A new approach to parathyroidectomy.

OBJECTIVE: To decrease the operative time for parathyroidectomy in patients with hypercalcemic (primary) hyperparathyroid disease, a combination of preoperative localization of a parathyroid tumor with an effective nuclear scan (scintigram) and intraoperative monitoring of parathyroid hormone (quick parathyroid hormone measurement) to ensure excision of all hyperfunctioning tissue was studied. SUMMARY BACKGROUND DATA: For many years, persistent hypercalcemia after parathyroidectomy (3% to 10%) has been constant and is usually due to the surgeon's failure to remove all hyperfunctioning glands. A marked decrease in parathormone level after excision of a single large gland predicts operative success and a return to normal calcium levels. Conversely, persistent high levels of parathyroid hormone indicate excess secretion by another gland(s) and the need for further exploration. Recently Tc-99m-sestamibi (MIBI) scintigraphy was shown to be more effective in localizing parathyroid tumors than previous methods. A combination of both techniques could be useful to the surgeon if they improve the operative success rate and are cost-effective. METHODS: Parathyroidectomy was performed on 18 patients with primary hyperparathyroid disease, with tumors localized by MIBI scintigrams. When excision of the identified parathyroid gland was accomplished, the operation was terminated and quick parathyroid hormone was measured to confirm that all hyperfunctioning tissue was removed. RESULTS: Sixteen patients with positive results of scintigram had successful parathyroidectomies confirmed by quick parathyroid hormone measurement with a cervical approach. Two patients with mediastinal tumors localized by MIBI scintigraphy could not be resected using this approach. One false-positive/false-negative scintigram was obtained. Compared with patients having parathyroidectomy without localization and hormone monitoring, the average operative time was shortened from 90 to 36 minutes. CONCLUSIONS: Localization and successful excision of parathyroid tumors with confirmation that no other hyperfunctioning glands were present by quick parathyroid hormone monitoring can predict a return to normal calcium levels and a decrease in operative time in parathyroidectomy.

Clinical usefulness of an intraoperative "quick parathyroid hormone" assay.

BACKGROUND: Intraoperative assays of parathyroid hormone (PTH) in the surgical management of hyperparathyroidism have been limited by an extended "turnaround" time, making it impractical for the operating surgeon. With our modification of a standard immunoradiometric assay for intact PTH, results are reported in 12 minutes. The operative usefulness and the ability of this "quick PTH" assay to predict postoperative serum calcium levels are reported here. METHODS: Quick PTH levels from whole blood samples taken 10 minutes after excision of hyperfunctioning parathyroid glands were compared with preoperative and preexcision samples in patients undergoing 63 parathyroidectomies. Patients were divided into two groups with assay incubation times of 10 and 6 minutes. The latter was clearly not sensitive enough and resulted in a 20% false-negative rate. However, with a 10-minute incubation time, a decrease of 54% or more in quick PTH levels resulted in postoperative normocalcemia in patients with primary hyperparathyroidism. RESULTS: With these criteria used to predict the postoperative return to normocalcemia in 29 patients with primary hyperparathyroidism, the quick PTH assay had a sensitivity of 96%, specificity of 100%, and overall accuracy of 97%. CONCLUSIONS: The quick PTH assay was especially helpful in predicting postoperative calcium levels when multiple excisions were necessary to remove all hyperfunctioning tissue or some normal parathyroid glands were not visualized.

Operative monitoring of parathyroid gland hyperfunction.

With a 20-year experience of more than 700 parathyroidectomies, our persistent hypercalcemic postoperative failure rate of 7% has remained constant. Reasons for failure have been misdiagnosis or inability of the surgeon to detect and excise all hypersecreting glands. We have modified a commercially available immunoradiometric assay for intact parathyroid hormone (PTH) resulting in a 15-minute turnaround time. Since intact PTH has a half-life measured in minutes, whole blood samples taken 10 minutes after gland excisions were monitored intraoperatively to confirm significant changes in circulating hormone. Quantitative evidence that all hyperfunctioning parathyroid tissue had been ablated during operation was obtained in 19 of 21 patients. Less than four glands each were identified in 53% of these patients. The PTH "quick" test correctly pointed to an inadequate excision requiring further parathyroid ablation in two patients, made bilateral neck exploration unnecessary in two patients who had previously undergone parathyroidectomy, and predicted persistent hypercalcemia in two patients with complications.

Flow cytometric analysis of RNA content in different cell populations using pyronin Y and methyl green.

Pyronin Y (PY) was used, in flow cytometric (FCM) systems, to estimate the RNA content per cell in formalin fixed EL4 leukosis tumor cells, enzyme dispersed R3327-G rat prostatic adenocarcinoma cells, mouse spleen cells stimulated with concanavalin A, and human peripheral blood lymphocytes stimulated with phytohemagglutinin. Preincubation of the cells with methyl green (MG) blocked PY binding to DNA such that the intracellular fluorescence from MG-PY was due primarily to its binding to RNA. Treatment of the cells with ribonuclease resulted in a 3- to 5-fold reduction in the fluorescence intensity of intracellular MG-PY. Mitogen stimulation of either mouse or human lymphocytes resulted in an increase in DNA (propidium iodide fluorescence) and RNA (MG-PY fluorescence) content per cell over resting levels. Further, the changes in stimulated human lymphocyte DNA and RNA contents following 24, 48, and 72 hr of cell culture were monitored. The results showed that RNA levels were significantly increased prior to that of DNA. Also, the effects of different cell cycle phase specific blocking agents on lymphocyte cell cycle traverse were investigated. We found that: a) actinomycin D inhibited the increases in cellular RNA and DNA; b) hydroxyurea inhibited the increases in cellular RNA were only slightly reduced; c) tritiated thymidine caused an accumulation of cells having high DNA and RNA contents; and d) Colcemid promoted an accumulation of cells having high DNA contents while causing a reduction of cells having high RNA contents. These results were nearly identical to reports by other investigators using the metachromatic dye acridine orange to quantitate RNA per cell. Thus, the MG-PY technique described is indicated to provide a stable and accurate measure of RNA content per cell.

High resolution proton magnetic resonance spectral characteristics of water, lipid, and protein signals from three mouse cell populations.

The high resolution proton magnetic resonance spectral properties of three C57BL/6J mouse cell populations (EL4 ascites tumor cells, normal spleen leukocytes, and normal erythrocytes) were investigated. Packed cell pellets were investigated at 100 MHz and 13.56 MHz. The 100-MHz spectra contained identifiable non-water proton resonances as well as the water resonance. The major non-water resonances from the EL 4 cells and normal leukocytes resembled resonances from lipid extracts, whereas the non-water resonances from erythrocytes resembled resonances from hemoglobin solutions. The reciprocals of the water proton spin-lattice relaxation times were roughly proportional to the total sample water content at both 100 and 13.56 MHz. The estimated slopes of these plots were frequency-dependent. The water proton relaxation rate generally increased with increasing total protein content of the packed cell pellets.