FDG-PET/CT in Evaluation of Cytological Indeterminate Thyroid Nodules to Prevent Unnecessary Surgery (EfFECTS)

Inclusion Criteria: 1. Documented history of a solitary thyroid nodule or a dominant nodule within multinodular disease, with (US-guided) FNAC performed by a dedicated radiologist or experienced endocrinologist or pathologist, demonstrating an indeterminate cytological examination (i.e. Bethesda category III or IV) according to the local pathologist and confirmed after central review; 2. Scheduled for surgical excision (preferably) within 2 months of the inclusion date; 3. Age ≥ 18 years; 4. Euthyroid state with a serum thyrotropin (TSH) or a free T4 level within the institutional upper and lower limits of normal, measured within 2 months of registration. In case of a suppressed TSH: a negative 123I, 131I or 99mTcO4- scintigraphy must be available ("cold nodule"); 5. In patients with multinodular disease and a dominant nodule, the nuclear medicine physician responsible for FDG-PET/CT scan interpretation must determine whether the nodule is likely to be discriminated on FDG-PET/CT imaging prior to enrolment; 6. Willing to participate in all aspects of the study; Exclusion Criteria: 1. High a priori probability of malignancy: * FNAC Bethesda category V or VI during local reading or central review; * Prior radiation exposure / radiotherapy to the thyroid; * Prior neck surgery or radiation that in the opinion of the PI has disrupted tissue architecture of the thyroid; * New unexplained hoarseness, change of voice, stridor or paralysis of a vocal cord; * In case a benign reason has been found (e.g. vocal cord edema), the patient is eligible; * Thyroid nodule discovered as a FDG-PET positive incidentaloma * New cervical lymphadenopathy highly suspicious for malignancy; * In case malignancy is excluded, patient is eligible; * Previous treatment for thyroid carcinoma or current diagnosis of any other malignancy that is known to metastasize to the thyroid; * Known metastases of thyroid carcinoma; * Known genetic predisposition for thyroid carcinoma: * Familiar Non-Medullary Thyroid Cancer (NMTC) * Familiar Papillary Thyroid Cancer (FPTC) * Familiar Adenomatoid Polyposis Coli syndrome (FAP, Gardner syndrome, APC-gene mutations on chromosome 5q21) * Morbus Cowden (PTEN mutation on chromosome 10q23.3) * PTC / nodular thyroid hyperplasia / papillary renal tumours. Linked to locus 1q21. 2. Proven benign disease or insufficient material for a cytological diagnosis: * FNAC Bethesda category I or II during local reading or central review 3. Performance of non-routine additional diagnostic tests that alter the patients treatment policy (e.g. mutation analysis on cytology) 4. Inability to undergo randomization: * Any patient that will receive thyroid surgery for other reasons (e.g. mechanical or cosmetic complaints). 5. Inability to undergo treatment: * Inability to undergo surgery in the opinion of the surgeon / anaesthetist. 6. Contra-indications for FDG-PET/CT: * Patient has evidence of infection localized to the neck in the 14 days prior to the FDG-PET/CT scan; * Inability to tolerate lying supine for the duration of an FDG-PET/CT examination (\~10-15min); * Poorly regulated diabetes mellitus (see next item); * Hyperglycaemia at time of FDG injection prior to PET/CT (fasting serum glucose \>200mg/dL \[\>11.1 mmol/L\]); * The use of short-acting insulins within 4 hours of the PET scan is not allowed * If female and fertile: signs and symptoms of pregnancy or a positive pregnancy test / breast-feeding; * A formal negative pregnancy test is not obligatory * (severe) claustrophobia; * Low dose benzodiazepines are allowed 7. General contra-indications: * Inability to give informed consent; * Severe psychiatric disorder;