Full text of DOI:10.1067/msy.2000.110431

Intraoperative decay profile of intact
1-84) parathyroid hormone in surgery
(
for renal hyperparathyroidism—a
consecutive series of 80 patients
Jonathan Lokey, MD, François Pattou, MD, Alejandro Mondragon-Sanchez, MD, Michele Minuto, MD,
Barbara Mullineris, MD, François Wambergue, MD, Philippe Foissac-Geroux, MD, Christian Noel, MD,
Henri Le Monies de Sagazan, MD, Pierre VanHille, MD, and Charles A. G. Proye, MD, Lille, France
Background. The utility of intraoperative parathyroid hormone (PTH) monitoring is unclear in the sur-
gical management of renal hyperparathyroidism. Our goal was to define the normal pattern of decay
during operation for renal hyperparathyroidism by using the rapid intact (1-84) parathyroid hormone
(
PTH) assay.
Methods. Eighty consecutive patients underwent neck exploration for renal hyperparathyroidism. Intact
PTH levels were monitored with a rapid immunochemiluminometric assay. Samples were assayed at the
induction of anesthesia, after dissection before resection, and 20 and 40 minutes after resection. Follow-
up ranged from 3 to 24 months.
Results. Twenty minutes after resection, PTH levels remained many-fold supranormal. Seventy-seven patients
(96%) were cured. Of these, 75 patients (94%) had PTH decay of more than 50% from the preoperative
level; 74 (99%) were cured. Only 1 of 3 patients (33%) in whom the PTH level decreased less than 40%
from the preoperative level was cured. Two patients had intermediate values and both were cured.
Conclusions. The intraoperative decay of PTH during operation for renal hyperparathyroidism is slower
than for patients with normal renal function. However, 20 minutes after resection, a decline to less than
5
0% of the preoperative level predicts cure, while a level greater than 60% predicts failure. (Surgery
000;128:1029-34.)
2
From the Surgical Professorial Unit, General and Endocrine Surgery, University of Lille, France
SECONDARY HYPERPARATHYROIDISM (HPT) is a perva-
sive complication of chronic renal failure. Medical
management is the mainstay, but in 5% to 10% of
cases, recalcitrant symptoms such as pruritis and
ther hypertrophied), a missed gland, or a super-
numerary gland.3
,4
The rapid intraoperative determination of
intact parathyroid hormone (PTH) with a 2-site
immunochemiluminometric assay (ICMA) has
become widely established in the operation of pri-
mary HPT.5 Removal of all hyperfunctioning
parathyroid tissue is confirmed by a prompt
decline in circulating intact PTH within 5 to 10
minutes.6 However, the role of the quick intact
PTH assay is not clearly defined in the treatment
of renal HPT.
1
bone pain require surgical therapy. In experi-
enced hands, both subtotal parathyroidectomy
and total parathyroidectomy with autotransplanta-
2
tion have good results. Recurrence indicates an
inadequate resection of hyperfunctioning tissue
-9
(often a remnant that is too large or that has fur-
Presented at the 21st Annual Meeting of the American
Association of Endocrine Surgeons (jointly hosted with the
British Association of Endocrine Surgeons), London, United
Kingdom, and Lille, France, May 22-25, 2000.
Early research with quick PTH in secondary
HPT demonstrated a stepwise decrease in circulat-
ing intact PTH corresponding to sequential gland
resection.10 Subsequent studies have shown a
reproducible decrease in PTH by using the rapid
Reprint requests: Charles A. G. Proye, Service de Chirurgie
Generale et Endocrinienne, Hôpital Claude Huriez, F59037
Lille, France.
ICMA, but these have been small series with limit-
ed follow-up.1
1,12
A decline in serum PTH 20 min-
Copyright © 2000 by Mosby, Inc.
0
039-6060/2000/$12.00 + 0 11/6/110431
utes after excision to less than 50% of the original
value has been observed, but the ability to detect
doi:10.1067/msy.2000.110431
SURGERY 1029

1030 Lokey et al
Surgery
December 2000
Table I. Patient characteristics
specimen was cryopreserved. No frozen section
analysis was used. PTH values were determined 20
(PTH ) and 40 minutes after final resection, and
Age (mean)
Sex
49.6 (range, 14-78)
41 male; 39 female
20
Preoperative intact PTH 947 pg/mL (range, 65-2960)
later samples were also obtained when necessary.
PTH levels were expressed as absolute values and as
the percentage decline from pre-excision values.
All patients had postoperative laryngoscopy.
PTH and serum calcium values were determined
on the first postoperative day and again later in the
first postoperative month. Intermediate follow-up
ranged from 3 to 24 months.
