Complications of thyroid surgery
M. Safioleas, M. Stamatakos, N. Rompoti, R. Iannescu, V. Salichou, P. Skandalakis, G. MouzopoulosReferate generale, no. 6, 2006
* 2nd Department of Propedeutic Surgery
* Department of General Surgery, General Hospital Sparta, Greece
Introduction
Thyroid surgery has a history of significant changes in the technique and the incidence of complications. During the early half of the nineteenth century thyroid surgery had a mortality rate over 20% and was performed only to confront with life-threatening situations (1). Kocher was the first who achieved a significant reduction in the mortality rate (0.18%) (2). Since then continuous developments in surgical techniques and better understanding of thyroid anatomy and pathology have increased the safety of thyroid surgery and reduced the incidence of complications. Nowadays, the rate of postoperative mortality is extremely low (3, 4). Bhattacharyya et al reported that the mortality rate of total thyroidectomy is a safe procedure, with an expected mortality rate of only 0,2% (5). Medical complications such as myocardial infarction, stroke and postoperative pneumonia are quite rare.
Nevertheless, the incidence of postoperative complications varies in literature from 7,4% to 53% of the operations performed (3, 6).
The most common and potentially life-threatening complications in thyroid gland surgery are vocal cord palsy and hypocalcemia (3, 4, 7).
Some reports in the literature correlate the complications of thyroid surgery with the experience of the surgeon performing it (8). Other reports mark that under the supervision of an experienced necksurgeon, thyroid surgery can be
equally safely performed at residency training centers (4, 6, 9). Nevertheless, the complication rates of thyroidectomy are related with the type of operative procedure and the
experience and the skills of the surgeon performing it (8, 10).
Recurrent laryngeal nerve (RLN) injuries
RLN injuries are undoubtly important complications and potentially debilitating. They represent 22.2% of total post-thyroidectomy complications (11). Permanent vocal cord palsy rate below 1% of patients undergoing thyroidectomy is issued by the British Association of Endocrine Surgeons (12, 13). The last five years authors report that the damage of RLN as complication of thyroid surgery occurred as permanent
paralysis in a range of 0.3%-5.8%, as temporary paralysis in a range of 0.9%-5.2%, unilateral paralysis as 0.5%-6.6% and bilateral paralysis as 0.4%-1.5% (14-17). The rates of RLN palsy differ between benign and malignant thyroid diseases. The incidence of recurrent laryngeal nerve injury occurs more commonly when thyroidectomy is performed for malignant disease (15,16). Tomoda et al reported a rate of RLN palsy 2.7% for benign thyroid diseases and 8.9% for thyroid cancer (18). Moreover secondary surgery was associated with significantly higher rates of permanent and temporary RLN palsies than primary surgery.
Loss of function of RLN can result from traction or handling of the nerve during its dissection, inclusion of the nerve in a ligature or inadverted sectioning of the nerve. Clinical vocal cord paralysis occurs when more than 50% of the RLN fibers are lost. If the RLN is injured unilaterally hoarseness occurs and the voice losses its timbre and focus. Furthermore, weak, breathy voice and aspiration can occur (19). When thyroidectomy is performed for malignant tumors, cancer invasion of the nerve necessitates nerve transaction.
The delayed onset of cord paralysis with dysphonia can be ascribed to initial flaccid paralysis that becomes spastic giving rise to dysphonia (11). If vocal cord paralysis appears in the late postoperative period the prognosis of the recovery is
generally good.
Definitive is considered a malfunction of vocal cords documented by laryngoscopy that does not regress within a year. It is caused by partial or complete nerve damage or the persistence of other causes (11). Whether the RLN should always be identified during thyroid procedures has been the subject of considerable debate in the past. Many surgeons consider that iatrogenic injury of the RLN or its branches might be better avoided by searching, identifying and exposing the nerve itself and by following its course with care (16, 17, 20). However, the opposite argument presents the possibility of injuring the nerve during the effort to identify it. Nowadays, most surgeons consider that injuring RLN is less likely if the nerve is clearly visualized during at least a portion of the procedure, agreeing that careful exposure does not cause RLN injury (11,18).
Intraoperative monitoring of RLN function has been proposed in order to identify, dissect and detect injury to the RLN (19, 21). Electrical identification and monitoring of the RLN has been proposed as an adjunct to standard visual identification of the nerve during thyroid surgery. In a multiinstitutional prospective study of more than 4000 patients, Thomusch et al found significantly lower rates of transient and permanent vocal cord palsy with intraoperative monitoring during surgery for benign goiters than with standard visualization alone (21).
Palpation to detect contraction of the PCA is a simple readily available technique for any thyroid surgeon and can be performed with a variety of handheld, disposable, widely available nerve stimulators. Randolph et al suggested that if contraction of the PCA is lost, several possibilities should be considered, including neural injury (22).
If the surgeon stimulated the distal site of the RLN,
contraction of the PCA would occur even though RLN palsy exists. False-negative results could be also caused by nerve stimulation of the PCA abductor fibers. Extralaryngeal division of the RLN has been reported in 80% and in as few as 35-43%. The distance of bifurcation or trifurcation from the inferior border of the cricoid
cartilage ranged from 0.6 to 4 cm, with an average distance of division occurring at 1.96 cm.
Especially in early studies but also in recent studies, hoarseness was considered a measure of vocal cord palsy. However, several cases of unilateral vocal cord palsy with no subjective hoarseness have been observed. Furthermore, hoarseness may be caused by a vocal cord hematoma or postoperative laryngitis. Along with direct laryngoscopy or laryngofiberoscopy, an examination should be performed in all cases to assess the integrity of the RLN postoperatively even if patients undergo palpation to detect contraction of the PCA during surgery and have a normal voice after
surgery (18).
The distal course of the nerve (2-3cm) is more vulnerable to injury (13). In most cases this portion of the nerve is
covered by the tubercle of Zuckerkandl or a portion of
ligament of Berry (or both) and this is where it is more likely to be at risk of injury (23).
Thyroidectomy remains the third most common cause of bilateral vocal fold immobility. Injury to the recurrent
laryngeal nerves bilaterally is usually immediately recognized after extubation or in the immediate postoperative period. The bilateral injury may not present for up to several hours after extubation, however as stridor may be delayed in
development if some abductors function is preserved initially. Bilateral paralysis mandates immediate attention and often emergent airway intervention. If the patient develops stridor during extubation or in the recovery room, flexible fiberoptic laryngoscopy is performed immediately to confirm the diagnosis and the patient is reintubated. In more severe cases of immediate airway obstruction, indirect laryngoscopy may need to be omitted initially in favor of emergent airway intervention. At this point, a decision needs to be made about the immediate management of the patients' airway. If the surgeon is confident that the recurrent nerves were preserved during surgery, corticosteroid therapy may hasten recovery of
function. After several days, a controlled extubation is
performed. If flexible fiberoptic laryngoscopy shows that the airway is adequate and that vocal fold mobility has returned, no further intervention is needed. If no recovery ensues, the patient is reintubated and a tracheostomy is performed. In the cases in which there was known injury to the bilateral
recurrent nerves intraoperatively, a tracheostomy may be
performed immediately.
