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NDT Advance Access originally published online on November 24, 2006
Nephrology Dialysis Transplantation 2007 22(2):522-528; doi:10.1093/ndt/gfl620
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Efficacy of percutaneous ethanol injection therapy (PEIT) is related to the number of parathyroid glands in haemodialysis patients with secondary hyperparathyroidism

Fumihiko Koiwa1, Takatoshi Kakuta2, Reika Tanaka2 and Shigeru Yumita3

1Division of Nephrology, Department of Internal medicine, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan, 2Department of Internal Medicine, Tokai University School of Medicine, Isehara 259-1193, Japan and 3Department of Nephroendocrinology, Kojinkai Central Hospital, Sendai, 983-0852, Japan

Correspondence and offprint requests to: Fumihiko Koiwa, MD, PhD, Division of Nephrology, Department of Internal Medicine, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba-ku, Yokohama 227–8501, Japan. Email: f-koiwa{at}showa-university-fujigaoka.gr.jp



   Abstract
Top
 Abstract
Introduction
 Subjects and methods
 Results
 Discussion
 Acknowledgement
 References
 
Background. Percutaneous ethanol injection therapy (PEIT) is used for advanced secondary hyperparathyroidism. We investigated the efficacy, remission period and risk of relapse to determine the effect of the number of hyperplastic glands and other factors on the therapeutic effect of PEIT.

Methods. We studied 321 patients divided into two groups: effective [serum corrected calcium (cCa) level ≤10.5 mg/dl and serum intact parathyroid hormone (iPTH) level ≤250 pg/ml], and ineffective (failed to achieve the target levels). Advanced hyperplasia was defined as an estimated volume ≥0.5 cm3 on ultrasonography.

Results. PEIT was effective in 201 patients (62.6%), in whom serum iPTH levels dropped from 603±292 to 183±62 pg/ml (ng/l) and serum cCa levels from 10.7±0.8 to 10.1±0.5 mg/dl. Univariate analysis identified age, the number of hyperplastic glands and iPTH level as factors related to the efficacy of PEIT. The odds ratio for success vs failure by multivariate analysis was 0.55 times for the number of hyperplastic glands ≥0.5 cm3 (≥2 vs 0,1) and 0.29 times for iPTH (≥500 vs <500 pg/ml). Using the Kaplan–Meier method, the number of hyperplastic glands ≥0.5 cm3 (≥2 vs 0,1) was a factor affecting the remission period, with a remission significantly longer seen in the group with one hyperplastic gland (P=0.0025).

Conclusions. Superior results in efficacy rate, remission period and risk of relapse are obtained when PEIT is restricted to patients with one hyperplastic gland ≥0.5 cm3.

Keywords: chronic renal failure; parathyroid hyperplasia; percutaneous ethanol injection therapy (PEIT); secondary hyperparathyroidism



   Introduction
Top
 Abstract
 Introduction
Subjects and methods
 Results
 Discussion
 Acknowledgement
 References
 
Secondary hyperparathyroidism (SHPT) is a common complication seen in long-term dialysis patients. In addition to fractures and bone pain caused by osteitis fibrosa, this condition causes ectopic calcification associated with an elevated CaxPi product. In recent years, hypercalcaemia and hyperphosphataemia have also been associated with reduced life expectancy [1,2].

The number of long-term dialysis patients undergoing parathyroidectomy (PTx) for advanced SHPT not responding to medical treatment, comprising activated vitamin D and appropriate management of calcium (Ca) and phosphate (Pi) levels, is increasing in comparison with patients in the early stages of dialysis therapy [3–5]. In Japan, with its high proportion of long-term dialysis patients, we can anticipate an increase in the incidence of SHPT. Active vitamin D preparations and analogues are used in the medical treatment of SHPT, but responsiveness to the drugs will be decreased when SHPT becomes advanced, and the serum parathyroid hormone (PTH), Ca and Pi levels will also become aggravated. Even though sevelamer hydrochloride, which is a non-Ca phosphate binder, became available from 2003 in Japan, suppression of the PTH level is still difficult, with the combination of vitamin D preparations and sevelamer.

In Europe and the United States, calcimimetics have shown a superior effect as a clinical treatment of SHPT but this preparation is not available in Japan. Therefore, parathyroid interventions, such as percutaneous ethanol injection therapy (PEIT) and PTx, are the treatment choices for SHPT that is resistant to medical treatment.