Preoperative calcium
Secondary HPT
10.3 mg/dL (range, 5.9-12.5)
73
7
Tertiary HPT
Years of dialysis
Years of renal graft (n = 15)
7.2 (range, 1-18)
2 (range, 1-15)
an inadequate parathyroid resection or supernu-
merary glands has not been proved. The goal of
our study was to define the decay profile of intact
PTH in patients undergoing subtotal parathy-
roidectomy for renal HPT and to evaluate the util-
ity of the rapid intraoperative PTH assay in such
interventions.
RESULTS
Overall surgical results. Seventy-seven patients
(96%) were considered cured after operation. Cure
was defined as a PTH level that remained less than
4 times the normal level and the absence of hyper-
calcemia. A slightly supranormal level of PTH
secretion was the specific goal of surgical therapy to
avoid the postoperative development of adynamic
bone disease.13 Three patients (4%) had persistent
HPT (ie, PTH greater than 4 times the normal level
within 6 months of operation). There were no
recurrences during the follow-up period (HPT
occurring more than 6 months after operation). A
summary of the surgical failures is presented in
Table II. One patient had a permanent unilateral
recurrent laryngeal nerve palsy. One patient (a
referral for a third-time operation) required even-
tual autotransplantation of cryopreserved tissue for
hypoparathyroidism. There was 1 hematoma, in a
patient who underwent a concomitant thyroidecto-
my. There were no deaths.
Number of parathyroid glands identified.
Overall, at least 4 glands were identified in 77
patients (96%). Supernumerary glands were found
in 28 patients (35%), 3 grossly evident and 25 small
thymic rests. In patients undergoing exploration
for the first time, 4 or more glands were seen in 71
of 74 patients (96%), and in the remaining 3
patients, 3 glands were identified. In patients
undergoing repeat operation, between 1 and 3
glands were identified at the time of reoperation,
accounting for a total of 4 glands in 2 cases and 5
glands in each of the remaining 4 patients.
PATIENTS
Eighty consecutive patients undergoing parathy-
roidectomy for renal HPT from January 1998 to
February 2000 were studied. Patient demographics
are shown in Table I. Typical for this patient popu-
lation, the mean PTH value was markedly elevated,
nearly 16-fold above the normal value, and few
patients demonstrated hypercalcemia. Seven of 15
patients who had undergone renal transplantation
had functioning grafts.
Seventy-four patients (93%) underwent primary
(
first-time) neck exploration in which the thera-
peutic goal was bilateral exploration, subtotal
resection of 4 or more parathyroid glands, and
bilateral transcervical thymectomy. Four patients
(
5%) had 1 previous parathyroid operation (in-
cluding 3 referrals), and 2 (2%) were explored for
the third time (both referred.)
METHODS
The PTH levels obtained in the preoperative
evaluation (PTHpreop) were determined by a stan-
dard immunoradiometric assay. Intraoperative
intact PTH levels were determined by using a rapid
2-site ICMA (Allegro PTH and intraoperative PTH;
Nichols Institute Diagnostics, San Juan Capistrano,
Calif). The normal range in our hospital is 10 to 60
pg/mL. This technique and its accuracy have been
Correlation of PTHpreop and PTHind. There was
some degree of correlation (r = 0.66) between the
preoperative PTH level and the level determined
after induction of anesthesia (Fig 1). However the
values did vary by as much as 3-fold. The preopera-
tive value (PTHpreop) was greater than the postin-
duction level (PTHind) in 50 of 80 cases (63%).
Intraoperative PTH. PTH levels 20 minutes after
resection remained quite elevated (mean, 182 ±
160 pg/mL), but significantly reduced from pre-
6
previously described. Baseline peripheral venous
blood samples were obtained just after induction of
anesthesia (PTHind), and after all parathyroid tis-
sue had been identified but before excision.
Subtotal parathyroidectomy, leaving a viable rem-
nant approximately twice the size of a normal
gland (~60-100 mg) and bilateral transcervical
thymectomy were performed. Half of 1 parathyroid

Surgery
Lokey et al 1031
Volume 128, Number 6
Fig 1. Correlation of preoperative and postinduction PTH levels. PTH levels determined preoperatively by
immunoradiometric assay are plotted against levels obtained immediately after induction of anesthesia by
immunochemiluminometric assay.
Table II. Surgical failures
Preoperative
PTH (pg/mL)
PTH20
(pg/mL)
Decay in PTH
(% of PTHpreop)
Parathyroids
(n)
Persistence or
recurrence?