Typically, the vocal cords fall in the paramedian position, and the voice is usually strong and may even be normal. Therefore, future intervention is usually aimed at the restoration of an adequate airway. It was traditionally taught that a waiting period of 9 months was necessary before any rehabilitation procedure was performed. This is believed to be the time necessary to rule out any possibility of spontaneous recovery. Laryngeal electromyography may be performed early, however, to help determine prognosis (14).
In order to reduce the rate of LRN injuries, every operative step should be executed carefully and attention should be given to the wide range of possible variations in the course of the nerve (13, 24). In order to prevent the thermical damage of the nerve, unipolar electrotome near the region of the nerve's course should be avoided and bipolar electrotome should be used very carefully (11). After careful mobilization of the tubercle of Zuckerkandl and its retraction medially, the nerve can be identified in this area. Moreover, in approximately 1% of cases, a nonrecurrent laryngeal nerve or direct branch from the vagus can be identified on the right side of this region (11, 13). RLN can occasionally bifurcate or even trifurcate proximal to its laryngeal entrance, and therefore no portion of the ligament of Berry should be cut or clamped until the surgeon is absolutely sure that a nerve branch is not within the tissue involved (13). Furthermore, when removing the thyroid from the laryngotracheal axis, the nerve should be covered with a lukewarm wet gauze. Vessel ligation should also be performed carefully in order to insure that the nerve will not be injured iatrogenic by hemostatic maneuvers (11). Strategies that prevent RLNP are of great interest. One way is to ensure the integrity of the nerves with routine identification of RLN, which is proposed by most surgeons today. However, RLNP may result from direct mechanical damage without disruption. This disparity between anatomic neural integrity and actual RLN function probably results from
trauma to the intact nerve. Nerve manipulation during
thyroid surgery may cause neural edema and consequent
dysfunction, resulting in anything from neurapraxia to axonotmisis (25).
Ling-Feng Wang et al demonstrated that the duration of temporary RLNP can be reduced with the use of single dose of intraoperative steroids in a prospective study (25). The absence of increased morbidity from the single dose of steroids, it may be efficacious to consider using the steroids, particularly in patients where difficult dissection around the nerves is anticipated, such as those with locally advanced cancers, Graves' disease, and patients undergoing reoperation. When vocal cord paralysis is recognized preoperatively, a
presumptive diagnosis of invasive disease is made and the
surgeon then is empowered to consider several important issues. The issue raised by the diagnosis of preoperative vocal cord paralysis is that patient-specific operative planning can be performed, including the potential need of tracheostomy and laryngotracheal resection and reconstruction. Preopera-tive knowledge of vocal cord function also is essential for intraoperative decision making. We and others have recommended that if preoperative vical cord function is present, every attempt should be made to resect all invasive disease, leaving, at most, microscopic disease on the functioning RLN, but not to resect the nerve.
In a recent large prospective study of 5,583 thyroid cancer patients, the US and German Thyroid Cancer Study Group found that preoperative voice abnormality was present in 8,2%, but laryngoscopy was performed preoperatively in only 6,1%.
Another reason for routine laryngoscopy on all patients undergoing thyroidectomy is the important and growing trend toward evidence -based outcome analysis of operative practice (22).
There is debate in the literature regarding the use of
routine vocal fold examination before thyroid surgery as well as a discrepancy in the incidence of asymptomatic vocal fold motion impairment.
We recommend vocal fold examination as a routine preoperative investigation for all patients undergoing thyroid surgery. We found a high incidence of asymptomatic vocal fold motion impairment (32%). Some patients (10%) with normal vocal fold mobility in our study had positive voice symptoms. Therefore, using preoperative voice quality as an indicator of vocal fold function and RLN function may not be reliable. Steurer et al found that 42.9% of patients with preoperative unilateral RLN palsy, which persisted after
surgery, did not present with a hoarseness before or after a surgery. Because in slowly progressive benign diseases functional changes and compensation occur gradually resulting in no voice change or minimal change that goes unnoticed.
RLN dissection and identification significantly reduces their risk of its injury and is superior to limited nerve
exposure. In some cases the vocal fold motion impairment was contralateral to the side of the thyroid lesion. Knowledge of preoperative vocal fold and RLN function may be especially helpful in planning the extent of surgery in these cases. Careful consideration of RLN preservation on the side of the pathology must be emphasized. Documenting asymptomatic vocal fold motion impairment preoperatively may provide the surgeon medico legal protection if postoperative voice change occurs (26).
RLN injury occurs more frequently when thyroidectomy is performed by less experienced neck surgeons (20). Moreover, the rate of this complication is greater in extensive resections and in cases of reoperation (3, 27). The paralysis rate in the reoperation setting is approximately 5%, with a range from 2% to 12% (19, 28). This is accosiated with the extensive scarring, distortion of anatomic relationships, and proximity if the disease that necessitates reoperation.
Kouffman et al classified nerve injury based on the
presence of spontaneous activity, recruitment and individual motor unit morphology (29). (Table 1)
Fewins J et al recommends examination of the patients vocal fold mobility with fiberoptic flexible laryngoscopy in the early postoperative period or in the recovery room if the surgeon during the operation suspects RLN injury (14). Indirect laryngoscopy is though to be by Fewins and others unsufficient to diagnose a minority of asymptomatic cases with unilateral RLN injury and subtle paresis (30).
The treatment of RLN injury starts when vocal cord paralysis is diagnosed. If an RLN injury is recognized during the procedure, the nerves function can be partially restored with the use of graft from the auricular nerve or with epineural sutures (14). When vocal cord paralysis is diagnosed postoperatively, it is important to start early, among other therapeutic approaches, logopedic rehabilitation (within 2-3 weeks) (11). In order to handle unilateral true vocal cord paralysis, injection laryngoplasty or medialization larygoplasty can be performed (29). The aim of all the surgical techniques used in the treatment of vocal fold paralysis is to restore a lumen sufficient to guarantee
adequate breathing through the natural airway, without the need to maintain a permanent tracheotomy tube, while
preserving acceptable phonatory quality.
The evolution of endoscopic microsurgery, now associated with the use of CO2 laser has opened new frontiers in the treatment of this condition.
