Predictors of early post-operative hypocalcemia after parathyroidectomy for secondary hyperparathyroidism

M Hamouda; N Ben Dhia; S Aloui; S El Mhamedi; H Skhiri; M Elmay

doi:10.4103/1319-2442.121273

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ORIGINAL ARTICLE

Year : 2013 | Volume : 24 | Issue : 6 | Page : 1165-1169

Predictors of early post-operative hypocalcemia after parathyroidectomy for secondary hyperparathyroidism

M Hamouda¹, N Ben Dhia¹, S Aloui¹, S El Mhamedi², H Skhiri¹, M Elmay¹
¹ Department of Nephrology, Fattouma Bourguiba Hospital; Department of Epidemiology, University Hospital of Monastir University Faculty of Medicine, Monastir, Tunisia
² Department of Preventive Medicine; Department of Epidemiology, University Hospital of Monastir University Faculty of Medicine, Monastir, Tunisia

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Date of Web Publication

13-Nov-2013

Abstract

We sought to identify predictors of development of early post-operative hypocalcemia after parathyroidectomy for secondary hyperparathyroidism. The patients were divided into two groups according to their serum calcium (Ca) levels within 24 hours of undergoing para-thyroidectomy: the hypocalcemia group (22 patients) with post-operative serum Ca levels of 2 mmol/L or less, and the normocalcemia group (48 patients), with post-operative serum Ca levels higher than 2 mmol/L. By using multivariate stepwise logistic regression analysis, high pre-operative serum Ca level had the strongest predictive value of development of early hypocalcemia with an adjusted odds ratio (aOR) of 3.01, followed by hypo-albuminemia (aOR = 2.72), younger age (aOR = 2.56), and high pre-operative alkaline phosphatase (ALP) levels (aOR = 2.28). We conclude that among patients with secondary hyperparathyroidism, age, levels of pre-operative serum Ca, ALP and albumin correlate positively with the development of early post-operative hypocalcemia. Patients with one of these factors should be monitored more closely in the early post-parathyroidectomy period.

How to cite this article:
Hamouda M, Dhia N B, Aloui S, El Mhamedi S, Skhiri H, Elmay M. Predictors of early post-operative hypocalcemia after parathyroidectomy for secondary hyperparathyroidism. Saudi J Kidney Dis Transpl 2013;24:1165-9

How to cite this URL:
Hamouda M, Dhia N B, Aloui S, El Mhamedi S, Skhiri H, Elmay M. Predictors of early post-operative hypocalcemia after parathyroidectomy for secondary hyperparathyroidism. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2021 Mar 1];24:1165-9. Available from: https://www.sjkdt.org/text.asp?2013/24/6/1165/121273

Introduction

Secondary hyperparathyroidism (2HPT) is a common complication in hemodialysis patients. The majority of patients with 2HPT can be managed by medical treatment with vitamin D sterols and calcimimetics. In severe cases of 2HPT, medical therapy alone may be ineffective. Some patients require surgical treatment in the form of parathyroidectomy (PTX). ^{[1],[2],[3],[4],[5]}

The reported incidence of hypocalcemia after PTX, defined by biochemical criteria, ranges from 26-47%. ^{[6],[7],[8],[9]}

It is important to have prior knowledge on patients who might be at high risk for developing hypocalcemia after PTX in order to monitor them more closely during the post-operative period.

In this study, we sought to identify the risk factors for developing early post-operative hypocalcemia after PTX for 2HPT.

Patients and Methods

Subtotal PTX was performed on 70 patients with end-stage renal disease (ESRD) with symptomatic 2HPT [intact parathyroid hormone (PTH) level >800 pg/mL, hypercalcemia, and/ or hyperphosphatemia] that was refractory to medical therapy. The study patients were divided into two groups according to their serum calcium (Ca) levels within 24-hours of performing PTX. The hypocalcemia group (n = 22) consisted of patients with post-operative serum Ca levels of 2 mmol/L or less, and the normocalcemia group (n = 48), with post-operative serum Ca levels higher than 2 mmol/L.

