Nephrol Dial Transplant (2003) 18: III71-III75
© 2003 European Renal Association-European Dialysis and Transplant Association
Original Article
Long-term prognosis of parathyroid function for chronic dialysis patients after minimally invasive radioguided parathyroidectomy (MIRP)
Departments of 1 Internal Medicine and 2 Radiology, Tokai University School of Medicine, Japan
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Abstract |
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Background. Minimally invasive radioguided parathyroidectomy (MIRP) for primary hyperparathyroidism for one gland, located by scanning with technetium 99m-labelled sestamibi (MIBI), has been performed. Total parathyroidectomy with autotransplantation or percutaneous ethanol injection therapy (PEIT) for severe secondary hyperparathyroidism (2HPT) has also been performed.
Methods. The present study examined the possibility of maintaining parathyroid function within a target range [intact parathyroid hormone (i-PTH) 
300 pg/ml] in the long term after MIRP for 2HPT. Three patients resistant to calcitriol therapy gave their informed consent for MIRP. The principle of MIRP for chronic dialysis patients is to extract a hyper-functioning parathyroid gland resistant to medical therapy, including calcitriol pulse therapy, and then control the remaining glands with medical therapy. The follow-up period for this study was 2 years.
Result. Two of the cases were controlled by MIRP followed by calcitriol pulse therapy. In all three cases, MIBI scintigraphy showed a solitary radioactive nodule; however, ultrasonography showed that in the two cases that were controlled by MIRP and calcitriol pulse therapy, there was one radioactive gland, but in the other case there were three, and this case required additional PEIT for control of hyperparathyroidism.
Keywords: minimally invasive radioguided parathyroidectomy; percutaneous ethanol injection therapy; secondary hyperparathyroidism; Tc-99m sestamibi
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Introduction |
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Several methods of treatment of severe secondary hyperparathyroidism (2HPT) resistant to medical therapy, such as calcitriol pulse therapy, have been reported [1–5] and include total parathyroidectomy (PTx) with autotransplantation, percutaneous ethanol injection therapy (PEIT) [6–9] and percutaneous calcitriol injection therapy (PCIT) [10], depending on the number of enlarged glands and the degree of parathyroid function. To date, we have used mainly PEIT for severe secondary hyperparathyroidism caused by chronic renal failure, and have already reported its efficacy [7,9]. Our principle for PEIT is to destroy all parathyroid glands (PTGs) resistant to medical therapy and then control the remaining glands [6–9].
The progress in modern imaging techniques has made localization of enlarged glands in the neck almost always successful, and the imaging method of first choice is ultrasonography (US). Scintigraphy with Tc-99m sestamibi (MIBI) is also sensitive for the detection of hyperfunctioning PTGs, and is particularly useful for locating aberrant or ectopic glands [11–13].
Recently, we have used the single gland resection technique of minimally invasive radioguided parathyroidectomy (MIRP) for selected chronic dialysis (CD) patients with 2HPT. Our aim is to extract the hyperfunctioning PTG resistant to medical therapy and to control the remaining glands with calcitriol pulse therapy. We describe our surgical technique and the post-operative long-term follow-up results.
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Subjects and methods |
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Three patients (two women and one man) undergoing maintenance haemodialysis for end-stage renal failure caused by chronic glomerulonephritis were referred to Tokai University Hospital (Kanagawa, Japan) for MIRP treatment (Table 1
). These patients fulfilled the following criteria for the indication for MIRP: (i) serum intact parathyroid hormone (i-PTH) concentration >360 pg/ml; (ii) high turnover bone disease confirmed by subperiosteal resorption on plain radiography, a high bone turnover pattern on scintigraphy and relatively high serum alkaline phosphatase activity (ALP, normal range 73–189 IU/l); (iii) resistant to medical therapy, including calcitriol pulse therapy; and (iv) Tc-99m MIBI scintigraphy shows a solitary radioactive nodule (Figure 1).
