Key words
primary hyperparathyroidism - aortic intima-media thickness - parathyroid hormone
Introduction
Atherosclerosis occurs in the tunica intima and media layers of the vessel wall and
causes an increase in intima-media thickness (IMT) in the early period of the disease.
IMT can be measured clearly by ultrasonography (USG). In adult and pediatric patients
IMT evaluation is performed from carotid artery and abdominal aorta (C-IMT and A-IMT).
Besides atherosclerosis, vascular IMT measurement is used for target organ damage
detection in many systemic diseases.
Primary hyperparathyroidism (PHPT) is an endocrine disorder associated with long-term
subclinical elevated parathyroid hormone (PTH) and mineral abnormalities [1]. Increased levels of calcium and PTH in this disease have been shown to negatively
affect vascular function, especially by impairing vasodilation [2]. In the literature, there are conflicting results about the effects on C-IMT in
patients with PHPT. In some of these studies it has been shown that C-IMT has been
increased [3]
[4]
[5]
[6], but no significant increase in C-IMT has been found in the other significant part
of the studies [7]
[8]
[9]
[10]
[11].
The abdominal aorta is exposed to shear stress due to its size and branching, and
according to studies performed, is the first vascular site to develop atherosclerosis.
Therefore, abdominal A-IMT measurement can be used to detect the development of early
atherosclerosis [12]. There is no study in literature on A-IMT evaluation obtained from abdominal aorta
in adult PHPT patients. For this reason, the importance of A-IMT in patients with
PHPT is unknown; it is not a routine examination and is not used. For this reason,
we also hypothesized that in patients with PHPT, the accumulation of calcium and the
IMT increase due to elevated PTH may be earlier and more prominent in A-IMT than C-IMT.
In our study, we aimed to determine whether there is an increase in A-IMT values measured
from the abdominal aorta in addition to the traditional C-IMT in patients with PHPT
and to determine the parameters closely related to A-IMT.
Materials and Methods
Study population
This prospective study included 65 patients (mean age: 57.4±12.8 years, male/female:
9/56) biochemically diagnosed with PHPT and 30 healthy controls with normal serum
PTH, calcium and phosphate levels (mean age: 56.9±9.8 years, male/female:10/20). In
the control and PHPT group, care was taken to avoid any other major cardiovascular
(CV) risk factors that may increase IMT such as hypertension (HT), smoking, diabetes
mellitus (DM), hyperlipidemia (HL). The participants of the study was divided into
3 groups as the control or Group I (healthy-controls), the medical treatment or Group
II (patients with asymptomatic PHPT and no surgery indications), and the planned surgery
or group III (patients with symptomatic PHPT and asymptomatic PHPT who had to surgery
indications). According to the National Institutes of Health consensus panel as the
surgical criteria for PHPT patients, symptomatic PHPT patients and asymptomatic PHPT
patients who has (i) the serum calcium value exceeds the reference value by 1 mg/dl
, (ii) significant hypercalciuria (>400 mg / 24 h), (iii) in dual x-ray absorptiometry
(DEXA) the T score is<- 2.5, (iv) younger than 50 years(<50 years) (v) more than 30%
reduction of creatinine clearance without any cause [13]. Patients with alcohol addiction, cerebrovascular disease, secondary or malignant
HT, abdominal aortic aneurysm or dissection, inflammatory diseases, hematologic diseases,
coronary artery disease, peripheral vascular disease, congestive heart failure, severe
heart valve dysfunction, smoking, obesity, HT, DM and HL diseases, cancer, pregnancy
or kidney failure were excluded from both groups. While identifying HT and HL patients,
ESC / EAS 2016 hyperlipidemia and ESC 2013 HT guidelines were used and the presence
or absence of HL and HT were determined according to the limit values in these guidelines[14]
[15]. The Local Ethics Committee approved the study protocol and each participant gave
written informed consent.
After a detailed medical history and a complete physical examination, baseline characteristics
(age, sex, pulse rate, systolic and diastolic blood pressure) of all groups were recorded.
Body mass index was calculated by measuring weight and height. Then routine laboratory
tests and vascular USG examinations were performed on all patients. All patients were
evaluated for renal stones or nephrocalcinosis in renal USG for surgical indications.
Also the bone mineral density was measured on anterior-posterior and lateral lumbar
vertebra (L1-L4) in all the patients. The measurements were performed with DEXA (Lunar
iDXA, GE, Madison, WI, USA). DEXA was not performed because there was no indication
in the control group.
Biochemical measurements
Serum PTH concentration and 25-hydroxyvitamine D [25(OH) Vit D] were measured using
chemiluminescence immunoassay and Beckman Coulter DXI800. Complete blood count was
measured using a Beckman Coulter DXH 800 . Serum glucose, HbA1c, total cholesterol,
triglyceride, low-density lipoprotein, high-density lipoprotein, hs-CRP, uric acid,
blood urea nitrogen (BUN), creatinine, calcium, phosphorus and urine calcium levels
were measured using an automated chemistry analyzer (Abbott Aeroset, MN, USA) and
using appropriate commercial kits (Abbott). The corrected serum calcium levels were
calculated using the most commonly used formula in clinical practice, if serum albumin
level was lower than 4 mg/dl: Corrected calcium=measured total calcium (mg/dL)+0.8
(4.0 − serum albumin [g/dL]) [16].
