Hypocalcaemia following total thyroidectomy : Experience at a tertiary care center

Introduction Hypocalcaemia following thyroidectomy can cause life threatening complications such as laryngeal spasm and cardiac arrhythmias. Hypocalcaemia can be either transient or permanent. Aim To investigate the factors associated with the occurrence of hypocalcaemia in patients who undergo thyroidectomy. Methods A retrospective analysis of 240 patients who underwent total thyroidectomy in the professorial surgical unit, Teaching Hospital, Jaffna were included in this study. It was an institution-based, retrospective, descriptive cross-sectional study to identify the factors associated with the occurrence of hypocalcaemia after thyroidectomy. Results Hypocalcaemia occurred in 26 of the 240 patients (10.83%), among whom 24 developed transient hypocalcaemia and two had permanent hypocalcaemia. Factors that showed a significant association with post-operative hypocalcaemia were hyperthyroid state(p=0.01) and prolonged surgery (p=0.011). The occurrence of post-operative hypocalcaemia was least when a most experienced surgeon performed the thyroidectomy (p=0.03). Conclusions Hypocalcaemia following thyroidectomy was mostly transient and associated factors were toxic goitre and prolonged surgery. Occurrence was low when the most experienced surgeon performed the operation. Factors associated with occurrence of hypocalcaemia should be informed to surgeons for extra caution and preventive measures during thyroidectomy surgery. Corresponding Author: Ratnasingam Vaaheesan, E-mail: <drvahees@gmail.com> https://orcid.org/0000-0001-6979-162X Received: November 2017, Accepted revised version: June 2018, Published: June 2018 Competing Interests: Authors have declared that no competing interests exist © Authors. This is an open-access article distributed under a Creative Commons Attribution-Share Alike 4.0 International License (CC BY-SA 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are attributed and materials are shared under the same license. Introduction Hypocalcaemia is a common complication in the immediate post-operative period of thyroidectomy. The early symptoms of hypocalcaemia are circumoral numbness, tingling sensation and carpopedal spasm. Life-threatening complications of hypocalcaemia include laryngeal spasm and cardiac arrhythmias [1]. The rate of transient hypocalcaemia following thyroidectomy is between 6.9% to 49% while that of permanent hypocalcaemia ranges from 0.4% to 33% [2,3,4] Journal of the Postgraduate Institute of Medicine 2018; 5 (1): E70 1-8 http://doi.org/10.4038/jpgim.8170 2 Justification of research and objectives Thyroidectomy is a common operation in all parts of Sri Lanka including the northern region. The indications for thyroidectomy include malignant thyroid lesions (6.1 per 100,000 women and 1.3 per 100,000 men) thyrotoxicosis, cosmetic reasons and obstructive goitres [3,5,6]. Hypocalcaemia is a well-known complication after thyroidectomy and needs urgent attention in the post-operative period. Knowledge on factors associated with the occurrence of hypocalcaemia following thyroidectomy can help to prevent parathyroid gland injuries sustained during thyroidectomy and thereby occurrence of hypocalcaemia. Aim Our aim was to describe the factors associated with the occurrence of hypocalcaemia following thyroidectomy. Methods This was an institution based, retrospective, descriptive cross-sectional study carried out at the professorial surgical unit, Teaching Hospital, Jaffna from 1 January 2011 to 1 July 2016. The study was designed as per STARD guidelines. A total of 240 patients who underwent total thyroidectomy in this unit were included. All patients were assessed for serum calcium levels daily for the first 05 post-operative days. Total serum calcium level was measured and was corrected for albumin method using Arsenazoll dry chemistry method by Vitros 250 analyzer. Patients were followed up monthly for seven months and serum calcium level was checked during their clinical visits. Patients with at least one postoperative total serum calcium level of <8.5mg/dl were considered to have hypocalcaemia. The need for calcium supplements and calcitriol for more than six months was considered as permanent hypocalcaemia and others as transient hypocalcaemia. Data were collected from patient records and clinic records by 03 pre-intern doctors, trained by the principal investigators The study assessed whether age, gender, type of goitre, hormonal status, operative time, experience of the surgeon or nodal dissection were associated with occurrence of hypocalcaemia following total thyroidectomy. This information was extracted from patient records and intra-operative notes. Chi-Square test was used to identify associations. A p value ≤0.05 was considered significant. The study was approved by the Ethics Review Committee, Faculty of Medicine, University of Jaffna. Results Of the 240 patients in this study, 43(17.92%) were male and 197(82.08%) were female with a male to female ratio of 1:4. The distribution of gender and occurrence of hypocalcaemia is shown in Table 1. Journal of the Postgraduate Institute of Medicine 2018; 5 (1): E70 1-8 http://doi.org/10.4038/jpgim.8170 3 Table 1: Distribution of gender and post-operative hypocalcaemia Hypocalcaemia present N (%) Hypocalcaemia absent N (%) Total N (%) Males 05(11.62) 38(88.38) 43(100.00) Females 21(10.65) 176(89.35) 197 (100.00) Total 26(10.83) 214(89.17) 240(100.00) Five males (11.62%) and 21 females (10.65%) developed hypocalcaemia. There was no significant association between gender and the occurrence of post-operative hypocalcaemia. The distribution of age and the occurrence of hypocalcaemia is shown in Table 2. Table 2: Distribution of age and post-operative hypocalcaemia Age Hypocalcaemia present N (%) Hypocalcaemia absent N(%) Total N(%) <19 years 05(7.35) 63(92.65) 68(100.00) 20-49 years 14(13.46) 90(86.54) 104(100.00) >50 years 07(10.29) 61(89.71) 68(100.00) Total 26(10.83) 214(89.17) 240(100.00) There was no significant association between age and the occurrence of post-operative hypocalcaemia. The distribution of post-operative days and occurrence of hypocalcaemia during the first five post-operative days is shown in the Table 3. Table 3: Distribution of post-operative days and the occurrence of hypocalcaema Hypocalcaemia was observed in 26 patients (10.83%), by the end of the 5th post-operative day. Highest occurrence of hypocalcaemia was on post-operative days 02 and 03 (5% and 4% respectively). Of the 26 patients who developed hypocalcaemia, 24 (92.31%) patients had transient hypocalcaemia while 2 (7.69%) developed permanent hypocalcaemia. The distribution of the type of goitre and post-operative hypocalcaemia is shown in Table 4. Post Op day Number of patients with serum calcium<8.5mg/dl N (%) Cumulative number of patients with hypocalcaemia N (%) 1 3(1.25) 3(1.25) 2 12(5.06) 15(6.25) 3 9(4.00) 24(10.00) 4 1(0.46) 25(10.4) 5 1(0.46) 26(10.83) Journal of the Postgraduate Institute of Medicine 2018; 5 (1): E70 1-8 http://doi.org/10.4038/jpgim.8170 4 Table 4: Distribution of type of goitre and occurrence of hypocalcaemia Classification of goiter Hypocalcaemia present N(%) Hypocalcaemia absent N(%) Total N(%) Simple multinodular 04(5.20) 73(94.80) 77(100.00 Toxic multinodular 06(23.10) 20(76.90) 26(100.00) Malignant multinodular goitre 06(15.80) 32(84.20) 38(100.00) Malignant solitary 03(5.20) 55(94.80) 58(100.00) Grave disease 05(17.90) 23(82.10) 28(100.00) Recurrent 02(15.40) 11(84.60) 13(100.00) Total 26(10.83) 214(89.17) 240(100.00) Among the 240 patients, 131(54.58%) presented with multinodular goitres (MNG), 58(24.16%) with malignant solitary goitre, 28(10.42%) with Grave disease and 13(5.41%) with recurrent goitres. There was no significant association with the type of goitre. The distribution of malignancy and the occurrence of hypocalcaemia is shown in Table 5. There was no significant association between thyroid malignancy and the occurrence of post-operative hypocalcaemia. Table 5: Distribution of malignancy and post-operative hypocalcaemia Type of goitre Hypocalcaemia present N(%) Hypocalcaemia absent N(%) Total Malignant goitre 09(9.38 87(90.62 96(100) Non-malignant goitre 17(11.80) 127(88.20) 144(100) Total 26(10.83) 214(89.17) 240(100) The distribution of hormonal status and the occurrence of hypocalcaemia is shown in Table 6. Table 6: Distribution of hormonal status and post-operative hypocalcaemia Classification of goiter Hypocalcaemia present N(%) Hypocalcaemia absent N(%) Total N(%) Euthyroid 15(8.06) 171(91.94) 186(100.0)0 ) Hyperthyroid 11(20.37) 43(79.63) 54(100.00)


