Inclusion Criteria

 

In order to be eligible for participation, a subject must meet ALL of the following criteria:

 

  • 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;
    • If a core needle biopsy was performed instead of a FNAC, the patient is eligible if the biopsy procedure was felt to be minimally disruptive to the nodule architecture, based on a review by the principal investigator or nuclear medicine investigator.
  • Scheduled for surgical excision (preferably) within 2 months of the inclusion date;
  • Age ≥ 18 years;
    • This disease is rare in children and therefore the study will be limited to adults.
  • Euthyroid state with a serum 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”);
    • Mild deviations from the institutional normal limits may be considered acceptable if the patient has achieved a clinically euthyroid state with medication at a stable dose for >3 months, and the TSH is considered to be at target by the patient's treating physician. In patients with hyperthyroidism requiring treatment, this euthyroid state may be achieved with administration of a thionamide prior to FDG-PET/CT exam. Patients with hyperthyroid inflammatory conditions such as thyroiditis and toxic multinodular goitre often exhibit increased glucose uptake resulting in diffuse uptake of FDG which may obscure visualization of a thyroid tumour.
  • 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;
  • Willing to participate in all aspects of the study;
    • confirmed by a signed and dated written informed consent obtained from the patient (or the patient's legally acceptable representative) prior to study participation.

 

 

Exclusion Criteria

 

A subject who meets ANY of the following criteria will be excluded from participation:


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 oedema), the patient is eligible;
  • Initial diagnosis of the thyroid nodule through the coincidental discovery of a FDG-avid thyroid incidentaloma on PET-scan;
  • 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), assumed if ≥2 primary or 1 primary and ≥3 secondary criteria are met:
      • Primary criteria:
        • PTC in 2 or more 1st degree relatives
        • Multinodular hyperplasia in 3 or more 1st or 2nd degree relatives
      • Secondary criteria:
        • Age <33 year;
        • Multifocal or bilateral tumour
        • T4-tumours
        • Metastases (N1, M1)
    • 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).

 

Proven benign disease or insufficient material for a cytological diagnosis:

  • FNAC Bethesda category I or II during local reading or central review.

 

Performance of additional diagnostic test(s) prior to inclusion (or during the course of the trial), (potentially) affecting patient management:

  • Any additional diagnostic test performed prior to inclusion, provided that this test is not yet part of routine clinical care (e.g. molecular testing, mutation analysis of cytological material) and that its results might affect patient management or the patient’s/referring physician’s willingness to participate in the study.

 

Inability to undergo randomization:

  • Any patient that will receive thyroid surgery for other reasons (e.g. mechanical or cosmetic complaints).

 

Inability to undergo treatment:

  • Inability to undergo surgery in the opinion of the surgeon / anaesthetist.

 

Contra-indications for FDG-PET/CT:

  • Patient has evidence of infection localised to the neck in the 14 days prior to the FDGPET/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 insulines 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

 

General contra-indications:

  • Inability to give informed consent;
  • Severe psychiatric disorder.

 

 

(the information stated above is in accordance with the study protocol version 1.4, §4.2 Inclusion Criteria and § 4.3 Exclusion Criteria)