Recurrence after Total Thyroidectomy for Benign Multinodular Goiter
Total thyroidectomy is now the preferred option for the management of benign multinodular goiter (BMNG), and it ought not be associated with recurrent disease. The aim of the present study was to examine the efficacy of total thyroidectomy for BMNG and to review reasons for recurrence.
Material and methods
The study group comprised all patients from January 1980 to December 2005 who underwent a definitive procedure to remove all thyroid tissue for BMNG, and who were subsequently identified as having developed a recurrence. Included were patients who underwent primary total thyroidectomy at our unit, or a two or more stage procedure where a definitive secondary total thyroidectomy was performed at our unit.
There were 3,044 total or secondary total thyroidectomies performed for BMNG during the study period. Ten patients were identified as having developed recurrent BMNG requiring reoperation despite previous complete “total” thyroidectomy. There were 11 sites of recurrence in 10 patients. Only one was a true local recurrence in the thyroid bed. Another 9 recurrences related to the embryology of the thyroid gland, 4 in the pyramidal tract and 5 in the thyrothymic tract. There was one recurrence at another site (submandibular) in a patient with presumed metastatic thyroid cancer despite benign histology. There were no complications in any of the 10 patients.
Total thyroidectomy for BMNG is not only a safe procedure but is efficacious in preventing recurrent disease. Failure to remove embryological remnants such as thyrothymic residue or pyramidal remnants during total thyroidectomy is the major cause of recurrence.
Over two decades ago, total thyroidectomy replaced subtotal thyroidectomy as the preferred option for the management of benign multinodular goiter (BMNG) in the Endocrine Surgical Unit, University of Sydney, Sydney, Australia.1,2 Since then many major endocrine surgery centers worldwide have adopted the same approach,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 which should now be considered as part of every endocrine surgeon’s armamentarium.14 Over that time, total thyroidectomy for BMNG has proven to be a very safe procedure with a minimal complication rate.15 What has not been as well studied to date is how efficacious the procedure is.
We define total thyroidectomy as the attempted removal of all visible thyroid tissue in the neck and, as such, it should be associated with negligible rates of recurrence. Likewise near-total thyroidectomy, leaving less than 1 cm of tissue, often posterior to the recurrent laryngeal nerve near the ligament of Berry, should also be associated with a low recurrence rate, although this procedure has not been our practice. Subtotal thyroidectomy, on the other hand, where a remnant of thyroid tissue is intentionally left in the thyroid bed is associated with a significant rate of recurrence.
The aim of the present study was to examine the efficacy of total thyroidectomy for BMNG to and to review reasons for recurrence.
MATERIALS AND METHODS
This was a retrospective case series study comprising all patients in the period from January 1980 to December 2005 who underwent a definitive procedure or procedures to remove all thyroid tissue for BMNG, and who were subsequently identified as having developed a recurrence. Included were patients who underwent primary total thyroidectomy at our unit, or who underwent a multiple stage procedure where the definitive secondary (total) thyroidectomy with the intent to remove all remaining visible thyroid tissue was performed at our unit. Excluded were patients in whom the initial pathological diagnosis showed a clinically significant thyroid cancer; however, patients with incidental papillary microcarcinoma found on histological examination were included.
Information was obtained from the University of Sydney Endocrine Surgical Unit Database, as well as from patient records and contacts with general practitioners. All patients provided informed consent in relation to the storage and analysis of data.
Patients who developed recurrent bilateral multinodular goiter (BMNG) despite previous total thyroidectomy
Age at complete thyroidectomy
Age at recurrent surgery
Site/s of recurrence
Mode of presentation
Atypical chest pain
Lower neck lump
Right thyroid bed & pyramidal
True recurrence, pyramidal (dyshormonogenesis)
Neck lumps (×2)
There were 2 males and 8 females. Mean age at initial intended total or secondary total thyroidectomy was 45 years (range: 10–64 years). The mean time to reoperation for recurrent disease was 57 months (range: 12–151months). Mean age at operation for recurrent disease was 52 years (range: 15–73 years).
