| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1
Department of Radiology and Cancer Biology, Nagasaki University School of
Dentistry, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.
2
First Department of Internal Medicine, Nagasaki University School of Medicine.
1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Received December 13, 1999;
accepted after revision February 8, 2000.
Address correspondence to T. Nakamura.
Abstract
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
SUBJECTS AND METHODS. MR imaging features of the salivary glands, salivary function, immunologic abnormalities, and plasma lipid profiles were analyzed in 24 patients with hyperlipidemia and symptoms of sicca syndrome and compared with those of 50 patients with Sjögren's syndrome.
RESULTS. Swelling of the parotid gland, impaired salivary flow, or both were observed in 20 (83%) of 24 patients with hyperlipidemia and symptoms of sicca syndrome. MR imaging findings included an enlarged parotid gland replaced with extensive lipid infiltration, whereas sialography of the parotid gland revealed normal findings. Immunologic studies and analyses of the labial glands of the mouth revealed distinctive features in patients with Sjögren's syndrome. Importantly, elevated levels of plasma triglyceride correlated with parotid gland swelling, and increased cholesterol levels significantly affected salivary flow.
CONCLUSION. Our findings suggest a distinct entity of sicca syndrome in patients with hyperlipidemia compared with patients with Sjögren's syndrome. Characteristic MR imaging findings of salivary glands in patients with hyperlipidemia included extensive lipid infiltration and gland enlargement.
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Recent studies have revealed that MR imaging features of the salivary glands correlate well with the severity of salivary dysfunction in patients with Sjögren's syndrome [6, 7]. Therefore, we assessed changes in MR imaging features of salivary glands in a relatively large population of patients with hyperlipidemia and symptoms suggestive of Sjögren's syndrome. We also correlated abnormalities of the salivary glands with plasma levels of triglyceride and total cholesterol.
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
150 mg/dL), total cholesterol (220 mg/dL), or
both were identified as patients with hyperlipidemia. The plasma levels of
lipids were monitored just before patients underwent MR imaging. None of the
patients underwent treatment for hyperlipidemia. MR imaging was also performed on 50 patients with Sjögren's syndrome (50 women; average age, 50 ± 13 years; age range, 25-75 years) and on 209 control subjects (109 men and 100 women; age range, 4-88 years). The diagnosis of Sjögren's syndrome was determined on the basis of sialography, biopsy of the labial glands of the mouth, and decreased salivary and lacrimal flow, as previously described [6, 7]. The control subjects were selected from the MR imaging files of our hospital. The control subjects had no history of disease that affected the salivary glands and no abnormalities of the salivary glands revealed on MR imaging.
MR Imaging
Control subjects, patients with hyperlipidemia, and patients with
Sjögren's syndrome underwent imaging on a 1.0-T
MR scanner (Expert; Siemens Medical Systems, Erlangen, Germany). A head coil
was used to image the parotid gland, and a neck coil was used to image the
submandibular gland. Axial T1-weighted (TR/TE, 530/17; excitations, two) and
fat-suppressed T2-weighted MR images (3200/96; excitations, two) were obtained
with conventional and fast spin-echo sequences, respectively. The section
thickness was 5 mm for all sequences. Fat-suppressed T1-weighted MR images
(530/17; excitations, two) were also obtained. MR imaging was performed using
a 224 x 256 matrix and no interslice gap. We did not use contrast
material.
MR Imaging Morphometry of the Parotid Gland
We measured the size of the parotid gland in patients with hyperlipidemia
or Sjögren's syndrome. Additionally, we assessed
age-related changes in the size of the parotid gland in 209 control subjects.
The parotid gland emanated on 8-15 consecutive axial MR images. A larger gland
would have a greater maximum area on one of the consecutive axial MR images.
