Nephrol Dial Transplant (2003) 18: III34-III37
© 2003 European Renal Association-European Dialysis and Transplant Association
Original Article
Evaluation of blood supply to the parathyroid glands in secondary hyperparathyroidism compared with histopathology
Division of Nephrology, Kasukabe Shuwa Hospital, Saitama, Japan
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Abstract |
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Background. In chronic renal failure patients, the parathyroid glands progress from diffuse hyperplasia to nodular hyperplasia, and it is important to distinguish between these as the latter form is more aggressive. This progress can be confirmed histologically, but the present study aimed to determine whether the different types of hyperplasia could be distinguished by power-Doppler ultrasonography (US).
Methods. Twenty-one consecutive renal failure patients were scheduled to undergo parathyroidectomy (PTx). Of 70 resected parathyroid glands, 63 were assessed by pre-operative power-Doppler US, classified into four groups based on the flow signal pattern and then correlated with the post-operative histopathology.
Results. With power-Doppler US imaging, 60.0% of glands without a signal inside the gland were diagnosed as diffuse hyperplasia or diffuse hyperplasia with early nodularity. Of glands with in-gland signals, 83.7% were nodular or had a single nodule typical of nodular hyperplasia. Even when the focus was on parathyroid glands weighing 
0.5 g, similar results were obtained.
Conclusions. Power-Doppler US imaging is a useful method for determining the pathological features of parathyroid glands and is recommended for selecting the most suitable therapy.
Keywords: chronic renal failure; nodular hyperplasia; parathyroidectomy (PTx); power-Doppler ultrasonography; secondary hyperparathyroidism.
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Introduction |
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Secondary hyperparathyroidism is a very serious complication of chronic renal failure. Because of humoral changes related to uraemia, the parathyroid glands progress histologically from diffuse to nodular hyperplasia [1]. Histological analyses show that there are fewer calcitriol receptors and calcium-sensing receptors in nodular hyperplasia than in diffuse hyperplasia [2,3], which partly explains why patients with nodular hyperplasia are usually more resistant to medical treatments, such as vitamin D pulse therapy. As most patients with nodular hyperplasia eventually require parathyroidectomy (PTx) or percutaneous ethanol injection therapy (PEIT), it is important to distinguish between the two types of hyperplasia before choosing the therapeutic procedure.
Formerly, the only criterion for diagnosing nodular hyperplasia was enlargement of the parathyroid glands. Although histopathology suggests that most glands exceeding 0.5 g in weight have nodular hyperplasia or a single nodule, some glands weighing 0.5 g can also have nodular hyperplasia; therefore, an alternative method to discriminate between these conditions is needed [1].
The aim of the present study was to determine whether power-Doppler ultrasonographic (US) imaging could be used to determine the type of hyperplasia in patients with secondary hyperparathyroidism [4].
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Patients and methods |
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TopAbstractIntroductionPatients and methodsResultsDiscussionReferences |
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Patients
Twenty-one consecutive end-stage renal failure patients scheduled to undergo PTx from November 1996 to August 1999 were selected for the present study. There were 15 men and six women, aged 52.6±8.8 (mean±SD) years. Twenty patients were undergoing haemodialysis (HD) treatment and one was undergoing continuous ambulatory peritoneal dialysis (CAPD). The HD/CAPD duration was 125.8±46.4 months. The aetiology of renal failure included 18 cases of chronic glomerulonephritis and one case of each of diabetes mellitus, nephrosclerosis and gestational toxicosis. The pre-operative intact parathyroid hormone (i-PTH) concentration was 1034.8±351.8 pg/ml.
Ultrasonography
Pre-operative US examinations were performed by an experienced thyroid endocrinologist using an SSD-2000 ultrasound system (Aloka, Japan) connected to a 7.5 MHz high-resolution probe. Parathyroid identification was performed by B-mode, and parathyroid blood flows were evaluated by power-Doppler colour imaging that was highly sensitive at the capillary level [4]. To minimize variation, the sensitivity time control (STC) was fixed in a neutral position and colour gain was kept just below the level at which artefact noise appeared.
Of 70 resected parathyroid glands, 63 were located by US, which gives a 90.0% sensitivity, comparable with that reported previously [5]. These 63 glands were also analysed histologically.
Power-Doppler criteria
Figure 1A
shows the power-Doppler images used to assess peripheral (P) and central (C) blood flow signals from each gland. Four groups based on the signal pattern were defined (Figure 1B). Group A represents cases with no blood flow signal, group B those with only a peripheral signal, group C those with some signals inside the gland, and group D those with many signals in the gland. The peripheral signals had no bearing on the definitions of groups C and D.
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Statistics
Data were analysed either by Fisher's exact probability or the 
2 test, depending on the sample size. An odds ratio (OR) with a 95% confidence interval (CI) was used.