In relation to the initial intended total procedure, 7 patients underwent initial total thyroidectomy and 3 patients underwent more than one procedure on their thyroid gland before complete “total thyroidectomy” was considered achieved.
All patients had BMNG on histopathological examination of the thyroid gland at the original procedure/s. Three patients had additional pathology at the time of the primary or secondary procedure. One patient (IL) had 2 incidental papillary carcinomas (1 mm and 1.5 mm) on histopathology of no clinical significance. One patient (FB) underwent a left hemithyroidectomy for a Hurtle cell adenoma, followed 7 years later by a completion right hemithyroidectomy for BMNG. A third patient (MN, patient 10 in Table 1) underwent secondary total thyroidectomy and neck clearance in our unit for bilateral nodular recurrence after two previous thyroid procedures performed elsewhere for benign disease. The histology demonstrated BMNG with reactive lymphadenopathy. She then presented with a right submandibular swelling, and FNA demonstrated thyroid tissue. After further surgery, histology has demonstrated evidence of bony metastases on radioactive ablation (administered with the intent of eliminating any residual benign disease), although no cancer had ever been identified histologically.
Sites of recurrence of BMNG despite total thyroidectomy
Classification of recurrence
There were no complications in any of the 10 patients, specifically no cases of either permanent recurrent laryngeal nerve palsy or permanent hypoparathyroidism.
Total thyroidectomy has been the operation of choice for BMNG in our unit since the early 1980s. It has been well demonstrated that total thyroidectomy is a safe operation with minimal complications if performed by surgeons and trainees well trained in the technique.16, 17, 18 This article examines whether total thyroidectomy for BMNG is also efficacious, i.e. it is associated with minimal rates of recurrence.
Less than total thyroidectomy, either subtotal or near-total thyroidectomy involves removal of most of the thyroid gland, leaving behind a small variable remnant of tissue. It aims to eliminate postoperative hypocalcemia by preserving the blood supply of the superior parathyroid glands by leaving in situ a small amount of thyroid tissue adjacent to these glands and their vascular pedicles. The recurrent laryngeal nerve is also theoretically protected by leaving thyroid tissue around the ligament of Berry in situ, thereby leaving the nerve untouched. Although the incidence of postoperative temporary hypocalcemia is reduced, less than total thyroidectomy has not been shown to be associated with a lower complication rate than total thyroidectomy4,9,19, 20, 21. Moreover, it leads to recurrent goiter in up to 23% of patients.22 This high recurrence rate, along with good evidence that total thyroidectomy is a safe operation with almost the same complication rate, and that reoperative surgery has a higher relative risk of complications than extensive primary surgery,23 has rendered subtotal thyroidectomy for BMNG an operation of the past.21
Total thyroidectomy, which aims to remove all visible evidence of thyroid tissue, ought not in theory at least, to be associated with recurrent BMNG if expertly performed. This study has demonstrated that thyroid bed recurrences are almost completely abolished (1 out of 3,044) with total thyroidectomy. However, recurrences still occur, and in most cases can be explained on the basis of embryological descent of the thyroid gland, either the pyramidal tract or the thyrothymic tract.
The thyroid gland begins to develop as early as 3–4 weeks gestation. It results from the fusion of two parts—the medial and lateral thyroid components. The medial component begins as a diverticulum in the pharyngeal endoderm, which descends and forms a bilobed structure anterior to the trachea. This reaches its final position by 7 weeks and undergoes histological differentiation into the typical follicles during weeks 10 and 11. The lateral thyroid components (also known as ultimo-branchial bodies) develop from proliferation of pharyngeal endoderm and are derived from the ventral portion of the endodermal fourth branchial pouch and the vestigial fifth pouch. It is from these lateral components that the C-cells originate. Ultimately the medial and the lateral components fuse. The pedicles of the lateral components detach themselves from the pharynx and are replaced with mesenchyme; the residual of this posterolateral projection becomes the tubercle of Zuckerkandl.24,25 The right and left lobes of the thyroid grow caudally with growth of the fetus, taking up their final position at either side of the 2nd to 4th tracheal rings. This line of normal embryological descent of the thyroid is known as the thyrothymic tract.
