Treatment Modalities

Patients with parathyroid carcinoma frequently present with symptomatic hypercalcemia. They need prompt treatment and correction of renal and cardiac dysfunction because of the metabolic consequences of the high serum calcium levels. Rehydration with saline and additional electrolytes, including magnesium, restores glomerular function and increases urinary excretion. Loop diuretics also increase urine calcium secretion, provided that the patient is well hydrated. Calcitonin is an osteoclast inhibitor and promotes urinary calcium excretion. Its duration is short, waning after 48 to 72 hours of use. For preoperative treatment, however, a longer acting regimen is not always necessary. Plicamycin is an effective, short-acting osteoclast inhibitor that can be administered repeatedly. Its disadvantage is potential toxicity and patients' inability to tolerate adverse reactions such as nausea and vomiting. Phosphate, as either an oral or an intravenous compound, is effective in lowering serum calcium levels but is also poorly tolerated because of gastrointestinal side effects, and it can cause severe calcification in soft tissues when used intravenously.

The bisphosphonates are pyrophosphate analogs and potent osteoclast inhibitors by inhibiting bone resorption when binding to hydroxyapatite. They also act as direct inhibitors of the formation of osteoclasts.48 50'51"53 Three bisphosphonates are available at present, pamidronate, etidronate, and clodronate. The three compounds vary slightly in their mechanisms of action with regard to the effect on bone mineralization. Pamidronate is the most potent agent and causes a reduction in serum calcium levels within 24 to 48 hours. In patients with impaired renal function, repeated doses over 2 to 4 days may be given. Etidronate and clodronate also exist as oral compounds but are poorly absorbed. For prolonged use, clodronate can be given initially as an infusion with an expected effect after 2 to 5 days and then administered orally. No series have compared the effect of the various types of bisphosphonates in parathyroid carcinoma, but Ralston and colleagues showed in a small series that pamidronate had the longest median time to relapse, 23 days, compared with 12 days for the other two in cancer-associated hypercalcemia.49'54 Only anecdotal reports on treated parathyroid carcinoma patients exist. With an initial good response and few side effects, however, the bisphosphonates are the preferred antihypercalcemic drugs.25'42 52'53 Gallium nitrate is a radionuclide that also has antineoplastic properties, and it lowers serum calcium levels by inhibiting bone resorption. Its effect on parathyroid carcinoma is limited to a few cases reported in the literature. WR 2721 acts by inhibiting PTH secretion, but, as with gallium nitrate, the experience is limited.53'55

It is highly unlikely that radiation therapy or different kinds of chemotherapy are of any benefit to patients with recurrent disease. Nonetheless, each case should be assessed individually because responders to either therapeutic modality have been described.54 56

In approximately 20% of all primary operations, the diagnosis of parathyroid carcinoma was not expected either preoperatively or during the procedure.2,35 Nevertheless, the initial neck exploration is the most crucial time for achieving adequate local excision. The tumor should be excised en bloc with any locally invaded tissue such as a contiguous ipsilat-eral thyroid lobe. Capsular rupture must be avoided. Under no circumstances should an open biopsy be performed on a suspicious parathyroid tumor during an operation. Even rupture of a benign parathyroid tumor may cause future problems. It may be very difficult to differentiate benign tumor seeding (parathyromatosis) from carcinoma.57,58 If the tumor looks suspicious for carcinoma, it should be regarded as such until proved otherwise. Wider excisions and prophylactic neck dissections do not improve the prognosis.2,26 Lymph node metastases are uncommon, but any enlarged nodes in the ipsilateral central compartment should be excised. The recurrent laryngeal nerve has only rarely been infiltrated by tumor growth. Therefore, a careful dissection of the nerve is worthwhile unless it was proved dysfunctional preoperatively.

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