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Korean Journal of Clinical Oncology > Volume 9(1); 2013 > Article
Kwon, Lee, Kwon, Choi, Koo, Kim, and Youn: Preoperative parathyroid hormone level as a predictive factor for post-thyroidectomy hypoparathyroidism

ABSTRACT

Purpose:

Whether the level of the preoperative parathyroid hormone (PTH) is a risk factor of postoperative hypoparathyroidism remains unclear. The aim of this study was to evaluate the predictive value of preoperative PTH for the hypoparathyroidism following total thyroidectomy.

Methods:

Five hundred two patients performed total thyroidectomy from January 2009 to July 2010 in Seoul National University Hospital were enrolled. Demographics, operative variables, and the development of hypoparathyroidism were collected and evaluated.

Results:

A total of 502 patients were enrolled during the study period. Patients had a mean age of 48.1±12.1 years (range, 16 to 95 years) and showed a female predominance (n=420, 83.7%). Preoperative PTH of 44.5 pg/㎖ was recommended as cut-off value. Transient hypoparathyroidism developed 2.4 times (95% confidence interval [CI], 1.1 to 5.1) more frequently in low PTH group (P=0.021). Percentage decline of the preoperative PTH also showed significant association with transient hypoparathyroidism. When the value of 73.9% decline was used, the chance of transient hypoparathyroidism was 3.3 times (95% CI, 2.0 to 5.5) higher in high percentage decline group (P<0.001). Correlation between postoperative PTH level and development of transient hypoparathyroidism was not found (P=0.171). In regard to the permanent hypoparathyroidism, there were no significant differences in all factors.

Conclusion:

Preoperative PTH level and percentage decline can be used as a predictive factor for postoperative hypoparathyroidism. In patients with low PTH level (<44.5 pg/㎖), caution should be given to prevent injury of the parathyroid glands.

INTRODUCTION

Postoperative hypoparathyroidism is one of the most frequent complications after thyroid surgery with the incidence being reported to vary from 1.6% to 50% [1-4]. The causes of the postoperative hypoparathyroidism include surgical trauma to the parathyroid glands, inexperience of the surgeon, hyperthyroidism, retrosternal goiter, extent of neck dissection, and thyroid carcinoma.
Post-thyroidectomy hypocalcemia may be categorized into three types according to the symptomatic and biochemical status [5]. Symptomatic and biochemical hypocalcemia is the most significant problem and can progress to the permanent hypocalcemia. Asymptomatic and biochemical hypocalcemia is not a predisposing factor of permanent hypocalcemia. This condition has been presumed to be perioperative hemodilution, or a stunning of parathyroid during the thyroidectomy. Some patients experienced symptomatic and mismatched biochemical hypocalcemia, defined as deOriginal crease of serum calcium levels despite normal parathyroid hormone (PTH) levels. The latter two categories can be managed conservatively and make no serious problems. Therefore, identification and prediction of the symptomatic and biochemical hypocalcemia is a matter of great importance.
Although many studies have aimed to find the risk factors for transient and permanent hypoparathyroidism following thyroidectomy [1,6-13], whether the level of the preoperative PTH is a risk factor remains unclear. The aim of this study was to evaluate the predictive value of preoperative PTH for the hypoparathyroidism following total thyroidectomy.

METHODS

This study was approved by the Institutional Review Board of the Seoul National University Hospital. Between January 2009 and July 2010, 531 patients underwent total thyroidectomy by a single surgeon. Twenty-nine patients with incomplete preoperative assessment and concomitant parathyroid disease including adenoma were excluded. A total of 502 patients were analyzed in this study. Demographic data including age, sex, and body mass index were collected. Preoperative thyroid function, operative method, pathologic diagnosis of malignancy, extent of node dissection, stage of tumor, numbers of removed lymph nodes, and numbers of sacrificed parathyroid glands were analyzed as well as the development of hypoparathyroidism.
Serum levels of calcium, phosphorus, ionized calcium, and PTH were measured within preoperative three months, on postoperative day 1, and on day 2. In cases of postoperative hypoparathyroidism, defined as a total serum calcium level lower than 8.0 mg/dL (normal range, 8.5 to 10.2 mg/dL) associated with hypocalcemic symptoms, patients were supplemented with 1,000–2,000 mg of oral calcium and 0.5 μg of a vitamin D analogue. Hypoparathyroidism was considered permanent in patients whose PTH level was less than 5 pg/㎖, and who required calcium and vitamin D supplementation for longer than 6 months after surgery. All patients were followed up at 2 weeks, 3 months, 6 months, and annually.