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The patients gave their informed consent and each was followed-up with medical therapy, including calcitriol pulse therapy, to maintain the PTH concentration within the optimal range (i-PTH <360 pg/ml) monitored by monthly laboratory tests.
Scintigraphy with Tc-99m MIBI
Anterior images of the neck and chest were obtained 20 and 120 min after injection of 370 MBq of Tc-99m MIBI. Each image was collected for 10 min and a solitary radioactive nodule was found in each of the patients (Figure 1
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MIRP procedure
An early phase image of the neck was obtained 20 min after injection of 250 MBq of Tc-99m MIBI. The site of the PTG was confirmed with US and marked on the skin of the patient. Approximately 1.5 h after injection of Tc-99m MIBI, the affected PTG was confirmed and surgically removed (Figure 2) [14]. All procedures were performed with the patient under general endotracheal anaesthesia.
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Using the mark made on the skin as a guide, a small incision (2–3 cm) was made at the expected location of the gland [as determined by both Tc-99m MIBI scanning and measurement of
emissions with a probe (Navigator GPS Gamma Guidance System 097010: United State Surgical)]. The incision was transverse to allow extension or conversion to bilateral exploration if necessary. The strap muscles were then separated along the midline and another self-retaining retractor was placed at 90° to the original. The direction of the dissection and location of the radioactive gland were indicated by increasing counts. Histological confirmation of haemostasis was obtained before closure of the wound.
Blood chemistry
Serum i-PTH concentrations were determined by dual-antibody radioimmunoassay (Nichols Institute, San Juan Capistrano, CA, USA). Other serum analyses, including total ALP, were measured using an autoanalyser (Hitachi Model 736-60, Hitachi Electronics Co. Ltd, Tokyo, Japan).
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Results |
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MIRP
Thyroid gland
radiation counts/s in cases 1–3 were 360, 320 and 300, respectively, and for the parathyroid they were 490, 410 and 400 counts/s, respectively. The weight of the PTG resected from cases 1–3 was 5.0, 0.65 and 0.55 g, respectively (Table 2).
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Histological examination showed hyperplasia in each of the resected glands.
Case 1
The i-PTH concentration was reduced from 980 pg/ml before treatment to 19 pg/ml 7 days after surgery and 78 pg/ml after 2 years. Serum calcium (Ca) concentration was reduced from 11.5 mg/dl before treatment to 8.0 mg/dl after 7 days and 10.5 mg/dl after 2 years. ALP increased from 259 U/l before treatment to 370 U/l after 1 year and then reduced to 298 U/l after 2 years (Figure 3).
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Case 2
The i-PTH concentration decreased from 515 pg/ml before treatment to 399 pg/ml 7 days after surgery (Figure 3). As this was not within the optimal range, we performed calcitriol pulse therapy, but this case was resistant and we decided to use PEIT. The i-PTH was then reduced to 200 pg/ml; Ca was reduced from 11.8 mg/dl before treatment to 10.8 mg/dl after 7 days and increased to 11.2 mg/dl 1 year after the additional PEIT treatment. Ca was reduced to 10.6 mg/ml after 2 years. ALP was reduced from 251 U/l before treatment to 231 U/l after 2 years (Figure 3).
Case 3
The i-PTH concentration decreased from 641 pg/ml before treatment to 168 pg/ml after 7 days and to 79 pg/ml after 2 years. Serum Ca was reduced from 9.7 mg/dl before treatment to 9.4 mg/dl after 7 days and maintained at 9.7 mg/dl after 2 years. ALP increased from 809 U/l before treatment to 1192 U/l after 3 months and reduced to 456 U/l after 2 years (Figure 3).