Reason for
failure
Predictive value
of I/O PTH
Patient
AC
JW
HC
700
711
405 (903)*
147
491
387
79
31
4 (57)*
3
4
Persistence
Persistence
Persistence
Missed gland
Supernumerary
Missed gland
Incorrect
Correct
Correct
3 (4)*
*See results section
excision values. Seventy-five patients (94%) had
PTH levels decay to more than 50% of the preop-
erative value (PTH20 < 50% PTHpreop), and all but
of the patient’s tenuous medical condition. A large
mediastinal parathyroid was removed the following
week. Fig 2 depicts the PTH level through the
patient’s course. Twenty minutes after resection of
4 cervical glands, the PTH dropped noticeably, but
not below 50% of the preoperative baseline.
Twenty minutes after the mediastinal gland was
resected; the PTH had dropped more than 50% of
the new baseline value. In the second surgical fail-
ure of this group (patient H.C. in Table II), there
was discordance between the 2 baseline PTH val-
ues. Fig 3 depicts the PTH levels in this case. The
postinduction PTH level was more than 2 times
greater than the preoperative value. The PTH 20
minutes after resection had fallen to less than 50%
of the postinduction level, but not of the preopera-
tive level. Four parathyroid glands were thought to
have been resected, the preoperative level was
1
(99%) of these patients were cured (patient A.C.
in Table II). Four or more glands were identified in
all but 2 patients in this group. In the 1 surgical fail-
ure in this group, only 3 parathyroid glands were
identified at operation.
Three patients (4%) had PTH20 that remained
greater than 60% of the preoperative value (PTH20
>
60% PTHpreop). Two of these 3 patients (67%)
were not cured. One of the 2 surgical failures in
this group (patient J.W. in Table II) had a preoper-
atively identified mediastinal fifth gland, and a
combined cervical and mediastinal procedure was
planned. After successful cervical exploration and
the resection of 4 enlarged glands, the planned
resection of the fifth gland was postponed because

1032 Lokey et al
Surgery
December 2000
Fig 2. Intraoperative PTH of patient JW. This patient with secondary HPT had 5 glands identified by pre-
operative sestamibi scintigraphy. A cervicomediastinal approach was planned. The graph depicts the PTH
level during the cervical exploration and resection of 4 eutopic glands (after which the initial operation
was halted because of the patient’s medical status) and the subsequent resection of the mediastinal fifth
gland. The finely dashed line indicates 50% of the preoperative PTH value. The heavy dashed line indicates
50% of the new baseline established between operations.
Fig 3. Intraoperative PTH of patient HC. In this patient, the PTH20 did not decay to less than 50% of the
preoperative level (heavy dashed line), but did drop to less than 50% of the postinduction baseline (fine
dashed line). In fact, this patient had only 3 parathyroid glands resected and was not cured.
interpreted as spurious, and the procedure was
concluded. However, histopathologic examination
revealed 3 parathyroid glands; the fourth specimen
was thyroid tissue. The PTH level remained greater
than 4 times normal in follow-up (3 months). The
third patient in this group was cured after resection
of 5 glands, but demonstrated a very slow decay in
circulating PTH, reaching a normal value 36 hours
after resection.
There were also 2 patients (2%) in an interme-
diate region with PTH decay at 20 minutes of
between 40% and 50% of the preoperative level.
Both of these patients had 4 glands identified at
operation and both were cured.
2 of the 3 failures were also in this group (patients
A.C., H.C.) and, conversely, none of the 3 patients
who had a PTH decrease less than 40% of the
postinduction PTH was a failed operation.
Furthermore, 4 patients (5%) remained in the
intermediate zone (decay between 40% and 50%
of PTHind), including 1 patient not cured (J.W.).
Patients with tertiary HPT (n = 7) demonstrated
a decline in PTH levels similar to that of primary
HPT. Ten minutes after resection, PTH values had
not only decreased more than 60% from the pre-
operative level, but were also within the normal
range in all but 1 patient. This 1 exception, in
chronic rejection of her transplant and with limit-
ed renal function, had a PTH decay profile similar
to the patients receiving hemodialysis. Each of
these patients had at least 4 glands identified and
all were cured.
A similar analysis of PTH decay can be per-
formed by using the postinduction PTH as the
baseline: 73 patients (91%) had PTH values fall
more than 50%. Seventy-one were cured. However,

Surgery
Lokey et al 1033
Volume 128, Number 6
DISCUSSION
decayed more than 50% from the baseline value,
confirming adequate therapy in this small interme-
diate group.
