POLSKI
PRZEGLĄD CHIRURGICZNY
2010, 82, 1, 24–28
10.2478/v10035-010-0005-1
Postoperative PTH measurement as a predictor of
hypocalcaemia after thyroidectomy
Monika Proczko-Markuszewska, Jarosław Kobiela, Tomasz Stefaniak,
Andrzej J. Łachiński, Zbigniew Śledziński
Department of General, Endocrine and Transplant Surgery, Medical University in Gdańsk
Kierownik: prof. dr hab. Z. Śledziński
Hypocalcemia after thyroidectomy is the most common postoperative complication with reported incidence from 0.5% to even half of the operated patients. Hypoparathyroidism could be a result of careless
or inadequate preparation during the surgical procedure. There is a variety of proposed options for
prediction of the incidence of hypocalcemia. The most effective of them are the perioperative and intraoperative measurements of PTH level.
The aim of the study was to assess the potential correlation between the iPTH levels after the operation and development of hypocalcaemia. The possible prediction value of postoperative iPTH levels
was to be evaluated assessed.
Material and methods. A prospective study was performed on 100 patients who underwent total
thyroidectomy from January 2007 to June 2009. The total calcium level and intact human PTH (iPTH)
levels were measured 24 hours before, 1 and 24 hours after the surgery.
Results. We have presented a significant correlation between early iPTH measurement and risk of
hypocalcaemia. Moreover a significant correlation between the iPTH level 1 hour after operation with
the calcium level 24 hours after the operation was demonstrated.
Conclusions. Early postoperative assessment of iPTH levels can be used to identify the group of
patients at risk of hypocalcaemia after thyroidectomy. Pre-emptive calcium supplementation can lead
to avoidance of complications causing prolonged hospital stay and most importantly to prevent severe
hypocalcemia.
Key words: hypocalcaemia, postoperative parathyroid hormone measurement, thyroidectomy, calcium supplementation
Hypocalcaemia remains the most common
complication after the thyroidectomy. Its reported incidence varies from 0.5% to even half
of the operated patients. Parathyroid gland
function can be markedly impaired by surgical
manipulation either due to direct trauma to the
gland or its ischemia due to vascular compromise. In some cases, despite careful visualization and prevention of parathyroids during the
operation, symptomatic hypocalcaemia may
occur. The lowest calcium levels are typically
recognized 24-48 hours after thyroidectomy,
though hypocalcemia may be delayed and present on the fourth postoperative day or even
later on. This leads to longer hospitalization
and increased final cost of the treatment (1, 2,
3). Although there has been much effort put
into the research in prevention of recurrent
nerve palsy over the last years (4, 5, 6), postoperative hypoparathyroidism remains a widely
underrated complication. That’s why it is important to develop strategies to prevent and/or
quickly treat this pathology. The traditional
approach involves in-hospital clinical assessments and monitoring of calcium level requiring
repeated blood sampling. This policy although
troublesome and inconvenient is still used by
most of the surgical centres worldwide.
However, it was repeatedly suggested that
measurement of intact parathyroid hormone
(iPTH) after thyroidectomy is very useful in
prediction of postoperative hypocalcaemia.
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Postoperative PTH measurement as a predictor of hypocalcaemia after thyroidectomy
There are two modalities of iPTH measurement. Intraoperative measurement, is a very
valuable method which allows for autotransplantation of the unintentionally resected
parathyroid gland during the same procedure
before the skin closure, but it still remains an
expensive and not widely accessible method.
Selective intraoperative PTH measurement
guided parathyroid autotransplantation reduces a risk of permanent and transient postoperative hypoparathyroidism (7, 8). The alternative solution is the early post-operative
measurement of iPTH based on standard
laboratory assessments of this hormone.
Material and methods
A group of 100 patients, who underwent
total thyroidectomy in Department of General,
Endocrine and Transplant Surgery between
January 2007 and June 2009 was prospectively analysed. Six of the patients from this
group were excluded because of accidentally
diagnosed concurrent hyperparathyroidism
(two patients) or already taking calcium supplementation due to osteoporosis (four patients).
Hypocalcemia was symptomatic in 9 patients. The symptoms onset were observed
between second and forth postoperative day.
Total calcium level before the operation, 1
and 24 hours after the surgery were assessed.
The iPTH level was assessed before, 1 and
24 hours after thyroidectomy. Specificity and
sensitivity of iPTH level assessments 1 and
24 hours after surgery was calculated aiming
to evaluate its potential usage as a predictor
of postoperative hypocalcaemia.
Serum calcium levels were measured in mg/
dl with reference ranges 8.5-10.5 mg/dl. Hypocalcaemia symptoms are rather uncommon
unless serum level is below 8.0 mg/dl and thus
we considered hypocalcaemia when the level
was below 8.2 mg/dl. Typical hypocalcemiarelated symptoms such: paresthesia in the face
or upper and lower limbs, nervousness and
anxiety were observed in different severity
from asymptomatic cases to severe tetany.
