2023 European Thyroid Association Clinical Practice Guidelines for thyroid nodule management

Abstract

With the widespread use of sensitive imaging techniques, which include neck visualization, a conspicuous number of thyroid nodules emerge and demand attention. Most lesions are benign, asymptomatic, and do not warrant treatment. In the case of cancer diagnosis, most are small, intrathyroidal and indolent neoplasms that can safely be managed conservatively. There is a pronounced need for more cost-effective, risk-adapted approaches to the management of this highly prevalent condition, taking the wishes of the patient into consideration. Thus, the present guidelines aim at providing a clinical practice guide for the initial workup and the subsequent management of adult individuals harboring thyroid nodules. Importantly, these guidelines are not intended to cover the management of thyroid malignancy. The manuscript and the specific recommendations were developed by reconciling the best available research evidence with the knowledge and clinical experience of the panelists and updating aspects of a number of previous European Thyroid Association guidelines.

Keywords: fine-needle aspiration; follow-up; management; minimally invasive treatment; molecular biology; surgery; thyroid nodule; treatment; ultrasound.

Figure 1

Initial evaluation for the investigation and diagnosis of the etiology of nodular thyroid disease. 1) Based on current evidence, the guideline panel cannot recommend for or against the routine use of calcitonin determination in the initial evaluation of a patient with thyroid nodule disease. Calcitonin determination should be considered in selected conditions (for details see the guideline text). 2) If the FT4 is normal, FT3 should be measured. 3) Based on the clinical context TSH receptor antibody determination may be considered to define the etiology of hyperthyroidism. 4) Consider TPOAb determination in case of clinical and US suspicion of thyrotoxicosis related to thyroiditis. 5) In current or previous iodine-deficient areas, the use of scintigraphy may be considered for nodular goiter and also for individuals with normal TSH. 6) See main text for management (paragraph ‘Radioiodine therapy’). 7) In case of clinical or US suspicion of chronic lymphocytic thyroiditis and negative TPOAb, Tg antibody determination may be considered. EU-TIRADS, European Thyroid Imaging and Reporting Data System; FNA, fine-needle aspiration; FT3, free tri-iodothyronine; FT4, free thyroxine; Tg, thyroglobulin; TPO, thyroid peroxidase; TRAB, TSH receptor antibody; TSH, thyroid-stimulating hormone; US, ultrasound.

Figure 2

Diagnostic workup and the recommendations faced with a newly diagnosed thyroid nodule. Panel (A) describes the first-line approach, where clinical action is based on the US risk stratification. 1) There is no evidence for the length and modalities of follow-up and no consensus among the authors. Based on the ability to predict growth rate (mean change in the largest diameter over 5 years: 4.9 mm (95% CI, 4.2–5.5 mm)) (83), changes in TIRADS category which qualify for further workup (rate of change over 5 years: 6.3–8.3%) (126), risk of overlooking malignancy over the next 5 years (rate: 0.6%) (106), we find it appropriate to offer re-evaluation in 3–5 years. Independent of the Bethesda class, symptomatic nodules not offered treatment, for whatever reason, should be re-evaluated within 1 year. 2) An increase ≥20% in at least two nodule diameters with a minimum increase of 2 mm, or nodule volume increase >50% (35), or in case of local compression symptoms. 3) Irregular shape, irregular margins, microcalcifications, marked hypoechogenicity. 4) For 5–10 mm EU-TIRADS 5 nodules, FNA is recommended if there are suspicious lymph nodes, risk of extra-thyroidal extension, or location in worrisome areas (e.g. close to trachea, laryngeal nerve area). 5) If no changes are observed after 2 years, decreasing the intensity of follow-up may be considered. Panel (B) describes second-line approach, where the clinical action is based on the cytological report and US risk stratification. 1) When re-biopsy is considered relevant, the adequacy of the sample seems independent of the time interval between procedures. 2) There is no evidence for the length of and modalities with which to follow-up and no consensus among the authors. Based on the ability to predict growth rate (mean change in the largest diameter over 5 years: 4.9 mm (95% CI, 4.2–5.5 mm)) (106), changes in TIRADS category which qualify for further workup (rate of change over 5 years: 6.3–8.3%) (126), risk of overlooking malignancy over the next 5 years (rate: 0.6%) (106), we find it appropriate to offer re-evaluation in 3-5 years, with the potential of classifying/reclassifying and thereby allow stopping further follow-up. 3) No need to repeat the biopsy after two Bethesda class II results. 4) An increase ≥20% in at least two nodule diameters with a minimum increase of 2 mm, or nodule volume increase >50%, or in case of local compression symptoms. 5) A repeat benign cytology strongly reduces the likelihood of malignancy and favors surveillance. 6) In the case of 5–10 mm EU-TIRADS 5 nodules undergoing FNA and coming out as Bethesda class IV, surveillance may be offered as an alternative option. Consider close clinical follow-up in nodules smaller than 15 mm, with favorable ultrasound features. 7) In the case of 5–10 mm EU-TIRADS 3, 4, and 5 nodules undergoing FNA and classified as Bethesda class V or VI, surveillance or minimally invasive treatment may be offered as alternative options in the absence of suspected lymph node involvement or extra-thyroidal extension. CNB, core-needle biopsy; FNA, fine-needle aspiration; ROM, risk of malignancy; US, ultrasound.

Figure 3

Diagram for making the location of lymph nodes using the levels nomenclature. Only a small portion of level VII can be visualized by US. For this reason, level VII was merged into level VI (modified from reference (15)).