Palpation of the thyroid and of locoregional lymph nodes is a routine procedure but is not sensitive enough for assessing persistent or recurrent disease.

Ultrasound imaging supplements the clinical examination and is an operatordependent method. It allows the identification of locoregional recurrences as small as 2–3 mm in diameter, and lymph nodes with abnormal morphology suggestive of malignancy, thereby making it possible to distinguish reactive and metastatic lymph nodes. Suspicious lymph nodes can be subjected to fine needle aspiration cytology (FNAC) under ultrasound guidance coupled with the measurement of thyroglobulin in lavage fluid [9]. This method allows detection of lymph-node metastases of the neck in almost all cases. Ultrasound monitoring at regular intervals are required for each lymph node >5 mm in diameter.

Radiography: Patients with unmeasurable thyroglobulin values are not subjected to chest radiography [9]. Radiography does not allow evaluation of lung metastases <1 cm in diameter which, conversely, can be visualized using ¹³¹I total-body scintigraphy. Micronodular metastases, however, are best viewed with non-contrast CT or MRI. Radiography shows bone metastases from thyroid carcinomas as osteolytic lesions. Scintigraphic imaging detects them as hypocaptating or moderately hypercaptating foci [9].

Fluorodeoxyglucose positron emission tomography FDG-PET: In patients with evidence of distant metastases, FDG PET scintigraphy provides information about the prognosis. In fact, in a study of 125 patients who underwent FDG-PET, FDG uptake over a larger volume of tissue correlated with shorter survival [9].

Determination of thyroglobulin: Thyroglobulin is an extremely useful tumor marker in the follow-up of CTD patients. It is a high-molecular-weight (660 kDa) glycoprotein from which thyroid hormones are derived. It is produced by follicular cells (normal and neoplastic).

Thyroglobulin production is controlled by TSH, which stimulates the transcription genes of the protein and its release into the bloodstream. Therefore, it is essential that, whenever thyroglobulin is determined, TSH is also measured. During the follow-up of WDCs of the thyroid, determination of the thyroglobulin level when TSH levels are high (thanks to discontinuation of LT4 or administration of rhTHS) allows more sensitive results than during LT4 suppressive therapy.

After surgery and after radioablation, serum levels of thyroglobulin remain relatively high for a few months. Therefore thyroglobulin should not be measured until after 3 months, at which point in time it should be undetectable. Increased thyroglobulin values during hormone suppressive therapy are associated with distant metastases in the overwhelming majority of cases [20]. Thyroglobulin levels are directly correlated with the extension and severity of the tumor [21]. However, only 60% of patients with thyroid cancer forming local or distant metastasis during therapy with LT4 have detectable serum thyroglobulin levels [20]. In 20% of patients with isolated lymph-node metastases and in 5% of patients with small lung metastases not visible on radiography, thyroglobulin levels are undetectable: these are false-negatives. Other important causes of false-negative results may be methodological problems, structural abnormalities of thyroglobulin or presence of monoclonal antibodies that make the protein unrecognizable by standard measurement methods [20]. Patients with undetectable thyroglobulin levels while hypothyroid are free from disease 20 years after the diagnosis, whereas those with detectable circulating thyroglobulin (>10 ng/mL) develop neck or distant metastases in 60–80% of cases.

In low-risk patients not undergoing radioiodine ablation, the risk of tumor recurrence is very low, and TSH stimulation by discontinuation of LT4 or administration of rhTSH is not recommended. These patients can be cared for by measuring thyroglobulin during LT4 treatment and ultrasound of the neck. A total of 93% of low-risk individuals during hormone replacement therapy have undetectable thyroglobulin levels and, in the remaining 7%, thyroglobulin is detectable with levels <5 ng/mL. Thyroglobulin serum levels in low-risk patients after lobectomy are undetectable in 2/3 of patients on suppression therapy.