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Results |
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Glandular weight and histopathology
The correlation between glandular weight and histopathology is shown in Table 1
. Diffuse hyperplasia progresses to nodular hyperplasia via diffuse hyperplasia with early nodularity, characterized by the formation of nodules without fibrous bands [1]. At the time of resection, 32/43 glands (74.4%) heavier than 0.5 g had progressed to nodular hyperplasia or the final single nodule stage [OR, 4.4 (95% CI, 1.4–13.5), P=0.0083 by 2 test]. Note that even among the glands weighing 0.5 g, 12/20 (60.0%) had progressed to the nodular stage.
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Relationship between power-Doppler pattern and histopathology
As shown in Figure 2, in groups A and B (the groups with no signal inside the gland), 12/20 (60.0%) had diffuse hyperplasia or early nodularity. In groups C and D (the groups with any magnitude of blood flow in the gland), 36/43 nodules (83.7%) were either single or had nodular hyperplasia. Groups C and D had more single nodules or definite nodular hyperplasia [OR, 7.7 (95% CI, 2.3–25.8), P=0.0004 by 2 test].
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We also found that parathyroid glands weighing
0.5 g gave similar results. In groups A and B, seven out of 10 glands (70.0%) showed diffuse hyperplasia or early nodularity, whereas of the glands in groups C and D, nine of 10 (90.0%), showed nodular hyperplasia (data not shown). [OR, 21.0 (95% CI, 1.8–248.0), P=0.0098 by Fisher's exact probability]. These observations show that the parathyroid histopathology predicted by pre-operative power-Doppler imaging was not influenced by glandular weight.
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Discussion |
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TopAbstractIntroductionPatients and methodsResultsDiscussionReferences |
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A characteristic histopathological finding of secondary hyperparathyroidism in chronic renal failure is an asymmetrical enlargement of the parathyroid glands. Diffuse and nodular types of hyperplasia are often found together in the parathyroid glands of the same patient. A recent clinical report suggested that if a parathyroid gland grows beyond 0.5 cm3 evaluated by US, the patient will respond poorly to vitamin D pulse therapy [6], which is understandable as most glands heavier than 0.5 g have progressed to nodular hyperplasia or to the single nodule stage [1]. Given the substantial difference in the proliferative behaviour of the two types of hyperplasia, including the decreased number of calcitriol receptors [2] and calcium-sensing receptors [3], it is important to determine the pattern of hyperplasia before initiating medical treatment.
When the parathyroid glands were divided into weight categories above and below 0.5 g, the incidence of nodular hyperplasia or a single nodule was higher in the heavier group (74.4% vs 60.0%; Table 1
). Although the rate of nodular hyperplasia/single nodule is certainly higher in the heavier group, large parathyroid glands are not always nodular. Considering that patients with nodular hyperplasia are refractory to conventional medical therapy, a reliable way of distinguishing the type of hyperplasia is needed to predict better the therapeutic response.
The high sensitivity of US has made it the technique of choice for evaluating enlarged parathyroid glands. The detection rate in the present study was 90.0% among patients suffering from severe hyperparathyroidism who were to undergo PTx. In addition to the B-mode grey scale observations, power-Doppler images made it possible to detect the blood supply to the parathyroid glands [7–9]. After defining four groups based on the signal pattern (Figure 1), we determined that those with in-gland flow (groups C and D) had a higher prevalence of nodular hyperplasia or single nodules (Figure 2). In fact, the patients in groups C and D were more likely to have progressed to nodular hyperplasia or the single nodule stage than patients with glands weighing >0.5 g (OR 7.7 vs 4.4). Note that almost the same results were observed in parathyroid glands weighing 0.5 g.
Percutaneous ethanol injection therapy (PEIT) has been adopted recently in Japan [10]. Ablation of nodular lesions by ethanol is indispensable, and the Doppler information presented here may assist in identifying hypervascular lesions that can be destroyed by ethanol injection. Our results also suggest that when performing autotransplantation of parathyroid tissue after total PTx, it may be beneficial to implant less vascular tissue because there is less likelihood of recurrence if the tissue is not derived from hyperfunctioning nodular lesions.
The Doppler data obtained in the present study were under specific US system settings. Even though we fixed STC and colour gain throughout all examinations, the comparison by Doppler imaging may be relative rather than absolute, as the flow sensitivity is influenced by the distance between the probe and the targeted tissue. Although mechanical improvements will be necessary to minimize this technical error, it is obvious that the blood flow signals inside the gland reflect the vascular-rich tissue commonly observed in nodular hyperplasia.
In conclusion, power-Doppler US imaging can determine the pathological features of parathyroid glands and assist in therapeutic decision making.
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Notes |
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Correspondence and offprint requests to: Noritaka Onoda, MD, Division of Nephrology, Kasukabe Shuwa Hospital, 1-55 Ohnuma, Kasukabe-shi, Saitama-ken, 344-0038, Japan. Email: onoda{at}ksh.smds.co.jp
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References |
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