DNA patterns in parathyroid disease predict postoperative parathyroid hormone secretion

Flow cytometric analysis of the nuclear deoxyribonucleic acid (DNA) content of parathyroid glands excised from patients with hypercalcemic hyperparathyroidism has identified three distinct DNA patterns. The most frequent pattern showed a high percentage of cells with tetraploid DNA, which indicated an increase in the G2 and M phase of the cell cycle. Thirty-four patients were found to have abnormal tetraploid DNA content. One patient had a normal diploid pattern, and seven were found to have an aneuploid DNA population in their excised parathyroid glands. This unexpected finding of aneuploid DNA appears to be an unique feature of these endocrine glands because they have no histologic or clinical characteristics of malignant change. All patients have remained normocalcemic and clinically well after excision of only grossly enlarged glands. Postoperative parathyroid hormone (PTH) levels were correlated in 17 patients with DNA analyses of biopsy specimens from 30 normal-sized glands which were left in situ. Seven patients with elevated PTH postoperatively had high tetraploid or aneuploid DNA in all 13 glands from which biopsy specimens had high tetraploid or aneuploid DNA in all 13 glands from which biopsy specimens had been taken. In 10 patients with normal PTH levels, six had normal diploid patterns, whereas four had high tetraploid DNA in their gland biopsy specimens. DNA content present in biopsy specimens of normal-sized, in situ glands was predictive (p less than 0.042) of parathyroid gland secretory activity. These findings suggest that the stimulus for parathyroid gland hyperfunction often affects more than a single enlarged gland and persists after clinical cure, as shown by a more rapid cell turnover in some remaining glands and continued hypersecretion of hormone.     

Hemolysis falsely decreases intraoperative parathyroid hormone levels

Background

Intraoperative parathyroid hormone (IOPTH) measurement is used to confirm biochemical cure during parathyroidectomy. Falsely decreased IOPTH measurements could result in false-negative or false-positive results and lead to failed parathyroidectomy or unnecessary additional exploration.

Study design

The records of all patients who underwent parathyroidectomy with IOPTH between May and August 2007 were retrospectively reviewed, and the frequency of hemolysis of IOPTH samples was determined. Separately, 10 split-samples were hemolyzed using the freeze-thaw technique.

Results

Forty-seven patients underwent parathyroidectomy, and 226 IOPTH samples were sent. Seventeen (7.5%) specimens from 9 (18.8%) patients were hemolyzed. In 8 split-samples, the range of decrease caused by hemolysis was 24.5% to 53.8% compared with nonhemolyzed controls.

Conclusions

Hemolysis of IOPTH samples occurs commonly and falsely decreases IOPTH levels. Unrecognized hemolysis in pre-excision specimens could result in false-negative IOPTH results and lead to unnecessary continued exploration. Unrecognized hemolysis in postexcision specimens could lead to false-positive IOPTH results and lead to failed parathyroidectomy and the need for reoperation. Thus, hemolysis may be an easily preventable cause of erroneous IOPTH measurements.     

Utility of rapid intraoperative parathyroid hormone assay to predict severe postoperative hypocalcemia after reoperation for hyperparathyroidism

BACKGROUND: Patients undergoing reoperative parathyroidectomy may develop severe transient or permanent hypoparathyroidism. This study's purpose was to determine the utility of intraoperative parathyroid hormone (IO-PTH) values in predicting the development of severe hypocalcemia for patients undergoing reoperation for primary hyperparathyroidism. METHODS: Between March 1999 and October 2001, 68 patients with persistent or recurrent hyperparathyroidism underwent reoperation using IO-PTH measurements. The maximum percent decrease and lowest actual PTH value obtained at surgery were compared to determine any correlation with the development of postoperative hypocalcemia requiring supplementation. RESULTS: Of 68 patients, 25 required calcium and calcitriol postoperatively and 43 did not. There was a significant difference between the 2 groups with respect to lowest IO-PTH value (18.4 +/- 2.6 vs 28.0 +/- 3.9 pg/mL; P =.02), percent decrease in IO-PTH (89% +/- 1% vs 80% +/- 3%; P =.03), and lowest postoperative ionized calcium (1.06 +/- 0.01 vs 1.19 +/- 0.01 mmol/L; P <.001). A percent decrease in IO-PTH of 84% or greater was found to be predictive of patients experiencing hypocalcemia requiring supplementation with a positive predictive value of 46% and a negative predictive value of 82%. CONCLUSIONS: Although a maximum percent decrease in IO-PTH of 84% or greater was associated with an increased incidence of postoperative hypocalcemia requiring supplementation in the 68-patient cohort, on further analysis the association was significant only for patients with multiglandular disease and not those with single adenomas. This value may be useful for identifying patients who will need closer postoperative monitoring or prophylactic supplementation.     

