the Diagnosis and Management of Thyroid Nodules

- Executive summary

These guidelines offer evidence-based recommendations on the targeted levels of clinical practice guidelines and provide healthcare professionals with practice guidance on the surgical management of thyroid nodules and its complications.

· Initial evaluation should include age, personal and family history of MEA, Previous head or neck irradiation, physical evaluation, thyroid function testing, and neck US, (Strong recommendation).

·  Neck US, including the thyroid gland and the central and lateral cervical compartments, should be performed in all patients suspected with nodular thyroid disease, (Strong recommendation).

· It is recommended for the US report to describe nodule(s) size, location, US features, and expected risk of malignancy using EU-TIRADS, (Strong recommendation).

·  Doppler imaging, elasto-sonography, and CEUS may be recommended as ancillary techniques (Conditional recommendation).

·  CEUS may be recommended for defining the size and boundaries of the ablated area after minimally invasive procedures, (Conditional recommendation).

·  Thyroid scintigraphy is recommended when serum TSH is subnormal to diagnose functioning nodules and/or multinodularity, avoid FNA and determine eligibility for RAI as an alternative to surgery, (Strong recommendation).

· The use of CT and/or MRI in the study of thyroid nodules should be limited to the assessment of local extension or retrosternal growth of nodular goiter, (Strong recommendation).

·  FNA may be recommended after clinical assessment, laboratory evaluation, and US risk stratification, in a shared decision with the patient, (Good practice statement).

·   FNA is advised in:

-   EU-TIRADS 3: >20 mm, (Conditional recommendation).

·       FNA is recommended in:

-  EU-TIRADS 4: >15 mm.

-   EU-TIRADS 5: >10 mm, (Strong recommendation).

·  In high suspicion pattern, we recommend FNA if ≥10 mm, (Strong recommendation).

·       In intermediate suspicion pattern, we recommend FNA if ≥10 mm, (Strong recommendation).

·       In low suspicion pattern, we advise FNA if ≥15 mm, (Conditional recommendation).

·       In very low suspicion pattern, we advise FNA if ≥20 mm (or ultrasound observation), (Conditional recommendation).

·       In benign pattern, we recommend against FNA, (Strong recommendation).

·       We recommend FNA regardless of lesion size when patients have a history of neck irradiation, a family history of medullary thyroid cancer or MEN2, extracapsular growth, metastatic cervical lymph nodes or Coexistent suspicious clinical findings (e.g., dysphonia), (Strong recommendation).

·       Repeat FNA is recommended in case of a first non-diagnostic sample, (except in case of a solitary cyst), a Bethesda class III cytology, discrepancy between US risk score (i.e. high risk) and cytological findings (i.e. benign cytology), and significant nodule growth (an increase ≥20% in at least two nodule diameters with a minimum increase of 2 mm at the time of re-evaluation) of thyroid nodule(s), (Strong recommendation).

·       FNA is recommended in suspicious lymph nodes, with thyroglobulin or calcitonin washout dependent on phenotype, (Strong recommendation).

·       Core-needle biopsy is not recommended as a first-line tool to assess thyroid nodules after US but could be considered a second line procedure for specific conditions e.g. repeat Bethesda class III cytology and suspicion of poorly differentiated thyroid cancer, thyroid lymphoma, thyroid metastases), (Strong recommendation).

·       We recommend correlation of the cytological diagnosis with clinical, ultrasound and laboratory results, (Good practice statement).

·       For Bethesda I (non-diagnostic), repeat FNA is advised. If repeat FNA is still non-diagnostic, consider CNB. If still non-diagnostic, consider surgery (Conditional recommendation).

·       For Bethesda II, (Benign), we are against further immediate diagnostic studies or treatment, (Strong recommendation).

·       For Bethesda III, (Atypia of Undetermined Significance, (AUS)) we recommend repeating FNA and with repeat Bethesda III, consider molecular testing if available or offer surgery, (Conditional recommendation).

·        For Bethesda IV, (Follicular Neoplasm), we advise molecular testing or diagnostic lobectomy, (Conditional recommendation).

·       For Bethesda V, (Suspicious for malignancy), we recommend molecular testing, lobectomy, or near-total thyroidectomy, (molecular testing may help to decide whether to perform a total thyroidectomy or a thyroid lobectomy), (Strong recommendation).

·       For Bethesda VI, (Malignant), we recommend lobectomy or near-total thyroidectomy, (Strong recommendation).

•      We recommend multidisciplinary workup in case of advanced cancer, (Strong recommendation).

•      Molecular testing is recommended in cytologically indeterminate nodules, if available, or offer surgery (Strong recommendation).

•       Thyroid hormone treatment is not recommended in euthyroid individuals with nodular thyroid disease, (Strong recommendation).

•       Iodine and/or selenium supplementation is not recommended unless individuals are deficient in these micronutrients, (Strong recommendation).

•       RAI is recommended as an alternative to surgery and MIT in hyper-functioning solitary thyroid nodules, (Strong recommendation).

•       RAI may be recommended as an alternative to surgery in benign normo-functioning multinodular goiter, (Conditional recommendation).

•       EA is recommended for pure, or dominantly cystic, thyroid lesions, (Strong recommendation).

•       TA is recommended for the treatment of solid benign thyroid nodules that cause local symptoms as an alternative to surgery and for cystic lesions that relapse after EA, (Strong recommendation).

•       Benign cytological diagnosis is recommended before MIT. Except for EU-TIRADS 2 nodules, (Strong recommendation).

•      After MIT, we recommend follow-up with clinical, biochemical and US assessments after 6 and 12 months and re-evaluating the patient after 3–5 years, (Strong recommendation).

•      Surgery is recommended in the following scenarios: Symptomatic nodular thyroid disease, nodules that have been classified as benign at cytology and/or US and become symptomatic over time, calcitonin levels higher than the established cut-offs, responsive calcitonin after stimulation test in RET-mutated gene carriers, nodules with indeterminate cytology (Bethesda class III and IV) that are not suitable for active surveillance and nodules with a Bethesda class V and VI cytology, (Strong recommendation).