Nephrol Dial Transplant (2003) 18: III58-III61
© 2003 European Renal Association-European Dialysis and Transplant Association
Original Article
Long-term (3 years) prognosis of parathyroid function in chronic dialysis patients after percutaneous ethanol injection therapy guided by colour Doppler ultrasonography
Division of Nephrology, Tokai University School of Medicine, Kanagawa, Japan
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Abstract |
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Background. Secondary hyperparathyroidism (2HPT) is one of the most important complications in chronic dialysis (CD) patients. Percutaneous ethanol injection therapy (PEIT) of the parathyroid glands was introduced initially as an alternative treatment to parathyroidectomy and, with the technical progress of parathyroid imaging, it has now become a useful adjunct to medical therapy. The present study examined the possiblity of maintaining parathyroid function in the long term (3 years) after PEIT.
Method. PEIT, guided by power-Doppler flow mapping, was performed in 33 CD patients with severe 2HPT, and all glands >5.0 mm in diameter were destroyed.
Results. All patients showed a decline in the serum intact parathyroid hormone (i-PTH) concentration, on average from 695.5 to 248.0 pg/ml, after 1 year. After 3 years, the i-PTH concentration was controlled at <300 pg/ml in 85% of patients. The mean serum alkaline phosphatase (ALP) concentration also decreased from 322.7 to 154.4 IU/l after 1 year. In 76% of patients, ALP was maintained within the normal range (between 76 and 260 IU/l) at 3 years. Patients were classified into four groups according to the number of parathyroid glands detected by ultrasonography: one gland in group 1, two in group 2, three in group 3, and four in group 4. At 3 years after PEIT, i-PTH was controlled at <300 pg/ml in 100, 79, 83 and 82% of the patients in groups 1–4, respectively.
Conclusions. It was possible to maintain long-term parathyroid function after PEIT in patients with 2HPT by using medical therapy, such as oral calcitriol pulse therapy and additional PEIT.
Keywords: dialysis; ethanol injection; parathyroid hormone; renal failure; secondary hyperparathyroidism
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Introduction |
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Secondary hyperparathyroidism (2HPT) is one of the most important complications of chronic dialysis (CD) patients [1,2], and the standard medical treatment consists of prevention and suppression with phosphate binders, physiological doses of oral active vitamin D sterols and intermittent administration of high doses of calcitriol [3,4]. In the most severe cases that are resistant to calcitriol pulse therapy, parathyroidectomy (PTx) has been the only practical choice of treatment until recently [1,2]
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Percutaneous ethanol injection therapy (PEIT) of the parathyroid glands (PTGs) was introduced originally by an Italian group as an alternative to PTx [5]. With the technical progress in parathyroid imaging, PEIT of the PTGs is now widely used and regarded as a routine treatment [6]. We have used PEIT to treat patients with severe 2HPT and have already reported its 1 year efficacy [7]. Our method is simultaneously to destroy targeted PTGs and then to control the remaining glands. Here we report the long-term (3 years) evolution of parathyroid function in 33 CD patients.
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Patients and methods |
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Fifty-six CD patients with severe 2HPT were referred to Tokai University Hospital (Kanagawa, Japan) between April 1994 and October 1998 for PEIT and were followed-up until October 2001. Of these, 23 patients were excluded: five died from other diseases, 15 were followed-up by their referring hospital for maintenance haemodialysis, and three patients were referred for thyroidectomy and PTx because of thyroid carcinoma coincidentally detected by the initial ultrasonography. In total, 33 patients (25 men, eight women) were enrolled in the present study.
Patient ages ranged from 29 to 68 years (49.3±9.9 years) and all had been undergoing maintenance dialysis therapy for 8–25 years (16.7±4.1 years). The causes of chronic renal failure were chronic glomerulonephritis in 24 patients, polycystic kidney disease in two, hypertensive nephropathy in two, and uncertain aetiology in five patients.
The patients fulfilled the criteria for the indication of PEIT: (i) serum i-PTH concentration >360 pg/ml; (ii) symptoms such as severe itching or bone pain; (iii) evidence of high turnover bone disease; (iv) exclusion of aluminium bone disease by desferrioxamine testing; (v) resistance to medical therapy, including oral calcitriol pulse therapy; (vi) the long axis of the target PTG (detected by ultrasonography) exceeding 5 mm and shown to have a positive blood flow by power-Doppler ultrasonography; and (vii) giving informed consent after an explanation of the benefits and risks of PEIT.
PEIT procedure and follow-up protocol
Patients were classified into four groups according to the number of PTGs detected by ultrasonography: one gland in group 1, two in group 2, three in group 3, and four in group 4. Under direct real time ultrasonographic guidance with a 7.5 MHz transducer (GE Yokogawa Medical LOGIQ 500 power Doppler ultrasonography), a 22 g PEIT needle (Hakko Shoji, Tokyo, Japan) with a blind tip and three side holes was inserted into the selected PTG and a mixture of 90% ethanol with 1% lidocaine was injected slowly.