Use of intraoperative parathyroid hormone measurement does not improve success of bilateral neck exploration for hyperparathyroidism

HYPOTHESIS: Use of intraoperative measurement of intact parathyroid hormone (iPTH) to confirm complete excision of hyperfunctioning parathyroid tissue does not improve overall operative success rates. DESIGN: Case series of patients undergoing parathyroidectomy with or without intraoperative iPTH measurement. SETTING: University teaching hospital. PATIENTS AND INTERVENTIONS: Fifty patients undergoing parathyroidectomy before our institution of intraoperative iPTH sampling in March 1999 (group 1) were compared with 50 patients undergoing parathyroidectomy after this technique was adopted (group 2). Overall, 100 patients underwent operation between December 1996 and May 2000. Serum calcium and iPTH levels were measured at 1- and 3-month intervals. Intraoperative frozen sections and operative times were also analyzed. RESULTS: Mean preoperative calcium levels were 2.85 and 2.82 mmol/L (11.4 and 11.3 mg/dL) in groups 1 and 2, respectively. One-month postoperative calcium values were identical in both groups at 2.35 mmol/L (9.4 mg/dL) (group 1 SD = 0.18 [0.74], group 2 SD = 0.20 [0.82]). At 1 month, all but 1 patient in group 1 had normalized calcium values (2% failure rate), while 3 patients in group 2 (6%) remained hypercalcemic. All 3 patients in group 2 had intraoperative iPTH levels that returned to normal. There was a significant difference in the number of intraoperative frozen sections between groups, with a mean (SD) of 3.4 (1.7) in group 1 and 2.0 (1.6) in group 2 (P<.01). There was no significant difference in operative times between groups. CONCLUSIONS: Use of intraoperative iPTH sampling did not significantly affect the overall success of parathyroidectomy, as determined by postoperative normocalcemia. There was, however, a significant decrease in the number of frozen sections sent at operation.     

Human parathyroid hormone does not influence human erythropoiesis in vitro

Background. Although renal anaemia is associated with secondary hyperparathyroidism, the relationship of both conditions remains obscure. Previously it was reported that high levels of bovine parathyroid hormone (PTH) did not inhibit in vitro human erythropoiesis, but whether human PTH inhibits in vitro human erythropoiesis has not been determined. Method. To clarify the direct effects of human biologically active N-terminal (1-34) PTH and intact (1-84) PTH on human haematopoietic progenitor growth, we investigated colony assays of human erythropoiesis and granulomonopoiesis. Results. Neither N-terminal PTH (300 ng/ml) nor intact PTH (5000 pg/ml) inhibited haematopoietic progenitor growth. Conclusion. Our findings confirm that human PTH does not directly inhibit human erythropoiesis.     

Preoperative oesophageal motor activity does not predict postoperative dysphagia.

OBJECTIVE: To evaluate the ability of preoperative manometric examinations to predict temporary or permanent dysphagia after antireflux procedures. DESIGN: Retrospective study. SETTING: Teaching hospital, Sweden. SUBJECTS: 191 patients who had partial fundoplication. Interventions: Stationary manometry with a perfused catheter system. MAIN OUTCOME MEASURES: Correlation between preoperative manometric examinations and the incidence of dysphagia before and after operation. RESULTS: 98 of 191 patients had dysphagia preoperatively (51%), but 52 of the 98 had no stricture or motor disorder to explain it; 25 of 59 patients with motor disorders shown manometrically (42%) did not complain of dysphagia. The number of patients with dysphagia was reduced to 43 postoperatively. 8 who did not complain of dysphagia preoperatively did so postoperatively; 4 of 8 had defective peristalsis and 4 had normal preoperative tracings. CONCLUSIONS: Manometric examination does not help us to understand the mechanism of preoperative dysphagia, nor does it predict who will develop dysphagia postoperatively.     

