The surgical treatment of parathyroid disease relates mainly to hyperparathyroidism.
ANATOMY
Parathyroid glands are normally small, yellowish-brown tissues measuring 2 × 3 × 5 mm. Each gland on average weighs 30 to 40 mg. Pathologic glands, whether they are parathyroid adenomas or hyperplasia, appear grossly enlarged and reddish-brown. Both are hypercellular microscopically.
At least four parathyroid glands are present in all individuals, residing posterior to the thyroid. Embryologically, the upper or superior paired glands arise from the fourth branchial pouch, located in a plane posterior to the recurrent laryngeal nerve (RLN), usually within 1 cm where the RLN and inferior thyroidal artery cross. The lower or inferior paired glands along with the thymus arise from the third branchial pouch, located in a plane anterior to the RLN within 2 cm of the lower thyroid pole. Superior glands can also be found more lateral than inferior glands. All four glands receive their blood supply from the inferior thyroidal artery, sharing it with the thyroid gland (Figs. 13-1, 13-2, and 13-3).
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Figure 13-1 • The pharyngeal pouches. The inferior parathyroid arises from the third pouch and the superior arises from the fourth. |
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Figure 13-2 • Normal siting of the upper parathyroid glands. |
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Figure 13-3 • Normal siting of the lower parathyroid glands. |
Ectopic locations of parathyroid glands are based on embryology and are the key to localization. Aberrant lower glands rarely are intrathyroidal but can be found undescended, with thymic tissue high in the neck near the hyoid bone (Fig. 13-4).
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Figure 13-4 • Ectopic parathyroid gland locations secondary to aberrant migration. |
PHYSIOLOGY
Parathyroid glands are endocrine organs regulating calcium and phosphate metabolism. The parathyroid hormone (PTH), which can be biochemically detected in its intact 84 amino acid form, works on bone as well as kidney tubules to increase blood calcium. PTH is regulated through a feedback system.
Hyperparathyroidism exists in several forms. Primary hyperparathyroidism (HPT) results from excess PTH, which causes mobilization of calcium deposits from bone, inhibition of renal phosphate reabsorption, and stimulation of renal tubular absorption of calcium. Overall, both total body calcium and phosphate wasting occur, leading to osteoporosis and bony mineral loss.
Secondary HPT is from hyperplasia of the parathyroid glands, occurring in those with chronic hypocalcemia, as is usually seen in patients with renal disease. The hyperphosphatemia suppresses calcium levels, leading to excess PTH production.
Tertiary HPT is the consequence of secondary HPT becoming autonomous. Long after a renal dialysis patient undergoes successful renal transplantation, the hyperplastic parathyroid glands will eventually function normally. Therefore, it is rare to intervene surgically.
Pseudohyperparathyroidism or humoral hypercalcemia of malignancy leads to hypercalcemia as well as hypophosphatemia similar to primary HPT; however, it is PTH-related protein that is the cause. This latter molecule is not detected in the assays for PTH. The malignancy causes hypercalcemia as a result of these mechanisms: PTH-related protein, lytic bone metastases, and ectopic calcitriol secretion.
EPIDEMIOLOGY
HPT is the most common cause of hypercalcemia, followed by malignant disease. The majority of HPT cases occur sporadically or in a nonfamilial form, often from a single hyperfunctioning gland or adenoma.
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Patients with multiple endocrine neoplasia 1 (involvement of the three Ps: parathyroid, pituitary, pancreas) and multiple endocrine neoplasia 2A (hyperparathyroidism, pheochromocytoma, and medullary cancer of the thyroid) have HPT involving multigland hyperplasia of the parathyroids.
PATHOLOGY
Solitary parathyroid adenoma accounts for 80% of primary HPT. Nearly 15% of cases are due to hyperplasia, where up to all four glands are involved. It is thought that single-gland disease and multigland disease lie within a spectrum. Double adenoma lies between solitary adenoma and hyperplasia. Parathyroid carcinoma is rare, occurring in fewer than 2% of cases. Typically the hypercalcemia is more
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pronounced in value and presentation. The lesions can be encapsulated like their benign counterparts but tend to be more ill defined, possibly invading the thyroid or nearby structures.
