Thyroid disorders
and their surgical management are common in surgical practice
worldwide. Thyroidectomy is frequently recommended for patients with
thyroid nodules, especially when thyroid cancer is suspected [1, 2]. Among
various types of thyroidectomy, total thyroidectomy is one of
the most common endocrine surgeries [3].
Postoperative
complications after thyroid surgery are numerous and reported more frequently
with learning surgeons [4, 5]. Hypocalcemia and hypoparathyroidism are frequent
complications of thyroidectomy. Transient hypocalcemia is reported to
complicate 9.2 to 25% of cases, while the incidence of permanent hypocalcemia
ranges from 0.5 to 2% [6].
Injury or
devascularization of the parathyroid glands is mostly recognized as the most
common cause for post-thyroidectomy hypocalcemia [7]. Postoperative
hypoparathyroidism is a clinical challenge for thyroid surgeons due to the
relatively high frequency and limited preoperative predictors
[8]. Many patient-related, disease-related, biochemical, and surgical
factors may influence the risk of postthyroidectomy hypocalcemia [9].
This study aimed
to determine the overall frequency of post-thyroidectomy
hypocalcemia, whether symptomatic or asymptomatic, transient
or permanent, and risk factors associated with the development of
hypocalcemia.
Patients and methods
this case series
was conducted in the Department of General Surgery at Cairo University hospital
and Assiut police hospital from November 2016 to May 2018. The study
included 166 patients who had total, subtotal, or hemithyroidectomy due to
toxic, simple, or malignant goiter. All participants of the study provided
informed consent, and the study was approved by the Ethical Committee of
the Faculty of Medicine, Cairo University.
Included are
euthyroid patients aged >18 years. Exclusion criteria were current or
previous parathyroid diseases, or laryngeal or vocal cord lesions, abnormal serum
creatinine, renal disease, osteopenia, osteoporosis, metabolic bone
diseases, other malignancies, previous neck surgery, or drugs like
calcium, vitamin D, menopausal hormone replacement therapy, thiazide
diuretics, and antiepileptic agents.
All patients were
subjected to preoperative full clinical assessment and laboratory
investigations, including serum ionized calcium and thyroid function tests
(TSH, free T3, and free T4) in addition to neck
ultrasound and thyroid scan if needed. The intraoperative policy was to
identify and preserve all parathyroid glands after the identification of
their vascular pedicles. If one of the glands was accidentally compromised, it
was fragmented and auto-transplanted on the contralateral sternomastoid
muscle immediately.
Postoperative assessment
The assessment
included the occurrence of postthyroidectomy hypocalcemia by detecting any
clinical signs for hypocalcemia as paresthesia, Chvostek's sign, and
Trousseau's sign and by close monitoring of serum calcium, phosphorus, and
parathormone (PTH) on postoperative days 1 and 7.
The normal level
of serum calcium was defined to be between 6.8 and 10.4 mg/dl. Critical value
of serum calcium is <6.0 mg/dL, and the critical value of serum ionized
calcium is <3.2 mg/dL. Patients with low serum calcium (<6.8 mg/dL)
were treated with oral or parenteral calcium according to the level
of hypocalcemia and severity of symptoms.
Management protocol
Serum ionized
calcium was checked 8 hours and 24 hours postoperatively. If two consecutive
calcium values were within the normal range or increasing, the check
was discontinued, and the patient was discharged and re-evaluated one week
later. If calcium level was decreasing, oral calcium was started with a
dose of 3 gm elemental/day. If calcium level was stabilized with this
dose, gradual tapering of oral calcium was started. The magnesium level was
checked and corrected if needed. The calcium level was rechecked one week
later.
If serum calcium
continued to decrease, or the patient became symptomatic, 0.5 μg of
1,25-dihydroxy vitamin D was added per day. If serum calcium level
continued to decrease or the patient developed symptoms, the dose was
increased to 0.5 μg twice daily. If the patient required vitamin D, the
patient was sent home on the dose of oral calcium and vitamin D that
stabilized the ionized calcium. The calcium level was checked one week after
discharge. If the level of calcium was within the normal
range, gradual Tapering of oral calcium and vitamin D was started.
For patients
severely symptomatic with ionized calcium <3.2, IV calcium was administered.
One amp of calcium gluconate (10 ml calcium gluconate 10% containing
1 gm calcium gluconate) in 500 ml sodium chloride was given IV over 5 hours.
The calcium level was re-checked after administration. If the infusion did
not stop the symptoms, this was repeated. The magnesium level was checked
and corrected if needed. Oral 1,25-dihydroxy vitamin D and oral elemental
calcium were maximized in consultation with the Endocrinology department.
The patient was checked one week after discharge. If serum
ionized calcium was within the normal range, oral calcium and vitamin
D were tapered gradually.