Thyroglobulin is a protein with many antigenic epitopes. In general, thyroglobulin antibodies are markers of autoimmune thyroid diseases. In patients with thyroid cancer, thyroglobulin antibodies are present in 20% of cases. The reasons for the increase in antibodies are not well understood. Their disappearance is associated with a reduction of the tumor and its severity (most likely linked to a lower antigenic stimulus [21]). Their presence interferes with the measurement of thyroglobulin serum levels, so patients with positive levels of thyroglobulin antibodies and with undetectable serum thyroglobulin cannot be considered in remission of disease. They should be monitored periodically with diagnostic whole-body imaging and ultrasound of the neck. The disappearance of thyroglobulin antibodies in the follow-up could be considered clear evidence of remission.

The importance and role of serum thyroglobulin in the follow-up of WDCs is well established. The option of avoiding the diagnostic examination with ¹³¹ I, with the consequent advantages that derive from this, have allowed rhTSH and the induction of hypothyroidism through LT4 discontinuation to play a crucial part in monitoring the possible recurrence of cancer.

Some studies have concluded that the diagnostic accuracy of thyroglobulin in patients negative for thyroglobulin antibodies is sufficient to decide if treatment is necessary because the test with ¹³¹I adds very little information compared with thyroglobulin alone. It is however, recognized, that serum thyroglobulin concentration after discontinuation resulting in increased stimulation by TSH plays an important part in follow-up [9].

In the early 2000s, the US FDA and the European Medical Device Directive approved the use of ultrasonic coagulating-dissecting and electrothermal bipolar vessel sealing systems to seal thyroid gland vessels and parenchyma [22].

Due to the vascularization of the thyroid gland, many surgeons utilize these instruments rather than bipolar cautery, ties, or clips. Some studies comparing these instruments with other haemostatic methods showed a decrease in operating time and intraoperative blood loss with no increase in complications [23–29].

Surgeon preferences may also include the use of intraoperative nerve monitoring with an electrode attached to an endotracheal tube to allow detection of stimulation of the recurrent laryngeal nerve. This may be helpful in the identification of the recurrent and superior laryngeal nerves (even though studies have not identified a significant decrease in the rate of vocal-cord paralysis with this technology [30]). Common indications for the use of this technology are thyroid revision surgery or tumors with extrathyroid extension when identification of the nerve is more difficult.

Although drains are used for major surgical procedures of the head and neck, their use for routine thyroidectomy has been questioned. A Cochrane review of studies on drain use did not show a decrease in complications for patients undergoing goiter surgery without substernal extension, lateral neck dissection, or coagulation abnormalities, but it did find an increase in the duration of hospital stay [31]. However, the decision to use drains should be guided by the surgeon’s experience and intraoperative findings.

WDCs of the thyroid are more prevalent in young women, and usually show favorable biological behavior and better prognosis than other cancers of the head and neck. Furthermore, the evolution of minimally invasive methods for the treatment of thyroid cancer has been driven by cosmetic results [32].

Video-assisted thyroidectomy (VAT), first described by Miccoli et al. in 1999, [33] is an entirely gasless method. It involves a 1.5–2.5-cm incision directly over the thyroid and reproduces the same steps used in conventional surgery with the technical support of a camera and a set of dedicated instruments [34–38].

A problem which remains partially unsolved is the treatment of malignant thyroid disease. However, several authors, after developing, evaluating, validating and standardizing the procedure, have proposed that VAT can also be used in the treatment of in low-risk, small size PTCs (T1) [39, 40].

Concerns regarding the adequacy of resection were addressed by Miccoli et al. in a prospective randomized trial for papillary cancer. Postoperative thyroglobulin, levels of uptake of radioactive iodine, and complication rates were found to be equivalent to those of patients treated with conventional open thyroidectomy or minimally invasive video-assisted thyroidectomy (MIVAT). This method was described initially with some contraindications, including large nodules (>2.5 cm to 3.0 cm), thyroiditis, an enlarged thyroid gland (>20 cm³), previous neck surgery, central compartment neck metastases, and large malignant tumors with extrathyroid extension. Recently, some authors explored several cases using expanded indications for MIVAT, and demonstrated oncologic completeness by evaluating postoperative uptake of radioiodine [41, 42].