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thyroid malignancy and serum calcitonin

thyroid malignancy and serum calcitonin

Overview 

Medullary thyroid cancer (MTC) is a rare type of thyroid cancer. It’s known to have poorer outcomes than differentiated thyroid cancer. In this article, the researchers aimed to identify areas for improvement in the preoperative evaluation of patients with possible MTC in a high-volume endocrine surgery unit in accordance with current practice guidelines. The researchers hypothesized that the selective use of serum calcitonin (sCT) as a biomarker for possible MTC could act as a guide for the extent of initial surgical management. 

Medullary Thyroid Cancer (MTC)

The management and diagnosis of MTC can often be difficult. MTC can originate from the thyroid parafollicular calcitonin secreting cells. These cells have increased levels of serum calcitonin which serves as a biomarker for tumor burden. 

According to data, hereditary MTC can be found in around 14-52% of patients while sporadic MTCs are found in 48-86% of patients. Also, in two of these forms, regional nodal metastasis is reported to occur in around 80% of the patients. Also, approximately 20% have distant metastases at presentation. The average 5-year survival rate for MTC is 73-97% with predictors of survival including TNM stage, disease extent at diagnosis, as well as the extent of thyroidectomy. 

Because of this, accurate and preoperative diagnosis is very important in expedient and precise initial management. A preoperative diagnosis can often be established by fine needle aspirate (FNA) cytology, the sensitivity of which ranges from 50% to 80%. 

Though, higher sensitivity can be attained by the addition of calcitonin measures. At present, the American Thyroid Association (ATA) 2015 guidelines do not recommend either for or against the routine measurement of sCT in patients with thyroid nodules. This is contrary to that of the European Thyroid Association (ETA) consensus, which highlights sCT as an important diagnostic tool and recommends its measurement in the initial workup of all thyroid nodules. 

In this study, we aimed to determine the role of sCT in the workup of patients with thyroid nodules, in the context of these practice guidelines. We hypothesized that a selective approach to measuring sCT may improve the preoperative diagnosis of MTC and initial surgical planning.

Methods 

The researchers recruited MTC patients from the years 2000 to 2020 from the Monash University Endocrine Surgery Unit database. Demographics, tumor characteristics, preoperative evaluation, operative management, and outcomes were analyzed for these thyroid cancer patients.

The mean age of the 43 MTC patients was 57.317.6 years at the time of diagnosis. Gender distribution was relatively even with a slight predilection for females (56%). Seven(16%) patients had a family history of thyroid malignancy—four with a family history of MTC and RET mutation and three with family history of non MTC-thyroid malignancy.

Eighteen patients had RET germline mutation testing due to either young age at presentation or suspicious clinical features of multiple endocrine neoplasms—two patients preoperatively and16 patients postoperatively—of these, four (9%) patients were positive for a RET germline mutation.

Eighteen (53%) patients had positive lymph nodes. Of the six patients with an elevated preoperative sCT, three had TT and LND; one had LND for recurrence; one had TT without due to the absence of visible lymph nodes to dissect; the remaining patient was planned for a TT with central LND, but an RLN palsy recognized by IONM resulted in an HT with central LND instead. 

As the disease burden was low, a decision was made for ongoing surveillance rather than completion of thyroidectomy according to the patient’s preference. Of the seven patients with indeterminate cytology who did not have preoperative sCT, three underwent TT—two for goiters and one for Bethesda 5 cytology (suspicious for malignancy).

None of them proceeded to complete thyroidectomy at a later date due to advanced metastatic disease,1patient decision3anddeath from lymphoma. A total of 34 patients (79%) underwent LND. Of these,19 patients (56%) underwent central LND only, and 15 patients (44%) experienced both central and lateral LND (n=11), or lateral alone for recurrence (n=4). 

Limitations of the Study 

There were some limitations in this study. Due to its retrospective nature, it is susceptible to limitations of a retrospective study such as incomplete medical records. There is the possibility of selection bias by clinicians regarding pre-operative assessment, and surgical and adjuvant therapy. 

Additionally, not all patients in our cohort had their germline RET mutation status tested. Despite the long period included in this study, the follow-up period varied significantly, and the sample size was small due to the rarity of MTC. For these reasons, we were not able to stratify survival patterns according to pre-operative or postoperative CT, stage of disease, or RET mutation status. 

Due to the small sample size of this study, the results and conclusions should be interpreted with this in mind. Future multi-centered studies with clinical outcomes and cost-benefit analysis may be able to provide more clarity in the Australasian setting.

Results 

Of 1454 thyroid cancer patients, 43 (3%) had MTC. Preoperatively, 36 (84%) patients with MTC confirmed on cytology (28, 65%), elevated sCT (6, 14%) or RET mutation (2, 4%). Of these 36 patients, 31 (86%) had the optimal extent of thyroidectomy and lymph node dissection (LND). Five (14%) had less than total thyroidectomy due to nerve injury. 

Thirty-four patients had compartmental LND. In the 12 (27%) patients with indeterminate non-diagnostic cytology, 5 had elevated sCT and were managed as above. None of the remaining seven had LND, thus potentially suboptimal surgery. 

Thirty patients (70%) had a total thyroidectomy (TT), 9 patients(21%) had a hemithyroidectomy (HT) and 4 patients (9%) had a lymph node dissection (LND) alone for recurrence (all had TT at another institution previously). 

Of the nine patients who had HT, five had a preoperative diagnosis of MTC and therefore also had central. However, contralateral thyroidectomy was abandoned due to recurrent laryngeal nerve (RLN) injury indicated by intraoperative neuromonitoring (IONM) (four cases) or nerve sacrifice (one case).

Conclusion

The researcher’s findings reflect the rare entity that is MTC and its challenges in diagnosis. From an observational standpoint, sCT improves pre-operative evaluation of MTC presenting as indeterminate cytology and aids operative planning. 

There are no strong conclusions or recommendations found in this study. The researchers believe that there is an argument for more liberal use of sCT in the workup of cytologically indeterminate thyroid nodules in select patients, particularly when there is clinical, radiological, or cytological suspicion of malignancy. 

Although the selection criteria in addition to indeterminate cytology,  as well as the cost effectiveness in the Australian setting. The study also requires further investigation. The researchers believe this practice may lead to better tailoring of the index surgery, which may further lead to reduced morbidity and even mortality. 

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