Posterior cordectomy is an effective, reliable technique in the treatment of vocal fold paralysis. The technique is, furthermore, faster and simpler to perform than total
arytenoidectomy. It can be carried out even in the acute phase without prior tracheotomy and is rarely accompanied by complications (31). When bilateral vocal cord palsy occurs symptoms of airway obstruction are noted when the patient is extubated at the end of the surgery. The patient should be then reintubated and if an extubation 48 hours later fails, tracheostomy is required. If voluntary movement of the vocal cords does not return after 9 months or if electromyography data show that recovery is unlikely, a definitive procedure can be planned.
Laryngeal superior nerve(LSN) injuries
The internal nerve: Its course is distant from the thyroid bed, and it is rarely injured during thyroid or parathyroid dissection. The external branch innervates the cricothyroid muscle and typically descends in close relation to the superior thyroid artery. The course of the nerve is usually medial to the artery. Anatomic variants are not infrequent, however, and place the superior laryngeal nerve in close proximity to the superior
thyroid artery at the level of the superior pole of the thyroid. Cernea et al reported that the nerves at "high risk" cross the superior pedicle below the upper border of the superior pole of the thyroid (32). Transient or permanent injury of the external branches of the LSN is a relatively frequent complication. Inadequate exposure or extensive disease at the superior pole will often lead to injury of the external branch of the
superior laryngeal nerve which leads to paralysis of the cricothyroid muscle. As the function of this muscle is no lengthen, stiffen, and thin the true vocal cord, the patient will have difficulty increasing the pitch of their voice, vocal fatigue, and difficulty singing note intonation along with inability to make explosive sounds (11). Other symptoms include vocal fatigue, hoarseness, volume disturbances or
ticking. In unilateral paralysis, the unaffected side may
adequately compensate and allow for pitch changes. As a result, few casual voice users complain of or even notice any dysfunction (14). If the omolateral LRN lesion is present,
dysphagia of the liquids often occurs (11).
The nerve is injured either by clamping or the imprudent use of electrotome, when used to control bleeding in the region of the cricothyroideus muscle.
In order to reduce to a minimum the risk of LSN lesions, an anatomic dissection of the upper pole of the thyroid gland should be performed (13). Injury of the LSN can also be avoided by stretching out the superior poll of the thyroid
laterally and ligating carefully the three branches coming from the thyroid artery next to the grandular tissue (11). Great care should also be taken to avoid direct injury to the crico-thyroideus muscle (13).
Cervical sympathetic damage
It is a rare but severe complication, which results from
forceful retraction on the carotid sheath. The clinical outcome is Horner's syndrome and the symptoms are not rarely permanent. To prevent rare but severe paralysis caused by brancial plexus stretching, the patients must be positioned with arms adducted (11).
Hypoparathyroidism and hypocalcemia
Hypocalcemia caused by transient or definitive hypoparathyroidism is the most frequent complication after thyroidectomy. Postthyroidectomy hypoparathyroidism has been
reported with a varying incidence, ranging from less than 1% to as high as 15% (33-35). Many surgeons believe that with a meticulus surgical technique the rates can be reduced to 0.5% to 4.0% (36-38). In the literature, the incidence of hypo-parathyroidism when permanent had a range of 0,1% to 32% and as a temporary the range was found as 14,4% to 35% (7, 8, 39). The risk of permanent hypoparathyroidism is higher for cancer surgery and ranges from 3%-32%. Most published reports in the last five years however quote a figure below 10% (8, 40). Although it was expected that the range of hypo-calcemia will follow the one of hypoparathyroidism the value range was different. These data lead to the conclusion that, despite hypoparathyroidism, various factors may account for the decrease in serum calcium levels. Hypocalcemia as
permanent complication varied from 1% to 12,5% and as temporary had an appearance up to 26% (15, 17). The
incidence of temporary hypocalcemia was reported between 6,9% and 25%. Other investigators, however, reported that transient drops in measured serum calcium levels occurred in nearly all patients drops in measured serum calcium levels occurred in nearly all patients following thyroid surgery. Manipulation of the parathyroid glands producing transient parathyroid insufficiency is a commonly accepted mechanism. The fact that in literature postoperative rates of hypocalcemia vary and rise up to 50% of the cases is also associated with
differences in the definition of hypocalcemia, the type of
thyroid disease and the technique of the operation performed (34). Hypocalcemia reverses spontaneously in many cases. Nevertheless, irreversible injury to the parathyroid glands such as damage to the arterial or venous vascular anatomy of the parathyroids, may result in permanent hypocalcemia (11, 34). The problem of how many parathyroids must be preserved to maintain a normal serum calcium level remains unresolved. Most authors believe that a single functioning gland is enough to restore normal parathyroid activity, whereas others believe that the integrity of at least three glands is necessary (34, 41).
Technical precautions can reduce to a minimum the persistent hypocalcemic complications. In the non-capsular dissection technique the parathyroid gland is vulnerable to devascularisation or inadvertent removal with the thyroid gland during such a procedure. Success of capsular dissection in reducing this complication (8). Handling of the parathyroids should be avoided, especially if the glands are anatomically well protected in the parathyroid capsule. However, if they are attached to the thyroid capsule, they must be accurately separated. In order to safeguard venous vascularization, ligature of the branches of the inferior
thyroid artery must be carefully executed. There are
surgeons who believe that ligating the inferior thyroid artery at the main trunk will not interact with the glands function (42, 43). Moreover, if a parathyroid is incidentally devascularized, it is necessary to reimlant it in a sternocleidomastoid muscle pouch (44, 45). None of the patients who had autotransplanted parathyroid glands intraoperatively
suffered from hypocalcemia after the operation (10). The surgeon must be alert in case venous congestion or
gland hemorrhagic infiltration occurs, complications that neseccitate the decompression by incising the parathyroid capsule (44). Most authors agree that identifying para-thyroid glands during surgery can result in a lower incidence of incidental parathyroidectomy. However, incidentally excised parathyroids can be found in an intrathyroid location in up to 40% to 50% of cases (10, 46, 47). Therefore, surgeons experience is inadequate in those cases of
incidental parathyroidectomy. An excellent technique for locating them intraoperatively is to follow the branches of the inferior thyroid artery distally until the glands are encounterd. In a minority of patients, the superior para-thyroid gland may draw its blood supply from the superior thyroid artery. It is important that the surgeon be familiar with this possibility.
The severity of clinical presentation of hypocalcemia may vary from an asymptomatic laboratory finding to a severe life-treatening condition. The symptomatic patient will usually first present with perioral numbness or tingling, abdominal pain, nervousness, paraesthesias of the extremities, or muscle cramping (Chvostek's sign, Trousseau's sign). Severe hypocalcemia may lead to seizyres and cardiac
dysfunction.
