|Year : 2014 | Volume
| Issue : 3 | Page : 98-102
Oral calcium and vitamin D supplementation after total thyroidectomy
Mohamed El-Shinawi, Aly El-Anwar, Mohamed Nada, Tarek Youssef, Essam Fakhry, Salah Raslan, Hatem El-Gohry
Department of General Surgery, Ain Shams University, Cairo, Egypt
|Date of Web Publication||13-Aug-2014|
Associate Professor of General Surgery, Ain Shams University, Cairo 11566
Source of Support: None, Conflict of Interest: None
Introduction: Hypocalcemia is an important and common complication following thyroid surgery with reports varying from 0.5% to 75%. Despite being self-limiting in most patients, symptomatic hypocalcemia is of particular concern because of a delay in its manifestation and the consequent need for prolonged patient hospitalization or re-admission. Aim of the Work: The aim of this study is to evaluate the clinical usefulness of oral calcium and vitamin D administration after total thyroidectomy in the prevention of post-operative hypocalcemia. Materials and Methods: Fifty patients who underwent total thyroidectomy for non-toxic goiters were randomly assigned to routinely receive or not receive oral calcium (1.5 g/d) and vitamin D (0.5 μg/d) for 4 weeks. Hypocalcemic symptoms and signs and total serum calcium levels were monitored and compared between the 2 groups. Results: The incidence of symptomatic and laboratory hypocalcemia was lower in the treatment group receiving the supplement than in the control group not receiving the supplement: 6 of 25 patients (24%) versus 11of 25 (44%). The hypocalcemic symptoms were minimal in the treatment group but more severe in the control group not receiving the supplement. Serum calcium levels decreased in both groups after surgery but were less in the treatment group. Conclusion: Routine administration of a supplement containing oral calcium and vitamin D may be effective in reducing the incidence and severity of hypocalcemia after total thyroidectomy.
Keywords: Calcium, thyroid, total thyroidectomy, vitamin D
|How to cite this article:|
El-Shinawi M, El-Anwar A, Nada M, Youssef T, Fakhry E, Raslan S, El-Gohry H. Oral calcium and vitamin D supplementation after total thyroidectomy. Thyroid Res Pract 2014;11:98-102
|How to cite this URL:|
El-Shinawi M, El-Anwar A, Nada M, Youssef T, Fakhry E, Raslan S, El-Gohry H. Oral calcium and vitamin D supplementation after total thyroidectomy. Thyroid Res Pract [serial online] 2014 [cited 2019 Dec 13];11:98-102. Available from: http://www.thetrp.net/text.asp?2014/11/3/98/138553
| Introduction|| |
Hypocalcemia is an important and common complication following thyroid surgery with reports varying from 0.5% to 75%. This wide variation is partly due to differences in defining hypocalcemia and variance in laboratory ranges for normocalcemia.  In most cases, post-thyroidectomy hypocalcemia is temporary, but may take several months to resolve. 
Despite being self-limiting in most patients, symptomatic hypocalcemia is of particular concern because of a delay in its manifestation and the consequent need for prolonged patient hospitalization or re-admission. 
Maitland and Miell in 2010 emphasized that there are various causes for post-operative hypocalcemia, which have been suggested including hemodilution or increased urinary calcium excretion secondary to surgical stress, calcitonin release secondary to thyroid gland manipulation, hungry bone syndrome (reversal of toxic thyroid osteodystrophy) and interference with the function of the parathyroid glands either through direct injury, removal or devascularization. 
Routine oral calcium and vitamin D supplements have been proposed to prevent the development of symptomatic hypocalcemia and to increase the likelihood of early hospital discharge after bilateral surgical treatment of the thyroid gland. 
| Materials AND METHODS|| |
A prospective randomized controlled study of 50 patients undergoing total thyroidectomy was performed in the Department of General Surgery at Ain Shams University hospitals. All patients underwent total thyroidectomy [Figure 1] for non-toxic goiter using the same surgical technique for all types of diseases by the same surgeons unaware of the study group allocation. Informed consent was obtained from all patients before inclusion in the study and it was approved by the Ethics Committee at Ain Shams University.
All patients had preoperative serum calcium levels; albumin and renal function within normal ranges, and none were undergoing calcium or vitamin D replacement for any chronic disease.
Patient demographic and clinical characteristics, including age, sex, pathology, operative procedure and a number of parathyroid glands preserved or devascularized and autotransplanted into the sternocleidomastoid muscle were recorded. The presence of hypocalcemic symptoms and signs also was recorded.