All patients with
hypocalcemia were followed up till normalization of serum calcium. If oral
calcium or vitamin D were still required after six months,
the patient was defined to have permanent hypocalcemia and
hypoparathyroidism. Patients with serum calcium levels of more than 9 mg/dL on
the first postoperative day and did not have any other complications were
discharged on the same day and re-evaluated after seven days.
Statistical analysis
Statistical
analysis was done using IBM© SPSS© Statistics version 22 (IBM© Corp., Armonk,
NY, USA). Numerical data were expressed as median and range as
appropriate. Qualitative data were expressed as frequency and percentage.
The Chi-square test (Fisher's exact test) was used to examine the
relation between qualitative variables. A two-tailed p<0.05 was considered statistically significant.
Results
The study included
166 patients; 122 (73.5%) females and 44 (26.5%) males, with a median
age of 39 years (range 18-67 years). Table 1 shows the disease
characteristics and types of management procedures.
Table 1. Clinical and histological
characteristics of thyroid disease and its management procedures
During the
follow-up period, 48 (28.9%) patients developed hypocalcemia. Of these 48
patients, 44 recovered from hypocalcemia within 6 months,
i.e., transient hypocalcemia (26.5%), and four patients need oral
calcium or vitamin D after six months postoperatively, i.e., permanent hypocalcemia
(2.4%). 37 (77.1%) patients with hypocalcemia
developed manifestations of hypocalcemia within the first 48 hours. 5
(10.4%) patients did not develop signs or symptoms of hypocalcemia.
Table 2 shows a
comparison between patients developed hypocalcemia and those who did not,
concerning demographic and clinical characteristics.
Table 2. Relation between the
development of hypocalcemia and demographic and clinical characteristics of the
studied group
Development of
hypocalcemia was not affected by age, sex, or surgeon experience. Meanwhile,
preoperative clinical suspicion of malignancy was associated with a
significantly higher proportion of postoperative hypocalcemia compared to toxic
or simple goiter. The type of surgical procedure and final diagnosis were
the main factors affecting the development of hypocalcemia. All of
the 11 patients with thyroid malignancy eventually developed hypocalcemia.
Among 14 patients with Grave's disease, 9 (64.3%) developed postoperative
hypocalcemia. Patients with lymphocytic thyroiditis and those with thyroid
adenoma were the least affected by hypocalcemia. Completion thyroidectomy
and total thyroidectomy with neck dissection were associated with a
significantly higher proportion of patients with postoperative
hypocalcemia. Hemi-thyroidectomy was the safest surgery; only 6.3% of the
patients developed hypocalcemia.
Characteristics of the four patients who developed
permanent hypocalcemia
3 of the 4
patients (75%) were 40 years or older. They were 2 males and 2 females. 2
patients had completion thyroidectomy, and 2 had total thyroidectomy; one
of them had neck dissection in addition. 2 patients had malignant thyroid
disease, one had Grave's disease, and the last one had
Hashimoto's thyroiditis.
Discussion
Hypocalcemia is
the most frequent complication after thyroid surgery [9]. However, different
studies reported a wide variation in the incidence of postthyroidectomy
hypocalcemia. In the current study, 26.5% developed transient
hypocalcemia, while 2.4% developed permanent hypocalcemia. Ozogul et
al. reported an incidence of 24% in 196 patients (24%) with total
thyroidectomy [10]. Edafe et al. reported an incidence of 29.0% [11].
Nevertheless, these authors found that the incidence of
post-thyroidectomy hypocalcemia was underestimated by 6% when
only measurements during postoperative day one were considered.
Another study reported a much lower incidence of hypocalcemia in 5846
patients subjected to bilateral thyroid surgery for benign and malignant
thyroid disease. The authors reported an overall incidence of transient
and permanent hypoparathyroidism was 7.3 and 1.5%, respectively [12].
A retrospective
study evaluated the incidence of complications in 1020 patients submitted to
thyroidectomy in a cancer hospital. The authors reported that transient
hypocalcemia was the main postoperative complication affecting 13.1% of
patients. Permanent hypocalcemia affected only 1.4% of the patients
[13]. Generally, the frequency of transient hypocalcemia after thyroid surgery
is between 6.9 and 49% [9].
The mechanism of
post-thyroidectomy hypocalcemia is not precisely revealed. Probably, it is
accepted to be multifactorial, including patient-related, disease-related, and
surgical technique-related factors. In the current study, age and sex were
not associated with the development of hypocalcemia. These results are in
agreement with previous studies [9, 14, 15]. However, the literature
is separated as to whether age is a risk factor for hypocalcemia after
thyroidectomy. Some studies found a significant association of
hypocalcemia with advanced age [14-17]. Other studies reported an association
with younger age [18-20]. Noureldine et al. found a positive association
between young age and development of hypocalcemia on univariate analysis,
but on multivariate analysis, age was no more an independent predictor of
hypocalcemia [21]. A recent meta-analysis of 115 studies,
including 2576 patients, found no significant difference in mean age
between patients with hypocalcemia and those without [7]. Similarly, the
literature contains conflicting reports regarding the association
with sex. Some studies did not find an impact of sex on postoperative
hypocalcemia [22, 23]. Conversely, several studies found that females were
significantly more prone to hypocalcemia compared with males [7, 21,
24-26].