Therefore, to assess the possible enlargement of the parotid gland in patients
with hyperlipidemia, we measured the maximum area of the parotid gland on
axial T1-weighted MR images obtained from patients with hyperlipidemia or
Sjögren's syndrome and control subjects. Then we
averaged the bilateral data for each patient or control subject. For this
purpose, we calculated the area using the following formula:
Area (cm2) = (pixels included in area of the parotid gland on the MR image) / 148.4
Accordingly, a parotid gland in a patient with hyperlipidemia was considered enlarged when it had a maximum area greater than the average maximum area plus two standard deviations of the parotid gland in a control subject of a corresponding age. All procedures for MR imaging morphometry were performed using an onboard computer that was part of the 1.0-T MR imaging system.
Serologic Studies
Antinuclear antibodies were assessed in sera with an indirect
immunofluorescence procedure using human epithelial cell line type 2 (Fluoro
Hep Ana Test; Medical & Biological Laboratories, Nagoya, Japan).
Antibodies against SS-A antigen and SS-B antigen were determined by ELISA
(Mesacup SS-A/Ro Test and Mesacup SS-B/La Test; Medical & Biological
Laboratories).
Sialography
Sialography was performed on the parotid gland of all patients with
hyperlipidemia or Sjögren's syndrome using
iopamidol (Iopamiron; Schering, Berlin, Germany). The sialographic stages of
Sjögren's syndrome were determined on the basis
of lateral views, according to the criteria of Rubin and Holt
[8]. The patients were
categorized into three groups on the basis of their sialographic stage: mild
(punctate pattern of sialectasia), moderate (globular pattern of sialectasia),
or severe (cavitary or destructive pattern of sialectasia). This
classification was well correlated with the extent of salivary flow
dysfunction and classification of MR imaging features of the parotid gland
[7].
Biopsy of the Labial Glands of the Mouth
The labial glands of the mouth were excised through the mucosa of the lower
lips in three patients with hyperlipidemia and in all patients with
Sjögren's syndrome. The focus score was
determined according to the criteria of Greenspan et al.
[9].
Salivary Flow
Salivary flow was quantified using the Saxon test and expressed in grams/2
min, as previously described
[7]. A previous study showed
that control subjects produced more than 2.75 g of saliva every 2 min
[7].
Lacrimal Flow
Lacrimal flow was quantified using the Schirmer's test. A drop of
anesthetic was not used in this study. The flow of each patient was calculated
by averaging the data from both glands and expressed in millimeters/5 min;
normal values are more than 5 mm/5 min
[10].
Data Analysis
Differences in the salivary flow among patient groups (hyperlipidemia with
impaired or normal salivary flow and mild, moderate, or severe
Sjögren's syndrome) were analyzed with the
Student's t test. Differences in the incidence of clinical
abnormalities (parotid swelling and impaired salivary flow) among patients
with hyperlipidemia with elevated levels of triglyceride or total cholesterol
were analyzed with the Kruskal-Wallis test. All statistical analysis was
performed using StatView II software (Abacus Concepts, Berkeley, CA).
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
|
MR Imaging and Sialographic Features of the Parotid Gland in Patients
with Hyperlipidemia
Sialographic and MR imaging features of the parotid gland in patients with
hyperlipidemia were compared with those of patients with
Sjögren's syndrome. Sialography of patients with
Sjögren's syndrome revealed characteristic
patterns of sialectasia in all patients
(Fig. 2A), whereas none of the
patients with hyperlipidemia exhibited these characteristic sialographic
findings (Fig. 2B).
|
|
MR imaging features of the parotid gland in patients with hyperlipidemia were characterized by swelling and increased signal intensities on T1-weighted MR images (Figs. 3A and 3B). Fat-suppression sequences revealed decreased signal intensity of the enlarged parotid gland in patients with hyperlipidemia (Fig. 3C), indicating that the gland was associated with extensive lipid infiltrations. However, normal-sized glands in patients with hyperlipidemia revealed MR imaging features similar to those of control subjects (Fig. 3D). The parotid gland in patients with Sjögren's syndrome did not show any swelling, and the gland parenchyma were characterized by irregular (41 patients) or homogeneous (nine patients) distributions of increased signal intensity on T1-weighted MR images (Fig. 3E). The submandibular gland was less severely affected by disease in patients with hyperlipidemia, exhibiting slight increases in signal intensity and mild swelling (Figs. 4A and 4B). Abnormalities of the submandibular gland were seen in eight (33%) of 24 patients with hyperlipidemia. These MR imaging features were also different from those of patients with Sjögren's syndrome (Fig. 4C).
