**4. The Indeterminate Thyroid Nodule**

The detection of a thyroid nodule begins a cascade of investigations with neck ultrasound and fine-needle aspiration (FNA) at the heart of the algorithm. Benign cytology should allow patient discharge in most cases. Since it is not always possible to unequivocally exclude malignancy at FNA cytology, surgery may be recommended for these 'indeterminate' lesions. However, the cancer rate at final histology after surgery is less than 30% [36]. The problem of indeterminate cytology and 70% of unnecessary thyroid operations may be addressed in some cases with the identification of mutations in molecular panels that are promising [37,38]. Molecular testing, however, adds further expense to the diagnostic workup (£2160–£2880) [39] and usually reduces the risk of rather than guaranteeing the absence of cancer. A recent review of available molecular panels concluded that the more accurate molecular-based test methods are still expensive and restricted to a few, highly specialised and centralised laboratories [40]. Molecular testing is therefore not currently provided by taxpayer-funded healthcare systems since value (benefit/cost) remains unproven.

The cost of mutation panels however needs to be put in the context of the potential saving of unnecessary surgery and the benefit of patient discharge, assuming that this actually occurs. Several cost-effectiveness studies have been performed, comparing lobectomy to genetic testing [37], molecular panel testing [41], or lobectomy and frozen section to total thyroidectomy for thyroid nodules suspicious of cancer [42]. Most studies suggest that a diagnostic lobectomy remains overall preferable to genetic testing as a strategy for ruling out the malignancy of indeterminate thyroid nodules. The conclusions are determined principally by the consequence of "closure" after a hemithyroidectomy versus living under surveillance after using molecular panels which appears to remain the recommendation. A systematic review concluded that the test specificity had to be >68% and the amount of surgery decreased by over 50% for molecular testing to be cost-effective [39]. This health economics model confirmed that molecular evaluation of thyroid nodules with indeterminate cytology could generate positive health outcomes by reducing the rate of unnecessary surgery on benign nodules and may find traction as the costs of the tests decrease.