Percutaneous ethanol injection of parathyroid tumours under ultrasound guidance was developed in Italy in 1985 as an alternative to PTx as an intervention for SHPT unresponsive to medical treatment [6]. This method grew in popularity in Japan during the 1990s as a treatment for resistant SHPT. Although the rate of successful reduction of PTH levels was only 40–50% when PEIT was first introduced [3,6–8], the success rate in Japan has increased following a number of technical improvements, such as the addition of three small holes in the side of the needle to improve ethanol infiltration and post-PEIT administration of vitamin D [9]. The application of PEIT to all parathyroid glands ≥5 mm in size on ultrasonography has also been reported to reduce intact parathyroid hormone (iPTH) levels to a manageable 200–300 pg/ml for at least 1 year [10]. Since the 1990s PEIT has become more popular as an alternative parathyroid intervention in Japan. Standardized therapeutic guidelines for PEIT of the parathyroid glands were produced in 2000 [11], confirming PEIT as an intervention tool for SHPT in Japan. The widespread use of PEIT has, however, unearthed a number of problems.

When multiple hyperplastic parathyroid glands are present, PEIT is somewhat ineffective, necessitating an increased number of injections. The incidence of injection-related complications of PEIT, including haemorrhage, recurrent laryngeal nerve palsy caused by ethanol leakage and adhesions to surrounding tissue, all increase as the number of injections increases. PEIT is therefore best indicated for a small number of hyperplastic parathyroid glands, because it is more likely they can be destroyed by a small number of injections [7].

In one study, the therapeutic effect of PEIT was reported to decline as increasing numbers of glands were treated [12], and in another study PEIT was effective in the treatment of single hyperplastic parathyroid glands, although the number of cases was small [13] and neither the recurrence rate nor the remission period was examined.

The therapeutic effect of PEIT is greatly influenced by the skill of the operator, making it difficult to fully assess the results from single-centre studies in previous reports, particularly the influence of factors such as the number of glands treated on efficacy and therapeutic effect.

The following therapeutic effects are expected from parathyroid intervention: (i) lower than target PTH level, (ii) appropriate control of serum Ca and Pi levels becomes possible and (iii) long-term result. However, these factors have not been clarified previously, and are the reason why interventional treatment of SHPT is not widely practiced except in Japan. In this study, we evaluated these three points in a large number of PEIT procedures performed at several centres under the same therapeutic guidelines, thereby reducing the influence of variations in skill level between institutions. We conducted a multicentre retrospective study of a follow-up patient cohort to determine the influence of the number of parathyroid glands identified or treated, and other background factors, on the efficacy of PEIT performed in Japan.



   Subjects and methods
Top
 Abstract
 Introduction
 Subjects and methods
Results
 Discussion
 Acknowledgement
 References
 
Subjects
A total of 321 patients with SHPT who underwent PEIT at three participating institutions (Tokai University Hospital, Showa University Fujigaoka Hospitals and Kojinkai Central Hospital) between April 1992 and March 2005, were included for the analysis. For privacy and for the purpose of data collection and analysis, patient information was labelled with an institution number and patient number only.

Methods
The study design was a retrospective cohort study. Prior to the publication of the Japanese PEIT Guidelines in 2000, PEIT was performed in accordance to guidelines at each institution. The following guidelines were common to all the three centres: (i) iPTH ≥300 pg/ml; (ii) the presence of hyperplastic parathyroid glands (no limit on the number of affected glands); (iii) serum cCa ≥10 mg/dl; (iv) SHPT resistant to medical treatment; (v) the use of activated vitamin D formulations as adjuvant therapy (no specification as to type or dosage); and (vi) the presence of high turnover bone disease according to the measurement of bone metabolism markers or plain X-ray.

After 2000, PEIT was performed at all three centres in accordance with the guidelines for PEIT of the parathyroid gland in chronic dialysis patients, published by the Japanese Working Group of PEIT of the Parathyroid [11]. In summary, these are as follows: (i) iPTH ≥400 pg/ml; (ii) verification of osteitis fibrosa or high bone turnover (confirmed radiologically or by bone metabolism markers); (iii) estimated volume of enlarged parathyroid glands ≥0.5 cm3 detectable by ultrasonography, or suspected nodular hyperplasia because of the increased intraglandular vascularity, and judged to treatable even if < 0.5 cm3; (iv) resistance to medical treatment; and (v) informed consent given to undergo PEIT.

