The efficacy and safety of total thyroidectomy in the management of benign thyroid diseases

The efficacy and safety of total thyroidectomy in the management of benign thyroid diseases

Bassem M Abou Hussein,a MD; Hatem F Al-Wagih,h MD; Ayman S Nabawi,h MD; Essam Gabr,h MD; Mohamed Moussa,h MD; Mustafa A Mneimneha MD

a) Division of General Surgery, Makassed General Hospital, Beirut, Lebanon. b) Division of General, Head & Neck and Endocrine Surgery, Alexandria Main University Hospital, Egypt.

Abstract

Background: Total thyroidectomy is currently  the preferred  treatment for thyroid cancer,

multinodular goitre and Graves disease,· however, many surgeons choose not to perform total thyroidectomy to treat benign thyroid diseases owing to the associated  risk of postoperative hypoparathyroidism and recurrent laryngeal nerve damage. We followed up 100 thyroidectomies performed for benign thyroid diseases when surgery was indicated. We sought to assess whether the results  support  the hypothesis that total thyroidectomy is as safe and more effective  as subtotal thyroidectomy and can be considered  as the optimal surgical approach for treating benign thyroid diseases.

Methods: A total of 100 patients underwent thyroidectomy between January 2008 and June

2009. We excluded patients with thyroid cancer or suspicion of thyroid malignancy. We evaluated operative time, intraoperative blood loss, cancer incidence, complication rates, local recurrence rate and long-term outcome after total and subtotal thyroidectomy.

Results: All patients were diagnosed before surgery to have benign thyroid disease by fine

needle aspirate. The incidence  of permanent  recurrent  laryngeal nerve palsy  (unilateral or bilateral) was 0% in both groups, whereas  the incidence of temporary unilateral recurrent laryngeal  nerve  palsy was 4% in cases of total thyroidectomy and 2% in cases  of subtotal thyroidectomy. Permanent hypocalcemia occurred in 2% in each group and overall temporary hypocalcemia occurred in 10% ofpatients with total thyroidectomy and 8% ofpatients with subtotal thyroidectomy. Hemorrhage requiring repeat surgery occurred in 2% of patients with total thyroidectomy and 4% of patients  with subtotal  thyroidectomy. There  was no wound infection, and postoperative mortality was 0%. Incidental finding of cancer appeared in 8% of patients with total thyroidectomy and 18% of patients with subtotal thyroidectomy. We observed no disease recurrence  during a follow-up of 18 months in patients with total thyroidectomy, while a high rate of recurrence (8%) appeared in patients with subtotal thyroidectomy in the same follow-up period.

Conclusion: Total thyroidectomy is safe and is associated with a low incidence of disabilities. Complication rates for recurrent laryngeal nerve palsy and hypoparathyroidism are approximately

similar to results of those with subtotal thyroidectomy. Furthermore, total thyroidectomy seems to be the optimal procedure, when surgery is indicated, for benign thyroid diseases as it has the advantages of immediate and permanent cure and no recurrences and higher rate of detection of occult cancer.

Introduction:

Historically, the risks associated with major surgery for treating thyroid diseases and the problems of adequate hormonal replacement have deterred surgeons from performing total thyroidectomies. In fact, thyroid surgery was rarely performed  until the late 19th century;

total  thyroidectomies were only  performed occasionally for indications other than cancer until the last quarter of the twentieth century.I The use  of total  thyroidectomy remains controversial for small differentiated  thyroid carcinomas, but even more controversial is its use to treat benign diseases.2 Most surgeons

avoid  the procedure owing  to the possible complications such as permanent recurrent laryngeal nerve palsy and  permanent hypoparathyroidism; subtotal thyroidectomy has been the preferred  operation for benign thyroid diseases.2 Although the  extent  of resection for  benign diseases remains controversial, an increasing  number of total thyroidectomies are currently  performed  in specialist endocrine surgery units,  and the indications for this procedure include Graves disease and multinodular goitre.