Interpretation of intraoperative parathyroid hormone monitoring in patients with baseline parathyroid hormone levels of <100 pg/mL

BACKGROUND: Common guidelines for intraoperative parathyroid hormone (IOPTH) interpretation are based on clearly elevated baseline parathyroid hormone (PTH) values. We hypothesize that patients with low-baseline levels (<100 pg/mL) have a higher incidence of multigland disease (MGD) and display differences in PTH kinetics compared with patients with high-baseline levels. METHODS: We retrospectively reviewed the cases of 1151 patients with primary hyperparathyroidism who underwent parathyroidectomy with IOPTH monitoring. Of these, 141 patients had low-baseline values. Multiple comparisons were made between the low-baseline and high-baseline groups. RESULTS: Twenty-six percent of the low-baseline patients had MGD versus 15% of the high-baseline patients (P = .002). The PTH kinetics differed between groups after gland excision at both 5 and 10 minutes. Adherence solely to the "50% rule" during minimally invasive parathyroidectomy potentially would have missed 25% of patients with MGD in the low-baseline group versus 10% in the high-baseline group; 5.7% of the low-baseline patients had persistent or recurrent hypercalcemia versus 2.9% of the high-baseline patients. CONCLUSION: MGD is significantly more prevalent among low-baseline patients, and PTH kinetics are somewhat different between groups. The current guidelines that are used for IOPTH monitoring may not be ideal for use in this low-baseline group and will likely need to be revised after further study of this group of patients.     

Current applications of the intraoperative parathyroid hormone assay in parathyroid surgery

Parathyroid hormone measurement using a two-site immunochemiluminometric assay has allowed for a rapid and accurate technique that has found its way into the operative armamentarium of some parathyroid surgeons. It can be used to assess the completeness of parathyroid gland resection and allow for a minimally invasive parathyroidectomy. This operative approach has become a popular marketing tool, providing patients with confidence in their surgical outcome. The purpose of this review is to provide the surgeon with the practical points and pitfalls of the use of intraoperative parathyroid hormone in the treatment of parathyroid disease.     

Applicability of intraoperative parathyroid hormone assay during thyroidectomy

OBJECTIVE: To evaluate the applicability of intraoperative parathyroid hormone (quick PTH) assay to monitor parathyroid function and to identify clinically significant hypocalcemia compared with postoperative serum calcium monitoring. SUMMARY BACKGROUND DATA: Close monitoring of serum calcium levels is a standard of care to identify post-thyroidectomy hypocalcemia due to parathyroid insufficiency. METHODS: Quick PTH assay was performed before and after thyroidectomy for 100 patients at risk of postoperative hypocalcemia and 20 control patients who underwent unilateral lobectomy. Postoperative serum calcium levels were closely monitored. RESULTS: Control patients had a normal but 38.9 +/- 5.9% (mean +/- SEM) decline in quick PTH after thyroidectomy. Eleven of 100 at-risk patients (11%) developed postoperative hypocalcemia. Hypocalcemic patients had significantly lower quick PTH values after thyroidectomy compared with that of normocalcemic patients. Serum calcium was significantly lower in hypocalcemic patients the morning after operation but not early after the operation (within 6 hours). A normal or less than 75% decline in quick PTH after thyroidectomy can accurately identify normocalcemic patients during surgery as compared to more than 24 hours by serum calcium monitoring. CONCLUSIONS: The quick PTH assay can monitor parathyroid function during thyroidectomy and identify patients at risk of clinically significant hypocalcemia much earlier than serum calcium monitoring. It may facilitate early discharge and the use of parathyroid autotransplantation during thyroidectomy.     

The dilemma of the normal baseline parathyroid hormone level using the intraoperative PTH assay.

OBJECTIVE: To analyze patients with "normal" baseline quick intraoperative parathyroid hormone (QPTH) levels during parathyroidectomy and to determine the prevalence of this finding, the usefulness of the assay in this situation, and to explain the possible causes for this phenomenon. STUDY DESIGN AND SETTING: Patients who underwent parathyroidectomy using QPTH in a tertiary hospital. METHODS: Retrospective analysis of 39 patients treated surgically for primary hyperparathyroidism using QPTH. RESULTS: Of the patients, 14 (36%) had normal baseline QPTH. 8 patients with localizing sestamibi scans had a single adenoma, and excision resulted in a mean decrease of 85.4% in QPTH. Six patients had nonlocalizing sestamibi scans, 1 patient had an 84% drop in QPTH level after removal of a single adenoma, and 5 patients had hyperplasia requiring > or =3 glands excision. At 11.36 months' mean follow-up, 13 patients (93%) were normocalcemic. CONCLUSIONS: A "normal" baseline QPTH level was found in 36% of patients. A 50% decrease in QPTH remains predictive of biochemical cures in patients with localizing sestamibi scans. The likely explanation for this variability in "normal" levels between different assays is the variability in detection of the 7-84 PTH fragment, which results in an overestimation of the PTH level. Assays such as the QPTH, which are more sensitive for the biologically active PTH molecule [(1-84) PTH] than other laboratory PTH assays will tend to have lower PTH levels that can be within the normal range. EBM rating: B-3.     