Thyroid rests are present in over 50% of patients and occur within the line of the thyrothymic tract. These rests are more commonly seen as an extension or prolongation of thyroid tissue attached to the lower pole of the thyroid by a narrow pedicle or even just a fibrovascular band.26 They can, however, be located within the anterior mediastinum. They may be mistaken for small lymph nodes or even parathyroid glands, and mostly they cause no problems.
This series has supported our hypothesis that total thyroidectomy almost completely abolishes the incidence of true local recurrence. The only patient in this series who had a true local recurrence (in the thyroid bed) was a 15-year-old male who had a dyshormonogenetic multinodular goiter. He also had a simultaneous pyramidal recurrence. The pathological process behind his goiter differs from that of BMNG. Benign MNG, as is well known, results from heterogeneity of the thyroid suppressing hormone (TSH) receptor, resulting in nodular change between areas of degeneration. In contrast, dyshormonogenetic goiter results from chronic stimulation of the TSH receptor as a result of a disturbance in the feedback system of thyroid hormone synthesis.27 Dyshormonogenetic goiters are characterized by hypercellular nodules that are solid and microfollicular. Nuclei may be enlarged, irregularly shaped, and often bizarre, and they can be difficult to distinguish from thyroid carcinoma.28,29 Whether dyshormonogentic goiter is a greater risk factor for goiter recurrence than BMNG is unknown, as there are few cases reported in the literature, all with inadequate follow-up. Chronic stimulation of all TSH receptors would lead to recurrence even if only minimal numbers of thyroid cells were left behind at thyroidectomy. This explains the two recurrences at different sites in this young man. Interestingly, all patients were under regular review by an endocrinologist, and the TSH levels for the group with recurrence were not noted to be significantly different from those of the remainder of the group as such. Indeed, of note, the TSH levels for the recurrence group as a whole were at the lower end of the normal range before the final procedure (mean 1.27 mIU/l and 0.47 SEM), consistent with regrowth of autonomous thyroid tissue.
Metastatic thyroid cancer with no obvious primary lesion has been previously described.30, 31, 32, 33 The last patient (MN, patient 10 in Table 1) with probable metastatic disease has not had an identified primary lesion or tissue evidence of secondary disease, despite repeated histopathologic review. Although this may represent a metastasis from a small primary cancer not ever sectioned, it may also represent a form of thyroid cancer that is undetectable by current modes of pathological examination, especially given the aggressive nature of the local recurrence.
A limitation of the present study is the possibility that other patients with recurrent BMNG who had a previous total thyroidectomy within our unit have presented elsewhere, as this was not a systematic follow-up of all operative patients. However, given the nature of referral patterns for this unit and the relative stability of the Australian population, the number of patients with recurrence who were lost to follow-up would be very small indeed. Presumably, there is also another unidentified cohort of patients who have asymptomatic recurrences that are not clinically apparent. The only way that this group could ever be identified would be to perform routine follow-up screening ultrasound on every patient after total thyroidectomy. However, given that this group has not presented clinically with symptoms, such a program would not be cost-effective and would only be of academic interest.
Total thyroidectomy for BMNG is not only safe but also efficacious in preventing recurrent disease, although a clear understanding of thyroid embryology is essential to ensure successful surgery. Embryological remnants are the major cause of failure of total thyroidectomy for BMNG. Special attention must be paid to these areas with every routine thyroidectomy. Failure to remove a thyrothymic rest or pyramidal remnant can result in recurrence of BMNG years later.
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