|
|
|
|
|
|
|
|
To further substantiate swelling of the parotid gland in patients with hyperlipidemia, we determined the maximum area of each gland on MR images. Then we compared the results with those of control subjects (Fig. 5A,5B). In 14 (58%) of 24 patients with hyperlipidemia, the maximum area of the parotid gland was greater than that of the parotid gland in control subjects of corresponding ages. The remaining 10 patients (42%) had glands that were in the normal-sized ranges. These findings did not correlate with those of patients with Sjögren's syndrome, in whom gland size did not exceed the normal upper limit.
|
|
Histopathologic and Immunologic Abnormalities in Patients with
Hyperlipidemia
The labial glands of the mouth obtained from two patients with
hyperlipidemia, who also had elevated levels of plasma triglyceride, revealed
extensive lipid infiltration in the gland lobes with a resultant loss of
acinar cells (Fig. 6A).
Conversely, the labial gland of the mouth from one patient with
hyperlipidemia, who also had an elevated cholesterol level, revealed a less
extensive lipid infiltration observed mainly in the interlobular connective
tissue (Fig. 6B). The
infiltration and aggregation of mononuclear cells, a characteristic feature of
Sjögren's syndrome
(Fig. 6C), were minimal in the
glands of patients with hypertriglyceridemia only
(Fig. 6A), whereas foci of
mononuclear cell aggregation were observed in the glands of patients with
hypercholesterolemia only (Fig.
6B). Conversely, lipid infiltration was rarely seen in the labial
glands of the mouth in patients with Sjögren's
syndrome.
|
|
|
Different features of the two patient groups with sicca syndrome were also evident in the plasma levels of antinuclear antibodies, anti—SS-A and anti—SS-B antibodies, and rheumatoid factors. These proteins were elevated in various percentages among the 50 patients with Sjögren's syndrome, whereas only one patient with hyperlipidemia had elevated levels of antinuclear antibodies and rheumatoid factors (Table 1).
|
Relationship Between Plasma Lipid Levels and Salivary Gland Swelling
or Impaired Salivary Function
Figure 7 shows
relationships between plasma triglyceride or total cholesterol levels and
parotid gland swelling in patients with hyperlipidemia. Triglyceride and total
cholesterol levels were elevated in 14 (58%) and 15 (63%) patients,
respectively, and both lipids were elevated in five patients (21%). All
patients with elevated triglyceride levels also had parotid gland swelling,
whereas in patients with elevated levels of total cholesterol, the parotid
gland was not enlarged, suggesting a close relationship between parotid gland
swelling and serum triglyceride levels
(Table 2; p <
0.0001, Kruskal-Wallis test).
|
|
Next, we tested whether any correlation was present between serum lipid levels and salivary dysfunction in patients with hyperlipidemia. All patients with elevated levels of total plasmo cholesterol or elevated levels of both total cholesterol and triglyceride also had impaired salivary flow, whereas the salivary flow was normal in 44% of patients with elevated levels of plasma triglyceride alone (Table 2). Therefore, our results suggest that the plasma total cholesterol level significantly contributes to salivary flow impairment in patients with hyperlipidemia (Table 2; p = 0.0216, Kruskal-Wallis test).
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Our MR imaging findings and analysis of labial glands of the mouth suggest that fatty infiltration in the parotid gland is an important factor causing parotid enlargement. As revealed on MR imaging, parotid swelling and parenchymal changes suggestive of lipid infiltration occurred concomitantly in patients with hyperlipidemia; however, patients without parotid swelling did not have such parenchymal changes.
