Response to Letter to the Editor From Cuny et al: "Correlation of Preoperative Imaging Findings and Parathyroidectomy Outcomes Support NICE 2019 Guidance".

Dear Editor,

We wish to thank Dr. Cuny and colleagues for their interest in our paper (1). The international consensus definition of cure of primary hyperparathyroidism (pHPT) is indeed normocalcemia at 6 months, to which a purist might wish to add, accompanied by an appropriately accommodated parathyroid hormone (PTH) level in the same time frame. However, persistence of pHPT can either be obvious immediately after surgery due to hypercalcemia, or suspected due to normocalcemic hyperPTHemia that is usually evident at postoperative surgical follow up (2). In the series presented, to avoid duplication of surgical with endocrinological follow-up, delayed blood tests are trusted to the referring endocrinologist, who invariably return patients for surgical review in the event of any abnormal results. Any patient with delayed hypercalcemic persistence at 6 months in this study was classified as a persistence in either localization group.

Dr. Cuny and colleagues express the view that family members of patients with negative localization studies should undergo screening for hypercalcemia in order to guide genetic testing, in particular for benign familial hypocalciuric hypercalcemia (FHH). Leaving aside the challenging practicalities of familial screening, this approach is not one that most would readily endorse. The fact that FHH patients are more likely to have negative imaging is self-evident. However, localization studies are not a diagnostic tool for pHPT, or indeed FHH; therefore, resource management mandates that only patients with biochemically proven pHPT that would also wish to have parathyroid surgery, and where FHH has already been confidently excluded, should undergo localization imaging. If the patient’s biochemistry or family history raises any doubt, then genetic testing for FHH and susceptibility genes for syndromic hyperparathyroidism are appropriate and more reliable prior to considering localization investigations (3). It is clear that excluding FHH and syndromic pHPT prior to parathyroid surgery is highly desirable and we concur that the best outcomes in parathyroid surgery, especially in cases of nuanced or unlocalized disease, are achieved in multidisciplinary high-volume centers (4).