were analyzed. Survival rates were calculated using the Kaplan-Meier method. RESULTS: The penetrance of NFTP was 34% at age 50, making it the most frequent pancreaticoduodenal tumor in MEN 1 patients. Forty-three patients (40%) underwent surgery, 32 of them curatively. No patient died because of surgery. Average life expectancy for patients with NFTP was shorter than that for MEN 1 patients who did not have pancreaticoduodenal tumors. Thirteen patients died during follow-up, 10 due to NFTP. Tumor size was correlated with the risks of metastasis and death. These risks were low for patients with tumors

Current concepts in functioning endocrine tumors of the pancreas.

Duodenal and pancreatic endocrine tumors are uncommon and their surgical treatment is often difficult. The management of these tumors has changed with recent advancements in tumor localization, intraoperative hormone measurements, standardized surgical techniques, and a better understanding of the genetic basis of multiple endocrine neoplasia syndrome. We present our experience with 191 endocrine tumors and elaborate the contemporary management of functioning duodenopancreatic endocrine tumors.

Surgical management of primary hyperparathyroidism: the case for giving up quick intraoperative PTH assay in favor of routine PTH measurement the morning after.

OBJECTIVE: To analyze the utility of quick intraoperative parathyroid hormone (PTH) measurement in the surgical management of primary hyperparathyroidism. BACKGROUND DATA: The use of intraoperative PTH monitoring is well established in the surgery of primary hyperparathyroidism. However, some false-negative predictions lead to unnecessary explorations; furthermore, surgeons are becoming increasingly dependent on hormone measurement for intraoperative decisions, which raises concerns about the cost-effectiveness of the method. METHODS: A retrospective analysis of 268 neck explorations performed for primary hyperparathyroidism using intraoperative PTH monitoring from April 2001 to February 2003 was done. We used the criterion of "biologic recovery" of hyperfunctioning tissue, defined as a more than 50% decrease in PTH level from baseline value at 5 minutes after excision to predict the outcome of successful parathyroidectomy documented by normal postoperative serum calcium level. Additionally, we also sampled PTH at 10 minutes, 30 minutes, and the morning after surgery to compare the predictive value of delayed sampling. Patients were classified according to the prediction being concordant or discordant with the outcome. The data were analyzed using a 2 x 2 table construct for each of the sampling times, therefore providing sequential sensitivity, specificity, positive and negative predictive values, and overall accuracy of the predictions. RESULTS: Concordance or overall accuracy of prediction (true positives and negatives) was obtained in 229 cases (85.4%), and discordance or failure of prediction (false positives and negatives) was obtained in 34 cases (12.7%) at T5. On analyzing the iPTH prediction at T10, T30, and D1 among the group of 33 false negatives, we found that 28 (10.4%) patients reached the concordance at 30 minutes, while by the first day 32 patients (12.3%) had achieved concordance. Thus, there was a progressive increase in sensitivity and overall accuracy, but more importantly, in the negative predictive value reaching 88.9% on the day after surgery. CONCLUSIONS: The method of sampling PTH intraoperatively at 5 minutes has a high positive predictive value (99.5%) but a low negative predictive value (19.5%), which can lead to unnecessary explorations and a delay in the operative procedure. The negative predictive value increases substantially at 30 minutes and is best on the day after surgery. We suggest giving up the intraoperative measurement of PTH to adopt the first day postoperative measurement of PTH as a predictor of successful parathyroidectomy.

Fine needle aspiration and intraparathyroid intact parathyroid hormone measurement for reoperative parathyroid surgery.

Some authors have praised the value of fine needle aspiration (FNA) with measurement of intraparathyroid intact parathyroid hormone (iPTH) for localization of the hypersecreting gland(s) in recurrent or persistent primary hyperparathyroidism (HPT). The aim of the present study was to determinate whether FNA for iPTH assay is an effective procedure to distinguish between normal and hypersecreting parathyroid glands. We performed a prospective study of 170 patients who underwent cervicotomy. They were divided into three groups: group A, 50 patients with thyroid diseases; group B, 100 patients with primary HPT; group C, 20 patients with secondary HPT. We performed intraoperative FNA for iPTH measurement from the thyroid, and from the normal and enlarged parathyroid glands, and we compared the different intraglandular iPTH assays. In group A, the intraparathyroid iPTH level was < 1000 pg/ml in 68% of the patients. In group B, in the pathological parathyroid gland iPTH was > 1000 in 88%; conversely, in the normal adjacent parathyroid glands it was < 1000 in 79%. In group C, intraparathyroid iPTH of enlarged glands was > 1000 in 80%. Intrathyroid iPTH was < 100 pg/ml in 96% for the three groups. We conclude that FNA for intraglandular iPTH measurement is an effective tool for distinguishing between normal and pathological parathyroid glands in the setting of primary HPT (p < 0.05), and between thyroid and parathyroid glands in groups A and B. But the procedure should be carried out in conjunction with the sestamibi scan and ultrasonography before surgical reintervention.

Unilateral surgery for hyperparathyroidism: indications, limits, and late results--new philosophy or expensive selection without improvement of surgical results?

We assessed the "late" results after unilateral parathyroidectomy (PTX) performed for selected indications. From October 1998 throughout March 2001 we operated on 454 patients for hyperparathyroidism (HPT). A positive unifocal (99m)tc-MIBI scan was required for the unilateral approach to be used. Intact parathormone (PTH) measurements were done intraoperatively. Postoperative calcium and PTH serum levels of unilaterally operated patients were checked. Follow-up has been 16.2 months (range 6-40 months). Of the 454 patients, 336 (74.0%) were not eligible for the unilateral approach; and 125 (27.5%) of the 454 patients had renal HPT. Among the 329 patients with primary HPT, 125 (38.0%) were excluded for well established reasons, and in 77 other cases (23.5%) preoperative imaging results did not allow the unilateral approach. Altogether, 126 patients (38.3%) with primary HPT were selected for the unilateral approach. Of the 126 unilateral operations, 8 (6.3%) had to be converted to a bilateral procedure. Among the 118 patients with a unilateral approach, 3 patients have been reoperated for overlooked contralateral disease, and 13 dropped out of the study. A total of 102 postoperative calcium and PTH serum late levels are known: 90 (88.2%) patients had normal levels; 10 (9.8%) had a high PTH level, and 2 (1.9%) had high ionized calcium levels. The failure rate in selected cases was 4.2% (5/118) (three were reoperated, and two had a supranormal postoperative ionized Ca level). Even with stringent indications, the late results of unilateral surgery (95.8% cure rate) barely matched those of conventional bilateral surgery (97.6% cure rate). The economic impact of such a surgical strategy should be clarified.