Introduction
Hypocalcaemia following thyroidectomy can cause life threatening complications such as laryngeal spasm and cardiac arrhythmias.Hypocalcaemia can be either transient or permanent.Aim To investigate the factors associated with the occurrence of hypocalcaemia in patients who undergo thyroidectomy.Methods A retrospective analysis of 240 patients who underwent total thyroidectomy in the professorial surgical unit, Teaching Hospital, Jaffna were included in this study.It was an institution-based, retrospective, descriptive cross-sectional study to identify the factors associated with the occurrence of hypocalcaemia after thyroidectomy.Results Hypocalcaemia occurred in 26 of the 240 patients (10.83%), among whom 24 developed transient hypocalcaemia and two had permanent hypocalcaemia.Factors that showed a significant association with post-operative hypocalcaemia were hyperthyroid state(p=0.01)and prolonged surgery (p=0.011).The occurrence of post-operative hypocalcaemia was least when a most experienced surgeon performed the thyroidectomy (p=0.03).Conclusions Hypocalcaemia following thyroidectomy was mostly transient and associated factors were toxic goitre and prolonged surgery.Occurrence was low when the most experienced surgeon performed the operation.Factors associated with occurrence of hypocalcaemia should be informed to surgeons for extra caution and preventive measures during thyroidectomy surgery.