Persistent hypoparathyroidism requires lifetime treatment. Tetany develops within 12 hours after the operation. Fihlo et al (2004) reported that the symptomatic range of hypoparathyroidism varies from 4% to 42% and that the permanent hypoparathyroidism has a range of 0% to 8%. Neck dissection and paratracheal dissection are the most important risk factors for the occurrence of hypocalcemia (27). Pattou et al(1998) reported that a higher risk for
permanent hypoparathyroidism existed if fewer than tree parathyroid glands were preserved, the early serum PTH level was lower than 12pg/ml, the delayed serum calcium level was lower than 8 mg/dl or the delayed serum phosphorus level higher than 4 mg/dl under calcium therapy (34). The incidence of postoperative hypocalcemia was higher in patients with mediastinal immersion of the goiter (15%) in patients suffering from the autoimmune diseases (33%) and cancer (5%). Hypocalcemia also seemed to be long-lasting or permanent in case of hyperfunction (6,25%) and recurrence (6,25%). Hypoparathyroidism is more frequent in patient operated on for Graves' disease and thyroid cancer than in other thyroid disorders.
Usually the lowest serum calcium level is seen 48-72 hours after surgery and returns to normal in seven days after surgery. Symptoms usually occur 24 to 48 hours after the operation. Temporary hypocalcemia is more common after total thyroidectomy. After total thyroidectomy transient falls were found not only in calcium but also in magnesium. Furthermore, hypocalcemia correlated to hypomagnesemia and patients are more likely to be symptomatic when both cations are low (48).
Serum calcium, albumin, and magnesium levels should be drawn every 6 to 8 hours in the immediate postoperative period. Serum calcium levels should be corrected for the depletion of albumin. The formula "calcium+ s4-Albumin (g/dl)t" is used for corrected calcium. If the corrected
calcium level is lower than the laboratory's reference low value, the total free calcium considered depleted. Calcium levels should reach a nadir within 48 hours.
It was found that a PTH level of less than 10 pg/ml at 4 or 6 hours after surgery identified all but one patient who suffered hypocalcemia. Quiros et al also used 10 pg/ml as a cutoff value. Patients who were below this level postoperatively were significantly more likely to be on Vitamin D supplementation at 1 month postthyroidectomy. (49). Payne and colleagues used a combination of PTH values (<28 pg/dl) and corrected calcium levels (<8,56 mg/dl) to define a critical level at 6 hours post thyroidectomy. A further study by Lam and Kerr where hypocalcemia was defined as less than 0,9 mmol/L demonstrated a critical PTH level of 8 pg/ml to accurately separate hypocalcemic from normocalcemic patients. Richards et al also used a PTH level of 10 pg/ ml to demonstrate which patients actually became symptomatic of hypocalcemia. At 15 pg/ml or lower, more patients became hypocalcemic when compared with patients whose postoperative PTH levels were greater than 15 pg/ml. Although the presence of postoperative hypo-calcemia can significantly collate with lower PTH values, the presence of a low calcium level postoperatively is not always associated with a low PTH value.
Postoperative hypocalcemia usually occurs 24 to 48 hours after surgery, which makes it difficult to predict (by calcium level alone) immediately postoperatively which patients will experience this complication. One of the
primary goals of using the intraoperative PTH level is to be able to safely and reliably send thyroidectomy patients home the day of surgery without the need for hospital admission and serial calcium levels because this would allow for a better allocation of resources in the setting of an increasingly costly health care environment. The most important statistical tool for making this decision is the sensivity of the PTH cutoff value, which measures the
ability of the perioperative PTH value to show the presence of hypocalcemia. The timing of the intraoperative PTH level is of significance. The PTH value drawn 10 min
postexcision was less accurate than the level drawn in the recovery room. Perhaps manipulation of the surgical bed may artificially elevate serum PTH levels and mask a true underlying hypoparathyroidism.
Scurry et al identified two separate tools to help predict postoperative hypocalcemia. Their data showed a cutoff value of 7 pg/ml as a useful measure to predict hypocalcemic patients.
Perioperative PTH levels, especially those drawn in the recovery room, can be used in a clinically relevant way to predict the relative risk of postoperative hypocalcemia after thyroid-related surgeries that place total parathyroid
function at risk (50).
Cohen concluded that perioperative PTH values can identify patients who are at high risk for postoperative hypocalcemia. His latest data required a recovery room PTH that is both greater than 10 pg/ml and increasing
relative to the intraoperative PTH value to indicate a low risk of hypocalcemia.
Higgins et al state that 64% of hypocalcemics in their study had greater than a 75% drop in PTH at 20 min postoperatively and that 75% of normocalcemics had less than a 75% drop in PTH. We suggest two methods for predicting postthyroidectomy hypocalcemia using serum PTH levels and 1) the calculation of a percent change in PTH and 2) the absolute postoperative PTH drawn at 10 min after gland removal.
Patients undergoing completion thyroidectomy incur a greater risk of experiencing postoperative hypocalcemia than patients undergoing total thyroidectomy. This finding could be caused by the risks of re-operation or the operation being performed in a potentially irradiated neck, which may have compromised vascular supply.
Neither Graves disease nor cancer proved to be a risk factor for hypocalcemia (51). Post thyroidectomy hypo-calcemia seems to reach the lowest values in patients
who undergo TET for malignant diseases, especially on the second postoperative day (52).
The positive slope or increasing serum calcium level between 6 hours and 12 hours after total thyroidectomy is a reliable method to identify patients who will not develop significant hypocalcemia.
Patients with a positive serum calcium slope after total thyroidectomy are safe to discharge within 24 hours after
surgery with patients education and with or without calcium supplementation. In addition, patients with a nonpositive slope and a serum calcium level>8 mg/dl at 12 hours postoperatively are unlikely to develop significant hypocalcemia, especially beyond 24 hours postoperatively ,and therefore can be safely discharged within 24 hours after total thyroidectomy with patient education and oral calcium supplementation (53).
Hypothyroidism
Hypothyroidism after TT is an important complication which can be successfully treated by therapy, although its management in young persons and pregnant women is not easy
Chow TL et al (2001) showed that the percentage of hypothyroidism in STT, NTT and TT was 39,5%, 50%, 42,3% respectively (8,28). The incidence of postoperative hypothyroidism after near-total thyroidectomy has a range from 44% to 46,3% (8).
In any case of total thyroidectomy or complete thyroidectomy, permanent thyroid insufficiency should be expected. Hence, Rosato et al (2004) noted that hypothyroidism is
considered an expected result and is not a clear complication if we consider that TT has its own logic (11).
The subtotal thyroidectomy may minimize the possibility of postoperative hypothyroidism.