Statistical analysis

All results are expressed as mean±standard deviation, proportions, or absolute numbers. RPART, a recursive partitioning procedure or tree classification algorithm in R 2.15.3 (R Development Core Team, Vienna, Austria, http://www.R-project.org) was used to identify optimal cutting points for PTH level. Statistical analysis including the Student t-test, Fisher's exact test, and Mann-Whitney U-test was performed using SPSS ver. 18.0 (SPSS Inc., Chicago, IL, USA). Results were considered statistically significant when a two-sided P-value was 0.05 or less.

RESULTS

A total of 502 patients were enrolled during the study period (Table 1). Patients had a mean age of 48.1±12.1 years (range, 16 to 95 years) and showed a female predominance (n=420, 83.7%). The operative procedures comprised 328 open, 164 robotic, and 10 endoscopic thyroidectomies. Modified radical neck dissection was performed in 149 patients (29.7%). Central lymph node dissection without lateral node dissection was performed in 341 patients (67.9%). Most patients underwent total thyroidectomy due to malignancy (n=484, 96.4%), and the mean size of the lesion was 0.9±0.7 cm (range, 0.1 to 6.8 cm). The mean number of resected lymph nodes was 8.9±9.1 (range, 0 to 61), and the mean number of sacrificed parathyroid glands was 0.6±0.8 (range, 0 to 4). Transient and permanent hypoparathyroidism occurred in 85 patients (16.9%) and 5 patients (1.0%), respectively. In RPART model, preoperative PTH level of 44.5 pg/㎖ was recommended as cut-off value. Transient hypoparathyroidism developed 2.4 times (95% confidence interval [CI], 1.1 to 5.1) more frequently in low PTH group (P=0.021). There were no differences in other risk factors, including age at diagnosis, sex, extent of lymph node dissection, associated hyperthyroidism, and number of sacrificed parathyroid glands (Table 2). Percentage decline of the preoperative PTH also showed significant association with transient hypoparathyroidism. When the value of 73.9% decline was used, the chance of transient hypoparathyroidism was 3.3 times (95% CI, 2.0 to 5.5) higher in high percentage decline group (P<0.001). Correlation between postoperative PTH level and development of transient hypoparathyroidism was not found (P=0.171). In regard to the permanent hypoparathyroidism, there were no significant differences in all factors.

DISCUSSION

Thyroid nodules are a common clinical problem and the incidence of thyroid nodules has increased with the use of screening ultrasonography. As in other countries, the incidence of thyroid cancer is rapidly increasing in Korea and is becoming the most common cancer in Korean women [14]. Therefore, the concern about complications of thyroidectomy has been highlighted. Despite of every effort of endocrine surgeons to preserve all parathyroid glands, postoperative hypoparathyroidism is still one of the most common and serious complications [5]. Postoperative hypoparathyroidism extends the duration of hospital stay, requires additional laboratory tests, and significantly increases the overall cost of thyroidectomy. Prediction of hypoparathyroidism after total thyroidectomy is important for early treatment, avoiding troublesome symptoms, and safe discharge.
Many studies have tried to predict postoperative hypoparathyroidism. Laboratory tests including postoperative PTH level, ionized calcium, total calcium, and phosphorus level were evaluated [1,6-13]. In most of the studies, to predict post-thyroidectomy hypocalcemia, the use of postoperative serum PTH was recommended with a sensitivity ranging from 64% to 100% and a specificity ranging from 72% to 100%. However, some studies questioned the role of the postoperative PTH. Del Rio et al. [15] reported that a single measurement of PTH was not predictive of hypocalcemia by evaluating more than 1,000 patients. Lombardi et al. [16] examined 523 patients and demonstrated that PTH lacked accuracy to predict hypocalcemia. These results showed that the postoperative PTH alone was not sufficient as a predictor of hypocalcemia.
The role of preoperative PTH level has not been established. Few studies reported that percentage decline of the preoperative PTH level in the immediate postoperative period was useful to predict hypoparathyroidism [5]. In the present study, the percentage decline of preoperative PTH level, using the cut-off value 73.9%, showed significant difference in the chance of transient hypoparathyroidism (P<0.001). However, there was no study to evaluate the role of single preoperative PTH level. Because the most common cause of significant hypoparathyroidism is surgical trauma to parathyroid gland, to predict hypoparathyroidism in the preoperative period is very important. Caution can be given to prevent injury of the parathyroid glands in high risk patients. Using cut-off value 44.5 pg/㎖ of preoperative PTH, transient hypoparathyroidism was developed 2.4 times higher in low PTH group (P=0.021). There were no differences in known risk factors, including age at diagnosis, extent of lymph node dissection, associated hyperthyroidism, and number of sacrificed parathyroid glands. Vitamin D level which might influence the PTH level showed no difference in both groups. These results suggested that single preoperative PTH level can be used as a predictive tool for postoperative hypoparathyroidism.
There are some limitations in this study. First of all, there may be confusion in the interpretation of the PTH level by the circadian nature of PTH secretion [17,18]. Life style and nutritional intake also modulated the pattern of PTH secretion. Second, the definition of hypoparathyroidism is arbitrary. The literature does not offer any common definition for hypoparathyroidism, and many studies have used their own definitions [10,19-24]. Therefore, it is challenging to compare the result directly and apply it to the patients of other institution.
In conclusion, preoperative PTH level and percentage decline can be used as a predictive factor for postoperative hypoparathyroidism. In patients with low PTH level (<44.5 pg/㎖), careful surgical technique would be recommended, with cautions against preventing injury of the parathyroid glands. Additional research is warranted for more comprehensive conclusion.

