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ORIGINAL ARTICLE
PREDICTION OF HYPOCALCEMIA AFTER USING 1- TO 6-HOUR
POSTOPERATIVE PARATHYROID HORMONE AND CALCIUM
LEVELS: AN ANALYSIS OF POOLED INDIVIDUAL PATIENT
DATA FROM 3 OBSERVATIONAL STUDIES
Jeffrey Saad Jumaily, BS,1 J. Pieter Noordzij, MD,1 Alex G. Dukas, BS,1
Stephanie L. Lee, MD, PhD,2 Victor J. Bernet, MD,3 Richard J. Payne, MD, FRCS(C),4
Ian K. McLeod, MD,5 Michael P. Hier, MD, FRCS(C),6 Martin J. Black, MD, FRCS(C),6
Paul D. Kerr, MD, FRCS(C),6 Marco Raffaelli, MD,7 Rocco Bellantone, MD,7
Celestino P. Lombardi, MD,7 Mary S. Dietrich, PhD, MS8
1
Department of Otolaryngology–Head and Neck Surgery, Boston University Medical Center, Boston,
Massachusetts. E-mail: [email protected]
2
Section of Endocrinology, Diabetes and Nutrition, Boston University Medical Center, Boston, Massachusetts
3
Department of Endocrinology, Walter Reed Army Medical Center, Washington, DC
4
Department of Otolaryngology–Head and Neck Surgery, Jewish General Hospital, McGill University,
Montreal, Quebec, Canada
5
Department of Otolaryngology–Head and Neck Surgery, Walter Reed Army Medical Center, Washington, DC
6
Department of Otolaryngology, University of Manitoba, Winnipeg, Manitoba, Canada
7
Division of Endocrine Surgery, Department of Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
8
Schools of Nursing and Medicine, Vanderbilt University, Nashville, Tennessee
Accepted 21 May 2009
Published online 24 September 2009 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/hed.21199
Abstract: Background. Parathyroid hormone (PTH) levels
up to 6 hours postthyroidectomy have been shown to have
excellent predictive power in determining hypocalcemia. In this
study, we investigate the usefulness of combining calcium and
PTH to increase the predictive power.
Methods. Individual patient data were obtained from 3
studies (152 patients) that fulfilled our criteria (using PTH assay
within hours postthyroidectomy to predict symptomatic
hypocalcemia).
Results. Changes in combined PTH and calcium
threshold levels checked 1 to 6 hours after thyroidectomy were
Correspondence to: J. P. Noordzij
C 2009 Wiley Periodicals, Inc.
V
PTH and Ca Predicting Hypocalcemia after Thyroidectomy
excellent in predicting postoperative hypocalcemia. A
decrease in PTH of 60%, coupled with a simultaneous
decrease in calcium of 10%, 5 to 6 hours postoperatively
resulted in a sensitivity and specificity of 100%. However,
combined PTH and calcium threshold changes were not
significantly better than using PTH threshold changes
alone.
Conclusions. Threshold changes in serum calcium and
PTH, checked hours after surgery, can be used together to
accurately predict whether a patient will become hypocalcemic
C 2009 Wiley Periodicals, Inc. Head
after thyroidectomy. V
Neck 32: 427–434, 2010
Keywords: thyroidectomy; hypocalcemia; parathyroid hormone
(PTH); postoperative management; rapid parathyroid hormone
assay
HEAD & NECK—DOI 10.1002/hed
April 2010
427
Postoperative
hypocalcemia is 1 of the most
common complications after thyroidectomy,
occurring in up to 30% of cases.1,2 The relatively
high rate of postoperative hypocalcemia is
directly related to the sensitivity of the parathyroid glands and their blood supply to surgical
manipulation. Hypocalcemia is usually not
apparent for 24 to 48 hours after thyroidectomy.
Thus, patients are often observed during this
time as inpatients to monitor for the possible development of hypocalcemia.1,2 If one could determine within hours of completing thyroidectomy
which patients would become hypocalcemic,
then earlier management decisions could be
made.
