Baseline characteristics of the SPTX and TPTX+AT groups
There was no statistical difference in gender, age, serum calcium and phosphorus level, common symptoms (orthopedic pain, pruritus, obvious fatigue) and combined chronic diseases (hypertension, diabetes, coronary heart disease, stroke) between the SPTX and TPTX+AT groups (all P>.05). Preoperative serum iPTH and ALP level was higher in SPTX group than that in TPTX+AT group (P<.05). Due to the change of the preference of our medical team, no patient underwent SPTX in this study(P<.05) (Table 1).
Table 1
Some baseline characteristics of patients undergoing parathyroidectomy
|
TPTX+AT(n=208)
|
SPTX(n=51)
|
P value
|
Female sex
|
96 (46.2)
|
28 (54.9)
|
0.262
|
Age, y
|
50.3 (11.9)
|
49.0 (10.4)
|
0.479
|
Number of parathyroid glands found by ultrasound
|
3.04 (0.94)
|
3.43 (0.70)
|
0.006
|
Number of hyperfunctional parathyroid glands found by MIBI
|
3.14 (1.03)
|
2.67 (1.09)
|
0.004
|
Orthopedic pain
|
|
|
0.114
|
Severe
|
55 (26.4)
|
18 (35.3)
|
|
Light
|
78 (37.5)
|
20 (39.2)
|
|
Pruritus
|
148 (71.2)
|
34 (66.7)
|
0.530
|
Obvious fatigue
|
35 (16.8)
|
7 (13.7)
|
0.590
|
Hypertension
|
159 (76.4)
|
41 (80.4)
|
0.530
|
Diabetes
|
20 (9.6)
|
5 (9.8)
|
0.967
|
Coronary heart disease
|
14 (6.7)
|
2 (3.9)
|
0.673
|
Stroke
|
7 (3.4)
|
0 (0)
|
0.397
|
iPTH, pg/mL
|
1577.4 (1152.9-2177.8)
|
1835.5 (1275.4-2621.0)
|
0.023
|
Serum calcium, mmol/L
|
2.53 (0.23)
|
2.52 (0.23)
|
0.934
|
Serum phosphorus, mmol/L
|
2.29 (0.47)
|
2.31 (0.52)
|
0.838
|
ALP, U/L
|
254.5 (137.3-437.8)
|
488.0 (193.0-825.0)
|
<0.001
|
Year of parathyroidectomy
|
|
|
<0.001
|
≤2013
|
11 (5.3)
|
12 (23.5)
|
|
2014-2017
|
72 (34.6)
|
39 (76.5)
|
|
≥2018
|
125 (60.1)
|
0 (0)
|
|
Values are numbers (percent), mean (standard deviation) or median (interquartile range).
TPTX+AT: total parathyroidectomy with autotransplantation; SPTX: subtotal parathyroidectomy; MIBI:99mTc-sestamibi radionuclide scan; IQR: interquartile range; iPTH: intact parathyroid hormone; ALP: alkaline phosphatase.
Surgical results of the SPTX and TPTX+AT groups
The number of parathyroid glands identified during operation between the two groups had no statistical difference (P=.120). More patients in TPTX+AT group underwent thyroidectomy concurrently than SPTX group (P=.006). The operation time in TPTX+AT group was statistically longer than SPTX group (both P<.05). Additional thyroidectomy would increase operation time, as a result, when patients who underwent thyroidectomy were excluded, the difference in operation time became no longer statistically significant (TPTX+AT: 125.4±38.8min, SPTX: 117.0±27.4min, P=.096). There are more patients diagnosed as parathyroid adenoma in TPTX+AT group than SPTX group (P<.05).
Short-term efficacy and complications of the SPTX and TPTX+AT groups
On postoperative day 1 (POD1), the levels of serum iPTH, calcium and phosphorus decreased significantly compared with those before operation (all P<.05). The level of iPTH was significantly higher than that in TPTX+AT group (P=.023). The POD1 serum calcium level is higher in TPTX+AT group than that in SPTX group (P=.012), however, this difference was not statistically significant by 7 days after operation (P=.355). The results of laboratory examination on POD7 were lacked because they were discharged at that time. The rate of persistent SHPT in SPTX group is statistically higher than that in TPTX+AT group (P=.020). Further binary logistic regression analysis showed that high level of preoperative ALP (OR 1.002, 95% CI 1.000-1.004, P=.036) and small number of parathyroid glands identified during operation (OR 0.046, 95% CI 0.006-0.379, P=.004) were the risk factors for persistent disease. In terms of complications, severe hypocalcemia (TPTX+AT: 23.6%, SPTX: 19.6%, P=.547) was the most common. The incidence of cervical hematoma, wound infection and recurrent laryngeal nerve injury was very low, and there was no statistical difference between the two groups (all P>.05). No patient died during postoperative inpatient period. One patient who underwent TPTX+AT had blockage of lower limb dialysis fistula, resulting in local and systemic infection. The postoperative inpatient days was longer in SPTX group (P<.001) (Table 2). Common symptoms of most patients were improved after operation, and no statistical difference was found between the two groups (all P<.05) (Table 3).
