Unexpected Results Using Rapid Intraoperative Parathyroid Hormone Monitoring during Parathyroidectomy for Primary Hyperparathyroidism

Abstract

Rapid intraoperative parathyroid hormone (RIOPTH) monitoring predicts complete removal of all hypersecreting tissue by means of a significant parathyroid hormone (PTH) decrease. In this study we have tried to provide an explanation for some unexpected results of RIOPTH monitoring observed during a series of 125 conventional parathyroidectomies for primary hyperthyroidism, discussing the possible consequences on the surgical strategy. Three main groups can be recognized: (1) spikes: a PTH increase 10 minutes after removal of the diseased gland was observed in three patients; (2) false-negative results: six patients showed an inadequate PTH decreases at 10 minutes, three of them resulting in cure at 20 minutes (all six patients were cured at follow-up); (3) false-positive results: five patients with multiglandular disease showed a PTH decrease to a cure level despite excision of one adenoma only (in two of these patients a 20-minute sample showed a PTH increase soon after manipulation of the second adenoma). We concluded that the spike, almost certainly a consequence of manipulating the adenoma, when detected should be considered the "true" baseline value. False-negative results are to some extent related to undetected spikes. The assay used for RIOPTH determination and PTH half-life variability may also play a role. A false-negative result usually prolongs the surgical time. False-positive results are usually related to a double adenoma, one functionally prevailing over the other. Because in our experience manipulation of the second adenoma brought a PTH increase detected with RIOPTH monitoring, we believe that the second adenoma should be excised.

PTH secretion of “manipulated” parathyroid adenomas

“…Even gentle handling of the hyperfunctioning parathyroid tissue during limited minimally invasive exploration using short incisions cannot prevent an increased excretion of PTH and its fragments. It was reported recently [11] and also confirmed in this study that manipulation of normal parathyroid glands does not lead to measureable PTH spikes.…”

“…A prolonged PTH decline into the required range (exponential decay from "spike value") may document cure. Emmolo et al [11] found a spike in only three of 125 patients but without drawing blood right before excision of the gland. One must suspect that the described false-negative results (no adequate decline within 10 min after extirpation despite cure) also result from unrecognized spikes.…”

Persistent primary hyperparathyroidism: an uncommon location for an ectopic gland - Case report and review

“…On the grounds of the Rome criterion, IOPTH 20 minutes post-excision should be within the reference range and/or less than 50% of the highest pre-excision level and/or at least 7.5 ng/L lower than IOPTH assay at 10 minutes post-excision. Based on the Vienna criteria, a decline in IOPTH levels of over 50% (from pre--operative baseline to 10 minutes post-excision) would predict surgical cure (19,27).…”

“…A slower decline in PTH levels, which occurs in case of chronic kidney disease, removal of large adenoma, parathyroid cyst rupture, longer PTH half-lives (that could vary from 2 to 5 minutes), and employment of assays unable to discriminate between biologically active PTH (1-84), and amino--terminally truncated PTH fragments (inactive metabolites, with longer half-lives) could account for such results. It can also be ascribable to undetected spikes in relation to manipulation of abnormal parathyroid glands (10 minute post-excision level might show a 50% reduction compared with pre-excision results, but it is still higher than half the pre-operative baseline value) (8,(18)(19)(20)(21)27).…”

“…Patients with multiglandular disease may present false-positive results, considering that PTH levels decline suddenly after parathyroid removal, but will eventually rise again, as soon as other abnormal gland(s) recover from previous suppression (18,22,27).…”