The short- and long-term outcomes of minimally invasive parathyroidectomy guided by
intraoperative parathyroid hormone (PTH) monitoring (IPM) have been extensively published
and remain excellent regardless of the intraoperative protocol used. Unfortunately,
the logistics of implementing IPM as a true point-of-care adjunct and the increased
number of patients with mild hyperparathyroidism (normocalcemic and normohormonal
hyperparathyroidism) have limited the usefulness of IPM in some centers. We all know
that IPM is an accurate tool in guiding parathyroidectomy in sporadic primary hyperparathyroidism.
What remains controversial is which intraoperative PTH protocol is the most accurate.
In reality, any protocol is adequate if it guides the surgeon to about 98% operative
success rate and allows minimally invasive parathyroidectomy in most patients. As
most of us use different criteria and intraoperative protocols, I can only share my
experience and describe what I have learned in the past 25 years of studying IPM in
patients with sporadic primary hyperparathyroidism. Around 2007, just before I left
the University of Miami for my current institution at the Medical University of South
Carolina, Dr George Irvin and I looked at the short- and long-term outcomes of his
patients who were operated on using the Miami criterion. This criterion requires a
≥50% PTH drop from the highest, either preincision or 0’, 10 minutes after removal
of the suspicious gland to predict postoperative normocalcemia with a 97% accuracy.
The reason for re-evaluating the operative outcomes of parathyroidectomy guided by
the Miami criterion was to adjust the intraoperative PTH criteria to decrease operative
failures by preventing false positive rates (approximately 1%) while keeping false
negative results and unnecessary further explorations to a minimum. The reevaluation
of these patients’ outcomes resulted in the Charleston criteria, which I have used
since 2007. The same protocol for blood drawing is used with peripheral samples collected
before neck incision (preincision), 0’ which is collected at the time the last vessel
to the parathyroid gland is ligated, 5’ sample, which is collected to expedite the
procedure in case the criteria is met at this time, and a 10’ sample. Part 1 of the
criteria requires either a ≥65% PTH drop from the highest level, preincision or 0’,
10 minutes after excision of a suspicious gland, or ≥50% PTH drop and a return to
normal range for the intraoperative PTH assay. Most patients will meet the intraoperative
PTH criteria with this requirement. About 3% of the patients will need part 2 of the
criteria, which requires a ≥50% PTH drop and a return to the normal range 20 minutes
after excision of the suspicious gland. Over 15 years, 1,115 patients with classic
sporadic hyperparathyroidism (hypercalcemia and elevated PTH levels) were operated
on using this protocol with the Charleston criteria guidance. Nine hundred and eighty-eight
(89%) patients were followed for >6 months with an average of 3.5 years (0.5–15 years).
As a result of this protocol, operative success (eucalcemia for at least 6 months
postoperatively) was achieved in 98% of the patients with an incidence of multiglandular
disease of 16%, which is slightly higher than before likely because of these more
stringent criteria. This adjustment of the intraoperative PTH criteria decreased the
false positive results to 0.5% from 1% with the Miami criterion.
- Carneiro D.M.
- Solorzano C.C.
- Nader M.C.
- Ramirez M.
- Irvin 3rd, G.L.
Comparison of intraoperative iPTH assay (QPTH) criteria in guiding parathyroidectomy:
Which criterion is the most accurate?.
Notably, false negative rates remained low at about 3%. The long-term outcome of
this protocol is acceptable, with a 2% recurrence rate (hypercalcemia and elevated
PTH following a period of eucalcemia of 6 months). It is important to mention that
during these 15 years, 3 different rapid intraoperative PTH assays were used at the
Medical University of South Carolina. Siemens Immulite turbo PTH assay was used in
49% of these procedures, and 41% of the cases were performed with The Future Diagnostics
(FD) STAT-IntraOperative-Intact-PTH, and recently with Roche Cobas e411in 10% of the
cases. The described protocol has performed similarly with all 3 assays with similar
rates of false positive and false negative results; however, these assays are not
equal. The different assays could affect operative outcome depending on the criteria
used to guide parathyroidectomy. For example, when the data of 914 out of 1,115 successfully
treated patients operated with this protocol followed over an average of 3.5 years
(0.5–15 years) was evaluated, the final peripheral PTH level at 10 minutes was above
the normal PTH range in 24% of the patients. When the Siemens assay was used, 10%
of the patients had a PTH above the normal range in 10 minutes, while 37% of the patients
operated on with FD assay and 16% with Roche had 10’ PTH above normal range at the
end of the procedure. In addition, the normal range for each assay is not always clearly
defined; therefore, it is important to determine the normal range in your own institution
if the PTH normal range is part of the intraoperative PTH criteria. This information
is important when the surgeon interprets the data from studies using different assays
and protocols. Surgeons should be aware of these nuances when implementing these results
in their practice, as the protocol with one assay might have different results with
another assay. Furthermore, recently it has been described that final PTH below 40
pg/mL is the best predictor of long-term postoperative normocalcemia.
- Claflin J.
- Dhir A.
- Espinosa N.M.
- et al.
Intraoperative parathyroid hormone levels ≤40 pg/mL are associated with the lowest
persistence rates after parathyroidectomy for primary hyperparathyroidism.
In this group of successfully treated patients guided by this protocol, 52% of the
cured patients had a peripheral PTH level >40 pg/mL at the final 10 minutes sample.
The incidence of PTH above 40 pg/mL 10 minutes after gland excision with these assays
was also different (Siemens 35%, FD 69%, and Roche 55%). On the other hand, it is
important to mention that although all operative failures and 50% of the recurrences
would have been predicted by a PTH level >40 pg/mL in 10’ after gland excision, about
half of cured patients would have been further explored unnecessarily. One could choose
to be very aggressive to decrease the operative failures to a minimum and maybe prevent
some recurrences; however, one also would need to decide if unnecessary bilateral
exploration in about half of the patients is worthwhile. It is important to remember
that reoperating on a patient following minimally invasive parathyroidectomy is usually
quite simple and feasible with low morbidity. Therefore, it is the surgeon’s choice
to be more or less aggressive to achieve the desired outcome. Personally, there are
significant benefits to being conservative and choosing a less stringent criteria
(less postoperative hypocalcemia, less scar tissue in case a reoperation for thyroid
and parathyroid disease is needed, shorter operations, and potentially fewer complications)
in exchange for operating on a handful of patients that might have failed or recurred.
This decision can also be tailored to the patient's input during surgical evaluation.
Some have wisely recommended to follow these patients with final PTH >40 pg/mL closely
as they have a higher chance of short- and long-term postoperative hypercalcemia.
- Wharry L.I.
- Yip L.
- Armstrong M.J.
- et al.
The final intraoperative parathyroid hormone level: How low should it go?.
- Rajaei M.H.
- Bentz A.M.
- Schneider D.F.
- Sippel R.S.
- Chen H.
- Oltmann S.C.
Justified follow-up: A final intraoperative parathyroid hormone (ioPTH) over 40 pg/mL
is associated with an increased risk of persistence and recurrence in primary hyperparathyroidism.
- Heller K.S.
- Blumberg S.N.
Relation of final intraoperative parathyroid hormone level and outcome following parathyroidectomy.