Definitions
Resistance to medical treatment is defined as PTH level above the target range despite administration of vitamin D or analogues, and uncontrollable serum Ca and Pi levels. Patients with hypercalcaemia were excluded when it was determined that the hypercalcaemia was drug induced. PEIT procedures performed at an interval of up to 6 months were regarded as one cycle of treatment. Activated vitamin D preparations were administered from immediately after each PEIT procedure. No limitation on the type or dosage of medications was given for the purpose of this study. The dose of ethanol injected depended on gland volume but never exceeded 80% of the estimated volume. The range of injected volume was from 0.1 ml to 1.0 ml, and there were no cases of a volume of injection >1.0 ml.

Based on the post-PEIT results, patients were divided into an effective group, who reached the serum level of iPTH <250 pg/ml with a physiological level of Ca (cCa ≤10.5 mg/dl), and an ineffective group, who failed to achieve these target levels. The treatment period was defined as the period from the day of commencement of PEIT until the day on which target levels were reached. The remission period was defined as the period from the day on which target levels were reached until the day on which either target level was exceeded. The relapsed patients initially responded, but then required repeat PEIT or PTx because of recurrent disease. Patients undergoing PEIT for whom the response and outcome were unknown, were excluded from this study.

The primary assessment parameters were the serum levels of cCa, Pi and iPTH measured on the day of commencing the cycle of PEIT, the day on which target levels were reached and the day on which either target level was exceeded. Estimations of parathyroid volumes were made from the number of parathyroid glands and measurements of the size of each gland on ultrasonography on the day of commencement at each institution. Based on these estimations, patients were divided into two groups: with an estimated gland volume ≥0.5 cm3 (advanced hyperplasia) or <0.5 cm3. We investigated the effect of the number of hyperplastic glands and the volume of the glands subjected to PEIT on the efficacy, remission period and relapse rate in these groups.

Measurements
Serum levels of Ca and Pi were measured at each institution, and cCa levels were derived from serum albumin levels. Serum iPTH was measured at all centres using the two-site immunoradiometric method (Nichols Institute, San Juan Capistrano, CA, USA). Ultrasound examinations were performed using Toshiba SSA-270A color Doppler units (Toshiba Medical Co. Ltd, Tokyo, Japan) at two centres, and an Aloka SSD-5000 unit (Aloka Co. Ltd, Tokyo, Japan) at the third centre, all with 7.5 MHz transducers.

Statistical analyses
Comparisons between groups were made using the paired t-test, unpaired t-test {chi}2 test and analysis of variance (ANOVA) according to the situation. Parameters identified as significant factors influencing efficacy rates and relapse risk, using a univariate logistic regression model, were then analysed using multivariate analysis. Remission periods were analysed using a logistic regression model, with the event of exceeding target levels as dependent variables. Remission periods were also compared between groups using Kaplan–Meier survival analysis of the derived variables.

The level of significance was defined as P<0.05.



   Results
Top
 Abstract
 Introduction
 Subjects and methods
 Results
Discussion
 Acknowledgement
 References
 
Efficacy of PEIT
The 321 patients suitable for analysis comprised 180 males and 141 females, with an average age of 54.0±10.8 years (range 22–79 years) and a mean period on dialysis of 14.0±5.8 years. At the time of commencement of PEIT, their serum levels of cCa were 10.7±0.8 mg/dl, Pi 6.0±1.3 mg/dl and iPTH 681±346 pg/ml. The effective group, which achieved the target levels of cCa and iPTH, comprised 201 patients (62.6%) whose mean pre-treatment level of cCa was 10.7±0.8 mg/dl, with Pi 6.0±1.2 mg/dl, and iPTH 603±292 pg/ml. There was no significant difference between the effective group and all patients. The number of patients undergoing PEIT according to institutional guidelines until 1999 was 101 (effective in 55, ineffective in 46), and according to the 2000 guidelines was 220 (effective in 146, ineffective in 74).

Table 1 shows that all serum parameters decreased significantly after PEIT in the effective group: cCa from 10.7±0.8 to 10.1±0.5 mg/dl, Pi from 6.0±1.2 to 4.9±1.1 mg/dl, and iPTH from 603±292 to 183±62 pg/ml (P<0.001). The average duration of treatment in the effective group was 3.4±2.5 months (range 1–70 months), with a mean 2.9 treatments (range 1–14).


