The two accepted surgical procedures for the management of SHPT are subtotal parathyroidectomy (sPTX) and total PTX with parathyroid autotransplantation (PTX + AT). Total PTX46 47 is still supported by some groups on the basis of lower recurrences, but in these patients the bone does not mineralize in the absence of PTH and the patient must undergo life-long treatment with vitamin D and oral calcium.5 The rationale for choosing a procedure to treat parathyroid hyperplasia and the relative merits and risks of each approach are discussed in detail in a separate chapter.
There are many reports supporting one procedure versus the other, but trials dealing specifically with SHPT are scarce. In a prospective randomized trial, Rothmund and coworkers48 found that PTX + AT was superior to sPTX in a group of 40 patients. During a mean follow-up of nearly 4 years, four patients in the sPTX group developed recurrence. Bone pain was alleviated in a significantly higher proportion of patients with PTX + AT. The other clinical responses were similar in both groups. One criticism of the study is that they left a larger remnant (60 to 80 mg) than the size recommended by other authors (40 to 60 mg). When evaluating this trial, one should keep in mind that the author's team was well known for their previous excellent results in a large series of PTX + AT.49
There are several reports comparing both techniques50"53 in a retrospective sequential design. They found both techniques to have similar results, but the authors recommended one procedure over the other on the basis of theoretical merits. Proye and coworkers considered the technique less important than the accuracy of indication for operation and the complete localization of all parathyroid tissue54 because one third to one half of the recurrences arise from an overlooked gland (ectopic or supernumerary, or both) in the neck.
Different ways to report results make comparison among the reports of a single technique inappropriate (Table 57-3). In assessing the merit of each technique, one should keep in mind that most authorities find the technique they routinely use and have more experience with to be most appropriate.
The success of sPTX depends mainly on the size and viability of the remnant. Remnants that are nodular are more likely to grow and cause recurrent disease.
sPTX has the theoretical advantage of inducing less postoperative hypocalcemia because the remnant continues to function. If persistent or recurrent hyperparathyroidism occurs, the gland is in the neck or, exceptionally, in the mediastinum, The main disadvantage is that reoperations are tedious and carry an increased risk of recurrent laryngeal nerve injury.
The overall results from large series showed that 10% to 16% had postoperative hypercalcemia, 8% required reoperation because of remnant growth, and 4% to 25 % had hypocalcemia longer than 12 months after operation. Compared with PTX + AT, successful sPTX provided less immediate relief of bone pain but carried less risk of postoperative low-turnover bone disease.55"58
TABLE 57-3. Common Problems in Reporting the Results of Parathyroidectomy for Secondary Hyperparathyroidism
Pre- and post-transplantation patients must be reported separately.
Vitamin D treatment modality, dialytic calcium level, phosphate management
Follow-up of pretransplantation patients should be considered separately once transplanted.
Postoperative clinical symptoms (pain, pruritus, psychological status) should be qualified by a questionnaire or (better) a visual analog scale.
Exact cause of death in all cases must be recorded.
Duration and treatment of hypocalcemia
Suspected or proven sites of persistence or recurrence should be reported (unknown, neck supernumerary, or graft or remnant overgrowth).
Patients with less than four parathyroids removed should not be included when comparing techniques.
Aimed remnant size; method to estimate it
Weight and/or size, exact number, number of pockets, origin (non-nodular or random) of autotransplanted tissue
Kidney graft function should be stated as percentage of glomerular filtrate rate.
Drugs, doses, duration of the immunosuppressive regimen
Renal failure is the main factor in overgrowth of parathyroid glands or graft.
Medical control of SHPT before and after PTX can determine the outcome.
Mixing follow-up of patients receiving dialysis and after transplantation is misleading.
Assessment of clinical status by the surgical team can be biased.
Severe complications indirectly related to persistent HPT can cause death.
Differentiation between transient and persistent hypoparathyroidism.
Overlooked glands ate the main cause of failure in both techniques.
Varies between authors. It may determine the recurrence rate.
All factors could determine the overgrowth of the graft.
Post-transplantation mild renal insufficiency may maintain SHPT,
Steroids and cyclosporine can affect clinical outcome.
AT = autotransplantation; HPT = hyperparathyroidism, sHPT parathyroidectomy secondary hyperparathyroidism; PTX = parathyroidectomy; sPTX = subtotal
Total Parathyroidectomy and Allotransplantation
Success of total PTX and autotransplantation depends mainly on the absence of nodularity of the gland from which the graft is obtained and the number and weight of the fragments implanted. Graft-dependent recurrence is three times higher when implanting a nodular gland instead of a diffusely hyperplastic one.59 Most published series did not consider this as a source of variability and therefore may have had higher recurrence rates than are theoretically possible.
