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Objectives/Hypothesis: An immediate method of accurately predicting postoperative hypocalcemia after total thyroidectomy would allow for selective early discharge of patients at low risk. The objective of the study was to determine the utility of perioperative parathyroid hormone measurement in predicting postoperative hypocalcemia after a thyroid surgery that places total parathyroid function at risk.
Study Design: Prospective case series.
Methods: Twenty-seven patients undergoing total or completion thyroidectomy had three blood samples drawn for parathyroid hormone measurement before dissection, 10 minutes after specimen removal, and in the recovery room. Serial ionized calcium levels were measured in the postoperative period. Preoperative, postresection, and recovery room levels were compared with postoperative ionized calcium levels.
Results: The average values before resection, after resection, and in the recovery room were 69.3 (range, 13–163), 42.3 (range, 0–120), and 37.4 (range 7–79) pg/mL, respectively. The incidence of hypocalcemia was 11% (3 of 27 patients). The rate of hypocalcemia was significantly higher (50%) in patients with recovery room parathyroid hormone values of 10 pg/mL or less relative to patients with recovery room parathyroid hormone values greater than 10 pg/mL (4%) in this setting (P = .01). Among patients with a parathyroid hormone value of less than 15 pg/mL in the recovery room, an increasing parathyroid hormone level in the recovery room relative to the level after resection predicted normocalcemia without calcium supplementation on [chi]2 analysis (P = .01).
Conclusion: The study demonstrated that perioperative parathyroid hormone values can help predict patients who are at highest risk for postoperative hypocalcemia after thyroid surgery.
We have previously reported the use of early postoperative calcium levels to predict hypocalcemia and found that the slope of a plot of serial postoperative calcium measurements could predict the postoperative calcium level. 4 However, the utility of this finding in preventing admission was limited by the fact that the measurements had to be obtained over an 8-hour period to be predictive. There was no correlation with levels obtained 2 hours after surgery. 5
Since the late 1990s, the introduction of rapid parathyroid hormone (PTH) assays has allowed for intraoperative measurement of hormone levels. The majority of published reports have focused on the utility of this assay in the setting of hyperparathyroidism in terms of its ability to predict removal of all hyperfunctioning parathyroid tissue and restoration of normocalcemia. We have recently focused on the utility of intraoperative PTH measurements in predicting postoperative hypocalcemia. 6 Our data indicated that there was an increased risk of hypocalcemia (50%) in patients with a PTH value after resection that was greater than 15 pg/mL. In a small subgroup (n = 4) of the patients who had a PTH value after resection of less than 15 pg/mL and a level checked in the recovery room, an increasing or stable PTH value correlated with postoperative normocalcemia. The purpose of the current study was to expand on the findings of our previous study and to determine in a larger number of patients whether the PTH level changes that occur between the operating room and the recovery room were more predictive of hypocalcemia absolute PTH value after resections.
PATIENTS AND METHODS^
Case records of 31 patients who underwent total or completion
thyroidectomy at Oregon Health and Science University (OHSU) (Portland, OR) from
January 1999 to November 2002 and had perioperative PTH assays performed were
reviewed. Patients had three parathyroid hormone levels obtained, one after
induction of anesthesia and before dissection, one at 10 minutes after
dissection was completed and the surgical specimen removed, and one when the
patient arrived in the recovery room. Two patients who received “prophylactic”
calcium supplementation were excluded from the statistical analysis. In
addition, two patients did not have preoperative PTH levels obtained and were
excluded from the study, leaving 27 patients for analysis.
Rapid PTH assays were performed on the samples by the OHSU General Clinical Research Center Core Laboratory. The Immulite turbo intact PTH assay (a chemiluminescent assay) was performed using the DPC Immulite system. The cost was $120 per blood sample. Postoperative ionized calcium levels were monitored every 6 hours while the patients remained in the hospital. The presence or absence of hypocalcemia and need for calcium supplementation were noted. Hypocalcemia was defined as symptoms of hypocalcemia or an ionized calcium value of less than 1.00 mmol/L (the corresponding total serum value was 7.6 mg/dL, approximating a true serum level of 8.0 mg/dL when corrected for postoperative decrease in albumin 2,3).
Statistical analysis was performed. Correlation coefficients between PTH values and calcium levels, the paired two-tailed Student t test, and [chi]2 analysis were calculated using Microsoft Excel software. Statistical significance was assigned to a P value equal to or less than .05.
