Primary hyperparathyroidism (PHPT) is the second most common disease treated by endocrine surgeons, with more than 100,000 new cases diagnosed annually in the United States.1 Success rates for treating hyperparathyroidism are regularly reported to be in excess of 95% in the hands of experienced parathyroid surgeons. However, these rates decrease to approximately 70% when the initial surgery is performed by an inexperienced surgeon.2 The morbidity associated with the initial operation for PHPT performed by a high-volume surgeon is minimal. Despite the excellent results reported for initial parathyroidectomies, those reported for reoperations are less impressive. After a failed initial operation, the success rate decreases, and the morbidity increases regardless of the experience of the operating surgeon. Claude Organ, MD, has been quoted as saying: “The decision to operate is the second hardest decision in surgery. The decision to reoperate is the hardest.”

In 2002, the National Institutes of Health released a consensus statement regarding the treatment of patients with PHPT.3 This statement specifically addressed the treatment of asymptomatic patients who have elevated calcium and parathyroid hormone (PTH) levels and represents a transition to a broader recommendation for surgery in hyperparathyroid patients. In conjunction with this tolerant recommendation for surgery in asymptomatic patients, many authors now suggest a more inclusive definition of symptomatic patients that allows for more global signs and symptoms, such as fatigue, sleep disturbances, difficulty with concentration, polydipsia, and polyuria. Even with this paradigm shift, many surgeons remain more conservative when considering reoperation for patients with persistent or recurrent hyperparathyroidism. The indications for reoperation are less well defined and frequently depend on the overall condition of the patient and ability to localize abnormal parathyroid tissue.

Persistent hyperparathyroidism is defined as elevated calcium and PTH within 6 months of neck exploration for hyperparathyroidism, and recurrent hyperparathyroidism is defined as elevated calcium and PTH that occurs more than 6 to 12 months after a seemingly successful parathyroidectomy. Many factors have been implicated in persistent or recurrent hyperparathyroidism. Six major reasons for recurrent or persistent hyperparathyroidism have been identified.4 These include multiple gland disease (MGD), ectopic gland location, supranumerary glands, surgeon inexperience, persistent or metastatic parathyroid carcinoma, and errors on frozen section or intraoperative PTH monitoring.

MGD has been implicated in 31% to 37% of patients with persistent or recurrent hyperparathyroidism.2,5 Levine and Clark4 reported that 37% of failures were the result of MGD, with 22% of patients having hyperplasia and 15% having double adenomas. These numbers are much higher than the 10% to 15% and 3% to 5%, respectively, that are typically quoted for patients undergoing first-time operations for PHPT. This increased incidence likely reflects the lower sensitivity of current localization measures in identifying MGD.

In recent years, intraoperative PTH monitoring has been added to endocrine surgeons’ armamentarium in an attempt to identify patients with MGD. This technique, initially described by Dr. George Irvin, uses the short half-life of intact PTH to demonstrate physiologic surgical success while in the operating room.6 This has promoted the development of focused, minimally invasive parathyroidectomy based on preoperative imaging for localization and documentation of decreased PTH levels while in the operating room. By combining these two elements, success rates similar to that for traditional four-gland exploration have been obtained by many surgeons. However, controversy remains regarding the interpretation of intraoperative PTH levels. Many authors advocate the initially described 50% reduction from the baseline level of intraoperative PTH as the determining factor for terminating the operation, but others espouse more rigorous criteria that include a decrease into the normal range. Proponents of this suggest that normalization of the intraoperative PTH would decrease the number of patients with persistent or recurrent hyperparathyroidism. Even with intraoperative PTH monitoring, missed MGD remains an important cause of recurrent or persistent hyperparathyroidism.

The embryologic development of the parathyroid gland allows a wide array of anatomic variation. The classic anatomic location for the parathyroid glands is described as within a 1-cm radius centered at the junction of the recurrent laryngeal nerve (RLN) and the inferior thyroid artery. Whereas the superior parathyroid glands tend to be located dorsal to the RLN, the inferior parathyroids are typically located ventral to the nerve. The superior glands develop from the fourth branchial pouch along with neuroendocrine cells that will ultimately become the parafollicular C cells. They migrate inferiorly, where they are often intimately associated with the posterior–lateral portion of the thyroid. The inferior glands develop from the third branchial pouch along with the thymus. Both structures migrate inferiorly to their normal positions. The inferior glands tend to have more anatomic variation because of their long migratory path and may be located ectopically in the thymus, mediastinum, or carotid sheath. Between 25% and 55% of failures are attributed to ectopic location of the parathyroid adenomas (Figure 9-1).2,7,8 Shen and associates2 reported that 50% of ectopically located glands were in the neck and 50% were in the mediastinum. Seventeen percent of ectopically located glands required median sternotomy for removal and accounted for 9% of all reoperations in their series. The authors concluded that the majority of ectopically located glands in the mediastinum could be accessed through a traditional transverse cervicotomy. Other authors advocate a thoracoscopic approach to address mediastinal parathyroid adenomas. Nilubol et al.9 reported that nine of 32 patients with mediastinal adenomas required either a limited sternotomy (n = 3) or a radioguided video-assisted thoracoscopic surgery (VATS; n = 4). Two patients required a conversion of VATS to conventional thoracotomy.