Hyperthyroidism
Recurrent hyperthyroidism after surgery for toxic goiter has been reported to occur in between 4% and 16,2% of cases. This is affected by amount of thyroid remnant the patients' age, and the duration of postoperative follow-up. Near-total thyroidectomy for toxic goiter seems to reduce the rate of recurrent hyperthyroidism compared to subtotal thyroidectomy (7% versus 21%)
Recurrent hyperthyroidism after near-total thyroidectomy is more amenable to repeat surgery, as dissection will be limi-ted to one side, an advantage over subtotal thyroidectomy (8).
Haemorrhage
Haemorrhage is a potentially dangerous complication of thyroid surgery that usually occurs within the first 24 hours postoperatively. Significant hematomas are usually detected within 6 to 8 hours (13). Most delayed bleeding is of venous origin and because of the negative pressure on the large
vessels of the neck, it occurs on walking or at the first cough (11). In literature, the rates of this complication vary from 0,3% to 1,5% of thyroidectomies (11,14). Rosato et al (2004) reported that the incidence of hemorrhage in there study was 1,2% and only 0,18% needed a blood transfusion (11,14). Hemorrhage may cause pressure on the airway and laryngeal edema resulting in acute respiratory embarrassment. Symptoms as respiratory difficulty, stridor and swelling of the wound should alert the surgeon to proceed immediately in surgical evacuation of the hematoma. Tracheostomy is not required if the clot is removed early. The risk of serious blood loss is high when the superior
thyroid vessels and the inferior and middle thyroid vein are not adequately controlled.
To prevent this complication, it is well to verify hemostasis at the end of the operation. For that cause the anesthetist simulates a Valsalva maneuver, raising the intrapulmonary pressure to 40 cm H2O (11). According to some authors
placement of a closed suction drain may help minimize the possibility of compression and airway compromise due to hematoma (14). Nevertheless, the use of drains after thyroid surgery is still controversial. The use of drains in thyroid
operations is traditionally supposed to drain a possible postoperative hemorrhage that could lead to airway compression. Drains have been also suggested when the dead space is large and the possibility of seroma formation is high.
Two recent meta-analyses showed no beneficial effect of routine drain use on postoperative complication rate.
(Drainage of the thyroidectomy bed is not effective in decreasing the rate of postoperative complications after
thyroid surgery). It causes a prolonged hospital stay and may increase the surgical site infection rate (53). Finally, Prim et al (2001) observed that serohematoma was linked with age and hemorrhage was associated with previous radiation of the neck (15).
Infections of thyroid surgery
Wound infection is not a common complication (11, 14, 27, 54). Throughout literature it occurs in 2%, although in some cases it is less frequent than 1% (11, 27, 54). Rosato et al (2004) observed that wound infection showed difference in each type of operation and had the following rates: 0.4% in TT, 0.13% in TL, 0.13% in STT with bilateral remnants and 0.1% in STT with monolateral remnants (11). It is interesting but not supprising the fact that no differences were noted among patients given an antibiotic as prophylaxis, as therapy, or not at all. On the other hand, the use of antibiotics is well justified for patients with severe diabetes, valvural heart
disease, or immunodeficiency. Nevertheless, disinfection and cleaning of the skin must be absolute. If there is a neoplastic pathology it is preferable to use a non-iodated disinfectant as not to invalidate an eventual postsurgical scintiscan. Again, closed suction drainage has been proposed by several authors to minimize the chance of fluid collection and postoperative abscess formation. The drain is attached to bulb suction until the output is less than 30 ml per day (14). Others find no
benefit from its use, hence they believe that it could increase the incidence of an infection (55).
Thyroid storm
This disorder, rarely seen today is an extreme form of thyrotoxicosis and is manifested by marked delirium, severe tachycardia, vomiting, diarrhea, dehydration and very often high fever. The mortality rate is high. Scholz et al (2003) suggested that early TT should be considered as the method of choice for older, chronically ill patients with thyrotoxic storm complicated by cardiorespiratory and renal failure, especially if high dose thionamide treatment, iopanoic acid, glucocorticoids and intensive care fail to improve the patient's condition within 12-24 hours. In case that thyroid storm is related to surgical treatment the manifestations usually develop during the operation procedure or in
recovery. Then the patient is hyperthermic with profuse sweating and tachycardia. Treatment is directed towards inhibiting the production of thyroid hormone and antagonizing the effects of thyroid hormone (56).
Respiratory complications-tracheal collapse
The complications concerning the airway are rare but fatal (14, 57). The main causes of respiratory complications postoperatively are the neck hematoma and tracheomalacia (57). Hematoma, as mentioned before, usually requires
reoperation. Tracheomalacia, due to pressure necrosis of the cartilaginous tracheal rings from a large goiter, is a rather rare complication. If it is present, dangerous consequences can result after removal of the thyroid, for collapse or
narrowing of the trachea would occur with inspiration, resulting in respiratory embarrassment. The treatment of choice for this complication is endotracheal intubation.
During difficult thyroidectomies, dissection often proceeds toward the pleura or mediastinum causing pneumo-thorax. This is an extremely rare complication. Unless the lung or trachea is perforated, the air will be absorbed approximately within a few days (14).
Relevance between complications
and conventional surgical techniques
The choice of surgical technique must take into account the potential benefits and complication of each procedure. The thyroid procedures performed today are total thyroidectomy (TT), bilateral subtotal thyroidectomy (BST), thyroid lobectomy (TL) and total lobectomy with partial lobectomy.
For patients with multinodular goiter (MNG) the main reason for performing BST is a presumed lower incidence of postoperative complications and an attempt to maintain the euthyroid status without thyroxine replacement (10). However it has the disadvantage of high recurrence rates (9-43%) and increased surgical morbidity during reoperation (38,58). Moreover a number of patients treated by sub-total thyroidectomy will still require thyroxine replacement postoperatively. Hence, leaving a small thyroid remnant in situ will not prevent the onset of hypothyroidism (58). Furthermore, in the presence of unrecognized malignancy, BST may represent inadequate surgery (59).
On the other hand, the potential benefits of TT include adequate removal of the disease, prevention of recurrence, and avoidance of the need for completion surgery in the presence of occult malignancy (58). The only real argument against TT is the potential increase in the rate of complications. There is no doubt that a well trained endocrine surgeon can achieve extremely low complication rates,
especially when using the technique of capsular dissection, staying close to the thyroid gland, and preserving the blood supply to the parathyroid glands, along with identification of the recurrent laryngeal nerve (10). In fact, there are increasing numbers of publications recommending TT for bilateral MNG with the argument that this procedure has low complication rates when performed by experienced
thyroid surgeons and an incidence of iatrogenic injuries that is similar to a subtotal procedure (10).