Therefore, a readily available laboratory test
that could accurately identify patients at low
risk to develop hypocalcemia would be beneficial. These patients, who comprise the vast majority of all thyroidectomy patients, could
potentially undergo same-day outpatient surgery, thereby significantly reducing unnecessary
health care resource allocations. Likewise, those
patients who could be identified early as high
risk for developing hypocalcemia could receive
immediate prophylactic treatment, thus avoiding or mitigating troublesome symptoms of
hypocalcemia and prolonged hospitalization.
Because parathyroid hormone (PTH) has a
short half-life (5 minutes), intraoperative parathyroid gland injury can be identified while the
patient is still on the operating room table and
certainly within hours of completing surgery. It
is known that PTH is a key player in calcium
homeostasis. Surgical insult to parathyroid
glands is the most common cause of hypocalcemia after thyroid surgery, attributed to lower
PTH production levels. Since 2002, 25 publications have reported on the ability of PTH,
checked minutes to hours after completing a
thyroidectomy, to predict hypocalcemia.3–27 In
these studies, sensitivity ranged from 64% to
100% and specificity ranged from 72% to 100%,
with regard to predicting postoperative hypocalcemia. Furthermore, the sensitivity and specificity of PTH in predicting hypocalcemia are better
if checked several hours after removing the thyroid gland, rather than when checked minutes
after gland removal.20,28 In our previous analysis of pooled individual patient data from 9 of
these studies, we concluded that a 65% decrease
in PTH levels 6 hours postoperatively predicted
hypocalcemia with 96.4% sensitivity and 91.2%
specificity.28
428
PTH and Ca Predicting Hypocalcemia after Thyroidectomy
Although PTH levels alone provided remarkable predictability, we considered other markers
to further increase the sensitivity and specificity. Intuitively, using calcium levels in conjunction with PTH levels in the first few hours after
thyroidectomy might improve predictive power.
Payne et al15 concluded that combined calcium
and PTH thresholds are better than PTH alone
in their single institution studies.
Based on a pooled individual patient data set
from 3 of the previously published studies,8,12,20
the goals of this analysis were to answer the following questions: (1) Does adding early calcium
levels to early PTH threshold changes improve
the prediction of hypocalcemia? (2) What is the
sensitivity, specificity, and positive predictive
value (PPV) of combined calcium and PTH in
predicting hypocalcemia (when checked within
hours after completing thyroidectomy)? (3)
When (on the day of surgery) is the best time to
check calcium and PTH to obtain the most accurate result?
MATERIALS AND METHODS
A medical literature search using PubMed was
performed with keywords PTH (parathyroid hormone) and thyroidectomy for English-language
articles published between 1966 and October
2007. Studies were included if calcium and PTH
were obtained within 24 hours of completing
total thyroidectomy or completion thyroidectomy. Studies were included irrespective of
whether the rapid intraoperative PTH assay or
traditional intact PTH assay was used. Only
observational studies were included. Outcome
studies that used early PTH measurements after thyroidectomy to change their management
of these patients were excluded.16,29,30 Studies
or data from studies were excluded if only a
hemithyroidectomy was performed. Studies
were excluded if all patients were given calcium
supplementation independent of their postoperative PTH or calcium levels17 or given calcium at
relatively high calcium levels, when patients
had not yet developed symptoms.3 All included
studies checked PTH from serum that was
obtained from peripheral venipuncture.
The corresponding author for each of the 25
studies published on this subject was emailed to
request sharing of individual data from that
study. These data (perioperative PTH and calcium levels and whether hypocalcemia occurred)
were kindly provided by 10 of the study
HEAD & NECK—DOI 10.1002/hed
April 2010
exact binomial-based method using Stata9 software (a maximum alpha level of 0.05 was used
to assess statistical significance).
RESULTS
FIGURE 1. Receiver operating characteristic curves demonstrating the accuracy of thresholds in % calcium (Ca) decrease,
% parathyroid hormone (PTH) decrease, and combined % Ca
and PTH decrease (in determining whether patients will
become hypocalcemic) at 1–2 hours after removal of entire thyroid gland.
groups.5–9,11,12,15,20,22 Of these 10 groups, 3
reported both calcium and PTH values in the
first 6 hours after thyroidecotmy (Tables 1–3).