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  		Table 1. Serum parameters prior to and following successful PEIT (effective group: n=201)

 
The distribution of hyperplastic glands within all 321 patients was as follows: 57.8% with one or two glands affected, 28.9% with three glands and 19.9% (60 patients) with four or more glands. Patients with more than two hyperplastic glands accounted for approximately half of the effective and ineffective groups alike, indicating that affected gland numbers were distributed fairly and evenly regardless of the therapeutic effect (Figure 1). If we examine only the patients with hyperplastic glands ≥0.5 cm3 (estimated volume ≥0.5 cm3 on ultrasonography), we can see that patients with single hyperplastic glands ≥0.5 cm3 or no hyperplastic glands ≥0.5 cm3, but with hyperplastic glands <0.5 cm3 comprise 80% of the effective group, compared with 66% of the ineffective group (Figure 1)B.


Figure 1
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  		Fig. 1. Ratio of the number of detected glands. (A) Total, (B) glands with volume ≥0.5 cm3.

 
The mean follow-up period for the effective group was 39.6±30.6 months (range 2.1–151 months). The breakdown is: follow-up only (120 patients; 59.7%), cases of relapse requiring further PEIT or PTx (45; 22.4%), and unable to be followed up (27; 13.4%), because of death (11; 5.5%), change of hospital (7; 3.5%), or lost to follow-up (9; 4.5%). The remission period (time until relapse occurred) was 40.1±30.1 months (range 2–151 months). In two cases, the causes of death were sudden death (1) and congestive heart failure (1), but it was unclear in the other nine cases. However, the mean remission period of the 11 who died was 52.8±39.6 (range 8–121) months, so the cause of death was not related to PEIT.

The PEIT efficacy rates according to the number of hyperplastic glands were 66.9% for one gland, 50.8% for two, 50.8% for three and 50.0% for four glands, tending to decrease as the number of affected glands increased, although the relationship was not significant. If we use the {chi}2 test to divide patients into those with one and two or more affected glands, the odds ratio (OR) is 2.09 (P=0.005); in other words, the risk of PEIT being ineffective there is twice the risk with two or more hyperplastic glands than with only one affected gland (Table 2).


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  		Table 2. Efficacy of PEIT and number of hyperplastic parathyroid glands (n=321)

 
In the univariate analysis for possible risk factors for PEIT being ineffective, we examined age, gender, duration of dialysis, number of hyperplastic glands and number of glands ≥0.5 cm3 in size, as well as the serum cCa, Pi and iPTH levels, as explanatory variables (Table 3). Of these, age (each 1 year of age), the number of hyperplastic glands (≥2 vs <0,1), the number of hyperplastic glands ≥0.5 cm3 (≥2 vs 0,1) and iPTH level (≥500 pg/ml vs <500 pg/ml) were identified as significant factors. These four factors were then used as explanatory variables in the multivariate analysis, which revealed that the OR for success vs failure for PEIT was 0.97-fold for each 1 year of age, 0.55-fold for ≥2 vs 0,1 hyperplastic glands ≥0.5 cm3 and 0.29-fold for iPTH ≥500 vs <500 pg/ml (Table 4).


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  		Table 3. Relative risk of success with PEIT using univariate logistic regression model (n=321)

 

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  		Table 4. Risk ratios of success with PEIT using multivariate logistic regression model (n=321)

 
Risk of relapse and remission period following PEIT
The risk of relapse was subjected to univariate and multivariate analysis using a logistic regression model, with the event of exceeding target levels (relapse) as dependent variable (Tables 5 and 6). The odds of relapse vs non-relapse (remaining effective without relapse) throughout the follow-up period were calculated. The significant factor identified was 0.96-fold risk for each 1 year of age, the presence of ≥2 vs 0,1 hyperplastic glands ≥0.5 cm3 in size, with a risk ratio of 2.37 (Table 6). Subdividing the effective group into relapse and non-relapse groups, remission periods were compared using Kaplan–Meier survival analysis of the significant variable derived using the logistic regression model: the number of hyperplastic glands ≥0.5 cm3 (≥2 vs 0,1) (Figure 2). Log rank analysis showed a significantly longer PEIT remission period for the group with 0,1 hyperplastic glands ≥0.5 cm3 (P=0.0025); in other words, those with only one hyperplastic gland ≥0.5 cm3 or hyperplastic glands <0.5 cm3.