The reference values for iPTH in our laboratory were 10-62 pg/mL, with the analytical
sensitivity of 2-3 pg/mL. The relationships between development of hypocalcaemia and iPTH
levels were analyzed using Pearson not-parametric correlation test. For every parametric
evaluation ANOVA was used, p level was con-
25
sidered significant when it was over 0.05, correlation was considered strong above 0.70.
Results
Hypocalcaemia was observed in 24 patients
out of 100 operated cases. Out of these patients
in 14 cases total calcium level was lower then
7.5 mg/dl.
In the group of patients with hypocalaemia
the average level of iPTH 1 h after surgery was
below 7.76 and after 24 h 9.91 pg/mL (p<0.001).
Average level of total calcium level 1 h after
operation was 8.39 mg/dl, after 24 h 7.89 mg/dl
(p<0.001) (fig. 1).
In all hypocalcaemic patients levels of iPTH
measured at 1 h after the operation ranged
between 7 and 20 pg/mL/. All patients with
iPTH levels at 1 h after surgery higher then
20pg/mL remained eucalcaemic.
The measurements of Ca2+ levels after 1 and
24 hours post-operatively were not signficantly different between the groups that later
developed hypocalcemia vs normocalcemic
patients (fig. 2).
A strong correlation between iPTH measured 1 h after subtotal thyroidectomy and the
risk of developing hypocalcaemia was found
(Pearson coefficient r=0.73, p<0.05), similar
correlation was found between the level of
iPTH assessed after 24 hours (Pearson coefficient r=0.68, p<0.05) (tab. 1). Diagnostic
specificity of iPTH assessment 1 hour after
operation equalled 83.87% and sensitivity
equalled 92.89% (tab. 2).
Fig. 1. PTH levels 1 and 24 hours after surgery in
hypocalcaemic and normocalcaemic groups. *p<0.05, tStudent test
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M. Proczko-Markuszewska et al.
Table 1
Parameter
iPTH 1 h
iPTH 24 h
Ca 1 h
Ca 24 h
Pearson r coefficient
p value
0,73
0,68
0,21
0,46
p<0,05
p<0,05
p<0,05
p<0,05
Table 2
Fig. 2. Calcium 1 and 24 hours after surgery, p<0.005,
t-Student test
Discussion
The number of patients with postoperative
transient hypoparathyroidism is still significant with most series reporting an incidence
around 20-30% (the rate of permanent hypoparathyroidism varies between 0.4-1.7%) (9,
10, 11). There are also many different definitions of persistent and transient hypocalcemia
(12, 13). In our study, the percentage of hypocalcemia reached 24% and the percentage of
symptomatic hypocalcemia was 9% (what represents 37.5% of the hypocalcemic patients).
The prospective analysis of perioperative
iPTH-kinetics could help to explain the mechanism of postoperative hypoparathyroidism
and calculate the cut-off iPTH level prognostic
for postoperative hypocalcaemia. It is obvious
that the most important factor determining
the presentation of hypocalcaemia is the success rate of preserving parathyroid function.
There have been several studies that evaluated the risk factors of postoperative hypocalcemia after subtotal thyroidectomy and also
some studies on patients after total thyroidectomy for cancer or benign thyroid diseases.
Some reports suggest that early postoperative
total or ionized calcium level predicts hypoparathyroidism after both total and subtotal
thyroidectomy (14, 15). Intraoperative iPTH
levels are thought to be an accurate predictor
of symptomatic hypocalcaemia (16), but this
method can not be used in many surgical centres due to financial conditions.
It has also been postulated that the biochemical and symptomatic hypocalcemia can
be prevented by routine administration of
PTH 1 hr
(for levels < 20
pg/mL)
PTH 24 hr
(for levels < 20
pg/mL)
Sensitivity
92,89%
85,71%
Specificity
83,87%
87,09%
calcium accompanied or not by vitamin D. In
a study by Roh the patinents undergoind large
neck dissections were randomised to receive
calcium plus vitamin D vs calcium alone vs no
supplementaion. Although the results clearly
pointed to the benefits of calcium and vitamin
D supplementaion, it should be mentioned that
even that extensive strategy did not entirely
prevent hypocalcemia, with 2% of symptomatic and 8.2% of biochemical hypocalcemia.
Moreover in a group of calcium supplementation alone corresponding percentages were as
high as 12.2 and 24.5 (17).
In even more radical strategy, proposed by
Abboud et al. the patients were treated with
routine parathyroid autotransplantation and
calcium plus vitamin D supplementation after
total thyroidectomy. Surpisingly, in this study
the frequency of biochemical hypocalcemia
reached 17% and minor symptoms were noted
in 1.6% of patients (18). These results might
suggest that in some patients standard supplementation alone may not be sufficient. We
believe that in those cases extra supplemantation should be proposed basing on the results
of intraoperative or early postoperative PTH
level assesment.
