Plate 185

Hyperparathyroidism is a common endocrine disorder usually cured by subtotal parathyroidectomy. Parathyroid overactivity documented by appropriate laboratory studies may be associated with general hyperplasia of the parathyroid glands or with an adenoma involving one of the four or more parathyroid glands. Kidney stones, gastrinoma, recurrent pancreatitis, or other conditions are some of the clinical disorders that imply a disorder of the parathyroid glands. Hypercalcemia is discovered as a result of more frequent calcium determinations performed as part of a general screening survey. Hyperparathyroidism is associated with gastrinoma in approximately one-third of patients with the familial multiple endocrine syndrome I (MEN I). A mitogenic cause for the relatively high incidence of recurrent hyperparathyroidism in the familial MEN I syndrome suggests the need for a radical approach, which may consist of total parathyroidectomy with autotransplantation of parathyroid slices into the muscle in the nondominant forearm or removal of 3½ parathyroid glands.

Evidence of hyperparathyroidism associated with hypercalcemia of 12 mg per dL after renal transplantation may be an indication to consider a radical parathyroidectomy. Hypercalcemia and extremely high parathyroid hormone (PTH) values may occur after renal transplantation. This condition often resolves spontaneously, usually within a year of the transplantation. In general, a conservative observational approach should be taken within the first 2 years after renal transplantation, with operative intervention on the parathyroids only in patients who demonstrate progressive bone disease and who are clearly symptomatic.

Parathyroidectomy should precede surgical procedures for gastrinoma in patients with the MEN I syndrome. There is an apparent increase in supernumerary parathyroid glands in those with the familial MEN I syndrome, which suggests the need to remove the thymus, where an accessory parathyroid gland may be located when the cervical exploration is negative. More rarely, thyroidectomy may also be considered in a valiant search for a parathyroid gland buried within the thyroid gland if a parathyroid is not visible under the thyroid capsule.

The presence of one endocrine tumor suggests the desirability of a general search for other endocrine tumors, such as gastrinoma, pheochromocytoma, prolactinoma, and others, before parathyroidectomy is performed.

Recurrence of hyperparathyroidism after a parathyroidectomy requires a review of previous surgical procedures and a review of the pathologist's report on the parathyroids. Were the usual four glands found, and where were they? Were any glands verified in the thyroid, thymus, anterior or posterior mediastinum, or above the thyroid? Which glands were removed or verified by frozen section examination? Every effort should be made to localize the parathyroids prior to any reoperation. Computed tomography, magnetic resonance imaging, radionuclide (sestamibi), and ultrasound scans may be useful for identifying large tumors. However, selective venous sampling with hormonal assays may be the last and best diagnostic option.

The surgeon should be familiar with the usual locations of the parathyroid glands as well as their common areas of migration (Figure 1). Attempts at localization of the glands are worthwhile, especially if previous surgery has been unsuccessful. Rarely, an adenoma of the parathyroid is large enough to be palpable. A variety of procedures may be used to localize the adenoma, including ultrasound at 10 MHz. Radionuclide imaging with Sestamibi is the preferred test for the localization of parathyroid adenomas. Cross-sectional imaging with CT and MRI may be helpful in evaluating retrotracheal and mediastinal locations but are usually reserved for patients with recurrent hyperparathyroidism. Selective venous samplings for determination of PTH can be useful in situations of recurrent hyperparathyroidism as well. Because of associated risks and poor accuracy, angiography is rarely used. The superior glands migrate upward or downward into the posterior mediastinum. The lower glands migrate into the thymus or anterior mediastinum (Figure 1). In symptomatic patients CT imaging with a stone protocol or intravenous pyelograms are made in a search of renal calculi. The kidney function is carefully reviewed. The vocal cords are inspected. The surgeon should review the variable location of the parathyroid glands, as well as their blood supply and the close relationship with the recurrent laryngeal nerves. A gastrin determination may be advisable if gastric symptoms are present.

General anesthesia with orotracheal intubation is desirable. No specific or general anesthetic drugs are specifically indicated. However, the potential exacerbation of renal dysfunction by some anesthetic agents should be considered in patients who have had a renal transplant. If there is a possibility of laryngeal nerve damage, spontaneous respiration should be prolonged with the intratracheal tube in place. There should be sufficient sedation to permit direct laryngoscopy immediately following extubation of the trachea.

The patient is placed in a semierect position with a folded sheet under the shoulders and the head sharply angulated backward.

The patient's hair is completely covered to avoid contamination of the field. The skin is routinely prepared. This should include not only the cervical region but also the upper thorax, since an upper sternal incision may be performed in a search for a mediastinal parathyroid adenoma. If available, the laboratory should be notified of the need for determination of parathyroid levels through the operation with rapid parathyroid hormone assay.