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Discussion |
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PTx with autotransplantation is the conventional surgical technique for resistant 2HPT, as residual PTGs always lead to recurrence. Initially, PEIT was considered an alternative to PTx but, with the development of US-guided methods, PEIT for 2HPT is now a routine treatment. Our goal for PEIT is to destroy all PTGs resistant to medical therapy and then control the remaining glands [6–9]. Our goal for MIRP in CD patients is to resect the hyperfunctioning PTG(s) resistant to medical therapy and then control the remaining glands.
Radioguided parathyroidectomy
Detection of sentinel lymph nodes using a probe and identification of metastasis in those lymph nodes by histological examination of biopsy specimens to determine the range of lymph node dissection are known to be useful for determining the extent of breast cancer and malignant melanoma, and have attracted considerable attention [15,16]. Radioguided parathyroidectomy, with pre-operative injection of Tc-99m MIBI and intra-operative identification and resection of the hyperfunctioning gland guided by a hand-held probe, is based on the same principle. The technique was developed by Norman and Chheda in the USA for treatment of primary hyperparathyroidism (PHP) [14].
A single affected PTG accounts for 85–90% of all PHP cases, and single-gland parathyroidectomy is the treatment of choice [11,12]. Because of the developments in diagnostic imaging technology, locating abnormally functioning enlarged glands is nearly always successful [7–9]. It has been reported that this method is not only useful for screening for hyperfunctioning glands, but also enables determination of whether the lesion is a PTG without rapid histology or PTH assay [17,18]. Thus, resected PTGs with radioactivity 20% of the surgical field background can be diagnosed because, if the radioactivity is <20%, the diagnosis is hyperplasia [19].
The three patients in the present study all had pathological parathyroid hyperplasia. The probe showed 360, 320 and 300 counts/s in the thyroid gland, and 490, 410 and 400 counts/s in the PTGs, a difference of 25% in all patients (Table 2), which corresponded to the data of Norman and Chheda [14]. The dosage of 250 MBq was selected because 370 MBq caused too much radioactivity in the thyroid gland, making it hard to identify the parathyroid. Although Tc-99m MIBI accumulates in the heart, this had no influence on detection of the gland.
Parathyroid function after MIRP
In cases 1 and 3, PTG function has been well controlled for 2 years, and hyperfunction of the contralateral PTG(s) has not developed. Blood Ca concentrations have also been well controlled for 2 years, indicating that the pre-operative localization and diagnosis were correct. All patients had hyperparathyroidism with a solitary hyperfunctioning gland showing a radioactive nodule with Tc-99m MIBI.
In case 2, the i-PTH concentration did not fall to within the optimal range after combined MIRP and calcitriol therapy, and PEIT and calcitriol pulse therapy were needed. This patient had hyperparathyroidism with a solitary hyperfunctioning gland with a radioactive nodule with Tc-99m MIBI as in cases 1 and 3. However, three PTGs were detected by US, so the one gland that showed a positive image with Tc-99m MIBI was not solely responsible for this patient's hyperparathyroidism.
The length of hospital stay was 8, 3 and 7 days for cases 1–3, respectively (Table 2), for stabilization of the low serum Ca concentration resulting from calcium absorption by the bones.
The least invasive surgical procedure should be selected for maximum reliability and minimal complications. In our procedure, the approach through a skin incision of 
2 cm immediately above the PTG to be resected does not cause adhesion to other sites, so if there is recurrence of 2HPT on the contralateral or ipsilateral sides, repeat treatment can be done without difficulty.
Conclusion
Three patients with 2HPT that was resistant to calcitriol pulse therapy underwent resection of one PTG under MIRP and were followed-up for 2 years.
Combined MIRP and calcitriol pulse therapy is effective in cases where MIBI scintigraphy shows a solitary radioactive nodule, but also where only one PTG is detected by US. If only one PTG is responsible for the hyperparathyroidism, MIRP may be an effective, less invasive therapy.
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Notes |
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Correspondence and offprint requests to: Takatoshi Kakuta, MD, Division of Nephrology, Tokai University School of Medicine, Bohseidai Isehara, Kanagawa 259-1193, Japan.
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