Patients were included in the study, if they had simple multinodular goiter involving the entire gland, malignant goiter by fine needle aspiration cytology (FNAC) and recurrent goiter. Patients were excluded if they had any concomitant parathyroid disease, extensive lymph node dissection because of thyroid malignancy, toxic goiter, using calcium supplementation for any chronic disease before the operation, abnormal renal function and hypoalbuminemia.
The study protocol required hospitalization of all patients for a minimum of 2 days after surgery in order to observe postoperative hypocalcemia and to perform the required blood tests. The follow-up visits for patients were at 1 week, 4 weeks and 8 weeks after surgery.
The patients are randomly classified into two groups, control group (25 patients) and treatment group (25 patients).
The control group did not receive routine supplementation treatment. The treatment group was routinely given a daily dose of oral calcium (calcimate) 500 mg in the form of one tablet every 8 hours combined with vitamin D3 (one-alpha) 0.25 μg in the form of one tablet every 12 hours.
In the treatment group, the administration was started on the first postoperative day and was terminated after four weeks. All patients were informed about the symptoms of hypocalcemia from perioral tingling and numbness to carpal and pedal spasm. If the patient had perioral tingling and numbness, serum calcium and phosphate levels were measured and the dose of supplementation therapy was increased to four calcimate tablets per day. Intravenous calcium gluconate was administered if carpal, pedal or carpopedal spasm developed or hypocalcemia, persisted despite oral supplementation.
In the control group, patients were administered the therapy only when perioral tingling and numbness developed, and the serum calcium and phosphate levels were measured.
Surgical procedure was total thyroidectomy in 48 patients and hemi-thyroidectomy followed by complete thyroidectomy in 2 patients, who showed to be malignant after the first operation. Every effort was made to identify and preserve all the parathyroid glands. All the four parathyroid glands were identified and preserved in 40 patients (80%), while 5 glands were identified in 6 patients (12%) and 3 glands in 4 patients (8%).
Monitoring of hypocalcemia
All patients were clinically evaluated for signs and symptoms of hypocalcemia from perioral tingling and numbness to carpopedal spasm and tetany. Postoperative hypocalcemia was defined as either symptomatic or laboratory, with the latter defined as total calcium concentrations <8.4 mg/dL, even if recorded only in a single measurement, either during the hospital stay or at any time after discharge. 
Hypocalcemic symptoms and signs were registered in detail. The reference range of total calcium was 8.4 to 10.4 mg/dL. Patients were discharged in a mean of two days after surgery (if no complications occurred), and discontinued the oral therapy within 4 weeks after the operation. All patients were followed up for one week, four weeks and two months after surgery in outpatient clinic. Serum calcium was checked preoperative, two days and four weeks after surgery. If symptoms or signs of hypocalcemia lasted, the therapy was continued until stable normalization of serum calcium.
Data are expressed as mean ± SD (range) or as number (%) of cases. Comparison of proportions between both groups was made by using the χ2 test and The Fisher's exact test was used when applicable. Chi-Square test χ2 was used to test the association variables for categorical data.
Unpaired (Student's) t test was used to assess the statistical significance of the difference between two population means in a study involving independent samples; used in comparison between serum Ca in the control and treatment groups.
Paired t-test was used to assess the statistical significance of the difference between two population means in a study involving matched or paired samples; used in comparison between serum Ca two days postoperative and serum Ca after four weeks in each group.
The Mann-Whitney U test - non-parametric test to assess the statistical significance of the difference between two population means, in a study involving independent samples. It is used in comparing number of parathyroid glands preserved in the two groups. Analysis was performed by using the Statistical Package for the Social Sciences (SPSS, version 15.0). The level P < 0.05 was considered the cutoff value for significance.
| Results|| |
During the study period, fifty patients underwent total thyroidectomy. The ratio of males to females in the control group was 5 to 20, and in the treatment group was 4 to 21. Patients' age in the control group ranged from 22 to 48 years, with a mean age of 36.04 years. And in the treatment group, age ranged from 17 to 60 years with a mean age of 39.40 years. As regard the duration of hospital stay, patients of the control group stayed with a mean of 2.88 days and the treatment group stayed with a mean of 2.28 days. Data showed in [Table 1]. There were no differences in age, sex and the duration of hospital stay between the 2 groups. (P > 0.05). Failure to localize parathyroid glands occurred in 10 patients. The mean number of preserved parathyroid glands was 4 in both groups.
|Table 1: Characteristics and hospital stay of patients with/ without routine oral calcium and vitamin D supplements |
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Postoperative histopathological results were simple multinodular goiter in 40 patients, hashimoto thyroiditis in 3 patients, papillary thyroid carcinoma in 4 patients and follicular thyroid carcinoma in 3 patients.