The incidence of temporary hypoparathyroidism is
higher for patients treated by TT than NTT and BST. The degree and duration of hypocalcemia increase with the extent of surgery. Some surgeons clame that transient hypoparathyroidism should be an accepted outcome of bilateral thyroid surgery rather than a complication. The incidence of permanent RLN palsy ranges from 0-0,7%
following TT and from 0-1,3% following BST. However, Rosato et al (2004) reported no statistically significant
difference in the rates of permanent hypoparathyroidism between TT, NTT and BST technique (10). Total lobec-tomy and MRST are associated with only about half of this incidence, as the approach to the nerve is unilateral (11, 13). This is justified by the fact that TT is a mandatory for the most complex cases (tumors, substernal goiter, multi-nodular goiter, Graves) with necessary higher risk (11). An other complication which rates very according to the
operation is haemorrhage. If thyroidectomy is performed according to the extra capsular technique, intraoperative bleeding is not usual. However it is more frequent in BRST patients because of the double resection of the thyroid lobes (11). It has been suggested that near-total thyroidectomy (NTT) combines the advantages of TT (no recurrences) with those of subtotal thyroidectomy (low incidence of
transient and permanent hypoparathyroidism) (10). However, Pappalardo et al suggested that no advantages be offered by this procedure when compared with TT, with the possible exception of a lower incidence of temporary hypoparathyroidism, with can easily be managed medically. Finally, postoperative hospital stay is similar for TT, NTT and BST (10).
Complications and minimally invasive
thyroid surgery
Several techniques for minimally invasive thyroidectomy have been described, with the primary aim to improve the cosmetic results of conventional surgery. The different techniques include endoscopic and videoassisted procedures and mini-access, non-endoscopic operations (60).
VAT (video assisted thyroidectomy) has been already adopted by several centers, especially in Europe. It is
performed mainly for benign diseases of the thyroid where the thyroid volume is relatively small. Patients with Graves' disease and preoperative estimated thyroid volume up to 30 ml, have also been considered eligible, as have patients with RET germline mutation without clinical evidence of medullary thyroid carcinoma and normal basal calcitonin levels. It has also been successfully applied in the treatment of small, low-risk, papillary carcinomas (PTC), with results comparable to those of conventional surgery in terms of the completeness of the surgical resection and no additional risk of cancer cell seeding (61).
VAT is a reproducible, safe and effective technique that can obtain the same results as conventional surgery, with advantages in terms of improved cosmetic result and reduced postoperative pain. The small skin incision, the absence of neck hyperextension and of a large subcutaneous flap and traction over the trachea may contribute to the
relatively painless postoperative course, although conventional surgery is generally associated with little and even minimal postoperative pain (61).
Relatively small comparative studies demonstrated that it can obtain the same results with that of conventional surgery with some significant advantages in terms of cosmetic results and postoperative pain: Larger multi-institutional series have further demonstrated its efficacy and safety in different clinical settings (61). VAT showed results comparable to those of conventional surgery in terms of the completeness of the surgical resection and no additional risk of cancerous cells seeding in the treatment of small, low-risk papillary thyroid carcinomas (PTC). The mean operative time was 59±21 min for thyroid lobectomy, 65±15 min for total thyroidectomy and 51±20 min for completion
thyroidectomy (60). Mean postoperative stay was 2.6±1.2 days (61).
The complication rate of this series compares well with those of conventional surgery, even in more recent reports, with a definitive recurrent laryngeal nerve palsy. In contrast to other experiences, we did not observe a high rate of definitive recurrent nerve palsy in the group of patients who underwent VAT. To avoid this complicatin, it is important not only to avoid excessive stretching of the nerve during extraction of the lobe but also a cautious use of the harmonic scalpel and unipolar cautery when dissecting close to the recurrent nerve. Our policy to use conventional ligatures and eventually, bipolar cautery in proximity to the recurrent nerve, as we usually do in conventional surgery, may have helped us obtain this result (61).
Postoperative complications included transient recurrent nerve palsies with a rate of 1% of the nerves at risk and with complete recovery of nerve function within month after surgery. Transient hypocalcemia had an incidence of 17.7% and required calcium and vitamin D administration for less than 6 months. Finally, postoperative hematoma and wound infections occurred in 0.2% and 0.4% of the operations performed respectively. VAT has no additional morbidity.
The introduction of VAT encountered several skepticism, which are focused mainly on its role in the treatment of thyroid malignancy and its real clinical impact. The results obtained in terms of the completeness of surgery are similar to those of conventional surgery. These results propose VAT for small, low-risk PTC in absence of overt lymph node involvement at preoperative work-up.Nodule size and thyroid volume remain the most important factors for VAT.
The minimally invasive thyroidectomy techniques are minimally invasive thyroidectomy (Sofferman technique) and minimally invasive video-assisted thyroidectomy: This
technique has been described and refined by Miccoli and his colleagues n38. The primary factors that limit performance of either of the two minimally invasive thyroidectomy
techniques include patient obesity, size of the nodule and/or thyroid gland, and the presence of thyroiditis. Video-assisted thyroidectomy is particularly challenging in the presence of thyroiditis, which predisposes to both-ersome oozing and impairs the ease of dissection of tissue planes (62).
Conventional thyroid surgery has stood the test of time for over a century after being described and perfected by Theodore Kocher. The minimally invasive video-assisted thyroidectomy is probably best performed by surgeons facile with the use of endoscopic technology (62).
Conclusion
Thyroid surgery can be performed in endrocrine surgery unit with almost now mortality and very low complication rates. Technological and medical development has a enabled the early diagnosis and accurate treatment of the majority of complication. Nowadays, hypocalcemia and RLN palsy have the highest complication rates. Several algorithms have been proposed for primary identification of symptomatic hypocalcemia, including PTH intraoperative and early postoperative measurements. The use of RLN stimulation test and corticosteroids intraoperatively has been proposed by several surgeons in order to prevent and ameliorate the prognosis of vocal cord paralysis. The
complications of minimally invasive thyroid surgery have not been widely documented and further studies need to be made towards this direction.
References
1. Bliss, R.D., Gauger, P.G., Delbridge, L.W. - Surgeon's approach to the thyroid gland: surgical anatomy and the
importance of technique. World J. Surg., 2000, 4:891.
2. Thompson, N.W., Osler, W.L., Hoffman, G.L. - The continuing development of the technique of thyroidectomy. Surgery., 1973, 73:913.
3. Fihlo, J.G., Kowalski, L.P. - Surgical complications after thyroid surgery performed in a cancer hospital. Otolaryngol Head Neck Surg., 2005, 132:490.
4. Calik, A., Kucuktulu, U., Cinel, A., Bilgin, Y., Alhan, E., Piskin, B. - Complications of 867 thyroidectomies performed in a region of endemic goiter in Turkey. Int. Surg., 1996, 81:298.