Persistently elevated parathyroid hormone levels after parathyroid surgery

BACKGROUND: Persistent elevation of serum parathyroid hormone (PTH), despite normocalcemia, occurs in 8% to 40% of patients after parathyroidectomy. Explanations have included hypocalcemia owing to vitamin D deficiency or bone remineralization, and persistent hyperparathyroidism. METHODS: A retrospective chart review of 816 consecutive patients who underwent surgery for primary hyperparathyroidism was conducted. RESULTS: One hundred fourteen patients (15%) had persistently elevated PTH levels (PPTH). Patients with PPTH had higher preoperative PTH levels than those with normal PTH levels postoperatively. They also had lower postoperative Ca(++) and vitamin D levels. Multiple gland enlargement was identified in fewer patients with PPTH than in those with normal postoperative PTH levels. In patients with PPTH and a postoperative Ca(++) less than 9.6 mg/dL (group I), there was a greater decrease in IOPTH, a higher initial postoperative PTH level, and a lower postoperative vitamin D level than in PPTH patients whose postoperative Ca(++) was > or =9.6 mg/dL (group II). Postoperative Ca(++) and vitamin D levels were also lower in patients whose PPTH did not ultimately resolve. Three patients in group II had recurrent disease. CONCLUSIONS: Persistent elevation of postoperative serum PTH levels in normocalcemic patients is associated with mild hypocalcemia, probably owing to vitamin D deficiency. In some patients it may also be indicative of mild persistent hyperparathyroidism.     

Intact parathyroid hormone levels in renal transplant patients with normal transplant function

Bleskestad IH, Bergrem H, Leivestad T, Gøransson LG. Intact parathyroid hormone levels in renal transplant patients with normal transplant function.
Clin Transplant 2011: 25: E566–E570. © 2011 John Wiley & Sons A/S. Abstract: Introduction: Chronic kidney disease mineral and bone disorder (CKD‐MBD) is common in patients who have undergone kidney transplantation. There is limited information on the extent to which patients with normal renal function after transplantation have persistent disturbances in their mineral metabolism. Aim: The aim of the study is to investigate the prevalence of elevated intact parathyroid hormone (iPTH) levels at least one yr after transplantation in patients living with a first renal transplant with normal transplant function. Methods: A retrospective, observational study of 607 patients was collected from the Norwegian Renal Registry. Of these, iPTH was recorded for 360 patients. Results: One hundred and eighty‐eight patients (52%) had elevated iPTH levels. Twenty‐six patients (7%) had iPTH levels >2.5 times the upper limit of normal (ULN). Patients with a pre‐emptive transplant were significantly younger than the patients who had received treatment with dialysis (p < 0.0001). The prevalence of iPTH > ULN was significantly higher in patients with a pre‐emptive transplant (p = 0.037). Conclusions: In post‐transplant patients with normal transplant function, our data indicate that more than 50% have elevated levels of iPTH more than one yr after transplantation. If elevated iPTH level is associated with mortality in this patient population, it may have major impact on clinical treatment guidelines.     

Focused parathyroid surgery with intraoperative parathyroid hormone measurement as a day-case procedure

BACKGROUND: This study assessed the feasibility, efficacy and safety of focused parathyroidectomy combined with intraoperative parathyroid hormone (IOPTH) measurement in a day-case setting. METHODS: Over 28 months 50 consecutive patients (mean age 63 (range 33-92) years) with clear evidence of unifocal disease on sestamibi scanning or ultrasonography underwent unilateral neck exploration via a small lateral incision. Blood samples for measurement of IOPTH were taken at induction of anaesthesia, before adenoma excision and after adenoma excision (at 5, 10 and 20 min). Ten patients were discharged within 23 h and 40 patients on the day of surgery. RESULTS: A solitary adenoma was identified in all but one patient, with a mean operating time of 30 (range 16-57) min. After parathyroidectomy, IOPTH levels fell appropriately except in one patient with multiglandular hyperplasia. No patient developed symptomatic hypocalcaemia during the 2 weeks after operation, enabling cessation of oral supplements. All patients remained normocalcaemic on follow-up (mean 26 (range 8-84) weeks) and histological examination confirmed parathyroid adenoma (48 patients), hyperplasia (one) or carcinoma (one). CONCLUSION: After accurate preoperative localization of uniglandular disease, patients with primary hyperparathyroidism may be managed successfully and safely by focused parathyroidectomy with IOPTH measurement as a day-case procedure.