HISTORY
Historically, patients presented with long-term complications related to "stones, bones, groans, and moans."
Today's surgical treatment of parathyroid disease is seen more in asymptomatic individuals rather than those sustaining long-term complications. Presently it is not uncommon to see postmenopausal women who have abnormal bone mineral densitometry to detect osteoporosis be screened on calcium blood tests and are found to be normal or hypercalcemic. This then prompts a workup for hypercalcemia where the PTH is elevated. The 2002 updated National Institutes of Health Consensus Development Conference on the Management of Asymptomatic Primary Hyperpara-thyroidism issued guidelines for surgery of the hyperparathyroid patient:
PHYSICAL EXAMINATION
Rarely will any abnormalities be found on the physical examination, as the early diagnosis is captured biochemically. Should a palpable neck mass be associated with HPT, one would then suspect parathyroid carcinoma.
DIFFERENTIAL DIAGNOSIS
In addition to medical conditions associated with hypercalcemia that must be excluded, it is important to distinguish benign familial hypocalciuric hypercalcemia (BFHH) from HPT, as the former is not treated. Thus surgical intervention will be of no benefit. BFHH can present with hypercalcemia associated with mildly elevated PTH levels. The test of choice for exclusion of BFHH is presence of low urinary calcium (Table 13-1).
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TABLE 13-1 Disease and Factors Causing Hypercalcemia |
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DIAGNOSTIC EVALUATION
A combination of elevated calcium and PTH levels is highly suggestive of primary HPT. Again, BFHH can be ruled out by presence of low urinary calcium.
TREATMENT
Primary HPT is a surgical disease, and only parathyroidectomy can successfully treat the disease. The success of the operation is measured by the return of
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calcium to normal limits. Those with hypercalcemic crisis such as coma, delirium, anorexia, vomiting, and abdominal pain must be initially stabilized with vigorous intravenous hydration and forced diuresis with furosemide. Associated hypokalemia and hyponatremia must also be corrected.
Once HPT is confirmed, preoperative localization of the suspecting gland may be performed in an attempt to perform minimally invasive surgery or assist in determining whether the source is from adenoma versus hyperplasia. Moreover, localization studies are indicated in those undergoing reoperative surgery for persistent or recurrent HPT. The preferred modality is technetium (Tc)-sestamibi scanning, including oblique and single photon emission computed tomography scans, but ultrasound and computed tomography may also be complementary
To maximize the success of surgery, preoperative Tc-sestamibi scanning and intraoperative rapid PTH assay are recommended. The intraoperative rapid PTH assay is a means to monitor adequate removal of the abnormal parathyroid gland. Once the tumor is removed, PTH levels should decrease to <50% of the baseline value in as short as 10 minutes. These two modalities also allow for a minimally invasive approach, decreasing operative time and length of stay.
SURGERY
Traditionally, the four gland bilateral neck exploration has been implemented without prior localization studies. Recently, with the assistance of preoperative Tc-sestamibi where a single adenoma is localized, a patient may undergo minimally invasive surgery, during which the gland of concern is targeted via a smaller incision, sometimes under regional anesthesia and as an outpatient procedure under experienced hands. If level of experience is sufficient, endoscopic parathyroidectomy is also used.
If there is no localization preoperatively and ultrasound is also nonrevealing, the likely finding is hyperplasia. Four-gland exploration should be used. All four glands are identified in their usual locations before any removal; their size, appearance, and color will usually determine presence of abnormality without resorting to biopsy and pathologic confirmation. If all glands are hyperplastic, a subtotal parathyroidectomy, which is the equivalent to 3.5-gland removal, or total parathyroidectomy with autotransplantation is performed.
If a missing gland is not identified in its usual location, the search for ectopic sites should be performed. These ectopic sites are related to the embryologic development. Thymic and thyroidal tissues may need to be encompassed as well.
After surgery, although calcium levels may return to normal, the patient may still develop symptoms of hypocalcemia, such as perioral numbness/tingling, distal extremity paresthesias, and signs of a positive Chvostek, where the facial muscle twitches with tapping of the facial nerve. Calcium should be replenished, even if normal, in these instances.
KEY POINTS