Introduction
Hypocalcaemia is a common complication in the immediate post-operative period of thyroidectomy.The early symptoms of hypocalcaemia are circumoral numbness, tingling sensation and carpopedal spasm.Life-threatening complications of hypocalcaemia include laryngeal spasm and cardiac arrhythmias [1].The rate of transient hypocalcaemia following thyroidectomy is between 6.9% to 49% while that of permanent hypocalcaemia ranges from 0.4% to 33% [2,3,4]

Justification of research and objectives
Thyroidectomy is a common operation in all parts of Sri Lanka including the northern region.The indications for thyroidectomy include malignant thyroid lesions (6.1 per 100,000 women and 1.3 per 100,000 men) thyrotoxicosis, cosmetic reasons and obstructive goitres [3,5,6].Hypocalcaemia is a well-known complication after thyroidectomy and needs urgent attention in the post-operative period.Knowledge on factors associated with the occurrence of hypocalcaemia following thyroidectomy can help to prevent parathyroid gland injuries sustained during thyroidectomy and thereby occurrence of hypocalcaemia.

Aim
Our aim was to describe the factors associated with the occurrence of hypocalcaemia following thyroidectomy.

Methods
This was an institution based, retrospective, descriptive cross-sectional study carried out at the professorial surgical unit, Teaching Hospital, Jaffna from 1 st January 2011 to 1 st July 2016.The study was designed as per STARD guidelines.A total of 240 patients who underwent total thyroidectomy in this unit were included.All patients were assessed for serum calcium levels daily for the first 05 post-operative days.Total serum calcium level was measured and was corrected for albumin method using Arsenazoll dry chemistry method by Vitros 250 analyzer.Patients were followed up monthly for seven months and serum calcium level was checked during their clinical visits.Patients with at least one postoperative total serum calcium level of <8.5mg/dl were considered to have hypocalcaemia.
The need for calcium supplements and calcitriol for more than six months was considered as permanent hypocalcaemia and others as transient hypocalcaemia.Data were collected from patient records and clinic records by 03 pre-intern doctors, trained by the principal investigators The study assessed whether age, gender, type of goitre, hormonal status, operative time, experience of the surgeon or nodal dissection were associated with occurrence of hypocalcaemia following total thyroidectomy.This information was extracted from patient records and intra-operative notes.Chi-Square test was used to identify associations.A p value ≤0.05 was considered significant.The study was approved by the Ethics Review Committee, Faculty of Medicine, University of Jaffna.

Results
Of the 240 patients in this study, 43(17.92%)were male and 197(82.08%)were female with a male to female ratio of 1:4.The distribution of gender and occurrence of hypocalcaemia is shown in Table 1.Five males (11.62%) and 21 females (10.65%) developed hypocalcaemia.There was no significant association between gender and the occurrence of post-operative hypocalcaemia.
The distribution of age and the occurrence of hypocalcaemia is shown in Table 2.There was no significant association between age and the occurrence of post-operative hypocalcaemia.
The distribution of post-operative days and occurrence of hypocalcaemia during the first five post-operative days is shown in the Table 3.

Table 3: Distribution of post-operative days and the occurrence of hypocalcaema
Hypocalcaemia was observed in 26 patients (10.83%), by the end of the 5th post-operative day.Highest occurrence of hypocalcaemia was on post-operative days 02 and 03 (5% and 4% respectively).Of the 26 patients who developed hypocalcaemia, 24 (92.31%)patients had transient hypocalcaemia while 2 (7.69%) developed permanent hypocalcaemia.