Serum levels of Ca, phosphate (Ph), albumin, and alkaline phosphatase (ALP) were assessed using standard laboratory methods and intact serum parathyroid hormone (PTH) levels by electro-chemiluminescence immunoassay (Roche Diagnostics); the normal ranges of these laboratory parameters were as follows: total Ca: 2.2-2.6 mmol/L, Ph: 0.81-1.62 mmol/L, ALP: 60-279 IU/L and PTH: 15-65 pg/mL.

Statistical Analysis

Data were analyzed using SPSS software (Statistical Product and Services Solutions, version 16.0, SPSS Inc). All results are expressed as mean values, standard deviations and percentages. Univariate statistical tests using Chi-square for binary variables and t-test for continuous variables were performed. Values of P less than 5% were accepted to be significant. Multivariate stepwise logistic regression was used to identify predictive factors of early hypocalcemia. Explicative variables with a univariate test value ≤0.25 were included. The final retuned variables were those significant at the level of 5%.

Results

The clinical and biochemical parameters of our study patients are summarized in [Table 1]. The average age of the patients was 39.4 years. Majority of the patients (96%) were on dialysis: 7.1% were treated by peritoneal dialysis and 92.8% were on hemodialysis.

Table 1: Clinical and biochemical parameters in the study patients.

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Post-operative hypocalcemia developed in 22/70 patients (31.4%) in whom, the serum Ca levels were equal to or less than 2 mmol/L (hypocalcemia group). In 48 patients, the serum Ca levels were higher than 2 mmol/L (normocalcemia group).

On univariate analysis, patients in the hypocalcemia group were significantly younger than those in the normocalcemia group (37 vs 42 years; P = 0.04). The pre-operative levels of serum Ca (2.57 vs 2.46; P = 0,03), ALP (1245 IU/L vs 768 IU/L; P = 0.01) and, intact PTH levels (1683 pg/mL vs 1269 pg/mL; P = 0.04) as well as the size of the parathyroid gland (2.93 vs 2.7; P = 0,04) were significantly higher in the hypocalcemia group when compared with the normocalcemia group [Table 2].

Table 2: Variables associated with early hypo-calcemia on univariate analysis.

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The duration on hemodialysis (9.36 years vs 7.01 years; P = 0.05) was longer in the hypocalcemia group when compared with the normocalcemia group. Duration on dialysis for more than five years was found in 72.9% of the hypocalcemia group versus 45.4% in the normocalcemia group. Gender of the patient, initial nephropathy, pre-operative serum Ph and histology of the parathyroid gland were not different between the two groups [Table 2].

The average length of hospital stay for patients with hypocalcemia was 7.82 days as against 4.1 days in the normocalcemia group. Symptoms of hypocalcemia occurred in 58.3% of the patients in the hypocalcemia group. All symptomatic patients had numbness of the perioral region or the extremities, muscle cramps and paresthesias; two patients had tetany; no patient had stridor, seizures or cardiac arrhythmias.

[Table 3] shows the significant results on multivariate analysis of the clinical and biochemical parameters that correlated with early hypocalcemia. High pre-operative ionized Ca had the strongest predictive value of early hypocalcemia with an aOR of 3.01 (95% CI = 1.10- 11.05), followed by hypo-albuminemia (aOR = 2.72; 95% CI = 1.00-29.89), younger age [(aOR) = 2.56; 95% CI=1.07- 9.21], and high pre-operative ALP level (aOR = 2.28; 95% CI = 1.09-10.01).

Table 3. Multivariate stepwise logistic regression.

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Discussion

In patients with chronic renal failure, secondary hyperparathyroidism is a common problem requiring surgical PTX, if medical treatment fails. ^[4],[5] Despite advances in dialysis technique and pharmacologic therapy, especially calcimimetics, there has been no change in the proportion of dialysis patients requiring PTX for 2HPT. ^{[4],[10],[11]} Calcimimetics are not available in Tunisia. Therefore, PTX still has an important role in the treatment of patients with 2HPT that is refractory to medical management. The standard surgical approach to patients with 2HPT has been either subtotal PTX or total PTX with auto-transplantation. ^[2],[3],[12]

In our center, the surgical technique used is subtotal PTX.