Many surgeons  still hesitate from doing

total thyroidectomy in benign thyroid diseases in order not to increase the rate of complications associated with  surgery such  as risk  of postoperative hypoparathyroidism (up  to

12.5%)  and recurrent laryngeal  nerve palsy (up to 2.3%).3 However, some studies showed that the complication rates of permanent recurrent laryngeal nerve palsy (0--1.3%) and permanent hypoparathyroidism (1%) following subtotal  thyroidectomy are similar  to those following total thyroidectomy.4-9 In addition, the disadvantages of subtotal thyroidectomy to treat Graves disease are that the procedure does not prevent persistent or recurrent disease in up to 20% of patients; it does not stop the process of the disease and, as a result, it cannot stop the progress  of ophthalmopathy; and it does not address hypothyroidism in up to 70% of patients.

The disadvantages of subtotal thyroidectomy to  treat  multinodular goitre are  that  the procedure does not reduce the risk of persisting symptoms and  has  a high  recurrence rate (30o/o-50%) owing to gland remnants,  even under suppression hormonal treatment with L­ thyroxine2. Disease recurrence usually requires a repeat surgery, which greatly increases the risk (up to 20 times) of damage to parathyroid glands and laryngeal nerves.lO In contrast, total thyroidectomy  eliminates all abnormal tissue in the neck  and lowers  recurrence rates for Graves disease and multinodular goitre. Furthermore, after  total thyroidectomy, hormone replacement with  L-thyroxine is relatively easy and can be achieved by monitoring the thyroid hormone serum levels.

In our institute,  surgeons always do total thyroidectomy  for thyroid cancer and total or

subtotal  thyroidectomy for benign  diseases and for recurrent disease after previous thyroid surgery.

We  sought to  assess whether total thyroidectomy is a safe procedure  with low complication rates  of permanent recurrent laryngeal nerve palsy and  permanent hypoparathyroidism. We  also  sought to evaluate the long-term outcomes including the management of hypothyroidism and the recurrence rates  for  benign  disease  and  to compare the results  with  those  of subtotal thyroidectomy in terms of efficacy and safety.

Methods:

Between January 2008 and June 2009, a prospective randomized (by closed envelope method) study of 100 patients who presented with  benign thyroid diseases undergoing thyroid surgery was conducted at Head and Neck  Surgery unit,  Faculty of  Medicine, Alexandria University and Makassed General Hospital. Patients were randomly assigned to one of two groups by closed envelope method: total thyroidectomy or subtotal thyroidectomy.

All patients were selected on the basis of the following criteria: evidence of thyroid diseases by  preoperative ultrasound examination, absence  of family  history  of malignant thyroid disease, absence of history of  previous neck   surgery or  irradiation.

All patients provided informed consent after a thorough explanation of the  surgical procedure by the surgeon. Each patient filled a history sheet that included the main data and symptoms of his disease.

Inclusion criteria:

All patients with benign thyroid  diseases

(by  FNAC), when  surgery is  indicated.

Exclusion criteria:

Patients with documented malignant thyroid disease.

Patients  showing suspicious findings of malignant disease during surgery.

Patients with previous parathyroid disease. Patients with  family  history of  thyroid

cancer.

Patients with previous neck surgery or neck irradiation.

Preoperative assessment:

Patient's data were collected including age, sex, past history, and family history. Routine laboratory  workup  was done for all of them including  complete blood count, coagulation profile, fasting blood sugar, and blood urea.

All patients  had measurements of serum thyrotropin, thyroxine, triiodothyroxine, thyroid antibodies and  calcium, and  ultrasound estimation of thyroid volume and morphology. Where appropriate (e.g., large or retrostemal goitres), we obtained a computed tomography scan of the neck. All thyrotoxic patients were rendered euthyroid before surgery to prevent perioperative thyroid crisis.