Post Op day
The distribution of malignancy and the occurrence of hypocalcaemia is shown in Table 5.
There was no significant association between thyroid malignancy and the occurrence of post-operative hypocalcaemia.The distribution of hormonal status and the occurrence of hypocalcaemia is shown in Table 6.When considering hormonal status, 186 were euthyroid, while 54 were hyperthyroid, there were no hypothyroid patients.Of the 54 hyperthyroid patients, 11(20.37%)developed hypocalcaemia, while 15 of the 186 patients (8.06%) with euthyroid state developed hypocalcaemia.Hyperthyroid state was significantly associated with higher occurrence of hypocalcaemia compared to euthyroid state (p= 0.010).
The distribution of operative time and the occurrence of hypocalcaemia is shown in Table 7.There was no significant association between the operative time and the development of hypocalcaemia.
The relationship between the level of experience of the surgeon and the occurrence of hypocalcaemia is shown in Table 8.Experience of surgeon was classified as 'less experienced' (<5 years as surgeon and/or <100 thyroidectomies), 'more experienced' (6 -10 years as surgeon and/or 101-200 thyroidectomies) and 'very experienced' (>10 years as surgeon and/or >200 thyroidectomies).The occurrence of hypocalcaemia was significantly lower (p=0.003)when a most experienced surgeon performed the operation compared to the other two levels of experience.Lymph node dissection was performed on 22 of 96 patients with malignant goitres.Development of hypocalcaemia had no association with whether or not lymph node dissection was performed although the results show a higher percentage of hypocalcaemia when nodal dissection was performed.

Discussion
The occurrence of hypocalcaemia following total thyroidectomy has been reported as 6.0% to 49.0% [2,3,4,Error!Reference source not found.].Hypocalcaemia following thyroidectomy can be due to unintentional removal of the parathyroid glands or compromised blood supply to the glands.In our study, hypocalcaemia was observed in 26 patients (10.3%).24 had transient hypocalcaemia.Two patients developed permanent hypocalcaemia due to unintentional removal of three parathyroid glands, later confirmed by histology.
Gender had no significant effect on development of hypocalcaemia after thyroidectomy in some studies [5,8].Other studies revealed that rates of transient and permanent hypocalcaemia were higher in women than in males [9].Our study did not reveal any statistically significant difference in the occurrence of hypocalcaemia between males and females.
Malignant lesions, toxic goitres and recurrent goitres (42.9% -44.4%) are associated with post-operative hypocalcaemia [8,9] in most studies.Our study also revealed a higher occurrence in toxic goitres but no significant association with malignant goitres and recurrent goitres.Nodal clearance and extensive nodal dissection in malignant lesions and hungry bones in toxic goitres play a role in causing post-operative hypocalcaemia in these patients [6,7,9].However, in our study, nodal dissection had no significant association with the development of hypocalcaemia, perhaps due to the small number of patients involved.
Experience of the surgeon had an impact on the development of hypocalcaemia in our study as in most other studies [2,5,7].In our unit, large goitres (WHO Grade 3) recurrent goitres, toxic goitres, and malignant goitres, which needed lymph node dissection, are operated on by the most experienced surgeon.When considering the complexity and technical difficulties of total thyroidectomy, experience of the surgeon was a significant determinant of post thyroidectomy hypocalcaemia in our study as well as other studies [3,7,9].
Transient hypocalcaemia in the majority of our patients could be due to ischaemia or venous oedema of the parathyroid glands, in the absence of intra-operative or histopathological evidence of accidental removal of the glands [5].

Conclusions
Hypocalcaemia is one of the most well recognized complications of total thyroidectomy.Our study showed the highest occurrence of hypocalcaemia on postoperative days 2 and 3. We recommend routine checking of serum calcium levels daily from 1st to 5th day of the post-operative period for early detection and treatment.
As hyperthyroid state is associated with high occurrence of hypocalcaemia, these goitres should be operated with utmost care.
The most common cause for post-operative hypocalcaemia is transient hypocalcaemia due to ischaemia to the parathyroid.Parathyroid ischaemia and oedema can be avoided by meticulous surgical technique to prevent morbidity due to transient hypocalcaemia.
Routine examination of the specimen to detect accidental dissection of parathyroid gland and immediate auto transplantation into either the sternocleidomastoid or brachioradialis muscles gives good functional recovery preventing permanent post thyroidectomy hypocalcaemia.The factors associated with occurrence of hypocalcaemia should be informed to surgeons for extra caution and preventive measures during thyroidectomy surgery.