The intraoperative decay of circulating intact
PTH after subtotal parathyroidectomy for sec-
ondary HPT in the patient receiving hemodialysis
is reproducible but markedly slower than in the
patient with normal renal function. This is in accor-
dance with the increased half-life of intact PTH in
renal failure (6.6 vs 2.2 minutes).14 Although there
was correlation between preoperative intact PTH
values (immunoradiometric assay) and postinduc-
tion intact PTH levels (ICMA), the former were
generally higher. The degree of correlation is simi-
lar to that seen in studies of primary HPT.9
CONCLUSIONS
The intraoperative decay of intact PTH after
operation for renal HPT is slower than that seen in
the patient with normal renal function. However,
20 minutes after resection, a decay of more than
50% of the preoperative baseline is predictive of
cure, while a decrease of less than 40% suggests a
missed or hyperfunctioning supernumerary gland
and is predictive of failure.
,15
The potential benefits of using the rapid intact
intraoperative PTH assay in the operation of sec-
ondary HPT are 2-fold: to confirm the adequate
resection of hyperfunctioning parathyroid tissue
and to alert the surgeon to the possibility of super-
numerary glands. In this study, a decline in circu-
lating intact PTH of more than 50% from the pre-
operative level at 20 minutes after resection was
highly predictive of cure, with a positive predictive
value of 93% and a sensitivity of 96%. The same
analysis using the postinduction PTH value as base-
line was slightly less sensitive, but more specific
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9
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1034 Lokey et al
Surgery
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PTH will fall dramatically, yet an additional tumor will
still be in the neck or chest.
Dr Barry Inabnet (New York, NY). Thank you for a
very important presentation. I beg to differ with your
conclusions and with those of Dr Weber’s. I think it is
very important to follow the assay out to 60 minutes, at
which time the PTH assay will predict a multigland dis-
ease.
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In the data that I presented at the meeting last year,
this phenomenon occurred in 4 patients in a series of
230 patients, which was less than 1% of all patients
undergoing operation. I think that if you see a value at
the upper end of normal, you must follow it out to 30 or
60 minutes or convert to a conventional parathyroidec-
tomy (bilateral neck exploration).
Dr Geoffrey Thompson (Rochester, Minn). I would
agree with the authors and Dr Weber. I have now had the
opportunity in 5 patients to test the sequential drop in
PTH. When you take out the largest of the 4 glands, the
PTH will often drop to below 50% of baseline, even
though you know that other enlarged glands remain. It is
only after you have performed a subtotal parathyroidec-
tomy that you get a PTH level that is back in the normal
range. I really think that for multigland disease a 50%
drop is insufficient. You really need to see the level back
in the normal range within 15 to 20 minutes after you
have removed what you think is all the abnormal tissue.
Dr Mondragon-Sanchez. From looking at our data, we
would agree with that entirely.
DISCUSSION
Dr Michael Demeure (Milwaukee, Wis). Would you
clarify the times that you actually drew the labs in rela-
tion to the 20-minute interval after resection of the last
parathyroid gland? What you are seeming to say is that
the half-life intact PTH may be different in a patient with
renal failure, which would be something novel. Several
reports, including a project we did with the not-so-quick
dual antibody PTH assay in 1988, showed after resection
of each abnormal gland, you would have a decrease. So
results could really depend on the timing of your blood
draws. Would you clarify that?
Dr Lokey. It is a little more difficult dealing with renal
HPT because obviously all glands are affected. The dis-
section may devascularize some of the glands, but the 20-
minute PTH is after resection of all of the tissue. So that
is when the clock starts, or the zero time value, if you will.
Dr Demeure. So then, do you really think the half-life
of PTH is longer?
Dr Lokey. It is difficult to say that we see a slower
decay, but this has not been analyzed with a mathemati-
cal model to determine half-life. I think it is more appro-
priate to say that the decay is slower, but I would be reluc-
tant to say that the actual half-life is slower.
Dr Collin Weber (Atlanta, Ga). I would like to second
the conclusions drawn from the data presented. This
slide outlines a case referred to me with a parathyroid
scan that showed a lesion in the mediastinum confirmed
by a CAT scan. At surgery, we began with a small neck
incision and split the sternum to find the lesion in the
mediastinum. The PTH fell from 135 to 55. This raised
the question, should I explore the neck in a patient in
And 50% is a man-made figure. It is a made-up figure,
but we are taking it as our baseline. You may want to
choose 20%.
Dr Barbara Kinder (New Haven, Conn). I agree com-
pletely with Dr Thompson, on the basis of our experi-
ence with a primary disease where you have suppressed
glands left, the 50% or 55% may be a reasonable drop.
But in secondary disease or primary hyperplasia, you
are left with abnormal glands and you have to get down
well within the normal range before you have cured the
patient. I completely agree, Dr Thompson, that has been
our experience.