[Table 2] shows that symptomatic laboratory-documented hypocalcemia developed in 8 patients (16%); 6 patients in the control group not receiving supplement (24%) and in 2 patients in the treatment group (8%). Asymptomatic laboratory-documented hypocalcemia developed in 5 patients (10%); 3 in the control group not receiving supplement (12%) and 2 in the supplement group (8%) (P > 0.05).
The incidence of hypocalcemia was lower in the treatment group than in the control group but it did not reach a significant level (P = 0.23). Intravenous calcium was administered to 6 patients in the control group but not to any patients in the treatment group (P = 0.02). There was no difference in the incidence of permanent hypocalcemia between the two groups.
[Table 3] shows the difference between the two groups as regard the severity of hypocalcemic symptoms. Hypocalcemic symptoms were minimal (perioral tingling and fingertips numbness) in the treatment group but more severe in the control group, including carpopedal spasms in 6 patients but not to any in the treatment group (P < 0.05).
|Table 3: Comparison of the severity of hypocalcemic symptoms between the two groups |
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[Table 4] and [Figure 2] show that total serum calcium levels decreased by 2 days after total thyroidectomy and completely recovered approximately after 2 months of surgery in both the groups; P = 0.02 and 0.003. Total calcium values measured at postoperative days 2 and 28 were lower in the group not receiving supplement than in the supplement group (P < 0.05).
|Figure 2: Chart showing comparison of the serum calcium levels between the two groups|
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| Discussion|| |
Improvement in surgical technique has led to a relevant decrease in severe postoperative complications after thyroid surgery such as recurrent laryngeal nerve injury and postoperative bleeding, and the surgeons are considering if one day of hospital stay would be feasible after total thyroidectomy. 
Severe hypocalcemia continues to represent a limiting factor for such a short stay in hospital, as tetany may affect a relevant number of patients after early discharge. Identification of perioperative risk factors associated with a high risk of postoperative tetany is an important step for patient selection for safe early discharge.  Hypocalcemia can cause serious complications and require close monitoring of the patient and intravenous calcium infusion to alleviate the clinical symptoms. If the symptoms of hypocalcemia occur after total thyroidectomy, they usually do so in the first 24 to 48 hours. 
In order to minimize the symptoms of postoperative hypocalcemia, we used oral calcium and vitamin D supplementation as a routine after total thyroidectomy to support the calcium level from the decrease in the early postoperative days. This regimen was applied to the treatment group, while the control group did not receive any supplementation.
In prior studies, regimens of oral calcium alone and of a calcium and vitamin D combination were effective. However, Bellantone et al., in 2002  published that the addition of vitamin D to oral calcium supplements was associated with significantly higher serum calcium concentrations on postoperative days 2 and 3 and with a lower incidence of hypocalcemia. Also, they reported in their study that only 3 of 26 patients (11%) receiving oral calcium supplement (3 g/d) had symptoms related to hypocalcemia after total thyroidectomy, whereas 11 of 27 patients (40%) not receiving calcium supplement had symptoms. 
The dosages and durations of calcium and vitamin D administration are also of concern. The present study shows that routine oral calcium (1.5 gm/day) and vitamin D (0.5 μg/day) reduce the incidence of hypocalcemia after total thyroidectomy.
The incidence of hypocalcemia in the control group was 44% compared to 24% in the treatment group. Symptomatic hypocalcemia occurred in 8 patients (16%). Control group had 6 patients, not receiving supplement (24%) and the treatment group had 2 patients (8%). Laboratory hypocalcaemia developed in 5 patients (10%); 3 in the control group not receiving supplement (12%) and 2 in the supplement group (8%) (P > 0.05).
In the supplement group, the symptoms were minimal and patients did not experience severe hypocalcemic symptoms. By contrast, hypocalcemic symptoms were more severe in the group that did not receive supplement. In the control group, 6 patients suffered from carpopedal spasms and they required intravenous calcium administration. In contrast, none of the treatment group had carpopedal spasm and required intravenous calcium.
Moreover, [Figure 1] showed that postoperative treatment prevented a significant decrease of serum calcium levels as well as the subsequent development of major hypocalcemic symptoms after total thyroidectomy. Total calcium values measured at postoperative days 2 and 28 were lower in the group not receiving supplement than in the supplement group. (P < 0.05).
Our results are similar to the study done by Jong-LyelRoh et al.,  in 2006, which showed that postoperative treatment prevented a significant decrease of serum calcium levels after total thyroidectomy. In the supplement group, the symptoms were minimal and patients did not experience carpopedal spasm. By contrast, in the non-supplement group, 3 patients suffered from carpopedal spasms and 5 patients required intravenous calcium administration after their persistent significant hypocalcaemia failed to respond to subsequent administration of oral calcium and vitamin D supplements.