The amount of ethanol at the initial injection was 80% of the estimated volume of the PTG (
/6xaxbxc, where a, b and c represent the diameters of the gland, in three dimensions).
The effect of PEIT was determined after 1 h and at 3 weeks by measuring the serum i-PTH concentration and confirming the absence of blood flow in the treated PTG using colour Doppler flow mapping. Then i-PTH concentrations were checked every 4 weeks, and those glands with evidence of residual blood flow underwent further ethanol injection with a minimal amount of ethanol. All patients were then treated with oral active vitamin D sterols and calcitriol pulse therapy (4.0 µg twice per week). When i-PTH concentrations became too low (<100 pg/ml) or serum calcium increased (>10.5 mg/dl), calcitriol was withdrawn to avoid excessive suppression of bone turnover. Calcium carbonate was also used to maintain serum phosphate between 4.0 and 6.0 mg/dl. When the i-PTH concentration began to increase again, we checked the PTG size and blood flow by colour Doppler flow mapping. If there was any evidence of recurrence of hyperparathyroidism, the patient underwent additional PEIT.
Serum biochemistry
Serum i-PTH concentrations were determined by dual-antibody radioimmunoassay (normal value, 10–65 pg/ml; Nichols Institute, San Juan Capistrano, CA, USA).
Other serum parameters were measured using an autoanalyser (Hitachi model 736-60; Hitachi Electronics Co, Ltd, Tokyo, Japan).
Statistical analysis
All results are expressed as mean±SD. Wilcoxon's non-parametric test was used for statistical analysis, and P<0.05 was considered significant.
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Results |
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In the 33 patients, 78 PTGs were detected by ultrasonography before PEIT, and during the follow-up period 13 previously undetected glands were found. In total, 71 PTGs measuring >5 mm in the long axis were destroyed with 174 injections of ethanol (2.1±0.8 injections per gland). Destruction of the gland was confirmed by the disappearance of blood supply on colour Doppler flow mapping.
Ultrasonographic follow-up examinations after PEIT showed that 11 injected glands (15%) had disappeared, and 56 (79%) had been reduced to less than half of their initial size, During the follow-up period, there were signs of re-growth and blood flow in 31 glands (43%), requiring additional ethanol injections. Eighteen patients (55%) needed additional PEIT during the 3 year follow-up period; however, in 15 patients (45%), a single ethanol injection was sufficient to destroy the parathyroid tissue completely.
Figure 1 shows the changes in serum biochemistry and volume of glands after PEIT. In all patients, serum i-PTH concentrations decreased, on average from 695.5±418.2 to 248.0±193.4 pg/ml at 1 year following PEIT. After 3 years, the i-PTH concentrations were controlled at <300 pg/ml (215.1±153.9 pg/ml) in 28 patients (85%), but were still >300 pg/ml in five patients. The mean value of ALP also decreased from 322.7±194.2 to 154.4±66.6 IU/l at 1 year. In 25 patients (76%), ALP was maintained within the normal range (between 73 and 260 IU/L) after 3 years. Before PEIT, the total PTG volume ranged from 293 to 5978 mm3 (mean 1437.6±1198.6 mm3) and, 3 years later, the mean total gland volume had decreased from 1437.6±1198.6 mm3 to 833.3±644.7 mm3. In 20 patients (61%), the total volume of PTG tissue was decreased by >40% after PEIT.
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There were six patients in group 1, 14 in group 2, six in group 3, and seven in group 4. Before PEIT, the i-PTH and ALP concentrations and the total volume of PTGs were greater in groups 2–4 than in group 1, although this did not reach statistical significance. Three years after PEIT, the i-PTH concentration was controlled at <300 pg/ml in 6/6 patients (100%) in group 1, 11/14 (79%) in group 2, 5/6 (83%) in group 3, and 6/7 patients (82%) in group 4. The mean value of ALP was also maintained within the normal range in 4/6 patients (67%) in group 1, 11/14 (79%) in group 2, 5/6 (83%) in group 3, and 5/7 patients (72%) in group 4. Mean serum calcium concentrations were >11 mg/dl, and phosphate concentrations were 6.0 mg/dl in groups 3 and 4.
Complications
All patients described slight, transient discomfort in the neck for several hours following PEIT. Hoarseness caused by unilateral recurrent nerve palsy and confirmed by laryngoscopy occurred in one patient, but disappeared within 2 months.
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Discussion |
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PTG size is a critical indication for therapy in 2HPT; large PTGs are generally composed of more proliferating cells that have a lower density of calcitriol and calcium-sensing receptors, otherwise known as nodular hyperplasia [8]. Over 90% of glands larger than 0.5 cm3 in volume or 1.0 cm maximum diameter have nodular hyperplasia [8], and are the initial target for PEIT. As ethanol injection carries a risk of leakage outside the PTG, the volume of ethanol, number of glands treated and number of treatments are limited [9,10].