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  		Table 5. Risk factors for relapse of PEIT using univariate logistic regression model (n=181)

 

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  		Table 6. Risk factors for relapse of PEIT using multivariate logistic regression model (n=181)

 

Figure 2
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  		Fig. 2. Kaplan–Meier curve for effect of the number of glands ≥0.5 cm3 on the remission period following PEIT.

 
The frequency of adverse effects was 18/335 cases (5.4%), and the breakdown was subcutaneous haematoma (4; 1.2%), hoarseness that disappeared within several days (13; 3.9%) and hoarseness that persisted for almost 1 month (1; 0.3%). There was no adverse effect of PEIT that required treatment during the observation period.



   Discussion
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
Acknowledgement
 References
 
In this study, which had the main aim of elucidating factors influencing efficacy and relapse following PEIT, we analysed a large number of patients in three institutions, in order to minimize the effect of operator skills, which is known to have the greatest effect of any factor on the therapeutic results.

Although many patients with advanced SHPT were included in the 335 studied, 62.6% (201 patients) reached the target levels of cCa ≤10.5 mg/dl and iPTH ≤250 pg/ml, after an average of 2.9 PEIT procedures. At this point, the average iPTH level was 183±62 pg/ml, which is within the management range for SHPT therapy, thus confirming the efficacy of PEIT.

When selective PEIT, the standard procedure in Japan, is performed, hyperplastic parathyroid glands that are resistant to medical treatment are destroyed, and then an adjuvant vitamin D preparation is administered to treat the remaining glands that are responsive to therapy. However, it is difficult to administer vitamin D preparations in sufficient dosages in the presence of post-PEIT hypercalcaemia, which leads to further progression of SHPT in the long-term. Moreover, in recent years hypercalcaemia has been reported to cause not only ectopic calcification, including in the vasculature [14], but also to be directly related to a reduced life expectancy [2,15]. Therefore, an appropriate post-PEIT Ca level has to be achieved if PEIT is to be a valid treatment choice for SHPT, so for the purposes of this study we added an upper limit of the serum cCa level as a therapeutic goal. This level is somewhat higher than the 10.2 mg/dl in the K/DOQI renal osteodystrophy (ROD) guidelines released in the United States in 2003 [16], for the following reasons: (i) in Japan, the permissible upper limit of the serum Ca level when vitamin D preparations are administered to treat SHPT is generally considered to be 10.5 mg/dl, slightly outside the normal range; (ii) the majority of the present patients were treated according to this target level during the follow-up period; and (iii) standardized Japanese target Ca levels for ROD treatment do not exist.

The possibility that the number of hyperplastic glands affects the therapeutic effect of PEIT has been suggested previously. The Japanese PEIT guidelines also point out that the long-term therapeutic effect may be unsatisfactory in cases with multiple hyperplastic glands, in particular when the number is three or more, because the risk of complications increases with the number of injections [11]. As shown in Figure 1, more than 90% of the present patients had less than two hyperplastic glands ≥0.5 cm3 in size, indicating that those with three or more glands and ≥0.5 cm3 in size are not considered suitable for PEIT. Similar to Nakamura et al. [12], we found that the efficacy of PEIT diminishes as the number of detected glands increases. Based on our finding of an efficacy rate near 70% for PEIT in patients with one hyperplastic gland, we compared results for patients with one or two or more affected glands. The risk of PEIT being ineffective in patients with two or more hyperplastic glands was apprximately 2-fold that for a single gland, providing statistical confirmation of previous clinical experience [7,12,13].

We identified age, the number of hyperplastic glands ≥0.5 cm3 (≥2 vs 0,1) and iPTH level (≥500 pg/ml vs <500 pg/ml) as significant explanatory variables, and when they were used as such in the multivariate analysis the OR for success vs failure for PEIT was 0.97, 0.55 and 0.29, respectively. The results for hyperplastic glands ≥0.5 cm3 in particular are approximately the same as the risk ratios obtained using {chi}2 analysis, confirming the reliability of our statistical analyses. If there is resistance to medical treatment, even glands <0.5 cm3 in size on ultrasonography are very likely to be hyperplastic because the ultrasonography method underestimates gland size. Therefore, it is recommended that PEIT be performed, despite the gland having an estimated volume <0.5 cm3, if nodular hyperplasia is suspected from the abundant intraglandular vascularity and the procedure is technically possible.