Because of the inherent variability between
assay types and different institutions, decreases
in percentage calcium and percentage PTH,
rather than absolute decreases in calcium and
PTH, were used to calculate sensitivity, specificity, PPV, and receiver operating characteristic
(ROC) curves (Table 4 and Figures 1 and 2). To
calculate percentage decrease, a preoperative
value was needed. This excluded 29,15 of the 5
groups of data from these final calculations
because preoperative calcium and PTH values
were not available.
Statistical analyses were performed using
SPSS version 15 (SPSS Inc., Chicago, IL) software. PTH and calcium values between normocalcemic and hypocalcemic patients were
compared at various points in time using t tests.
Comparisons of either PTH or calcium values
for hypocalcemic patients checked at both 1 to 2
and 5 to 6 hours posteroperatively were conducted using analysis of variance. Sensitivities,
specificity, and ROC curves were calculated
using observed contingency tables. Areas under
the ROC curves were calculated using the trapezoidal method and their associated 95% confidence intervals (CIs) were calculated using the
PTH and Ca Predicting Hypocalcemia after Thyroidectomy
The definition of when a patient became hypocalcemic differed between studies (Table 1).
Serum calcium values (corrected for serum albumin) below which a patient was deemed hypocalcemic ranged from 7.2 to 8.4 mg/dL (1.8–2.1
mmol/L). Individual patient data (N ¼ 152)
were obtained from the corresponding author
in 3 studies that met our initial inclusion criteria. The ensuing results are derived from data
supplied by these authors. The overall rate of
hypocalcemia for these 152 patients was 28.3%.
Preoperative PTH and calcium means were
60.82 pg/mL and 9.36 mg/dL, respectively, for
the patients who remained normocalcemic after
surgery, and 55.16 pg/mL and 9.60 mg/dL,
respectively, for those who became hypocalcemic
postoperatively (Tables 2 and 3). Preoperative
PTH and calcium values for patients who
remained normocalcemic after surgery were not
significantly different from those for patients
who became hypocalcemic (p ¼ .347 for PTH,
p ¼ .248 for calcium).
The mean values of PTH and calcium measured 1 to 2 hours postoperatively were 33.48 pg/
FIGURE 2. Receiver operating characteristic curves demonstrating the accuracy of thresholds on % calcium (Ca)
decrease, % parathyroid hormone (PTH) decrease, and combined % Ca and PTH decrease (in determining whether
patients will become hypocalcemic) at 5–6 hours after removal
of entire thyroid gland.
HEAD & NECK—DOI 10.1002/hed
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429
Table 1. Description of 3 studies included in pooled data analysis.
Study
Published
No of
patients
Lam
Dec 2003
39
Immulite (rapid; 10 to 72)
Lombardi
Dec 2004
53
Roche Elecsys E170 (not
rapid; 10 to 65)
McLeod
Feb 2006
60
Immulite (rapid; 10 to 72)
Total
PTH assay (type;
reference range [pg/mL])
Times PTH checked
preop, 1 and 6 h
postop
preop, intraop (after thyroid removed), 2, 4, 6,
24, and 48 h postop
preop, intraop (5 min after
thyroid removed), 1 h
postop
Definition of
hypocalcemia
Equivalent
cCa in mg/dL
iCa < 0.9 mmol/L
7.2
Ca < 8.0 mg/dL
8.4
sxs or cCa
< 8.0 mg/dL
8.0
152
Abbreviations: PTH, parathyroid hormone; cCa, serum calcium corrected for albumin decrease; iCa, ionized calcium; Ca, serum calcium; sxs, symptoms of hypocalcemia.
Note: Type of PTH assay was either rapid (with turnaround time of <1 hour and assay device is smaller/portable) or not rapid, which denotes the traditional 2-site immunoradiometric assay in which the turnaround time is longer (typically on the order of 24 hours. With respect to the equivalent cCa,
mg/dL ¼ 4 mmol/L; 2 ionized calcium ¼ total corrected serum calcium (because about 50% of serum calcium is bound to albumin).
mL and 8.84 mg/dL, respectively, for patients
who remained normocalcemic, and 5.58 pg/mL
and 8.60 mg/dL, respectively, for the patients
who became hypocalcemic (Tables 2 and 3). Oneto 2-hour postoperative PTH and calcium values
for patients who became hypocalcemic were significantly less than those for the patients who
remained normocalcemic (p < .05 for PTH, p ¼
.028 for calcium).