The management of metabolic problems following PTX in ESRD remains poorly defined. Hypocalcemia is a common and serious complication in the post-operative period. Prior studies had identified several risk factors for occurrence of post-operative hypocalcemia after PTX, which included weight of the adenoma, and elevated pre-operative ALP and intact PTH levels. ^[8],[13] The prevalence of postoperative hypocalcemia in our patients was 31.4 %, similar to reports from the literature. ^[7],[8],[9] Some other studies have also suggested that high pre-operative levels of serum Ca were predictive of the development of post-operative hypocalcemia. ^[13],[14]

When serum PTH stimulates osteoblastic activity, the levels of ALP increase, related to the degree of bone disease. ^[4],[5] The patients in the hypocalcemia group had higher pre-operative serum ALP levels. Similar to our findings, some studies on patients with hungry bone syndrome have shown higher pre-operative serum ALP levels. ^[13],[14]

The serum PTH level is related to the severity of renal osteodystrophy. Our patients who developed hypocalcemia showed higher levels of pre-operative serum PTH than patients with normal serum Ca after PTX. Other studies have also reported similar findings. ^[13],[14] In contrast, few other studies have reported that there was no correlation between post-operative hypocalcemia and serum PTH levels. ^[8],[15] Most studies have reported a correlation between weight of the adenoma and serum Ca levels. ^[16],[17] In our study, the difference was significant on univariate analysis.

Identifying pre-operative risk factors for development of post-PTX hypocalcemia in patients with ESRD is of particular importance. ^[18],[19] The risk of hypocalcemia following PTX can be reduced by strict monitoring of serum Ca levels and prophylactic administration of Ca and vitamin D analogues to patients at high-risk of developing hypocalcemia. By applying this protocol, severe hypocalcemia can be avoided and the immediate postoperative period can be made uneventful. ^{[20],[21],[22],[23],[24]}

Conclusion

Among patients with 2HPT, age, levels of pre-operative serum Ca, ALP, and albumin correlated with early post-operative hypocalcemia. These variables will allow clinicians to identify hemodialysis patients who are at greater risk of developing hypocalcemia after parathyroid surgery. Patients with any of the known risk factors should be monitored more closely in the post-operative period.