Procedures:

Group I with total thyroidectomy: Formal total thyroidectomy was done with dissection of  the  thyroid gland  after  identifying and preserving both recurrent laryngeal nerves and

3-4 parathyroid glands and keeping them in place with their vasculature. The strap muscles were then approximated and the neck closed.

Group II  with  subtotal thyroidectomy: dissection  was done in the same way as total thyroidectomy, once the superior pole vessels were divided and the thyroid lobe mobilized anteriorly, the thyroid lobe was cross-clamped with a Mayo  clamp, leaving  approximately

4 g of the posterior portion of the thyroid. The thyroid remnant was suture ligated, taking care to avoid injury to the recurrent laryngeal nerve. Inboth groups, patients were discharged within

3-4 days after surgery.

Intraoperative assessment:

The  data  concerning the following parameters were collected:  type of operation, operative time, intraoperative bleeding  and estimated blood loss, and  intraoperative evidence of malignancy.

Postoperative management:

Postoperative follow-up included indirect laryngoscope to check vocal cord mobility and measurement of serum calcium 24 hours and

48 hours postoperatively, hypocalcaemia was

defined as serum calcium less than 8.0 mg/ dl.

Patients were all assessed for postoperative wound complications including hematoma or wound infection.

The entire resected surgical specimens were pathologically examined with comment on the final pathological  diagnosis.

Data for all patients were then collected concerning final   pathological diagnosis, hospital  stay, and   complication  rate.

Patients  were further  followed-up by the means of careful neck  examination by palpation, calcium  level  in  blood  after  six months and neck ultrasonography at 12 months postoperatively.

In patients who were asymptomatic and did not require calcium supplementation, we defined temporary hypocalcemia as a calcium level lower than 8.0 mg/dL in at least 2 consecutive samples (daily for 2 consecutive days). In these patients, hypocalcemia resolved within days. Conversely, in patients who were symptomatic and required calcium supplementation, we considered temporary hypocalcemia to be severe when calcium levels remained lower than 8.0 mg/dL for more than

3 days.Inthese patients, hypocalcemia resolved within  6 months.  In patients who  required vitamin D and calcium supplementation for more than 6 months, we  considered hypoparathyroidism  to   be  permanent.

We defined recurrent laryngeal nerve palsy

as hoarseness associated with  vocal  cord paralysis  at laryngoscopy within  6 months postoperatively. After 6 months, we considered recurrent laryngeal nerve palsy to be permanent At the time of extubation, the anesthesiologist evaluated  vocal cord motility in all patients. Hormonal treatment with L-thyroxine began within 5 days after thyroidectomy in all patients.

The   data  of   the   two   groups, total

thyroidectomy (n =50), and  subtotal thyroidectomy (n =50)  were  analyzed and compared for their statistical significance with a P value less than 0.05 was considered statistically significant.

Follow-up:

The surgeons conducted the follow-up visits for  all  patients. At  1,  6  and  12  months postoperatively. The  surgeons evaluated patients' hormonal replacement, vocal cord motility, parathyroid function and therapeutic outcome. Evaluation included clinical examination, serum  thyroid  hormones and calcium measurements. In  patients with

recurrent laryngeal nerve palsy an otolaryngologist performed a laryngoscopy at

1, 6 and 12 months postoperatively to monitor vocal cord function.

Results:

Between January 2008 and June 2009, 100 patients with benign thyroid disease presented to the surgery department and undetwent either total (50 patients) or subtotal thyroidectomy (50 patients).  Of these, 15 were men and 85 were  women. The  first  group with  total thyroidectomy included 9 men and 41 women, while the  second group with  subtotal thyroidectomy included 6 women and 44 men. The median age of patients was 42.54 (range

17--69) years in the first group and 41.16 (range

20-56) in the second group. None of the patients had previous exposure  of his or her neck to radiation, which increases the risk of thyroid carcinoma. All patients were diagnosed before surgery to have  benign  thyroid  disease  by ultrasound and fme needle aspirate cytology, where  the  first  group  included 9 patients presenting with single thyroid nodule and 41 patients with multinodular goiter; whereas the second group included 12 patients with single thyroid nodule and  38 patients with multinodular goiter.

