Pathology of the parathyroid glands is fairly prevalent in the United States. Each year, approximately ten cases of primary hyperparathyroidism (HPT) per 100,000 people are diagnosed in those younger than 40 years. The incidence is estimated to be four times higher in patients older than 60 years of age [1]. Surgery for primary HPT, performed by an experienced surgeon, is curative in more than 95% of cases [2]. In contrast, the success rate for low-volume surgeons is only 70% [3]. Consequently, the hyperparathyroid state may not be cured for a number of patients following surgery. Those not cured either remain hypercalcemic in the immediate postoperative period or redevelop hypercalcemia after a period of normocalcemia. Hypercalcemia persisting or recurring within 6 months after initial parathyroidectomy is referred to as persistent HPT. Hypercalcemia recurring more than 6 months after an apparently curative initial parathyroidectomy is referred to as recurrent HPT. Regardless of terminology, in both cases, the patient is at continued risk of metabolic complications from hypercalcemia and may continue to have discomfort from the associated symptoms. Despite advances in preoperative imaging and adjunctive intraoperative tools, the incidence of persistent or recurrent HPT has been reported to be as high as 30% [4–6].

The indications for surgical intervention in reoperative cases must be clear, because the morbidity and technical difficulty are increased. Reoperations are unfortunately associated with a lower success rate than initial operations. Nonetheless, in experienced hands, the success rate of reoperative parathyroidectomy for persistent and recurrent HPT is reported to be more than 80–90% [7]. However, the ideal period to cure the patient is during the initial operation, when the risks of surgical complications are least likely and the likelihood of cure is greatest. This chapter aims to outline a perioperative scheme for approaching persistent and recurrent primary HPT .

It has been estimated that 2–10% of surgical failures may be attributed to an incorrect preoperative diagnosis of primary HPT [8, 9]. Accordingly, one of the key requirements for success in reoperative parathyroidectomy is a proper diagnosis. The initial step is to perform a thorough personal and family history for endocrine diseases and a physical examination. The history should be focused on ruling out differential diagnoses. By definition, HPT (primary or secondary) must be confirmed with an elevated serum calcium concentration and an elevated or inappropriately high serum parathyroid hormone (PTH) level. Patients may also present with elevated serum PTH and serum calcium levels at the upper limit of normal (the so-called normocalcemic hyperparathyroidism). Checking an ionized calcium level can help confirm the diagnosis of HPT in most of these patients. Elevated serum chloride and decreased serum phosphate levels are frequently noted. In addition, if not previously performed, benign familial hypocalciuric hypercalcemia should be ruled out with an appropriately elevated 24 h urinary calcium measurement and subsequent genetic testing if indicated. If all these parameters are not present, other causes of hypercalcemia must be considered (i.e., patients with normocalcemic HPT caused by hypoalbuminemia, hyperphosphatemia, vitamin D deficiency, or hypomagnesemia), because a repeat parathyroidectomy is almost guaranteed to be unrewarding in these circumstances. The diagnosis of HPT has been facilitated by the development of immunometric assays [10, 11]. Clinical analysis with immunometric PTH assays typically distinguishes hypercalcemic patients with HPT from patients with other causes of hypercalcemia. Diagnostic errors of hyperparathyroidism can result from medications (i.e., calcium, vitamin D, furosemide, thiazide diuretics, calcitonin, or lithium), malignancy (i.e., bone metastases or humoral hypercalcemia), granulomatous disease (i.e. sarcoidosis), acute renal failure, bone disease (i.e., Paget’s disease or immobilization), hyperthyroidism, or adrenal insufficiency. Given the complexity of alternative explanations, a close relationship with medical specialists including endocrinologists can be invaluable to ensure that consensus is reached before the decision for further intervention is made. Such a relationship is likewise imperative in situations of more virulent forms of HPT, such as MEN, where multigland removal may be necessary.

With a confirmed diagnosis of persistent or recurrent HPT, further information obtained by clinical evaluation, review of preoperative localization studies, operative reports, and pathology reports is critical to help determine the location of potentially normal and abnormal glands. The operative report should document the extent of the initial parathyroidectomy; which parathyroid glands were identified; whether these glands were excised, biopsied, and/or clipped to mark for future identification; where scar tissue can be expected to be encountered; the relationship of the glands to the recurrent laryngeal nerve; intraoperative PTH results if evaluated; and the number and the position of normal and abnormal glands. Unfortunately, it often doesn’t contain most of these components which are all critical to operative planning. The pathology report confirms how many parathyroid glands were indeed excised, whether biopsied glands were definitely parathyroid tissue, and whether parathyroid glands examined were normal or hypercellular. Review of old pathology slides may be required. It may be useful to correlate previous localization studies with intraoperative findings. Direct laryngoscopy is necessary before reoperation to assess vocal fold function.

A battery of localization studies prior to reoperation are usually employed, due to the associated risks of surgical complications and the lower likelihood of surgical cure. Approximately 90% of missed parathyroid tumors can be removed through the initial cervical incision. Successful localization permits a focused approach in most cases. This limits the amount of dissection required, preferably to a unilateral approach, as one prefers not to perform bilateral re-exploration when possible, avoiding the increased risk of hypoparathyroidism and RLN injury [12, 13]. Localization studies, in combination with previous information from operative and histologic findings, usually direct the surgeon to the abnormal parathyroid gland, thus minimizing complications and shortening the operative time. Knowledge of anatomy and expected locations of both normal and ectopic locations for parathyroid glands is paramount in reoperative parathyroidectomy, and the reader is referred to previous chapters. A variety of invasive and noninvasive techniques are available to image or localize abnormal parathyroid glands. Intraoperative PTH monitoring is a helpful adjunct for confirming when all abnormal parathyroid tissue has been removed [14–17].

As in the initial work up of primary HPT, a number of imaging studies are available for the evaluation of recurrent or persistent HPT. Unfortunately, all available imaging modalities are far from perfect, and it is common practice to obtain multiple studies in this setting as the accuracy of two concordant exams is higher than a single localizing exam [18]. Despite all efforts, there can be a high rate of nonlocalization which requires further workup with invasive tests. The abnormal parathyroid glands are mostly found in eutopic locations although there are higher rates of mediastinal, intrathyroid , and intrathymic glands as well as multigland disease in the reoperative setting. Local expertise and availability of imaging technology are the most important factors in determining which imaging algorithm is followed [19, 20].

Fine needle aspiration biopsy may be applied using both computed tomographic and ultrasound guidance for correct needle placement in suspected abnormal parathyroid tissue during localization in preparation for reoperative surgery. Investigations have shown FNA to be a specific modality in distinguishing between parathyroid and nonparathyroid tissues [26, 27]. Cytologic evaluation of tissue samples obtained by fine needle aspiration biopsy is less sensitive than measuring washout PTH levels of the aspirate material, because follicular thyroid tumors may be misinterpreted as parathyroid tissue under cytologic review. The role of FNA in reoperative parathyroid surgery can be especially helpful in situations where a thyroid nodule is noted and imaging is suggestive of a possible intrathyroidal parathyroid adenoma, which is otherwise rare. It may also be particularly helpful in a multiply operated patient where there is intense scarring and a focused surgery would be most prudent.