RESULTS^
Twenty-seven patients who underwent either total or completion
thyroidectomy and had PTH levels obtained perioperatively were studied. Seven
patients were placed on a regimen of calcium supplementation postoperatively,
five in the hypocalcemic group and two in the normocalcemic group (for
undetermined reasons).
The average preoperative PTH value was 69 (range, 13–163), the average value after resection was 43 (range 0–120), and the average recovery room value was 38.7 (range, 7–140) pg/mL. Three patients became hypocalcemic postoperatively (11%) (Table I). All patients who developed hypocalcemia returned to normocalcemia on longitudinal follow-up. There were no cases of prolonged hypocalcemia.
Comparison was made between postoperative ionized calcium levels and the following: preoperative PTH levels, PTH levels after resection, and the PTH levels in the recovery room. There was no significant correlation between preoperative PTH levels and postoperative ionized calcium levels. Postoperative calcium levels did not have a statistically significant positive correlation with postoperative PTH levels (correlation coefficient [r] = 0.30 [P = .10]). However, there was a statistically significant positive correlation with recovery room PTH levels (r = 0.35 [P = .05]).
There were six patients who had PTH levels after resection of less than 15 pg/mL; four were in the normocalcemic group (value range, 0–12 pg/mL) and two were hypocalcemic patients (value range, 6–14 pg/mL). In this group of patients with an intraoperative PTH of less than 15 pg/mL, the incidence of hypocalcemia was 33%. There was not a significant difference in the incidence of hypocalcemia in this group compared with those with an intraoperative PTH greater than 15 pg/mL on [chi]2 analysis (P = .14) (Table II).
Analysis of the PTH values after resection as they relate to the postoperative calcium level was performed in the present study. Our data indicated that there was not a statistically significant relationship between the PTH level after resection and the postoperative calcium level. This was evident in the lack of statistical significance in the t test, as well as the lack of correlation between the two. This point is further supported by the [chi]2 analysis that was performed on the patients with a PTH value after resection of less than 15 pg/mL. Of the six patients in this subset, two became hypocalcemic (33%). The analysis revealed there was not a statistically significant difference in the incidence of hypocalcemia between these two populations, indicating that the PTH value after resection was not predictive of postoperative hypocalcemia (Table II). This is in contrast to our previous study, which found that the value after resection was predictive. This discrepancy is most certainly associated with the small sample size in the present study.
Reviewing the data from the recovery room, we found that the value obtained at this time point is important relative to the postoperative calcium level. Although the t test indicated that the PTH level was not significantly different between the normocalcemic and hypocalcemic groups, there was a statistically significant correlation of the postoperative calcium level with the recovery room PTH value, as stated earlier. Supporting this further is the [chi]2 analysis that was performed at this time point, which showed that there was a statistically significant difference in the incidence of hypocalcemia in patients with recovery room PTH values of 10 pg/mL or less, compared with those with a recovery value greater than 10 pg/mL. This indicates that the PTH value obtained in the recovery room is predictive of postoperative hypocalcemia.
Although this information is useful in determining the likelihood of hypocalcemia, the change in the PTH value as the patient moves from the operating room to the recovery room may be even more informative. As seen in our analysis of patients with a recovery room PTH value of less than 15 pg/mL, no patients with an upsloping PTH value in the recovery room compared with the value after resection developed hypocalcemia in our study. This was statistically significant on [chi]2 analysis (Table IV).
Our results indicate that the perioperative PTH assay can predict the group at low risk for hypocalcemia (recovery PTH value >10 pg/mL, with an increasing PTH value from the time point after resection to the recovery room) who may be candidates for outpatient surgery. In addition, there may be additional predictive information in PTH values checked in the recovery room, as suggested by the fact that no patient who had an increasing PTH level at this time point compared with the intraoperative level developed persistent hypocalcemia requiring calcium supplementation. A stable PTH value from the intraoperative time point to the recovery room does not indicate whether a patient will or will not become hypocalcemic postoperatively (of the two patients who were stable, one became hypocalcemic and one remained normocalcemic). 6 As an extension of the results found in our previous study, testing in the recovery room does give further information about the risk of becoming hypocalcemic in patients who are undergoing thyroid surgery.
Our current study does have obvious limitations. The patient population in this study is relatively small with a low incidence of hypocalcemia. Thus, to draw more definite conclusions, our study requires further validation with a larger study group. This is also evident in the difficulty with establishing a cut-off value for the PTH level from our limited data. However, the use of the change in PTH levels as time passes after the procedure offers insight into whether parathyroid function will recover quickly or over a more prolonged period.