CONFLICT OF INTEREST

No potential conflict of interest relevant to this article was reported.

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Table 1
Demographics of patients (n=502)
Characteristic Result
Age (yr) 48.1±12.1 (16-95)
Gender
 Female 420 (83.7)
 Male 82 (16.3)
BMI (㎏/㎡) 23.5±3.2 (13.2-39.4)
Operative method
 Open total thyroidectomy 328 (65.3)
 Robotic total thyroidectomy 164 (32.7)
 Endoscopic total thyroidectomy 10 (2.0)
Extent of lymph node dissection
 No LN dissection 12 (2.4)
 CLND only 341 (67.9)
 MRND 149 (29.7)
Pathologic characteristics
 Diagnosis
  Malignancy 484 (96.4)
  Benign 18 (3.6)
 Size of the lesion 0.9±0.7 (0.1-6.8)
 No. of LN recruitment 8.9±9.1 (0-61)
 No. of parathyroid glands sacrificed 0.6±0.8 (0-4)
Transient hypoparathyrodism 85 (16.9)
Permanent hypoparathyroidism 5 (1.0)

Values are presented as mean±SD (range) or number (%).

BMI, body mass index; LN, lymph node; CLND, central lymph node dissection; MRND, modified radical neck dissection.

Table 2
Clinicopathological differences between low and high PTH group
Variable PTH group P-value
Low (n=411) High (n=91)
Age (yr) 47.6±12.2 50.1±11.6 0.086
Gender 0.075
 Female 77 (90.6) 343 (82.3)
 Male 8 (9.4) 74 (17.7)
BMI (㎏/㎡) 23.5±3.3 23.3±2.9 0.506
Operative method 0.168
 Open 48 (56.5) 280 (67.1)
 Robotic 35 (41.2) 129 (30.9)
 Endoscopic 2 (2.4) 8 (1.9)
Extent of lymph node dissection
 No LN dissection
 CLND only 91 (95.8) 422 (97.7) 0.560
 MRND 31 (33.3) 124 (28.7) 0.973
Pathologic characteristics
 Diagnosis 0.054
  Malignancy 85 (100) 399 (95.7)
  Benign 0 (0) 18 (4.3)
 Size of the lesion 0.87±0.67 0.97±0.59 0.188
 No. of LN recruitment 8.7±8.7 9.7±10.8 0.342
 No. of parathyroid glands 0.65±0.78 0.59±0.68 0.488
  sacrificed
Transient hypoparathyroidism (%) 18.7 8.8 0.021
Laboratory data
 Vitamin D (pg/㎖) 36.5±10.8 36.7±12.8 0.913
 TSH (μIU/㎖) 2.18±4.01 1.84±1.30 0.427
 Thyroglobulin antibody (U/㎖) 294.3±1,536.6 312.4±1,023.4 0.916

Values are presented as mean±SD or number (%).

PTH, parathyroid hormone; BMI, body mass index; LN, lymph node; CLND, central lymph node dissection; MRND, modified radical neck dissection; TSH, thyroid stimulating hormone.

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