The mean values of PTH and calcium measured 5 to 6 hours postoperatively were 34.41 pg/
mL and 8.89 mg/dL, respectively, for patients
who remained normocalcemic, and 4.43 pg/mL
and 8.39 mg/dL, respectively, for the patients
who became hypocalcemic (Tables 2 and 3).
Five- to 6-hour postoperative PTH values for
patients who became hypocalcemic were significantly less than those for the patients who
remained normocalcemic (p < .05 for both).
Although there was a trend of decreasing PTH
means for hypocalcemic patients as more time
elapsed from the point when thyroidectomy was
completed (Table 3), these differences were not
statistically significant (p ¼ .242).
ROC curves were created using calcium,
PTH, and combined calcium and PTH thresholds drawn at the 2 time periods after total or
completion thyroidectomy (Figures 1 and 2). In
general, the accuracy of a test is graded by the
following ROC area under the curve (AUC)
measurements: 0.90–1.00 ¼ excellent; 0.80–0.90
¼ good; 0.70–0.80 ¼ fair; 0.60–0.70 ¼ poor; and
0.50–0.60 ¼ fail.31 The maximum possible ROC
AUC is 1.00.
At 1 to 2 hours postoperatively, calcium
thresholds alone (decrease ranging from 1% to
40%) resulted in an AUC of 0.727 (95% CI:
0.624 to 0.831), which is fairly accurate (see Figure 1). In this same time period, PTH thresholds
alone resulted in an AUC of 0.966 (95% CI:
0.935 to 0.998), which is remarkably accurate.
Combined calcium–PTH ROC curves were calculated for each decreasing % PTH value between
10% and 100%, while varying the calcium
threshold values. In this time period, the greatest AUC for combined calcium–PTH ROC curves
occurred when PTH decreased >60%, 61%, or
62%, with a value of 0.998 (95% CI: 0.835 to
Table 2. Calcium means SD (mg/dL) before and after total or completion thyroidectomy.
Category
Preoperative
Ca, mg/dL
(N ¼ 140)
1–2 hours postop
Ca, mg/dL
(N ¼ 112)
% decline at
1–2 h postop
(N ¼ 109)
5–6 h postop
Ca, mg/dL
(N ¼ 77)
% decline at
5–6 h
postop (N ¼ 74)
All patients
Normocalcemic
Hypocalcemic
t test (normo vs hypo)
9.53 0.66
9.36 0.58
9.60 0.79
p ¼ .248
8.75 0.58
8.84 0.49
8.60 0.70
p ¼ .0275
7.28 6.37
5.45 4.87
10.87 7.41
p < .05
8.74 0.58
8.89 0.55
8.39 0.50
p < .05
9.74 6.33
7.31 4.35
15.11 6.81
p < .05
Note: Data derived from 3 studies supplying individual patient (8, 12, 20).
430
PTH and Ca Predicting Hypocalcemia after Thyroidectomy
HEAD & NECK—DOI 10.1002/hed
April 2010
Table 3. PTH means SD (pg/dL) before and after total or completion thyroidectomy.
Category
All patients
Normocalcemic
Hypocalcemic
t test (normo vs hypo)
Preoperative
PTH
(N ¼ 150)
1–2 h postop
PTH
(N ¼ 122)
% decline
at 1–2 h
postop
6 h postop
PTH
(N ¼ 85)
% decline
at 5–6 h
postop
59.23 32.90
60.81 35.13
55.16 26.25
p ¼ .3468
24.33 19.91
33.48 18.01
5.58 4.36
p < .05
51.55 37.41
32.91 31.82
87.93 12.17
p < .05
24.53 20.26
34.41 17.59
4.43 3.28
p < .05
46.74 40.37
26.86 33.61
87.22 13.93
p < .05
Abbreviation: PTH, parathyroid hormone.
Note: Data derived from 3 studies supplying individual patient (8, 12, 20).
