Nephrol Dial Transplant (2003) 18: III50-III52
© 2003 European Renal Association-European Dialysis and Transplant Association
Original Article
Surgical verification of percutaneous maxacalcitol injection therapy on enlarged parathyroid glands in chronic dialysis patients
Hiroyasu Yamamoto1,,
Naohiko Katoh1,
Hiroshi Takeyama2,
Masato Ikeda1,
Keitaro Yokoyama1,
Takashi Shigematsu1,
Yoshindo Kawaguchi1 and
Tatsuo Hosoya1
1 Division of Nephrology and Hypertension, Department of Internal Medicine and
2 Department of Surgery, Jikei University School of Medicine, Tokyo, Japan
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Abstract
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Selective percutaneous ethanol injection therapy (PEIT) has
been used to control parathyroid function in patients with secondary
hyperparathyroidism (2HPT) when one or more parathyroid gland
(PTG) progresses to the nodular hyperplasia stage. However,
PEIT can have adverse side effects, such as nerve paralysis
and adhesion, because the ethanol is destructive. Intraparathyroid
injection of a vitamin D analogue has been designed as a treatment
to control parathyroid function without destruction of the PTG
or causing adhesions to the surrounding tissue, and the present
study aimed to verify the effect of percutaneous maxacalcitol
(22-oxacalcitriol) as the vitamin D analogue. The study group
comprised two haemodialysis patients who needed parathyroidectomy
for uncontrolled 2HPT with a maximal PTG diameter >20 mm.
The treatment began with an ultrasonographically guided injection
of 10 µg of maxacalcitol solution into the largest PTG
and, 1 week later, parathyroidectomy was performed to examine
the effect of the maxacalcitol injection both macroscopically
and microscopically. The injected glands were swollen and inflamed,
and adhesions made it difficult to remove them. There was macroscopic
and microscopic evidence of haemorrhagic necrosis and adhesions
to the surrounding tissue. Direct vitamin D analogue injection
should not be performed as a primary treatment option because
the adverse side effects are not overcome by this technique.
Keywords: chronic renal failure; haemorrhagic necrosis; hyperparathyroidism; maxacalcitol; parathyroid gland
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Introduction
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Secondary hyperparathyroidism (2HPT), characterized by high
turnover bone disease and hyperplasia of the parathyroid gland
(PTG), is a common complication in chronic dialysis (CD) patients
[
1]. Supplementation with vitamin D analogues is a useful treatment
to suppress serum parathyroid hormone (PTH) secretion and to
prevent parathyroid enlargement [
2], but it is difficult to
control 2HPT, even with vitamin D pulse therapy, when one or
more PTGs progress to the nodular hyperplasia stage [
3]. Recently,
selective percutaneous ethanol injection therapy (PEIT) has
been used to control parathyroid function in patients with 2HPT
prior to parathyroidectomy [
4], but there are adverse side effects
such as pain and nerve paralysis. Moreover, it is difficult
to perform parathyroidectomy after PEIT because of the inflammation
around the injected PTG, which causes adhesions. Intraparathyroid
injection of a vitamin D analogue is designed to be a treatment
without these adverse effects [
5], and it has been suggested
that this treatment can control parathyroid function without
destruction of the PTG or causing adhesions to the surrounding
tissue. We aimed to verify the effect of percutaneous maxacalcitol
(22-oxacalcitriol), as the vitamin D analogue, injection therapy
(PMIT) into enlarged PTGs.
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Subjects and methods
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We examined two haemodialysis patients who needed parathyroidectomy
for uncontrolled 2HPT. Their intact PTH level had not decreased
to less than 1000 pg/ml, although they had been treated with
intravenous maxacalcitol injection therapy for >6 months.
Ultrasonography revealed four enlarged PTGs in the neck, with
the maximal PTG diameter >20 mm in each patient. The treatment
was commenced with an ultrasonography-guided injection of 10
µg of maxacalcitol solution (5 µg/ml oxarol, Chugai,
Tokyo, Japan) into the largest PTG. Parathyroidectomy was performed
1 week later in order to examine the effect of the maxacalcitol
injection both macroscopically and microscopically.
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Results
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The injected glands of both patients were swollen and inflamed,
and adhesions made it difficult to remove the parathyroid glands.
Macroscopic examination of the injected PTG showed haemorrhagic
changes, and the microscopic findings were degeneration of the
parathyroid cells and haemorrhage (Figure 1
).
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Fig. 1. (a) Macroscopic view of the parathyroid glands that did not receive maxacalcitol injection. (b) Macroscopic findings in the parathyroid glands following maxacalcitol injection; note the haemorrhagic changes. (c) Microscopic findings in the parathyroid glands following maxacalcitol injection. Parathyroid cells show degeneration with haemorrhage (H&E, x400).
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Discussion
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In the clinical setting, we often observe 2HPT patients with
enlarged PTGs >10 mm in diameter who are resistant to vitamin
D treatment [
6]. Parathyroid hyperplasia progresses from diffuse
to nodular in 2HPT. The density of vitamin D receptors and calcium-sensing
receptors in the parathyroid cells in nodular hyperplasia is
significantly lower than in diffuse hyperplasia [
7]. In such
cases, conventional vitamin D administration, including intravenous
pulse therapy, ceases to be beneficial, and up till now surgical
parathyroidectomy was considered the only treatment for these
advanced cases [
8]. Recently, selective PEIT of the PTG has
become an established strategy [
4] and is a powerful adjunct
to medical therapy [
9]. It uses ethanol to destroy all glands
with nodular hyperplasia selectively, followed by conventional
therapy to control the remaining glands exhibiting diffuse hyperplasia.
However, PEIT is not always safe, as the ethanol is destructive,
and adverse side effects, such as pain, nerve paralysis and
adhesion, can occur.
The technique of increasing the concentration of vitamin D in selectively enlarged PTGs (i.e. PMIT) may be useful as it acts specifically on the mechanisms of 2HPT and does not destroy tissue, which makes it different from and safer than PEIT, while still using direct injection into the PTG.
In the present study, we carried out PMIT for two 2HPT patients who were scheduled for parathyroidectomy in order to observe the macroscopic and microscopic effects of direct vitamin D analogue injection. The intact PTH concentration had not decreased 1 week after PMIT because we only injected maxacalcitol into one enlarged PTG in each patient. We proceeded with parathyroidectomy 1 week after PMIT, and the operative findings were greatly different from our expectation. The PTGs were swollen, and inflammation had caused adhesions, making the parathyroidectomy difficult. Macroscopically and microscopically there was haemorrhagic necrosis of the PTGs in both patients, which indicates that PMIT may have other mechanisms of tissue destruction, such as local stimulation of vitamin D receptors. It is generally believed that vitamin D analogues do not destroy the PTG and that its direct injection is a safe treatment for 2HPT; however, haemorrhagic necrosis occurred in the PTGs, and the adverse effects of PMIT were significant in both the PTG and the surrounding tissue.
We conclude that direct vitamin D analogue injection should not be performed as a primary treatment option. Further research of this procedure is required.
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Notes
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Correspondence and offprint requests to: Hiroyasu Yamamoto,
Division of Nephrology and Hypertension, Department of Internal
Medicine, Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi,
Minato-Ku, Tokyo, 105-8461, Japan. Email:
h-yamamoto{at}jikei.ac.jp 
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References
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- Slatopolsky E, 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
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Abstract
Introduction