The development of
hypocalcemia in the current study was not affected by surgeon experience.
However, this was controversial to most studies that emphasize the
significance of expertise and experience. It is believed that professional
expertise significantly affects the success of surgery. Then, the surgical
skill develops from appropriate training and continuous practice within a
specialty. Many studies confirmed the relationship between surgeon volume
and outcomes in thyroid surgeries [27-30]. It was reported that surgeons
who have performed 100 or more thyroidectomies showed the lowest rate
of complications, but the hospital volume is not statistically associated
with the outcomes [29, 30]. However, some studies demonstrated that
the operations are frequently accomplished by surgeons whose
experience is not mainly focused on endocrine surgery [31, 32].
A large
retrospective multicenter study was done to analyze the impact on patient
outcomes of total thyroidectomy performed by resident surgeons under close
supervision and the assistance of attending surgeons. The study involved 8908
patients. The overall postoperative morbidity was 22.3%. There was no
difference in recurrent laryngeal nerve palsy and hypoparathyroidism
between procedures performed by residents or attending surgeons.
Therefore, the authors concluded that total thyroidectomy could be
safely performed by appropriately supervised residents [33].
The nature of
thyroid disease has been shown as a predictive factor of postoperative
hypocalcemia. In the current study, the clinical diagnosis of malignancy
was a significant predictor of postoperative hypocalcemia. After surgery
and histological examination, all patients with thyroid malignancies developed
hypocalcemia. Also, 64.3% of patients with Grave's disease developed
hypocalcemia.
Literature
reported that several thyroid conditions carry a higher risk of developing
transient and permanent hypoparathyroidism postoperatively. These diseases
include Graves' disease, recurrent goiter, and thyroid carcinoma [12].
In agreement with
the current study, previous diseases reported and an increased risk of
hypocalcemia one day after total thyroidectomy for Graves' disease [34, 35]. It
was recommended that patients with Graves' disease patients should be
informed of the increased risk of hypocalcemia associated with
total thyroidectomy. Another study found that transient but not
permanent hypocalcemia was more common in patients with Graves' disease
than in patients with nodular goiter [36]. A large retrospective analysis included
215,068 patients who underwent total thyroidectomy; 5.2% of them had Graves'
disease, and 43.6% had thyroid malignancy. This study concluded that
Graves' disease patients are at increased risk of many postoperative
complications, including hypocalcemia [37].
A systematic
review of 35 studies found that malignancy, central neck dissection, total
thyroidectomy, and reoperation were significant risk factors of Incidental
parathyroidectomy during thyroid surgery [38]. However, many studies do
not found thyroid malignancy to be an independent risk factor for
developing hypocalcemia [39-41]. In fact, it is the extent of surgery,
rather than the thyroid disease, that increased the risk of
hypocalcemia. Neck dissection appears to be the most frequent cause
of hypocalcemia following thyroid surgery [42, 43]. In the current study,
total thyroidectomy with neck dissection was associated with a
significantly higher proportion (82%) of patients with postoperative
hypocalcemia, while only 6.3% of the patients subjected to hemithyroidectomy
developed hypocalcemia.
A large study of
119,567 patients who underwent thyroidectomy found that total thyroidectomy was
associated with a significantly higher incidence (9.0%) of hypocalcemia
compared to unilateral thyroid lobectomy (1.9%) [44]. In agreement with
the current study, these authors reported that thyroidectomy with
bilateral neck dissection was the most influential independent risk factor
of postoperative hypocalcemia (odds ratio, 9.42) [44]. Total thyroidectomy
was emphasized as an independent predictor of postoperative hypocalcemia in
many studies [45]. During total thyroidectomies, the risk of
injury to the parathyroid glans is clearly higher when dissecting both
lobes. Damaging the parathyroid glands can be avoided by careful detection
of the inferior thyroid artery branches entering the thyroid
capsule with the identification of the end-arteries supplying the
four glands [43]. It was found that the higher number of parathyroid
glands identified during the surgery, the lower risk of hypocalcemia. Identifying than two
glands is associated with a four-fold increase in the risk of permanent
but not transient hypocalcemia [12].
Conclusion
This study
demonstrated that 28.9% developed post-thyroidectomy hypocalcemia mostly of
transient nature. Only 2.4% of the patients developed permanent
hypocalcemia. The type of surgical procedure and final diagnosis were the
main factors affecting the development of hypocalcemia. Total thyroidectomy
with neck dissection was associated with a significantly higher
proportion (82%) of patients with postoperative hypocalcemia. Thyroid
malignancy and Grave's disease were significant predictors of
postoperative hypocalcemia. The development of hypocalcemia was not
affected by age, sex, or surgeon experience.
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