Table 2
Perioperative information of patients undergoing parathyroidectomy
|
TPTX+AT(n=208)
|
SPTX(n=51)
|
P value
|
Operation time, min
|
128.3 (38.8)
|
116.2 (27.0)
|
0.010
|
Number of parathyroid glands identified
|
3.93 (0.38)
|
3.80 (0.53)
|
0.120
|
Thyroidectomy performed concurrently
|
47 (22.6)
|
3 (5.9)
|
0.006
|
Pathological result
|
|
|
0.041
|
Hyperplasia
|
205 (98.6)
|
47 (92.2)
|
|
Adenoma
|
3 (1.4)
|
4 (7.8)
|
|
Diagnosed as thyroid carcinoma
|
14 (6.7)
|
0 (0)
|
0.119
|
POD1 iPTH, mmol/L
|
9.7 (5.4-24.2)
|
37.1 (7.0-121.8)
|
0.023
|
POD1 calcium, mmol/L
|
1.91 (0.28)
|
1.81 (0.23)
|
0.012
|
POD1 phosphorus, mmol/L
|
1.83 (0.53)
|
1.84 (0.53)
|
0.913
|
POD7 calcium, mmol/L (n=180)
|
1.86 (0.25)
|
1.90 (0.19)
|
0.355
|
POD7 phosphorus, mmol/L (n=180)
|
1.13 (0.38)
|
1.18 (0.53)
|
0.581
|
Persistent SHPT
|
4 (1.9)
|
5 (9.8)
|
0.020
|
Severe hypocalcemia
|
49 (23.6)
|
10 (19.6)
|
0.547
|
Hematoma
|
2 (1.0)
|
1 (2.0)
|
0.484
|
Recurrent laryngeal nerve injury
|
1 (0.5)
|
1 (2.0)
|
0.356
|
Wound infection
|
0 (0)
|
0 (0)
|
1.000
|
Postoperative inpatient days, d
|
7.32 (5.20)
|
10.29 (5.83)
|
<0.001
|
Values are numbers (percent) or mean (standard deviation).
PTX: parathyroidectomy; TPTX+AT: total parathyroidectomy with autotransplantation; SPTX: subtotal parathyroidectomy; IQR:interquartile range; iPTH: intact parathyroid hormone; POD: postoperative day; SHPT: secondary hyperparathyroidism.
Table 3
Changes of common symptoms in patients undergoing parathyroidectomy
|
|
|
Postoperative
|
Symptoms
|
Group
|
Preoperative
|
Completely improved
|
Partly improved
|
Barely changed
|
Orthopedic pain
|
Severe
|
TPTX+AT
|
55 (26.4)
|
43 (78.2)
|
8 (14.5)
|
4 (7.3)
|
SPTX*
|
18 (35.3)
|
12 (66.7)
|
5 (27.8)
|
1 (5.6)
|
Light
|
TPTX+AT
|
78 (37.5)
|
61 (78.2)
|
6 (7.7)
|
11 (14.1)
|
SPTX*
|
20 (30.2)
|
14 (70.0)
|
2 (10.0)
|
4 (20.0)
|
Pruritus
|
TPTX+AT
|
148 (71.2)
|
85 (57.4)
|
31 (20.9)
|
32 (21.6)
|
SPTX*
|
34 (66.7)
|
21 (61.8)
|
8 (23.5)
|
5 (14.7)
|
Obvious fatigue
|
TPTX+AT
|
35 (16.8)
|
13 (37.1)
|
10 (28.6)
|
12 (34.3)
|
SPTX*
|
7 (13.7)
|
5 (71.4)
|
1 (14.3)
|
1 (14.3)
|
Values are numbers (percent).
*P>.05 compared with TPTX+AT group postoperativelly
TPTX+AT: total parathyroidectomy with autotransplantation; SPTX: subtotal parathyroidectomy
Follow-up results and long-term outcomes of the SPTX and TPTX+AT groups
After follow-up of all patients included in this study, we excluded 45 patients who were missed follow-up due to telephone change, inability to connect, reluctance to collaborate, and unclear memory. The remaining 204 patients included 165 in TPTX+AT group and 39 in SPTX group. The all-cause mortality in SPTX group is significantly higher than that in TPTX+AT group (P<.001). The causes of death included heart failure (4 cases), electrolyte disorder (4 cases), intracerebral hemorrhage (3 cases), malignant tumor (2 cases), myocardial infarction (1 case), infection (1 case) and accident (1 case). Recurrent SHPT happened in 29.7% of patients in SPTX group and 12.3% of patients in TPTX+AT group (P=.013). But conversely, re-PTX was less common in SPTX group (2.6%) than that in TPTX+AT group (9.1%), though not statistically significant (P=.302). There was no statistical difference between the two groups in complications like adverse cardiovascular outcomes, fracture, hypercalcemia, and permanent hypoparathyroidism. The two groups were similar in symptom deterioration, renal transplantation, and long-term pharmacal therapies (all P>.05) (Table 4, 5). Kaplan-Meier are shown in Fig. 3. Log rank test indicated TPTX+AT group has lower risk in all-cause death than SPTX group(P=.018), and re-PTX was more common in TPTX+AT group than that in SPTX group (P=.011). However, there was no statistical difference in recurrence and adverse cardiovascular outcomes between the two groups (both P>.05).