All the patients included in the present study

were examined by indirect laryngoscopy for vocal folds mobility prior to surgery and all of them showed normal vocal fold mobility. All patients had normal thyroid laboratory function tests  and  normal  levels  of  serum calcium (8.5- 10.4 mg/dl) prior to surgery.

The mean operative time for the first group with total thyroidectomy was (120.1± 29.23 min), while for the second group with subtotal thyroidectomy, the mean operative time was (119.9± 27.03 min).

The amount  of intraoperative blood loss was estimated for  all operative procedures performed. The mean intraoperative blood loss for  cases of total thyroidectomy was (59.80±29.76  ml), while for cases of subtotal thyroidectomy the mean intraoperative blood loss was (71.50±31.56 ml).

Postoperative bleeding and hematoma formation requiring surgical intervention occurred in  1 patient (2%) with  total thyroidectomy and in 2 patients (4%)  with subtotal thyroidectomy.

Among all patients, there was no permanent

recurrent laryngeal nerve palsy, although, three cases of unilateral  temporary palsy occurred and they were divided as two cases with total thyroidectomy (4%) and one case with subtotal thyroidectomy (2%). Complete recovery was the rule  for  all the three  patients and they regained their  normal voice quality.

Transient hypocalcemia occurred  in five patients (10%) with total thyroidectomy and four patients (8%) with subtotal thyroidectomy. Permanent hypocalcemia (>6months) occurred in 1 patient (2%) in each group.

All thyroid specimens  were subjected  for histo-pathologic examination. Results showed benign disease  in 41 patients  in group I and

46 patients in group II. Among these results, multinodular goiter (78%) was  the  most common; followed by Grave's disease (11%), adenoma  (8%)  and   thyroiditis  (3%).

Incidental thyroid cancer was detected in nine (18%) patients in group I and four (8%) patients in group II, thus requiring completion thyroidectomy and indicating the possibility of many cases of undiagnosed cancer in the second group. Of these 13 cases, incidental papillary carcinoma appeared in 11 cases while medullary carcinoma appeared  in 2 patients.

We observed no disease recurrence during a follow-up of 18 months in patients with total thyroidectomy, while a high rate of recurrence (n=4, 8%) appeared in patients with subtotal thyroidectomy  in the same follow-up period.

None  of   the  patients  with  total

thyroidectomy required a second completion operation, while 8 patients (16%) with subtotal thyroidectomy required a completion surgery

(4 patients because of incidental cancer and 4 patients because of recurrence).

There  was  no wound infection and  no mortality in both groups.

Data of both groups,  total thyroidectomy (n =50), and subtotal thyroidectomy (n =50) were analyzed andcompared for their statistical significance with a P value less than 0.05 was considered  statistically  significant.

*Denotes statistically significant values.

Discussion:

Benign thyroid diseases are very common nowadays. The most common benign thyroid diseases are  multinodular goiter  (78.8%), Graves disease (17.8%) and recurrent (after previous partial thyroidectomy) nodular goiter (3.4%).11

Benign  multinodular goiter is one of the most common endocrine surgical problems; the  appropriate surgical procedure for  its effective and safe management is a matter of debate.I2 Although total thyroidectomy is the procedure of choice  in patients with thyroid carcinoma, this surgical approach has emerged

as a surgical option to treat patients with benign multinodular goiter  (BMNG),  especially in endemically iodine-deficient regions.13 Many surgeons still   hesitate from   doing total thyroidectomy in benign thyroid  diseases in order not to increase the rate of complications associated with  surgery such  as risk  of postoperative hypoparathyroidism (up  to