The alternative method could be the early
post-operative measurement of intact PTH to
identify the patients at risk of developing hypocalcaemia. In our study, iPTH levels were
assessed 1 h and 24 h after surgical procedure,
and strong correlation was found between
iPTH level measured 1 h after surgery and the
development of hypocalaemia (Pearson coefficient r=0.73, p<0.05) with measurement correlation at the level of r=0.68, p<0.05. IntrestUnauthenticated
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Postoperative PTH measurement as a predictor of hypocalcaemia after thyroidectomy
ingly Ca2+ level was not correlated signficantly with later presentation of hypocalcemia
either after 1 or 24 hours (respectively 0.21,
p<0.05 and 0.46, p<0.05). We presume that
early post-operative measurement of PTH
might be as accurate as results obtained several hours after surgery, because the half-life
of PTH is 2-5 min. In other trials different
combinations of PTH and calcium measurements were also used. Payene et al. published
results of PTH measurements at 6, 12, 20
hours after thyroidectomy, concluding that
PTH and calcium level at 6 h accurately identified patients at risk for developing hypocalcemia (18). Therefore, it seems crucial to set
optimal timing for measurement of PTH levels
after surgical procedure (19). In other studies
compared PTH levels assessed 1-12 h postoperatively with those at 24 h, finding that early
results are equally accurate. Vescan et al. in
a study on two hundred patients after thyroidectomy compared the results of PTH measured
1 h after surgery with level diagnosed next
morning after surgery. The levels did not differ
significantly. Similar timing of blood sampling
and PTH measurements was used by Roh &
Park. They assessed quick PTH (qPTH) levels
preoperatively and 10 min, 1 h, 24 h – postoperatively. Hypocalcaemic patients had significantly lower level of PTH measured 10 min
after surgery than the normocalcemic group.
It was suggested that PTH measured 10 after
surgery could be predictive for hypocalcaemia.
Ghaheri et al. in a group of 80 patients after
total thyroidectomy obtained less definitive
results (20, 21, 22). PTH was measured immediately after surgical procedure and it was
concluded that low PTH level correlated with
postoperative hypocalcaemia but could not
predict it.
Even more disappointing results were obtained by Lombardi et al. (24). In large series
of 523 consecutive patients undergoing thyroidectomy, 199 developed hypocalcaemia.
PTH level measured 4 h after surgery was
normal in 70 hypocalcaemic cases, and among
them 11 patients were clinically symptomatic.
Ultimately it was concluded that PTH level
alone did not accurately predict relevant postoperative hypocalcaemia. The guidelines of
The Society of Australian Endocrine Surgeons
has published a review of 458 patients after
thyroidectomy revealing that 7% of the patients despite with normal PTH level devel-
27
oped a mild self-limiting hypocalceamia that
did not require calcium supplementation (24).
Del Rio et al. studied a group of 1000 thyroidectomised patients, checking the accuracy of
the 24 h PTH measurement in the prediction
of hypocalcaemia. 253 patients developed hypocalcaemia, 152 were symptomatic by 24 h
and 101 presented delayed (>24 h) hypocalcemia. However only 49 patients had low PTH
level at 24 h. Therefore authors suggested that
PTH at 24 h after thyroidectomy was not a
predictive factor of postoperative hypocalcaemia (25, 26, 27).
As a conclusion of our study we suggest PTH
levels 1 and 24 hours postoperatively as good
predictors of postoperative hypocalcaemia with
sensitivity of 93%. There were no cases in our
study with hypocalcaemia and reference PTH
level. We also suggest that PTH measurement
obtained during the first hour after the surgical
procedure or even 24 hours after is still predictive one. Decreased prediction value could be
connected with undertaken lower limit of PTH
level or highest PTH level before the surgery.
Thanks to early diagnosis of potential hypocalcemia, it is possible to institute calcium
suplementation and avoid progress of it’s
symptoms. This would lead to further reduction in hospital stay, costs and risk for posttyroidectomy patients.
Summary
Summarizing, hypoparathyroidism after
thyroidectomy is still significant source of
morbidity and expences. To prevent severe
hypocalcaemia or even tetany it is critical to
identify the group of patients at risk, what
enables early supplementation of calcium.
With such policy normocalcemic patients with
normal iPTH level could be safely discharged
early after surgery. On the other hand we
should realize that the accuracy of early iPTH
measurement is about 93%. This is relieved by
the fact that in some patients who developed
symptomatic hypocalcaemia with normal PTH
level, hypocalcaemia was mild and self-limiting. They could be safely early discharged and
treated by oral calcium supplementation.
Conclusion
iPTH level at 1h after surgery is a strong
early predictor of hypocalcaemia after subtotal
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28
M. Proczko-Markuszewska et al.
thyroidectomy. iPTH level at 1h after surgery
could therefore differentiate between patients
at risk of hypocalcaemia and patients that that
could be safely discharged early.
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Adress correspondence: 80-211 Gdańsk, ul. Dębinki 7
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