1.000) in each case. With a PTH decrease of
>60%, the greatest combination of sensitivity
and specificity occurred with a calcium decrease
of >0%: sensitivity of 100% and specificity of
98% (Table 4).
At 5 to 6 hours postoperatively, calcium thresholds alone (decrease ranging from 1% to 40%)
resulted in an AUC of 0.854 (95% CI: 0.763 to
0.945), which is considerably accurate (see Figure
2). In this same time period, PTH thresholds alone
resulted in an AUC of 0.952 (95% CI: 0.903 to
1.000), which is significantly accurate. Combined
Ca–PTH ROC curves were calculated for each
decreasing % PTH value between 10% and 100%,
while varying the calcium threshold values. At 5 to
6 hours postoperatively, a 65% drop in PTH and
10% drop in calcium yielded a maximum AUC of
1.000 (95% CI: 0.800 to 1.000) and 100% sensitivity
and specificity (Table 4). It is worth noting, however,
that the AUC for combined Ca–PTH ROC is not significantly different from the AUC of PTH alone.
DISCUSSION
Monitoring for hypocalcemia is the most common
reason that patients after thyroidectomy are hospitalized beyond the 23-hour point.15,20 Over the
past 6 years, numerous studies supporting the
use of PTH to predict hypocalcemia within
minutes to hours of completing a total or completion thyroidectomy have been published.3–30
Although checking PTH minutes after removing
the thyroid gland has good predictive capabilities,20,28 waiting several hours after completing
surgery improves the predictive value of PTH.
Checking PTH 12 to 24 hours after completing
surgery no longer allows for same-day predictions
and potentially same-day discharge; thus, the
ideal time to check PTH after thyroidectomy
appears to be 1 to 6 hours postoperatively.
Payne et al16,29 reported that adding early
(6 hours postoperatively) calcium levels into
the protocol, which includes checking PTH, will
improve
the
prediction
of
postoperative
Table 4. Sensitivity, specificity, and PPV of combined PTH and calcium assay thresholds in predicting postoperative hypocalcemia.
1–2 h postop with
>60% decrease in PTH
5–6 h postop with
>60% decrease in PTH
% Ca decrease*
greater than
Sensitivity, %
Specificity, %
PPV, %
Sensitivity, %
Specificity, %
PPV, %
1
2
3
4
5
6
7
8
9
10
20
30
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
80.0
50.0
57.9
68.2
72.0
76.7
78.8
82.9
86.4
89.1
91.8
98.0
100.0
100.0
81.0
82.9
82.9
82.1
80.6
78.8
80.0
80.8
84.0
95.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
66.7
50.0
100.0
100.0
100.5
100.3
100.6
100.6
100.5
100.1
100.8
100.0
100.0
100.0
81.5
81.5
81.5
81.5
81.5
84.0
87.5
91.3
95.2
100.0
100.0
100.0
Abbreviation: PPV, positive predictive value; PTH, parathyroid hormone.
Note: Parameters checked at 2 time periods after thyroidectomy. Bold values indicate the largest sum of sensitivity and specificity for each time period.
*% decrease ¼ [(preop – postop)/preop] 100.
PTH and Ca Predicting Hypocalcemia after Thyroidectomy
HEAD & NECK—DOI 10.1002/hed
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431
hypocalcemia. In performing this pooled data
analysis of the aforementioned studies, our goal
was to obtain and compile as much of the individual patient data as possible, to allow a robust
statistical analysis from which solid conclusions
could be drawn about the combined predictive
value of early PTH and calcium levels after
thyroidectomy.
The results of this study demonstrate and confirm the usefulness of checking PTH and calcium
levels 1 to 6 hours after complete total or completion thyroid surgery. Although PTH alone, checked
1 to 6 hours after surgery, is excellent in predicting hypocalcemia, adding early calcium thresholds
improves the predictive power. When PTH and
calcium were checked 1 to 2 hours postoperatively,
their combined predictive power was nearly perfect, with an area under the ROC curve of 0.998
(1.0 being the ideal test) (see Figure 1). In our
data set, at 5 to 6 hours after surgery, using PTH
and Ca thresholds together resulted in perfect predictive capability (see Figure 2). In this time period, if PTH decreased >60% and calcium
decreased >10%, then sensitivity and specificity
with regard to predicting symptomatic hypocalcemia were both 100% (Table 4).
