Ultrasound , which is also frequently employed to localize anatomically abnormal parathyroid glands, offers a number of advantages, particularly when performed by the operating surgeon [34]. It is quick and noninvasive, avoids radiation, and permits differentiation between thyroid nodules, lymph nodes, and parathyroid lesions (Fig. 2.4) [2, 35]. Surgeon-performed ultrasound in the operating room immediately before incision allows the surgeon to triangulate the location of the adenoma relative to the surrounding structures, facilitating the subsequent dissection. Though the overall sensitivity of ultrasound for detecting parathyroid lesions is only 76% [36], experienced parathyroid surgeons know that there is often information to be gleaned in even “negative” studies.

Ultrasound reports, especially when they reportedly fail to definitively identify a parathyroid adenoma, deserve careful scrutiny to ensure that a parathyroid lesion is not mistaken for a “posterior” hypoechoic thyroid nodule. There will often be a rim of normal thyroid tissue along the deep surface of a posterior thyroid nodule, which will be absent when the hypoechoic lesion “just posterior to the thyroid capsule” is in fact the parathyroid adenoma. Biopsy of these posterior thyroid “nodules” may be reported as “suspicious for follicular neoplasm.” Even in this context, the lesion may still represent a parathyroid adenoma, which is difficult to distinguish from thyroid tissue on cytopathology [37]. If there is suspicion that a “thyroid” nodule might actually be a parathyroid adenoma, then a washout of the aspirate may be sent for PTH analysis. While this is rarely necessary and generally reserved for reoperative cases, aspiration of parathyroid tissue usually reveals an unequivocally high PTH level in the thousands, while aspiration of thyroid or lymph node tissue typically results in levels below 100 pg/mL [38]. Truly negative ultrasound studies also may offer helpful information and hint to the surgeon that the adenoma may be small, deep, or ectopic, or that multigland disease may be present [39, 40].

Parathyroidectomy may be both one of the most rewarding and most challenging surgical endeavors . Despite a high success rate with either four-gland or focused techniques, operative failures persist. If all four parathyroid glands cannot be identified with BNE or if IOTPH levels fail to decline as expected, it is important for surgeons to first verify their findings and “know what they know.” If the surgeon has any doubts, suspected parathyroid tissue may sampled away from its polar blood supply to be sent for frozen section confirmation that it is indeed parathyroid tissue and not lymph node, fat, thyroid, or thymus. While frozen section analysis can generally distinguish between parathyroid and non-parathyroid tissue, it is not able to reliably and consistently differentiate a normocellular parathyroid gland from one that is adenomatous or hyperplastic [62, 63]. Aspiration of the excised tissue for IOPTH analysis is also beneficial in confirming the presence of parathyroid tissue and can be performed more quickly than frozen section analysis [63]. Once the identity of the excised tissue is confirmed, a diligent search for the missing, and presumably hyperfunctional, tissue can commence. The preoperative localization studies should be reviewed, and the early- and late-phase sestamibi images, if available in the operating room, should be carefully scrutinized for any hint of additional abnormal foci. Attention should first be turned to the side of the neck where both glands have not yet been found. If more than one gland has not been identified or if IOPTH levels remain elevated after finding all four glands, simultaneous bilateral venous sampling of the internal jugular vein may help guide the dissection.

Each side of the neck should be carefully and fully explored. Identifying the recurrent laryngeal nerve will help guide the depth of dissection for a missing superior or inferior gland. If the inferior glands are missing, the thyrothymic tract and thymus should be explored or excised first. If the superior glands are missing, dissection should initially be directed deeply toward the esophagus or paraspinal musculature. If the missing glands are not found in these typical locations, all sites of potential ectopic tissue in the neck and upper mediastinum should be systematically evaluated. Intrathyroidal parathyroid adenomas have been reported in up to 7% of cases [64]. Thyroidectomy is discouraged unless there is clear ultrasonographic evidence of a suspicious lesion within the thyroid and thorough exploration for the missing gland has failed. Consent for thyroidectomy should be obtained. If all four glands have been positively identified and the patient remains biochemically hyperparathyroid, then the possibility of supernumerary parathyroid glands should be considered [45]. If no further parathyroid tissue is identified or if the single hyperfunctional gland cannot be located, then the surgeon should consider intraoperative consultation with another experienced surgeon. Surgeons should refrain from removing any grossly or histologically normal parathyroid tissue. This “debulking” provides no benefit to the patient, as these glands are biochemically quiescent, and such an approach predisposes the patient to a risk of permanent hypoparathyroidism if an abnormal gland is removed during a subsequent operation.

If all of these efforts still fail to identify the source of the hyperparathyroidism, then the operation should be terminated, before any undue morbidity occurs. All confirmed normal parathyroid tissue should be marked with a clip or permanent suture away from its blood supply. The surgical findings should be fully documented in the operative report, including which glands were positively identified , which were missing, what was removed, and which areas were explored. Prior to parathyroid surgery, every patient should be counseled about the possibility of a negative exploration and the possible need for additional procedures. This counseling helps temper the patient’s expectations of what may be perceived as “routine” or “minor” surgery and may help mitigate their disappointment if surgery is unsuccessful.

Although most patients with primary hyperparathyroidism can anticipate being cured after a single procedure, the sometimes challenging nature of parathyroid disease ensures that operative failures cannot be obviated completely. Surgeons should understand the potential causes of failed parathyroid surgery and be aware of possible pitfalls in the diagnosis and management of surgical parathyroid disease. Armed with a thorough understanding of parathyroid pathology, and with careful preoperative assessment, meticulous operative planning and execution, and thoughtful integration of surgical adjuncts, surgeons are well positioned to maximize the likelihood of successful initial parathyroid surgery.