We did not find any significant correlation between parotid swelling and impaired salivary flow; patients without parotid swelling showed similar levels of salivary flow (0.97 ± 0.28 g/2 min) compared with those with parotid swelling (1.57 ± 1.27 g/2 min). This finding may be caused by the relative refractoriness of the submandibular gland to the aberrant lipid metabolism in patients with hyperlipidemia; MR imaging showed that the changes in size and signal intensity of the parenchyma were less in the submandibular gland than in the parotid gland.
We found a close relationship between swelling of the parotid gland and plasma levels of triglycerides. A review of the preceding reports did not fully support the standing hypothesis for the possible correlation of parotid swelling and plasma triglyceride levels because those reports did not describe patients with low levels of triglyceride and high levels of total cholesterol [3, 4]. However, the most recent report by Sheikh et al. [5] showed that, in one patient with high levels of triglyceride and total cholesterol, lowering the triglyceride level by diet therapy conjugated with drug therapy resolved parotid swelling. This result may support the hypothesis for the possible role of plasma triglyceride levels in the development of parotid swelling in patients with hyperlipidemia. In this context, it should be noted that hyperlipidemia was suggested to be an early event in acute pancreatitis [11]. Because all patients with hyperlipidemia do not have symptoms suggestive of Sjögren's syndrome, hyperlipidemia may be a prerequisite for the sicca syndrome in these patients and may play a role in aggravating sicca symptoms.
Although the exact mechanism of how hyperlipidemia causes parotid gland abnormalities is unclear, reports in the literature provide evidence of a relationship between high plasma lipid levels and swelling of the salivary glands or impaired salivary function. First, cholesteryl esters, cholesterol, triglycerides, diacylglycerides, monoglycerides, and fatty acids were found to account for 96-99% of all salivary lipids, and cholesterol was found to be a major sterol in the salivary glands [12, 13]. Second, Man et al. [14] showed that hypertriglyceridemia resulted in triglyceride storage in the pancreatic islets, which subsequently inhibited glucose-induced insulin secretion at least in part via reduced glucokinase activity in the islets. Third, triglyceride accumulation in the salivary glands from diabetic rats was found to occur mainly in the serous acinar cells of the parotid and sublingual glands, but at lesser degrees in the seromucous acinar cells of the submandibular gland and scarce or not at all in the mucous acinar cells of the sublingual gland [15]. These findings may explain the mild involvement of the submandibular gland in patients with hyperlipidemia.
In conclusion, our findings and those of previous reports suggest a close relationship between high plasma lipid levels and salivary gland enlargement and salivary dysfunction in patients with hyperlipidemia. Our findings reveal a close correlation between the plasma triglyceride level and parotid gland enlargement in patients with hyperlipidemia. Conversely, the plasma cholesterol level may play an important role in the development of salivary gland dysfunction. We did not investigate the involvement of the lacrimal gland in patients with hyperlipidemia. Because some patients with hyperlipidemia complained of dry eyes, and lacrimal gland involvement can be revealed on MR imaging [16], it would be interesting to know whether the lacrimal gland is involved in a similar manner as the salivary glands in patients with hyperlipidemia.
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  B. M. Lodde, V. Sankar, M. R. Kok, R. A. Leakan, P. P. Tak, and S. R. Pillemer Serum lipid levels in Sjogren's syndrome Rheumatology, April 1, 2006; 45(4): 481 - 484. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Takagi, M. Sumi, T. Sumi, Y. Ichikawa, and T. Nakamura MR Microscopy of the Parotid Glands in Patients with Sjogren's Syndrome: Quantitative MR Diagnostic Criteria AJNR Am. J. Neuroradiol., May 1, 2005; 26(5): 1207 - 1214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Karlik Visualizing Radiologic Data Am. J. Roentgenol., March 1, 2003; 180(3): 607 - 619. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
) and control subjects (
).
), and control subjects (
) parotid swelling.
Dotted lines indicate normal thresholds for plasma levels of triglyceride
(vertical) and total cholesterol (horizontal).