Thus, early PTH and calcium levels are
extremely useful tools for stratifying patients as
low and high risk for developing postthyroidectomy hypocalcemia. Based on these results,
patients with >60% decline in PTH and 10%
decline in calcium obtained 1 to 6 hours after
surgery are at high risk of developing symptomatic hypocalcemia after total thyroidectomy.
Immediate initiation of calcium and vitamin D
supplements for these patients is warranted.
This practice could not only shorten or eliminate
bothersome hypocalcemic symptoms in this
patient group, but also potentially shorten their
duration of hospitalization.
Conversely, patients with 60% decline in
PTH and 10% decline in calcium 1 to 6 hours
postoperatively have a very low risk of hypocalcemia and could be discharged after appropriate observation for other complications such as a
hematoma. Nonetheless, these patients should still
be counseled about the symptoms of hypocalcemia
and be instructed to return immediately if these
occur. Early discharge should be considered only if
the patient appears reliable and has the means
and/or support to return, should hypocalcemic
symptoms develop after discharge.
There is a biochemical explanation as to
why checking early calcium levels after thyroid-
432
PTH and Ca Predicting Hypocalcemia after Thyroidectomy
ectomy improves predictive capabilities. Some
patients who become hypocalcemic after thyroidectomy do so without a significant decrease
in PTH production. These patients may have
an altered calcium metabolism caused by medications (corticosteroids, diuretics) or diseases
(renal failure, alkalosis, and blood transfusions); also, certain physiologic states have
higher calcium requirements such as pregnancy,
lactation, and during rapid growth. In these
types of patients, PTH alone may not be a good
predictor of hypocalcemia after thyroidectomy.
Calcium marginally improves predictability, but
it is not significantly different from that of PTH
alone. Assessment of Ca is a low-cost test and
is performed routinely in postthyroidectomy
patients. Some studies have shown that combining PTH and Ca improves predictability
under certain circumstances.35,36 Our study
suggests that Ca may be useful in combination
with PTH. The fact that it is not statistically
significant may be attributed to small sample
size, heterogeneity of data sources and associated hypocalcemia definitions, and superior predictability of PTH. One potential use for Ca
may be in a subgroup of patients with a borderline decrease in PTH.
The use of prophylactic calcium (with or
without vitamin D) replacement after thyroidectomy seems to be gaining popularity,32,33 and
some might argue that this practice makes the
early prediction of hypocalcemia unnecessary.
Although it is true that giving prophylactic calcium reduces the incidence of mild to moderate
symptomatic hypocalcemia, patients with more
severe hypocalcemia will still need intravenous
replacement and monitoring. We believe early
prediction of hypocalcemia and prophylactic
replacement can be complementary strategies in
managing postoperative thyroidectomy patients.
When used together, these 2 approaches could
reduce the frequency of symptomatic hypocalcemia and could allow for a safer protocol for early
discharge after thyroidectomy.
Limitations of this study include the inherent variability that exists between various PTH
and calcium assays and the variability in the
definition of hypocalcemia used in the studies
included in this metaanalysis (Table 1). In general, PTH assays have an interassay variation
of between 7% and 12%.34 To control for the
interassay and interstudy PTH and calcium variability, percentage decreases (rather than absolute values) were used in the analysis.
HEAD & NECK—DOI 10.1002/hed
April 2010
In summary, PTH assay checked 1 to 6 hours
after thyroidectomy provides excellent accuracy
in determining which patients will become significantly hypocalcemic. This predictive power is
improved to nearly perfect when early calcium
levels are considered as well. Obtaining preoperative PTH and calcium values is suggested so
that percentage decreases can be calculated.
Routine use of these assays should be considered to improve the postoperative management
of patients with total and completion thyroidectomy. Patients identified as low risk for
hypocalcemia could be discharged sooner. Conversely, patients identified as high risk for hypocalcemia could be treated earlier, potentially
shortening the duration of their hypocalcemic
symptoms and hospitalization.
REFERENCES
1. Glinoer D, Andry G, Chantrain G, Samil N. Clinical
aspects of early and late hypocalcemia after thyroid surgery. Eur J Surg Oncol 2000;26:571–577.