A low collar incision is made similar to that used in thyroidectomy and all bleeding is carefully controlled. The technical approach is similar to that in subtotal thyroidectomy (Plate 184), including division of the strap muscles on both sides. Self-retaining retractors may be inserted to maintain retraction of the skin flaps. A sample for baseline determination of parathyroid hormone is taken.

A four gland exploration is described. Image guided selective neck exploration is being more frequently employed. This procedure is not described or illustrated. The right lobe is freed by blunt index finger dissection (Plate 182) in preparation for identification of the course of the recurrent laryngeal nerve and the tan/yellow-colored parathyroid glands at the upper and lower poles of the thyroid gland. After the two glands on the right side have been identified, a similar search is made on the left side. The parathyroid glands may appear normal or only slightly enlarged when hyperplasia is involved, especially in the MEN I syndrome. A solitary adenoma, when found, may be the size of a small marble or several centimeters in diameter.

Further mobilization of the right lobe results when the middle thyroid vein is ligated and tied (Figure 2). A small hemostat is used to grasp the thyroid and retract it upward and medially. The surgeon may retract the thyroid with the left thumb over a piece of gauze on the upper pole of the thyroid. The relationship of the recurrent laryngeal nerve to the middle thyroid artery and the arterial blood supply to the upper pole of the thyroid should be clearly verified (Figure 3). The loose tissue is gently pushed aside with forceps and gauze until the color identifiable as parathyroid is visualized.

Many times it is difficult to be certain whether discolored tissue is the parathyroid or a hematoma in fatty tissue. Using fine-tooth forceps, the adenoma, if identifiable, is very carefully dissected from the adjacent tissue, constantly keeping in mind the location of the recurrent laryngeal nerve (Figure 3). Time is required to develop the rather frail vascular pedicle going to the superior parathyroid, which is double-clamped and ligated (Figure 4).

A portion of a gland may be excised for immediate frozen-section examination to determine that it is parathyroid tissue. In some instances, a small biopsy may be taken from several areas believed to be parathyroid glands. A numbered diagram should be made of all biopsy sites along with the individual frozen-section reports of the specimens removed.

The extent of the operation should not be limited to the excision of one obviously enlarged gland that makes a gross diagnosis of adenoma quite likely. If a single enlarged gland is found and removed, repeat determination of a rapid parathyroid hormone level should show a fall of at least 50% within 10 minutes or 85% by 15 minutes if this was the only abnormal gland. In a four gland exploration, the other three glands should be identified and their locations recorded. Some prefer a biopsy verification of each one (Figure 5), while others attach a fine, deep blue nonabsorbable suture to the gland remnant and bring a long end out into the subcutaneous tissue. The blue suture line serves as a visible guide to the site of the parathyroid biopsy should reoperation become necessary.

In patients with the familial MEN I syndrome, three normal-appearing glands may be excised as well as one-half of the fourth remaining gland. It is advisable to control any oozing with a small silver clip (Figure 6) in order to ensure certain identification of the location of any remaining parathyroid tissue should hyperparathyroidism recur.

In rare patients with the familial MEN I syndrome, there is a disturbing rate of recurrent hyperparathyroidism because of the mutagenic potential of the MEN I syndrome. As a result, a radical parathyroidectomy leaving only one-half of one gland should be considered. Resection of the thymus should probably be considered, especially if one of the lower parathyroid glands is missing.

In general, in a patient with recurrent hyperparathyroidism after parathyroidectomy, the surgeon should assume that one or more glands in the cervical region have been overlooked or are aberrantly located or that the patient has the familial multiple neoplasia syndrome. Mediastinal involvement varies but may be present in as little as 2.5 percent of patients. Upper mediastinal tumors are usually intrathymic, near the innominate vein.

In patients with recurrent hyperparathyroidism, preoperative imaging is helpful if it presents good evidence that a tumor is present in the upper mediastinum. At operation, an effort is made to bring the thymus up into view above the suprasternal notch in the hope of finding a readily recognizable parathyroid gland within it. A transsternal approach to the thymus is rarely required.

There are two primary complications of great concern. One is injury to the recurrent laryngeal nerve with persistent paralysis of a vocal cord. A second complication is hypocalcemia, even though one-half of one gland has been preserved with meticulous technique. Chvostek's sign, consisting of fascial muscle twitching when the fascial nerve is “thumbed” with the finger, indicates hypocalcemia. Careful monitoring of the serum calcium is carried out with appropriate administration of calcium gluconate daily as well as dehydrotachysterol. Calcium and PTH determinations every 6 months over a long term are worthwhile.