We report the parathyroid function in 33 patients with severe 2HPT for up to 3 years after initial PEIT. A single gland was detected in six patients, and multiple parathyroid glands were detected in the other 27 patients. The aim of PEIT of the PTGs is to decrease serum PTH concentrations by reducing the total parathyroid mass, so our goal was simultaneously to destroy all PTGs found by ultrasonography that were >5 mm in diameter.
An important breakthrough in treatment of 2HPT by PEIT was the ability to detect blood flow to the enlarged PTGs by power colour Doppler flow mapping. Destruction of tissue can then be confirmed by disappearance of the blood supply and, furthermore, cells that survive the first ethanol injection, as well as recurrent cell proliferation, can be detected precisely and destroyed safely with repeat injections of minimal volumes of ethanol. It is also necessary to confirm the needle tip position and the ethanol micro-jet echo visually during the injection to avoid ethanol infiltration to recurrent nerve and other tissues. These technological innovations have enabled ethanol to be injected into smaller glands, multiple glands and bilateral glands at the same time.
Despite this, it is still difficult to destroy all parathyroid cells with PEIT; in fact, in the present study, 50% of the glands remained after the therapy, but often could be controlled by medical therapy. After PEIT, all patients were treated with oral active vitamin D sterols and calcitriol pulse therapy (4 µg twice per week). Because of this treatment, we obtained more favourable results than other groups [9,10]. After PEIT of smaller glands, medical therapy was more effective. However, in some patients with three or four enlarged glands, the serum calcium concentration increased to >10.5 mg/dl and calcitriol had to be withdrawn to avoid hypercalcaemia, and these patients needed careful observation.
We conclude that it is possible to maintain long-term parathyroid function within the normal range after using PEIT as a powerful and safe adjunct to medical therapy for 2HPT.
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Notes |
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Correspondence and offprint requests to: Reika Tanaka, MD, Division of Nephrology and Metabolism Department of Internal Medicine, Tokai University, Shimokasuya 143, Isehara, Kanagawa 259-1143, Japan.
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References |
|---|
|
TopAbstractIntroductionPatients and methodsResultsDiscussionReferences |
|---|
- Coburn JW, Llach F. Renal osteodystrophy. In: Narins RG, ed. Clinical Disorders of Fluid and Electrolyte Metabolism. McGraw-Hill, New York: 1994:1299–1277
- Akizawa T, Fukagawa M, Koshikawa S, Kurokawa K. Recent progress in management of secondary hyperparathyroidism of chronic renal failure. Curr Opin Nephrol Hypertens 1993; 2:558–565[Medline]
- Slatopolsky EA, Weerts C, Thielan J, Horst R, Harter H, Martin KJ. Marked suppression of secondary hyperparathyroidism by intravenous administration of 1,25-dihydroxy-cholecalciferol in uremic patients. J Clin Invest 1984; 74:2136–2143
- Tsukamoto Y, Nomura M, Marumo F. Phamacological parathyroidectomy by oral 1,25 (OH) D3 pulse therapy. Nephron 1989; 51:130–131[Web of Science][Medline]
- Solbiati L, Giangrande A, Pra LD, Belloti E, Cautu P, Ravetto C. Percutaneous ethanol injection of parathyroid tumor under US guidance: treatment for secondary hyperparathyroidism. Radiology 1985; 155:607–610
[Abstract/Free Full Text] - Kitaoka M, Fukagawa M, Ogata E, Kurokawa K. Reduction of functioning parathyroid mass by ethanol injection in chronic dialysis patients. Kidney Int 1994; 46:1110–1117[Web of Science][Medline]
- Kakuta T, Fukagawa M, Fujisaki T et al. Prognosis of parathyroid function after successful percutaneous ethanol injection therapy guided by color Doppler flow mapping in chronic dialysis patients. Am J Kidney Dis 1999; 33:1091–1099[Web of Science][Medline]
- Tominaga Y, Tanaka Y, Sato K, Nagasaka T, Takagi H. Histology, pathophysiology, and indications for surgical treatment of renal hyperparathyroidism. Semin Surg Oncol 1997; 13:78–86[CrossRef][Web of Science][Medline]
- Giangrande A, Castiglioni A, Sorbiati L, Allaria P. Ultrasound guided percutaneous fine needle ethanol injection into parathyroid glands in secondary hyperparathyroidism. Nephrol Dial Transplant 1992; 7:412–421
[Abstract/Free Full Text] - Fletcher S, Kanagasundaram NS, Rayner HC et al. Assessment of ultrasound guided percutaneous ethanol injection and parathyroidectomy in patients with tertiary hyperparathyroidism. Nephrol Dial Transplant 1998; 13:3111–3117
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