2. Hundahl SA, Cady B, Cunningham MP, et al. Initial
results from a prospective cohort study of 5583 cases of
thyroid carcinoma treated in the United States during
1996. US and German Thyroid Cancer Study Group.
An American College of Surgeons Commission on
Cancer Patient Care/Evaluation Study. Cancer 2000;89:
202–217.
3. Lemaire FX, Debruyne F, Delaere P, Vander Poorten V.
Parathyroid function in the early postoperative period
after thyroidectomy. Acta Otorhinolaryngol Belg 2001;55:
187–198.
4. Lindblom P, Westerdahl J, Bergenfelz A. Low parathyroid hormone levels after thyroid surgery: a feasible predictor of hypocalcemia. Surgery 2002;131:515–520.
5. Warren FM, Andersen PE, Wax MK, Cohen JI. Intraoperative parathyroid hormone levels in thyroid and
parathyroid surgery. Laryngoscope 2002;112:1866–1870.
6. Lo CY, Luk JM, Tam SC. Applicability of intraoperative
parathyroid hormone assay during thyroidectomy. Ann
Surg 2002;236:564–569.
7. Richards ML, Bingener-Casey J, Pierce D, Strodel WE,
Sirinek KR. Intraoperative parathyroid hormone assay:
an accurate predictor of symptomatic hypocalcemia following thyroidectomy. Arch Surg 2003;138:632–636.
8. Lam A, Kerr PD. Parathyroid hormone: an early predictor of postthyroidectomy hypocalcemia. Laryngoscope
2003;113:2196–2200.
9. Payne RJ, Hier MP, Tamilia M, Young J, MacNamara E,
Black MJ. Postoperative parathyroid hormone level as a
predictor of post-thyroidectomy hypocalcemia. J Otolaryngol 2003;32:362–367.
10. Higgins KM, Mandell DL, Govindaraj S, et al. The role
of intraoperative rapid parathyroid hormone monitoring
for predicting thyroidectomy-related hypocalcemia. Arch
Otolaryngol Head Neck Surg 2004;130:63–67.
11. Warren FM, Andersen PE, Wax MK, Cohen JI. Perioperative parathyroid hormone levels in thyroid surgery: preliminary report. Laryngoscope 2004;114:689–693.
12. Lombardi CP, Raffaelli M, Princi P, et al. Early prediction of postthyroidectomy hypocalcemia by one single
iPTH measurement. Surgery 2004;136:1236–1240.
PTH and Ca Predicting Hypocalcemia after Thyroidectomy
13. Friedman M, Vidyasagar R, Bliznikas D, Joseph NJ.
Intraoperative intact parathyroid hormone level monitoring as a guide to parathyroid reimplantation after thyroidectomy. Laryngoscope 2005;115:34–38.
14. Scurry WC Jr, Beus KS, Hollenbeak CS, Stack BC Jr.
Perioperative parathyroid hormone assay for diagnosis
and management of postthyroidectomy hypocalcemia.
Laryngoscope 2005;115:1362–1366.
15. Payne RJ, Hier MP, Tamilia M, Mac Namara E, Young
J, Black MJ. Same-day discharge after total thyroidectomy: the value of 6-hour serum parathyroid hormone
and calcium levels. Head Neck 2005;27:1–7.
16. Payne RJ, Tewfik MA, Hier MP, et al. Benefits resulting
from 1- and 6-hour parathyroid hormone and calcium
levels after thyroidectomy. Otolaryngol Head Neck Surg
2005;133:386–390.
17. Quiros RM, Pesce CE, Wilhelm SM, Djuricin G, Prinz
RA. Intraoperative parathyroid hormone levels in thyroid surgery are predictive of postoperative hypoparathyroidism and need for vitamin D supplementation. Am
J Surg 2005;189:306–309.
18. Soon PS, Magarey CJ, Campbell P, Jalaludin B. Serum
intact parathyroid hormone as a predictor of hypocalcaemia
after total thyroidectomy. ANZ J Surg 2005;75:977–980.
19. Vescan A, Witterick I, Freeman J. Parathyroid hormone
as a predictor of hypocalcemia after thyroidectomy.
