Sestamibi-negative patients: to operate or image?

Parathyroidectomy is accepted as the most durable and cost-effective treatment for patients with primary hyperparathyroidism, with reported cure rates over 97 %. Surgical cure prevents—and in some cases reverses— complications such as frequency of nephrolithiasis, osteoporosis, cardiovascular disease, and neurocognitive symptoms. The large prevalence of single-gland disease has led to the practice shift to focused parathyroidectomy, requiring preoperative localization. Moreover, most patients in the United States present with mild or asymptomatic disease with minor biochemical abnormalities, making management increasingly challenging. In this study, Benzon and colleagues address the particular challenge of sestamibi-negative localization in patients with primary hyperparathyroidism and report the experience of a single highly reputable academic institution. Among the strengths of the study are the prospective collection of data and the large sample size. Of the 2681 patients who were referred for surgery in their cohort, 136 of patients (5.7 %) had sestamibi-negative imaging. The authors found that patients who localized with sestamibi had a 97 % 6-month cure rate compared to 90 % in those whose disease was not localized preoperatively, comparable to rates in the literature. Moreover, the study affirms the known correlation between sestamibi-negative imaging and multiglandular disease (32 % vs. 13 % in localized cases). The authors discuss the clinical dilemma presented to physicians in sestamibi-negative cases and include observation as well as additional imaging and surgery as a consideration in asymptomatic patients. One should be cautious, however, about the suggestion to consider observing patients whose disease is not localized. If one were to assess the appropriateness of our current standard of care, specifically criteria for parathyroidectomy in asymptomatic patients, a prospective trial with clearly defined inclusion criteria and a comparable control group (i.e., sestamibi-negative patients who are observed) would be needed. Until evidence contradicts our current understanding, practice ought to be based on the best available data and guidelines. It should be stressed, as the authors do, that the indication for surgery is the morbidity associated with the disease (i.e., continued bone loss, nephrolithiasis) and not the results of imaging. Frequently, patients labeled asymptomatic have improvement in subtle neurocognitive symptoms after parathyroidectomy. If it is possible that referring physicians are less likely to refer asymptomatic patients for surgery, as the authors suggest, perhaps our focus should be on education of the benefits of parathyroidectomy. The question to be answered is not whether to operate or not, as the cure rate is still excellent in poorly localized cases, but whether to obtain further localization studies or to proceed directly to surgery. Although preoperative localization strategies vary among institutions on the basis of availability and clinician preferences, adjunctive or alternative localization modalities can be considered. Although the authors report minimal benefit of adjunctive ultrasound (US) in their series, others have found US to be highly sensitive and cost-effective. US is increasingly performed in the surgeon’s office, costs less than other modalities, and has the advantage of imaging the thyroid simultaneously before surgery. Additionally, 4DCT scanning is a novel imaging modality that has shown improved sensitivity over ultrasound and sestamibi and should be considered, when available, for initial localization or in patients whose traditional imaging results are negative. 4DCT is particularly helpful in identifying ectopic glands, another frequent cause of surgical failure. Lastly, radioguided parathyroidectomy is an another useful modality Society of Surgical Oncology 2012