12.5%) and recurrent  laryngeal  nerve palsy

{up to 2.3%).14

There is increasing recognition that total thyroidectomy is also the appropriate surgical treatment for benign toxic  and nontoxic multinodular goitre, particularly when  the

nodular disease involves both lobes),4,10,15-17

The advantages of total thyroidectomy in such cases  are  the  prompt  relief  of  symptoms; provision of a defmite histological diagnosis, especially when the clinical features indicate the  possibility of  thyroid  malignancy (the reported risk is about 5%-10%); and no risk of  disease  recurrence. On the  other  hand, nontotal thyroidectomy, such  as  subtotal thyroidectomy or unilateral lobectomy, is a less satisfactory procedure because, by leaving residual thyroid tissue, the patient is exposed to a higher risk of recurrent disease (23o/o-45%) that is not treatable by thyroxine suppression therapy  and will,  therefore, involve  repeat surgery.1,2,18 Moreover, nontotal thyroidectomy does  not  avoid  the  risk  of  postoperative complications. In fact, the complication risk of nontotal thyroidectomy is similar to that of total  thyroidectomy, and  the risk of repeat surgery owing to recurrence is up to 20 times greater with   nontotal  thyroidectomy,lO The aim of this study  is to compare  the outcome  of   both  techniques  of   total thyroidectomy  and subtotal thyroidectomy in relation to  efficacy, safety and  possible complications. The groups of patients included in this study were well matched in the terms of age, gender,  preoperative laboratory  test results  and surgical  indications, therefore a

comparison seemed possible.

Preoperative estimation of thyroid disease by  ultrasound neck  examination, thyroid function tests  and fine  needle aspiration cytology were  considered to be the corner stone for selection  of patients  eligible  to be included in the study. In this series, the main inclusion characteristic was a benign thyroid disease as documented by ultrasound and FNAC.

There was no statistical difference between both  groups concerning preoperative data including age, sex, preoperative presentation, laboratory  investigations and FNAC results.

Operative time and intraoperative blood loss were estimated in both groups and showed no statistical difference (p=0.972 and p=0.59 respectively).

The main complications of thyroid surgery are associated with injury of parathyroid glands with subsequent  hypocalcemia and recurrent

laryngeal nerves. The risk of recurrence or incidental finding of cancer requiring completion thyroidectomy and a second operation with  its  subsequent hazards is extremely important.

In a certain study, it was proved that a grade C recommendation can be made about total thyroidectomy being  a safe  and  effective procedure for benign multinodular goiters in the hands of expert  surgeons, based  on the extensive level N evidence, and limited level II and level illevidence, which show that the risk  of  permanent vocal cord  palsy and hypoparathyroidism associated with total thyroidectomy is below the acceptable 2% rate, but not without exceptions.12

Hypocalcaemia caused by transient or definitive hypoparathyroidism is the most frequent complication after thyroidectomyl9.

A report  from  Eleni  I. Efremidou et al

showed that the rate of temporary hypocalcemia was  7.3%  while  permanent hypocalcemia occurred in  0.3%  of  patients after total thyroidectomy)! Gough and  Wilkinson! reported permanent hypoparathyroidism following total thyroidectomy at the rate of

2.2%. In our study, temporary hypocalcemia occurred in 10%  in patients with  total thyroidectomy and 8% in patients with subtotal thyroidectomy; while permanent hypocalcemia occurred in 2% in each group.

The above data show that the present results are comparable with other studies and that transient and  permanent hypocalcemia following total thyroidectomy occurs in acceptable rates when compared  to subtotal thyroidectomy, with statistically insignificant values (p=0.487).

Aytac Bet a1,2o reported that following total

thyroidectomy, unilateral vocal cord problems occurred in 3.8% of cases and in 1.2% of cases it became permanent.

The  present study showed transient unilateral recurrent laryngeal nerve palsy in 1 patient (2%) following subtotal thyroidectomy and   in  2  patients (4%)   following total thyroidectomy and all these patients improved within three months resulting in 0% of cases having permanent recurrent laryngeal nerve disease. The important issue  in the present results was  that  there was  no  statistical

significance between nerve injury following total and   subtotal  procedures (p=0.5).