The advantage of autotransplantation is that if hyperparathyroidism recurs, the graft can be partially resected under local anesthesia. Nevertheless, reresection may be necessary and sometimes a tumor-like growth develops in the implant, making it difficult to remove. The Casanova test requires total ischemic blockade of the arm bearing the parathyroid graft and measuring PTH levels proximally and distally to the blockade. It is used to assess graft function after PTX + AT or to determine the site of recurrence.60
Published series show a 5% to 38% rate of postoperative hypercalcemia, 2% to 6% rate of recurrence requiring graft resection, and 5% to 30% rate of hypocalcemia lasting more than 12 months.2149-61-65
Even surgeons who routinely perform sPTX for SHPT use PTX + AT in some selected cases: when thyroidectomy is necessary because of thyroid disease, when the viability of the remnant is in doubt in sPTX, or when the remnant overgrows and causes recurrence.24'54
The mortality after PTX for SHPT is less than 1%.4 Hyperkalemia is the single most preventable cause of death. Infection, cardiac complications not related to hyperkalemia, acute hypocalcemia, pancreatitis, and respiratory complications are other miscellaneous causes of mortality.
Hypocalcemia occurs in 20% to 85% of patients after PTX for SHPT. These patients usually develop the classic symptoms of numbness, paresthesias, and tetany cramps the day after PTX if hypocalcemia is not prevented. The causes of hypocalcemia include increased deposition of calcium in bone ("hungry bone" syndrome), uncoupling of bone formation and resorption,66 hypoparathyroidism resulting from failure of the parathyroid remnant or autograft, and hypomagnesemia.24 Hypocalcemia is more common in patients with more severe preoperative bone disease and can be anticipated in those with elevated serum levels of alkaline phosphatase.24 Serum potassium, calcium, phosphate, and magnesium should be carefully monitored. Intravenous calcium gluconate in 10% solution or diluted in 5% dextrose may be needed if the serum calcium falls below 7.5 mg/dL.
Once the acute episode is controlled or if the hypocalcemia is mild, oral calcium is given in doses of up to 6 g of elemental calcium per day.24 Phosphate binders should be adjusted to maintain serum phosphate concentration between
3.5 and 5.0 mg/dL. Oral calcitriol (0.5 to 4 |ig/day) should be given in addition to calcium to control hypocalcemia.67 When postoperative hypocalcemia is likely, prophylactic calcium and calcitriol administration can be started before or immediately after surgery. Calcitriol (2 ng) given during dialysis has been used for 5 days before the operation to prevent postoperative hypocalcemia.5
Patients receiving peritoneal dialysis can be given intraperitoneal calcium therapy to control hypocalcemia.62 Supplementation with elemental magnesium at 1 mEq/kg per day should be started if the serum magnesium concentration drops below 1.5 mg/dL.24 If not properly treated, hypocalcemia can lead to tetany and convulsions, especially during the later hours of hemodialysis. Hypocalcemic seizures can cause multiple fractures.5
The prevalence of permanent hypoparathyroidism varied greatly from 0%48 to 73 %2 in early series but is most commonly between 4% and 12%. Parathyroid autotrans-plants can fail and cause hypocalcemia up to 2 years after surgery.63 It is difficult to assess the exact percentage of hypoparathyroidism because of retrospective analysis and reporting heterogeneity (see Table 57-3).
Patients with hypoparathyroidism need vitamin D and calcium supplementation for life. The hypocalcemic symptoms can be exaggerated after a kidney transplantation reversing the acidemia. Hypercalcemia can also occur because of vitamin D intoxication.
The prevalence of persistent or recurrent hyperparathyroidism is between 2% and 12%. In one third to one half of the cases, the recurrence is due to an incomplete first operation: less than four glands were found, cervical thymectomy was not performed, or there were supernumerary glands in the neck or mediastinum.68 These patients have hypercalcemia, elevated iPTH levels, and persistence or worsening of clinical manifestations. If sPTX was the initial operation, reexploration of the neck and PTX + AT are indicated. If PTX + AT was the initial operation, the Casanova test should be performed. Graft resection or re-exploration of the neck is then indicated, depending on the site of recurrence. In all cases of repeated neck operations, imaging studies should be done to localize the recurrent disease. Reoperations for hyperparathyroidism are treated in detail in another chapter of this book. Some authors suggest that the recurrent tumor can be injected with ethanol under ultrasonographic guidance, but recurrent nerve injury has been reported.64'69 71
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