In our examination of factors related to the relapse risk and remission period, analysis using logistic regression model and survival analysis using the Kaplan–Meier method both showed a significant difference between zero to one and two or more hyperplastic glands ≥0.5 cm3 in size. In other words, this study has for the first time showed that limiting PEIT to no more than one hyperplastic gland ≥0.5 cm3 in size dramatically prolongs the remission period. Possible reasons for this may be that reliable glandular destruction is possible with fewer treatments, reductions in serum Ca and Pi levels and not just PTH are possible with accurate PEIT, and effective dosages of vitamin D preparations can be administered.

Our analysis of risk factors for relapse following PEIT identified the number of hyperplastic glands ≥0.5 cm3 in size (≥2 vs 0,1) as the only significant factor. The pre-treatment degree of SHPT, and the serum levels of Ca and Pi, did not affect the risk of relapse.

From the ORs for PEIT efficacy, the influence of age was not considered particularly strong, whereas PEIT efficacy was reduced in cases of advanced SHPT. With progression of SHPT, parathyroid tissue changes from diffuse hyperplasia to nodular hyperplasia, with a corresponding increase in mass [17]. As increased glandular size makes it technically easier to insert a needle, some reports suggest it is a favourable indication for PEIT [18]. In cases of advanced SHPT, however, when glandular destruction and vascular interruption by PEIT are insufficient, parathyroid tissue with a strong proliferative potential may remain, reducing the therapeutic effect of the procedure. We can also anticipate that the glandular remnant will have a reduced response to Ca and vitamin D (i.e. will be resistant to medical treatment). Studies of PEIT in cases of severe advanced SHPT with iPTH levels exceeding 1000 pg/ml have shown that it is ineffective, likely because of glandular remnants [19].

The result of the present study (i.e. a high level of efficacy for PEIT in patients with iPTH <500 pg/ml) suggests that this procedure is better indicated than PTx in the early phase of SHPT. However, a serum level of iPTH <500 pg/ml was not an effective indicator of the risk of relapse or the remission period in this study. When calcimimetics become available in the near future in Japan, it is expected that they will be an effective treatment for mild SHPT with PTH <500 pg/ml that is resistant to the conventional medical treatment. At that time, a control trial of PEIT and calcimimetics for the treatment of mild SHPT will be necessary.

Of the 201 patients in the effective group, the relapse rate was 22.4% (45/201) over the 39.6±30.6 months of follow-up. The number of relapsing patients at 12, 24 and 36 months post-PEIT was 11, 10 and 6, respectively, with 60% of all the relapses occurring within the first 3 years. In this study, additional PEIT procedures signified a deviation from the criteria for efficacy, so our results show the therapeutic effects of a single course of PEIT.

We did not examine the influence of the type or dosage of activated vitamin D preparations, used as adjuvant therapy, on the therapeutic effect of PEIT. Both oral and intravenous forms of vitamin D preparations were used in this study, and at present there is no consensus as to the efficacy of the different routes of administration in patients with SHPT [20]. Because these agents were administered without guidelines, vitamin D preparations were excluded from analysis of the long-term effects of PEIT, but in future studies the effect of post-PEIT medical treatments will need to be examined.

In conclusion, superior results with PEIT are obtained in terms of efficacy, remission period and risk of relapse when it is restricted to patients with no more than one hyperplastic gland ≥0.5 cm3.



   Acknowledgement
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Acknowledgement
References
 
The authors thank the Japanese Society for Parathyroid Intervention for invaluable suggestions throughout the study.

Conflict of interest statement. None declared.



   References
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Acknowledgement
 References
 

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Received for publication: 16. 5.06
Accepted in revised form: 26. 9.06


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C. Cappelli, G. Pelizzari, I. Pirola, E. Gandossi, E. De Martino, A. Delbarba, B. Agosti, E. Agabiti Rosei, and M. Castellano
Modified percutaneous ethanol injection of parathyroid adenoma in primary hyperparathyroidism
QJM, May 22, 2008; (2008) hcn062v1.
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