Eleni  I  Efremidou  et  alll  reported

postoperative hemorrhage requiring surgical hemostasis in 0.2%  of patients, no wound infection and no mortality. The present study showed that postoperative hemorrhage occurred in 2% and 4% of total and subtotal procedures respectively with no statistical significance between  both groups (p=0.5). There was no wound  infection  and  no   mortality.

Despite the  recent  wide  availability of ultrasonography and fine-needle aspiration biopsy, endocrine surgeons often encounter incidental papillary carcinoma (IPC) that is a papillary carcinoma that had gone undetected by  preoperative imaging studies but  was identified by  pathological examination of surgical specimens resected for benign thyroid

diseases.21

Incidental thyroid cancers are detected  in

3%-16.6% of apparently benign  goiters in numerous studies, mostly providing level IV evidence, one thirdof which would need further surgical treatment after subtotal thyroidectomy.12

In the present  study,  incidental thyroid cancers were detected in 4 patients (8%) after subtotal thyroidectomy and in 9 patients (18%) after total thyroidectomy. These patients with subtotal thyroidectomy needed a completion thyroidectomy for their malignant disease with more  complications. In addition, the  high number of incidental cancers detected after total thyroidectomy show that there are some cases with thyroid cancer left undiagnosed after subtotal thyroidectomy. Statistical analysis showed significant difference between both groups concerning detection of incidental thyroid cancer (p=0.017).

Another advantage of total thyroidectomy is the prompt relief of symptoms and no risk of  disease  recurrence. On the  other  hand, subtotal thyroidectomy is a less satisfactory procedure because, by leaving residual thyroid tissue, the patient is exposed to a higher risk of recurrent  disease  (23o/o-45%) that is not treatable by thyroxine suppression therapy and will,  therefore, involve repeat surgery.11

Moreover,  subtotal  thyroidectomy does not avoid the risk of postoperative complications.

In fact, the complication risk of subtotal thyroidectomy is similar to that of total thyroidectomy, and the risk of repeat surgery owing to recurrence is up to 20 times greater with subtotal thyroidectomy.to

In this study, and by ultrasound examination after  18 months of  surgery, there  was  no evidence of recurrence after total thyroidectomy while four patients (8%) showed a recurrent disease after  subtotal thyroidectomy; thus requiring a repeat surgery to complete thyroidectomy, with  a significant  statistical difference (p=0.049).

Completion thyroidectomy due to incidental

finding of cancer or for recurrence of disease was needed in 8 patients (16%) after subtotal thyroidectomy, while none of the patients who had total  thyroidectomy needed  that.  This showed a great statistical difference (p=0.003).

Conclusion:

Total thyroidectomy  can be safely done with a low  complication rate.  Data  from  many studies show no significant  difference in the rate  of  postoperative complications (e.g., recurrent laryngeal nerve injury, hypoparathyroidism, hemorrhage) associated with total  thyroidectomy compared with subtotal thyroidectomy.

As a result,  total  thyroidectomy is now widely accepted for the management of both malignant and benign thyroid diseases. Our data  support that  total  thyroidectomy is a valuable option, when surgery is indicated, for treating benign thyroid  conditions such as multinodular goitre.

It has been shown that total thyroidectomy

achieves immediate and permanent cure with no risk of disease recurrence or repeat surgeries.

Our  data  also  suggest that  there  is  an increased risk for malignancy among patients with  benign thyroid conditions, which  is detected more frequently when total thyroidectomy  is performed. In such patients total thyroidectomy offers a definite management of thyroid cancer.

References:

1- Gough IR,  Wilkinson D: Total thyroidectomy for management of thyroid disease. World JSurg 2000; 24: 962-965.

2- Bellantone R, Lombardi CP, Bossola M, et