Background: Although most patients with primary hyperparathyroidism (PHPT) are ideal candidates for minimally invasive parathyroidectomy, some will have more than one enlarged gland and require bilateral neck exploration to achieve biochemical cure. We evaluated the clinical evidence for when to choose bilateral neck exploration for patients with PHPT. Methods: We searched PubMed for English-language studies published from 1996 to 2008. The level of clinical evidence was determined according to the criteria proposed by Sackett (Chest 95[2 Suppl]:2S, 1989), and the grade of recommendation was established according to the criteria proposed by Heinrich et al. (Ann Surg 243:154, 2006). Results: Level III-IV evidence shows that patients with multiple endocrine neoplasia (MEN) 1 and PHPT should have a bilateral neck exploration (grade C recommendation). Only level IV evidence indicates that patients with familial PHPT should do so (no recommendation). Although most patients with MEN 2A have single-gland disease, bilateral neck exploration is still indicated, because they will have either a therapeutic or prophylactic total thyroidectomy for medullary thyroid cancer. A history of head and neck irradiation is associated with PHPT, but the risk of multi-gland parathyroid disease is apparently no higher than in sporadic cases (level IV evidence, no recommendation). Previous or current lithium therapy confers a higher risk of multi-gland disease (25%-45%; level IV-V evidence), which may require bilateral neck exploration. Preoperative localizing studies reliably identify most patients with single-gland but not multi-gland disease (level II-IV evidence). Negative localizing studies confer an approximately 50% risk of multi-gland disease and indicate that bilateral neck exploration is necessary. If two localizing studies are concordant, few patients will require bilateral neck exploration (level IV, no recommendation). Conclusions: No level I or II evidence reliably identifies preoperative clinical risk factors for determining which patients should have routine bilateral neck exploration for multi-gland disease or for intraoperative decision making to convert to bilateral neck exploration. Imaging studies are positive in most patients (level II). No randomized studies exist to determine when a bilateral neck exploration is indicated based on clinical risk factors or imaging studies that may suggest multi-gland disease.
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