Table 4
Long-term outcomes of patients undergoing parathyroidectomy
|
TPTX+AT(n=165)
|
SPTX(n=39)
|
P value
|
All-cause mortality
|
7 (4.2)
|
9 (23.1)
|
<0.001
|
Recurrent SHPT*
|
20 (12.3)
|
11 (29.7)
|
0.013
|
Re-PTX
|
15 (9.1)
|
1 (2.6)
|
0.302
|
Adverse cardiovascular outcomes
|
11 (6.7)
|
4 (10.3)
|
0.666
|
Fracture
|
3 (1.8)
|
2 (5.1)
|
0.244
|
Prevalent hypercalcemia
|
13 (7.9)
|
2 (5.1)
|
0.802
|
Permanent hypoparathyroidism
|
9 (5.5)
|
0 (0)
|
0.290
|
Orthopedic pain worsened
|
8 (4.8)
|
2 (5.1)
|
1.000
|
Pruritus worsened
|
7 (4.2)
|
0 (0)
|
0.412
|
Renal transplantation
|
2 (1.2)
|
1 (2.6)
|
0.473
|
*Persistent SHPT were excluded.
Values are numbers (percent).
TPTX+AT: total parathyroidectomy with autotransplantation; SPTX: subtotal parathyroidectomy; SHPT: secondary hyperparathyroidism; Re-PTX: recurrent parathyroidectomy.
Table 5
Long-term pharmaceutical therapies of patients undergoing parathyroidectomy
|
TPTX+AT(n=165)
|
SPTX(n=39)
|
Pvalue
|
Cinacalcet
|
17 (10.3)
|
2 (5.1)
|
0.488
|
Calcium
|
60 (36.4)
|
10 (25.6)
|
0.205
|
Vitamin D
|
53 (32.1)
|
9 (23.1)
|
0.269
|
Calcitriol
|
46 (27.9)
|
6 (15.4)
|
0.107
|
Phosphorus binders
|
54 (32.7)
|
15 (38.5)
|
0.496
|
Risk factors for all-cause death and recurrent SHPT
Cox regression analysis was performed for all-cause death and recurrent SHPT, and the covariate stroke was not included for the number was too small. In individual variable Cox regression analysis, the SPTX operation approach, older age, lower level of preoperative serum phosphorus was found to be associated with all-cause death after operation (all P<.05). However, after multiple Cox regression analysis, only the SPTX operation approach (HR 3.53, 95%CI 1.12-10.32, P=.021) and older age (HR 1.06, 95%CI 1.00-1.12, P=.035) were considered as risk factors for all-cause death (Table 6). No risk factor for recurrent SHPT was found in individual variable Cox regression analysis (all P>.05).
Table 6
Risk factors for all-cause death based on Cox regression analysis
Variables
|
Hazard Ratio
|
95% CI
|
Pvalue
|
Step 1: Individual variable analysis
|
Operative approach
|
TPTX+AT
|
Comparison
|
|
SPTX
|
3.29
|
1.17-9.25
|
0.024
|
Age at operation
|
|
1.06
|
1.01-1.12
|
0.018
|
Hypertension
|
No
|
Comparison
|
|
Yes
|
3.67
|
0.48-27.77
|
0.209
|
Diabetes
|
No
|
Comparison
|
|
Yes
|
3.47
|
0.92-13.00
|
0.064
|
Coronary heart disease
|
No
|
Comparison
|
|
Yes
|
2.25
|
0.50-10.05
|
0.288
|
Preoperative iPTH
|
|
1.00
|
1.00-1.00
|
0.880
|
Preoperative serum calcium
|
|
1.39
|
0.15-12.82
|
0.772
|
Preoperative serum phosphorus
|
|
0.32
|
0.10-0.97
|
0.045
|
Preoperative ALP
|
|
1.00
|
1.00-1.00
|
0.060
|
Number of parathyroid glands identified
|
|
1.13
|
0.35-3.69
|
0.839
|
Pathological result
|
Hyperplasia
|
Comparison
|
|
Adenoma
|
|
|
|
Step 2: Multiple analysis
|
Operative approach
|
TPTX+AT
|
Comparison
|
|
SPTX
|
3.53
|
1.21-10.32
|
0.021
|
Age at operation
|
|
1.06
|
1.00-1.12
|
0.035
|
Preoperative serum phosphorus
|
|
0.60
|
0.21-1.70
|
0.338
|
CI: confidence interval; TPTX+AT: total parathyroidectomy with autotransplantation; SPTX: subtotal parathyroidectomy; iPTH: intact parathyroid hormone; ALP: alkaline phosphatase.