Laryngoscope 2005;115:2105–2108.
20. McLeod IK, Arciero C, Noordzij JP, et al. The use of
rapid parathyroid hormone assay in predicting postoperative hypocalcemia after total or completion thyroidectomy. Thyroid 2006;16:259–265.
21. Roh JL, Park CI. Intraoperative parathyroid hormone
assay for management of patients undergoing total thyroidectomy. Head Neck 2006;28:990–997.
22. Di Fabio F, Casella C, Bugari G, Iacobello C, Salerni B.
Identification of patients at low risk for thyroidectomyrelated hypocalcemia by intraoperative quick PTH.
World J Surg 2006;30:1328–1333.
23. Khafif A, Pivoarov A, Medina JE, Avergel A, Gil Z, Fliss
DM. Parathyroid hormone: a sensitive predictor of hypocalcemia following total thyroidectomy. Otolaryngol
Head Neck Surg 2006;134:907–910.
24. Chia SH, Weisman RA, Tieu D, Kelly C, Dillmann WH,
Orloff LA. Prospective study of perioperative factors in predicting hypocalcemia after thyroid and parathyroid surgery. Arch Otolaryngol Head Neck Surg 2006;132:41–45.
25. Wong C, Price S, Scott-Coombes D. Hypocalcaemia and
parathyroid hormone assay following total thyroidectomy:
predicting the future. World J Surg 2006;30:825–832.
26. Ghaheri BA, Liebler SL, Andersen PE, et al. Perioperative parathyroid hormone levels in thyroid surgery.
Laryngoscope 2006;116:518–521.
27. Del Rio P, Arcuri MF, Ferreri G, Sommaruga L, Sianesi
M. The utility of serum PTH assessment 24 hours after
total thyroidectomy. Otolaryngol Head Neck Surg 2005;
132:584–586.
28. Noordzij JP, Lee SL, Bernet VJ, et al. Early prediction of
hypocalcemia after thyroidectomy using parathyroid hormone: an analysis of pooled individual patient data from
nine observational studies. J Am Coll Surg 2007;205:
748–754.
29. Payne RJ, Hier MP, Cote V, Tamilia M, MacNamara E,
Black MJ. Postoperative parathyroid hormone levels in
conjunction with corrected calcium values as a predictor
of post-thyroidectomy hypocalcemia: review of outcomes
1 year after the implementation of a new protocol. J Otolaryngol 2005;34:323–327.
30. Soon PS, Magarey CJ, Campbell P, Jalaludin B. Serum
intact parathyroid hormone as a predictor of hypocalcaemia after total thyroidectomy. ANZ J Surg 2005;75:977–
980.
HEAD & NECK—DOI 10.1002/hed
April 2010
433
31. Interpreting Diagnostic Testsby Thomas G. Tape, MD
from University of Nebraska Medical Center. http://
gim.unmc.edu/dxtests/roc3.htm (Accessed June 18,
2006).
32. Moore FD Jr. Oral calcium supplements to enhance
early hospital discharge after bilateral surgical treatment of the thyroid gland or exploration of the parathyroid glands. J Am Coll Surg 1994;178:11–16.
33. Terris DJ, Moister B, Seybt MW, Gourin CG, Chin E.
Outpatient thyroid surgery is safe and desirable. Otolaryngol Head Neck Surg 2007;136:556–559.
434
PTH and Ca Predicting Hypocalcemia after Thyroidectomy
34. Sokoll LJ, Wians FH Jr, Remaley AT. Rapid intraoperative immunoassay of parathyroid hormone and other
hormones: a new paradigm for point-of-care testing. Clin
Chem 2004;50:1126–1135.
35. Lombardi CP, Raffaelli M, Princi P, et al. Parathyroid
hormone levels 4 hours after surgery do not accurately
predict post-thyroidectomy hypocalcemia. Surgery 2006;
140:1016–1025.
36. Asari R, Passler C, Kaczirek K, Sheuba C, Niederle B.
Hypothyroidism after total thyroidectomy: a prospective
study. Arch Surg 2008;143:132–137.
HEAD & NECK—DOI 10.1002/hed
April 2010