In another study done in 2009,  the patients after total thyroidectomy and central neck dissection for differentiated papillary carcinoma showed that routine oral calcium and vitamin D supplements significantly reduced the incidence of postoperative hypocalcemia.
Prophylactic supplementation with calcium and vitamin D contributed to preventing the initial drop in serum calcium levels. In the group of patients receiving calcium and vitamin D supplements, serum calcium was almost normal in all patients except for 2 patients who experienced hypocalcemia .However, their calcium levels were back to normal earlier with no hypocalcemiac crisis. By contrast, hypocalcemic symptoms were more severe in patients, who did not receive supplements. In this group, 4 patients (8.0%) suffered carpopedal spasms, and 7 (14.0%) required intravenous calcium administration because of persistent and significant hypocalcemia after administration of oral calcium and vitamin D. 
The prevention of significant symptomatic hypocalcemia will allow early discharge of post-thyroidectomy patients from the hospital. Stiges et al., in 2010  discovered that despite the advantages for patients, multiple blood samplings and prolonged hospitalization increase the total cost of the country's medical healthcare system. In our study, the duration of hospital stay after total thyroidectomy decreased from 2.88 ± 1.54 days in the control group to 2.28 ± 0.61 in the treatment group but did not reach a significant value.
Whether total thyroidectomy can be done safely on an outpatient basis is still under discussion in the literature. Hypocalcemia is one of the major problems that can occur after total thyroidectomy. Its detection requires observation and biochemical testing; and therefore, if it cannot be predicted or reliably prevented, the possibility that hypocalcemia will develop is often a reason for extending a patient's hospital stay after surgery. Postoperative therapy with calcium and vitamin D may provide an alternative approach to postoperative treatment.
| Conclusion|| |
Our data suggest that routine oral calcium and vitamin D supplements are effective in reducing the incidence and severity of hypocalcemia after total thyroidectomy. This will ultimately lead to improved patient satisfaction and significant cost savings. However, this should be investigated by another, carefully designed study that includes a different dosages and durations of the supplementation.
| References|| |
|1.||Gac EP, Cabane TP, Amat VJ, Huidobro GF, Rossi FR, Rodríguez FF, et al. Incidence of hypocalcaemia after total thyroidectomy. Rev Med Chil 2007;135:26-30. |
|2.||Tartaglia F, Sgueglia M, Muhaya A, Cresti R, Mulas MM, Turriziani V, et al. Complications in total thyroidectomy: Our experience and a number of considerations. Chir Ital 2003;55:499-510. |
|3.||Lindblom P, Westerdahl J, Bergenfelz A. Low parathyroid hormone levels after thyroid surgery: A feasible predictor of hypocalcemia. Surgery 2002;131:515-20. |
|4.||Maitland R, Miell J. Hypocalcemia post total thyroidectomy: A clinical experience. Endocrine 2010;21:50. |
|5.||Bellantone R, Lombardi CP, Raffaelli M, Boscherini M, Alesina PF, De Crea C, et al. Is routine supplementation therapy (calcium and vitamin D) useful after total thyroidectomy? Surgery 2002;132:1109-12. |
|6.||Bentrem DJ, Rademaker A, Angelos P. Evaluation of serum calcium levels in predicting hypoparathyroidism after total/near-total thyroidectomy or parathyroidectomy. Am Surg 2001;67:249-51. |
|7.||Page C, Strunski V. Parathyroid risk in total thyroidectomy for bilateral, benign, multinodular goiter: Report of 351 surgical cases. J Laryngol Otol 2007;121:237-41. |
|8.||Warren FM, Andersen PE, Wax MK, Cohen JI. Perioperative parathyroid hormone levels in thyroid surgery: Preliminary report. Laryngoscope 2004;114:689-93. |
|9.||Roh JL, Park CI. Routine oral calcium and vitamin D supplements for prevention of hypocalcaemia after total thyroidectomy. Am J Surg 2006;192:675-8. |
|10.||Roh JL, Park JY, Park CI. Prevention of postoperative hypocalcaemia with routine oral calcium and vitamin d supplements in patients with differentiated papillary thyroid carcinoma undergoing total thyroidectomy plus central neck dissection. Cancer 2009;115:251-8. |
|11.||Stiges-Serra A, Ruiz S, Girvent M, Manjón H, Dueñas JP, Sancho JJ. Outcome of protracted hypoparathyroidisim after total thyroidectomy. Br J Surg 2010;97:1687-95. |
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]
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