References

1.	Coulston JE, Egan R, Willis E, Morgan JD. Total parathyroidectomy without auto-transplantation for renal hyperparathyroi-dism. Br J Surg. 2010 Nov;97(11):1674-9.
2.	Tominaga Y, Matsuoka S, Uno N. Surgi-cal and medical treatment of secondary hyperparathyroidism in patients on conti-nuous dialysis. World J Surg. 2009;33 (11):2335-42.
3.	Nichol PF, Starling JR, Mack E, Klovning JJ, Becker BN, Chen H. Long-term follow-up of patients with tertiary hyperpara-thyroidism treated by resection of a single or double adenoma. Surg. 2002 May;235 (5):673-8; discussion 678-80.
4.	Puccini M, Carpi A, Cupisti A, Caprioli R, Iacconi P, Barsotti M, Buccianti P, Mechanick J, Nicolini A, Miccoli P. Total parathyroidectomy without autotransplantation for the treatment of secondary hyperparathyroidism associated with chronic kidney disease: clinical and laboratory long-term follow-up. Biomed Pharmacother. 2010 May;64(5):359-62.
5.	Stracke S, Keller F, Steinbach G, Henne-Bruns D, Wuerl P.Long-term outcome after total parathyroidectomy for the management of secondary hyperparathyroidism. Nephron Clin Pract. 2009;111(2): 102-9.
6.	Meyers MO, Russell CP, Ollila DW, Yeh JJ, Kim HJ, Calvo BF. Postoperative hypocalcemia after parathyroidectomy for renal hyperparathyroidism in the era of cinacalcet. Am Surg. 2009 Sep;75(9):843-7.
7.	Saunders RN, Karoo R, Metcalfe MS, et al. Four gland parathyroidectomy without reim-plantation in patients with chronic renal failure. Postgrad Med J 2005;81(954):255-8.
8.	Mittendorf EA, Merlino JI, McHenry CR.Post-parathyroidectomy hypocalcemia: incidence, risk factors, and management. Am Surg. 2004 Feb; 70(2):114-9; discussion 119-20.
9.	Stewart ZA, Blackford A, Somervell H, Friedman K, Garrett-Mayer E, Dackiw AP, Zeiger MA. 25-hydroxyvitamin D deficiency is a risk factor for symptoms of postoperative hypocalcemia and secondary hyperparathyroidism after minimally invasive parathyroidectomy. Surgery. 2005 Dec;138(6):1018-25.
10.	Foley RN, Li S, Liu J, Gilbertson DT, Chen SC, Collins AJ.The fall and rise of parathy-roidectomy in U.S. hemodialysis patients, 1992 to 2002. J Am Soc Nephrol. 2005 Jan;16(1):210-8. Epub 2004 Nov 24.
11.	Gagné ER, Ureña P, Leite-Silva S, Zingraff J, Chevalier A, Sarfati E, Dubost C, Drüeke TB. Short- and long-term efficacy of total parathyroidectomy with immediate autografting compared with subtotal parathyroidectomy in hemodialysis patients. J Am Soc Nephrol. 1992 Oct;3(4):1008-17.
12.	Jovanovic DB, Pejanovic S, Vukovic L, et al. Ten years' experience in subtotal parathyroidectomy of hemodialysis patients. Ren Fail 2005;27(1):19-24.
13.	Brasier AR, Nussbaum SR: Hungry bone syndrome: clinical and biochemical predictors of its occurrence after parathyroid surgery. Am J Med 84:654, 1988.
14.	Farese S: The hungry bone syndrome-an update . Ther Umsch 64:277, 2007.
15.	Randhawa PS, Mace AD, Nouraei SA, et al: Primary hyperparathyroidism: do perioperative biochemical variables correlate with parathyroid adenoma weight or volume? Clin Otolaryngol 32:179, 2007.
16.	Zamboni WA, Folse R. Adenoma weight: a predictor of transient hypocalcemia after parathyroidectomy. Am J Surg. 1986 Dec;152(6): 611-5.
17.	Strickland PL, Recabaren J.Are preoperative serum calcium, parathyroid hormone, and adenoma weight predictive of postoperative hypocalcemia? Am Surg. 2002 Dec;68(12):1080-2.
18.	Vasher M, Goodman A, Politz D, Norman J. Postoperative calcium requirements in 6,000 patients undergoing outpatient parathyroidectomy: easily avoiding symptomatic hypocalcemia. J Am Coll Surg. 2010 Jul;211(1):49-54.
19.	Torer N, Torun D, Torer N, Micozkadioglu H, Noyan T, Ozdemir FN, Haberal M. Predictors of early postoperative hypocalcemia in hemodialysis patients with secondary hyperparathyroidism. Transplant Proc. 2009 Nov;41(9):3642-6.
20.	Zuberi KA, Urquhart AC.Serum PTH and ionized calcium levels as predictors of symptommatic hypocalcemia after parathyroidectomy. Laryngoscope. 2010;120 Suppl 4:S192. [PUBMED]
21.	Ikeda K, Kawaguchi Y, Nakayama M, Yamamoto H, Osaka N, Takeyama H, Hosoya T. Novel usage of alendronate to prevent profound hypocalcemia immediately after parathyroidectomy in patients with severe secondary hyperparathyroidism. Nephron. 1999;83 (2):186-8.
22.	Milas M,Weber CJ. Near-total parathyroidectomy is beneficial for patients with secondary and tertiary hyperparathyroidism. Surgery 2004; 136(6):1252-60.
23.	Cozzolino M, Gallieni M, Corsi C, Bastagli A, Brancaccio D. Management of calcium refillling post-parathyroidectomy in end-stage renal disease. Nephrol. 2004 17(1):3-8.
24.	Vallée M, Lalumière G, Déziel C, Quérin S, Madore F.Parathyroidectomy in end-stage renal disease: perioperative management of calcium-phosphorus balance. Ann Biol Clin (Paris). 2007;65(1):71-6.