This was a retrospective study of patients undergoing thyroid surgery from January 2018 to May 2019 at the Department of Thyroid Surgery, Xiangya Hospital, Central South University. This study was approved and agreed upon by the Ethics Committee of Xiangya Hospital of Central South University, and all patients participating in the study provided written informed consent. All operations were performed by the same experienced surgical team. The inclusion criteria were patients with PTH levels <10 pg/mL on the first day after thyroidectomy who could complete follow-up after surgery. The exclusion criteria were patients with a previous history of thyroid or parathyroid surgery, parathyroid disease, MEN Ⅰ or II, abnormal albumin levels before or after surgery, and chronic or acute renal insufficiency. In total, 111 patients were ultimately included in the study.
1. Patient's clinical data
The demographic information collected from the patients included sex and age. The data collected related to the operation included the scope of the operation, the number of parathyroid glands retained in situ (PGRIS) during the operation, and the postoperative pathological results of the thyroid nodules. Biochemical indicators including preoperative serum calcium, magnesium, phosphorus, and 25-hydroxyvitamin D3 levels and PTH levels, serum calcium, magnesium, and phosphorus levels were measured on days 1, 3, 7, and 30 after surgery
2. Preoperative preparation and parathyroid gland characterization
Examinations included laryngoscopy and ultrasonography of the thyroid and neck lymph nodes before surgery. Thyroid function, PTH, albumin, and serum ions were measured within one week before surgery. The scope of surgery was determined by preoperative diagnosis. All patients defaulted to having 4 parathyroid glands in the normal position of the parathyroid gland. During the operation, the surgeon did not intentionally search for ectopic parathyroid glands and recorded the number of parathyroid glands remaining in situ (PGRIS). Intraoperative parathyroid glands are based on visual recognition, and any suspicious parathyroid tissues were sent to intraoperative frozen section pathological biopsy. The number of PGRIS during the operation was divided into 5 groups: group 1, no PGRIS; group 2, 1 PGRIS; group 3, 2 PGRIS; group 4, 3 PGRIS; and group 5, 4 PGRIS. The parathyroid glands that were accidentally removed or had obvious color changes during the operation were excised and preserved in 0.9% saline. A thorough examination was performed to inadvertently identify parathyroid glands in the specimen after total thyroidectomy. Parathyroid autoimplantation was performed by cutting the parathyroid glands into 1-mm-sized pieces and placing them into the ipsilateral sternocleidomastoid muscle.
3.Postoperative management and follow-up
The patients prophylactic received intravenous infusion of calcium gluconate (0-2 g/day) from the first postoperative day, as well as oral calcium (1.2-3.6 g/day) and calcitriol (0.25-0.75 μg/day). Once the patient develops symptomatic hypocalcemia, we will increase the dose of continuous calcium supplementation. The dose at which the patient did not develop symptomatic hypocalcemia was considered adequate. All patients were discharged on the third day after surgery. Our hospital informed these patients to follow-up on the seventh day and one month after surgery so that the parathyroid function return to normal and serum ion concentrations could be measured, and the doses of calcium and calcitriol could be adjusted. Thereafter, the same surgical team followed these patients for at least one year at 3-month intervals.
4. Definitions
The symptoms and signs of symptomatic hypocalcemia include numbness or tingling around the mouth and fingers, muscle spasms, or cramps in the limbs. Other signs include the Chvostek sign, Trousseau sign. Normal parathyroid function was defined as PTH> 15 pg/mL without oral calcium or calcitriol replacement therapy, hypoparathyroidism was defined as PTH <15 pg/ml, and permanent hypoparathyroidism was defined as postoperative PTH <15 pg/mL lasting for more than 1 year and requiring oral calcium or calcitriol replacement therapy. PTH levels were determined using an electrochemiluminescence immunoassay (normal reference value range is 15-65 pg/mL), with a serum calcium concentration reference value range of 2.0-2.6 mmol/L, serum magnesium concentration reference value range of 0.66-1.07 mmol/L, and serum phosphorus concentration value reference range of 0.86-1.78 mmol/L.
5.Statistical analysis
According to the recovery trend of serum ions and PTH, linear interpolation and the linear trend of neighboring points are used for variables with missing values. These variables included the Pod3 PTH (2.7%), Pod3 Mg (1.8%), Pod3 Ca (1.8%), and Pod3 P (1.8%); Pod7 PTH (1.8%), Pod7 Mg (5.4%), Pod7 Ca (4.5%), and Pod7 P (5.4%); and Pod30 PTH (4.5%). The optimal cut-off values for serum phosphorus concentration, serum calcium concentration, and serum magnesium concentration on the seventh postoperative day and for PTH on the first and third postoperative days were determined by receiver operating characteristic (ROC) curve analysis. This analysis method uses the maximum value of the Youden index as the cut-off value[11]. The area under the ROC curve represents the predictive power of laboratory parameters. Categorical variables are represented by frequency, and the data of continuous variables conforming to a normal distribution are expressed as the mean ± standard deviation. If the data do not conform to a normal distribution, then they are expressed by the median and IQR. Continuous variables were compared using the Kruskal-Wallis test to examine the differences between groups, and categorical variables were compared using the chi-square test. If there were theoretical numbers <10 in the categorical variables, then Fisher's exact probability test was used to obtain the p-value. Logistic regression analysis was performed to determine the effects of these factors on normal parathyroid function on the seventh day after thyroid surgery. Statistical analysis was performed using SPSS 25.0, Medcalc 15.8, and Excel 2019. All tests were two-tailed tests, and P <0.05 was considered statistically significant.