Double adenomas revisited: Nonuniform distribution favors enlarged superior parathyroids (fourth pouch disease)

Background. A double adenoma (DA) is a recognized clinical entity of primary hyperparathyroidism (HPT) and is presumed to have uniform location distribution. We reviewed our experience with 2-gland parathyroid disease to identify anatomic patterns and implications for surgical management. Methods. Clinical characteristics were reviewed for 828 consecutive patients with HPT at 2 endocrine referral centers that practice bilateral neck exploration with intraoperative parathyroid hormone (IOPTH) measurement. Results. Fifteen peirent (127 of 828) of HPT patients demonstrated 2 enlarged glands; 13% (107 of 828), 3- or 4-gland hyperplasia; and 71% (592 of 828), single adenomas. DAs in superior parathyroids affected 57 of 127 (45%) patients, an observed frequency 3-fold higher than expected (P < .001, chi-square test). DAs were larger than normal glands (240 ± 575 mg vs 28 ± 23 mg, P < .001), and superior parathyroid adenomas were larger than adenomas at other sites (421 ± 983 mg vs 202 ± 353 mg,P =. 002). Technetium 99 metastable (Tc99m)-sestamibi imaging and IOPTH identified DAs correctly in only 5 of 84 (6%) and 19 of 75 (25%) of patients tested, respectively. Conclusions. DAs have nonuniform anatomic distribution with predilection for abnormal growth in bilateral superior parathyroids-embryologic remnants of the fourth branchial pouch. Since additional abnormal glands were detected by observation with technetium 99 metastable (Tc99m)-sestamibi imaging and IOPTH rarely aiding detection, unilateral neck exploration may predispose to persistent or recurrent HPT.