5. Bhattacharyya, N., Marvin, F. - Assessment of the morbidity and complications of total thyroidectomy. Arch. Otolaryngol Head Neck Surg., 2002, 128:389.
6. Shindo, L.M., Sinha, U.K., Rice, D.H. - Safety of
thyroidectomy in residency: a review of 186 consecutive cases. Laryngoscope., 1995, 105:1173.
7. Bergamaschi, R., Becouarn, G., Ronceray, J., Arnaud, J.P. - Morbitity of thyroid surgery. Am. J. Surg., 1998, 176:71.
8. Chow, T.L., Chu, W., Lim, B.H., Kwok, S.P.Y. -Outcomes and complications of thyroid surgery: retrospective study. HKMJ., 2001, 7:261.
9. Lamade, W., Renz, K., Willeke, F., Klar, E., Herfarth, C. - Effect of training on the incidence of nerve damage in thyroid surgery. Br. J. Surg., 1999, 86:388.
10. Ozbas, S., Kocak, S., Aydintug, S., Cakmak, A.,Ali Demirkiran, M.,Wishart, G. Comparison of the complications of subtotal, near total and total thyroidectomy in the surgical management of multinodular goitre. Endocrine Journal., 2005, 52:199.
11. Rosato, L., Avenia, N., Bernante, P., De Palma, M., Gulino, G., Nasi, P.G., Pelizzo, M.R., Pezzullo L. - Complications of thyroid surgery:Analysis of a multicentric study on 14,934 patients operated on in Italy over 5 years. World J. Surg., 2004, 28:271.
12. The British Association of Endocrine Surgeons (2000). Guidelines for the surgical management of endocrinedisease
13. Reeve,T., Thompson, N. - Complications of thyroid
surgery: How to avoid them, how to manage them, and observations on their possible effect on the whole patient. World J. Surg., 2000, 24:9971.
14. Fewins, J., Simpson, C., Miller, F. - Complications of thyroid and parathyroid surgery. Otolaryngol. Clin. North Am., 2003, 36:189.
15. Prim, M., De Diego, J., Hardisson, D., Madero, R., Galivan, J. - Factors related to nerve injury and hypocalcemia in thyroid gland surgery. Otolaryngol. Head Neck Surg., 2001, 124:111.
16. Lo, C., Kwok, K., Yuen, P. - A prospective evaluation of recurrent laryngeal nerve paralysis during thyroidectomy Arch. Surg., 2000, 135:204.
17. Herranz-Gonzalez, J., Galivan, J., Martinez-Vidal, J., Galivan, C. - Complication following thyroid surgery. Arch. Otolaryngol Head Neck Surg., 1991, 117:516.
18. Tomoda, C., Hirokawa, Y., Uruno, T., Takamura, Y., Ito, Y., Miya, A., Kobayashi, K., Matsuzuka, F., Kuma, K., Miyauchi, A. - Sensitivity and specificity of intraoperative recurrent laryngeal nerve stimulation test for
predicting vocal cord palsy after thyroid surgery. World J. Surg., 2006, 30:1230.
19. Yarbrough, D.E., Thompson, G.B., Kasperbauer, J.L., Harper, C.M., Grant, C.S. - Intraoperative electro-myographic monitoring of the recurrent laryngeal nerve in re-operative thyroid and parathyroid surgery. Surgery., 2004, 136: 1107.
20. Ardito, G., Revelli, L., D'Alatri, L., Lerro, V., Guidi, M., Ardito, F. - Revised anatomy of the recurrent laryngeal nerves. Am. J. Surg., 2004, 187:249.
21. Thomusch, O., Sekulla, C., Walls, G., Machens, A., Dralle, H. - Intraoperative neuromonitoring of surgery for benign goiter. Am. J. Surg., 2002, 183:673.
22. Randolph, G.W., Kamani, D. - The importance of preoperative laryngoscopy in patients undergoing thyroidectomy: voice, vocal cord function and the preoperative detection of invasive thyroid malignancy. Surgery., 2006,139:357.
23. Pelizzo, MR, Toniato, A, Gemo, G. - Zuckerkandl's tuberculum: an arrow pointing to the recurrent laryngeal nerve(constant anatomical landmark). J. Am. Coll. Surg., 1998, 187:334.
24. Kadowaki, M.H., Sclard, C., Kaplan, E.L. - Routine exposure o the recurrent laryngeal nerve is important during thyroidectomy. În “Debates in Clinical Surgery“ sub redactia lui Simmons R.L. Year Book (Chicago) 1990, pag. 190-207.
25. Wang, L.F., Lee, K.W., Kuo, W.R.,Wu, C.W., Lu, S.P., Chiang, F.Y. - The efficacy of intraoperative corticosteroids in recurrent langyngeal nerve palsy after thyroid surgery. World J. Surg., 2006, 30:299.
26. Farrag, T., Samlan, R., Frank, R., Tufano, R. -The utility of evaluating true vocal fold motion before thyroid surgery. Laryngoscope, 2006, pag.116.
27. Filho, J.G., Kowalski, L.P. - Postoperative complications of thyroidectomy for differentiated thyroid carcinoma. Am. J. Otolaryngol., 2004, 25:225.
28. Muller, P.E., Jakoby, R., Heinert, G., Spelsberg, F. - Surgery for recurrent goiter: its complications and their risk factors. Eur. J. Surg., 2001, 167:816.
29. Koufman, J.A., Postma, G.N., Whang, C.S., Rees, C.J., Amin, M.R., Belafsky, P.C., Johnson, P.E., Connolly, K.M., Walker, F.O. - Diagnostic
laryngeal electromyography: the Wake Forest experience 1995-1999. Otolaryngol. Head Neck Surg., 2001, 124:603.
30. Steurer, M., Passler, C., Denk, D.M., Schneider, B., Niederle B., Bigenzahn, W. - Advantages of
recurrent laryngeal nerve identification in thyroidectomy and parathyroidectomy and the importance of preoperative and postoperative laryngoscopic examination in more than 1000 nerves' at risk. Laryngoscope, 2002, 112:124.
31. Saetti, R., Silverstrini, M., Galioto, M., Derosas, F., Narne, S. - Contact laser surgery in treatment of vocal fold paralysis. Acta Otorhinolaryngol. Ital., 2003, 23:33.
32. Cernea, C.R., Ferraz, A.R., Nishio, S., Dutra, A.Jr., Hojaij, F.C., dos Santos, L.R. - Surgical anatomy of the external branch of the superior laryngeal nerve. Head Neck., 1992, 14:380.
33. Sakorafas, G., Stafyla, V., Bramis, C., Kostifopoulos, N., Kolttis, T., Kassaras, G. - Incidental parathyroidectomy during thyroid surgery: An underappreciated complication of thyroidectomy. World J. Surg., 2005, 29:1539.