As stated in the introduction, we have previously observed early postoperative calcium levels as a predictive factor for hypocalcemia, with some success. 4,5 Upsloping calcium levels predicted normocalcemia. The difficulty with our findings was that there was no definite cut-off point, and the required duration of observation still mandated inpatient observation at a minimum. The present study built on the work of Marohn and LaCivita, 1 who showed that upsloping calcium levels at 20 hours after surgery corresponded to normocalcemia. In 1991, Lo Gerfo et al. 7 found that patients undergoing total thyroidectomy required longer observation because of the higher incidence of hypocalcemia in this population. Pattou et al. 8 attempted to identify predictive factors of hypocalcemia in 1071 patients undergoing total or subtotal thyroidectomy. The researchers measured PTH levels in the postoperative period, and only in patients who developed hypocalcemia, at the time they became hypocalcemic. Pattou et al. 8 found that a PTH level of less than 12 pg/mL was associated with prolonged hypocalcemia. In 2002, Lindblom et al. 9 reported further work in this area. They measured intraoperative and postoperative PTH levels in 38 patients who underwent total or near-total thyroidectomy and found that a postoperative PTH level obtained the morning following surgery was predictive of biochemical hypocalcemia within the first 3 days after surgery. In addition, Lindblom et al. 9 found that the intraoperative PTH values were also predictive of biochemical hypocalcemia in that time frame, but they did not define a specific limit at which patients were at higher risk. The work of Pattou et al. 8 and Lindblom et al. 9 supports our theory that perioperative PTH levels can predict postoperative calcium status. In our previous work with intraoperative PTH levels, we further expanded on the findings of Lindblom et al. 9 and Pattou et al. 8 by measuring intraoperative PTH levels in patients undergoing thyroid surgery demonstrating that intraoperative PTH levels can predict the risk of postoperative hypocalcemia and found that a intraoperative PTH level greater than 15 pg/mL had a low risk of hypocalcemia. 6
Our current study brings us closer to being able to determine which patients are at highest risk for postoperative hypocalcemia after thyroid surgery. We have found that among patients with intraoperative levels below 15 pg/mL, an increasing PTH level in the recovery room indicates the patient will remain normocalcemic. Unfortunately, the number of patients in this subgroup was rather small. In addition, there were one patient (patient 16) who developed hypocalcemia despite the intraoperative value remaining greater than 15 pg/mL, and the recovery room value did decrease but remained above any level of concern. In this case, there was no indication that there was a risk of developing what is a rather “late” hypocalcemia, which would not have been detected if the patient had been discharged to home at the time of the procedure. This may indicate that there is a group of people who have low calcium stores who are more sensitive to shifts in PTH levels and thus at higher risk for hypocalcemia with a decrease in PTH.
Our current recommendations for the use perioperative PTH values in thyroid surgery are based on the data found in the present study. A patient who has a PTH value of greater than 10 pg/mL in the recovery room that is increasing relative to the value after resection is a candidate for outpatient surgery. Patients who undergo thyroid surgery as outpatients should be followed closely with calcium measurements and should be carefully counseled for awareness of symptoms of hypocalcemia on discharge. If a patient does not satisfy these criteria, he or she is at higher risk for postoperative hypocalcemia and would be admitted for calcium monitoring, as is standard at our institution.
In the future, we will continue to collect data and thereby increase the numbers of patients who have recovery room PTH levels. In addition, we will study a group of patients who satisfy the previously mentioned criteria as outpatients. This will enable us to determine more definitively whether a PTH level obtained in the recovery room can clearly identify patients who at highest risk for hypocalcemia.
CONCLUSION^
Perioperative PTH values can identify patients who are at high risk
for postoperative hypocalcemia. A recovery room PTH value greater than 10 pg/mL
and increasing relative to the intraoperative value indicates a low risk of
hypocalcemia.
Editorial
Comment^
Our reviewers have noted that while these observations are very
interesting and warrant further investigation, the small patient sample does not
support a conclusion that would change current standard patient care practices.
The authors are encouraged to accrue additional patients and to report their
findings when a larger sample has been achieved.
BIBLIOGRAPHY^
1. Marohn MR, LaCivita KA. Evaluation
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Key Words: Thyroid; parathyroid; perioperative; hypocalcemia; parathyroid hormone assay