34. Pattou, F., Combemale, F., Fabre, S., Carnaille, B., Decoulx, M., Wemeau, JL., Racadot, A., Proye, C. S. - Hypocalcemia following thyroid surgery:
incidence and prediction of outcome. World J. Surg., 1998, 22:718.
35. McHenry, C.R., Speroff, T., Weinthworth, D., Murphy, T. - Risk factors for postthyroidectomy hypocalcemia. Surgery, 1994, 116:641.
36. Ozbas, S., Kocak, S., Aydintug, S., Cakmak, A., Ali Demirkiran, M., Wishart, G. - Comparison of the complications of subtotal, near total and total thyroidectomy in the surgical management of multinodular goitre. Endocrine Journal., 2005, 52:199.
37. Koh, K.B.H., Chang, K.W. - Carcinoma in multinodular goiter. Br. J. Surg., 1992, 79:266.
38. Cohen-Kerem, R., Schachter, P., Sheinfeld, M., Baron, E., Cohen, O. - Multinodular goiter: The
surgical procedure of choice. Otoloryngol. Head Neck Surg., 2000, 122:848.
39. Moulton-Barrett, R., Crumley, R., Jalilie, S., Segina, D., Allison, G., Marshak, D., Chan, E. - Complications of thyroid surgery. Int. Surg., 1997, 82:63.
40. Harness, J.K., Fung, L., Thompson, N.W., Burney, R.E., McLeod, M.K. - Total thyroidectomy: complications and techniques. World J. Surg., 1986, 10:781.
41. Sasson, A.R., Pingpank, J.F., Wetherington, RW, Hanlon, A.L., Ridge, J.A. - Incidental para-thyroidectomy during thyroid surgery does not cause transient symptomatic hypocalcaemia. Arch. Otolaryngol. Head Neck Surg., 2001, 127:304.
42. Dolapci, M., Doganay, M., Reis, E., Kaama, N.A. - Trucal ligation of the inferior thyroid arteries does no affect the incidence of hypocalcaemia after thyroidectomy. Eur. J. Surg., 2000,166:286.
43. Araujo-Filho, V.J., Silva-Filho, G.B., Brandao, L.G., Santos, L.R., Ferraz, A.R. - The importance of the ligation of the inferior thyroid artery in parathyroid
function after subtotal thyroidectomy. Rev. Hosp. Clin. Fac. med. Sao Paulo., 2000, 55:113.
44. Henry, J.F., Denizot, A., Audiffret, J. - Autotransplan-tation Partathyroidienne de necessite en chirurgie thyroidienne. Ann Chir., 1990, 44:378.
45. D'Avango, A., Parangi, S., Morita, E., Duh, O.Y., Siperstein, A.E., Clark, OH. - Hyperparathyroidism after thyroid surgery and autotrasplantation of histologically normal parathyroid glands. J. Am. Coll. Surg., 2000, 190:546.
46. Beahrs, O.H., Vandertoll, D.J. - Complications of secondary thyroidectomy. Surg. Gynecol. Obstet., 1963,117: 535.
47. Bistrup, C., Nielsen, J.D., Gregersen, G., Franch, P. - Preventive effect of levothyroxine in patients operated for non toxic goiter: a randomized trial of one hundred patients with nine years follow-up. Clin. Endocrinol., 1994, 40:323.
48. Wilson, B., Erskine, C., Crowe, P. - Hypomagnesemia and hypocalcemia after thyroidectomy: prospective study. World J. Surg., 2000, 24:722.
49. Quiros, R.M., Pesce, C.E., Wilhelm, S.M., Djuricin, G., Prinz, R.A. - Intraoperative parathyroid hormone levels in thyroid surgery are predictive of postoperative hypopara-thyroidism and need for vitamin D supplementation. Am. J. Surg., 2005, 189:306.
50. Ghaheri, B., Liebler, S., Andersen, P., Schuff, K., Samuels, M., Klein, R., Cohen, J. - Perioperative parathyroid hormone levels in thyroid surgery. Laryngoscope., 2006, 116:518.
51. Scurry, W., Beus K, Hollenbeak C, Stack B. - Perioperative parathyroid hormone assay for diagnosis and
management of postthyroidectomy hypocalcemia. Laryngo-scope, 2005, 115:1362.
52. Pisaniello, D., Parmeggiani, A., Piatto, A., Avenia, N., d' Ajello, M., Monacelli, M., Calzolari, F., Sanguinetti, A., Parmeggiani, U., Sperlongano, P. - Which therapy to prevent post-thyroidectomy hypocalcemia? G. Chir., 2005, 26:357.
53. Nahas, Z., Farrag, T., Lin, F., Ruth, B., Tufano, R. - A safe and cost effective short hospital stay protocol to identify patients at low risk for the development of significant hypocalcemia after total thyroidectomy. Laryngoscope., 2006, 116:906.
54. Edwin, K., Sonia, S., Costa, E. - Surgery of the thyroid gland. In “The thyroid and its disease“. 1999, Chapter 21. www.thyroidmanager.org
55. Ozlem, N., Ozdogan, M., Gurer, A., Gomceli, I., Aydin, R. - Should the thyroid bed be drained after
thyroidectomy? Langenbecks Arch. Surg., 2006, 391:228.
56. Grimes, C.M., Muniz, H., Montgomery, W., Goh, Y. - Intraoperative thyroid strom: a case report. AANA J., 2004, 72:53.
57. Shen, W., Kebebew, E., Duth, Q., Clark, O. - Predictors of airway complications after thyroidectomy for substernal goiter. Arch Surg., 2004, 139:656.
58. Delbrigde, L., Guinea, Al., Reeve, T.S. - Total
thyroidectomy for bilateral benign multinodular goiter: effect of changing practice. Arch Surg., 1999, 134:1389.
59. Russell, C.F.J. - Mangement of benign nonendemic goitre. În “Duh. Textbook of Endocrine Surgery“ sub redactia lui Clark OH. WB Saunders (Philadelphia) 1997, pag. 22 - 31.
60. Lombardi, C., Raffaelli, M., Princi, P., De Crea, C., Bellantone, R. - Video-assisted thyroidectomy: report of a 7-year experience in Rome. Langenbecks Arch. Surg., 2006, 391:174.
61. Lombardi, C., Raffaelli, M., Princi, P., De Crea, C., Bellantone, R. - Video-assisted thyroidectomy: report of a 7-year experience of a sigle center in more than four hundred cases. World J. Surg., 2006, 30:794.
62. Terris, D., Gourin, C., Chin, E. - Minimally invasive thyroidectomy: basic and advanced techniques. Laryngoscope, 2006, 116:350.