Common carotid, internal carotid and abdominal aortic B-mode ultrasonography evaluation
The abdominal aorta and left and right common and internal carotid (CC and IC) arteries
were examined with a high-resolution ultrasound system (Philips EPIQ 7) equipped with
a 12 MHz linear and 5 MHz convex transducer (Philips Health Care, Bothell, WA, USA).
All arteries were examined both longitudinally and transversely. All arteries were
scanned longitudinally to visualize the IMT on the posterior or distal wall of the
artery. All measurements were made on frozen images. Two images of the best quality
were selected for analysis on each study. IMT was defined as the distance from the
anterior margin of the first echogenic line to the anterior margin of the second line.
The first line represents the intima-lumen interface and the second line represents
the collagen-containing top layer of adventitia. Vascular IMT was measured using ultrasonic
calipers in the presence of two independent and blind observers. All IMT values were
calculated as averages of six measurements.
The patients were examined in the supine position. Patients rotated their heads by
45° from where they were scanned for the examination of the carotid arteries. CC-IMT
and IC-IMT were accepted as IMTs measured from 10–20 mm proximal before bifurcation
(for the main carotid artery) and at the distal segment of the right and left main
carotid artery in the distal segment after bifurcation (for the IC artery) respectively.
Abdominal A-IMT was investigated at the level ranging from renal artery bifurcation
to iliac artery bifurcation. IMT measured from the posterior wall of the abdominal
artery was accepted as A-IMT ([Fig. 1], [2]).
Fig. 1 B-mode ultrasound image of a patient without primary hyperparathyroidism: normal
intima-media thickness on posterior wall of abdominal aorta.
Fig. 2 B-mode ultrasound image of a patient with primary hyperparathyroidism: increased
intima-media thickness on posterior wall of abdominal aorta.
Statistical analysis
The variables were divided into two as categorical and continuous groups. Continuous
variables were expressed as mean±standard deviation (mean±SD). Categorical variables
were given as numbers and percentages. Comparisons of continuous variables were performed
by One way ANOVA or Kruskal-Wallis 1-way ANOVA tests according to the distribution.
For normally distributed data, Scheffe and Games-Howell tests were used for multiple
comparisons of groups with respect to homogeneity of variances. For non-normally distributed
data, Bonferroni adjusted Mann Whitney U test was used for multiple comparisons of
groups. Chi Square Test was used to compare categorical variables. For independent
determination of patients who underwent surgery, multivariate logistic regression
analysis was performed. ROC curve analysis was performed to reassess markers that
independent for identifying patients to be surgically treated and to determine the
border value of these markers. The value of the area under the curve was used as the
accuracy criterion of the test. Univariate correlation analysis was performed using
Pearson’s correlation method to determine the parameters associated with A-IMT. Linear
regression analysis is performed with these parameters and independent indicators
affecting A-IMT have been identified. Statistical significance level was accepted
as p<0.05. All analyzes were performed with SPSS 20.0 (Chicago, IL, USA) statistical
software package.
Results
The participants of the study was divided into 3 groups as the control (Group I),
the medical treatment (Group II) due to PHPT, and the planned surgery (group III).
In our study we found that 8 of the PHPT patients (12.3%) had renal stones. There
was also no fracture in the PHPT patient group in the study.
Demographic, clinical and laboratory findings of the study groups
There was no difference between groups in terms of general demographic and clinical
parameters. BUN, creatinine and uric acid levels were highest in Group III and statistical
significance was found only between Group I and Group III ([Table 1]). Glucose and hs-CRP levels were significantly higher in Group II and Group III
compared to Group I ([Table 1]). Serum PTH, serum and urine calcium levels increased significantly from Group I
to Group III and serum phosphorus levels decreased significantly ([Table 1]). It was determined that serum PTH, calcium, phosphorus and urine calcium levels
were statistically different between all study groups ([Table 1]). Negatively T scores in DEXA and the presence of T scores in DEXA< ̶ 2.5 were significantly
higher Group III than Group I ([Table 1]). Other laboratory findings were similar among the groups ([Table 1]).
Table 1 Demographic, clinical and laboratory findings of the study groups.
|
Variable
|
Group I
n=30
|
Group II
n=34
|
Group III
n=31
|
p
|
|
Age (year)
|
56.9±9.8
|
57.9±7.1
|
56.8±15.2
|
0.895
|
|
Gender (female)
|
20
|
32
|
24
|
0.308
|
|
Systolic blood pressure (mmHg)
|
121.9±14.2
|
122.4±12.4
|
126.5±16.6
|
0.495
|
|
Diastolic blood pressure (mmHg)
|
75.1±9.2
|
76.5±10.2
|
78.7±11.2
|
0.368
|
|
Pulse (pulse/minute)
|
78.1±10.4
|
77.1±9.8
|
80.4±12.1
|
0.545
|
|
Body mass index (kg/m2)
|
26.1±3.7
|
26.2±3.5
|
27.2±3.5
|
0.204
|
|
White blood cell (µL)
|
6.50±1.57
|
6.92±1.19
|
6.66±1.41
|
0.465
|
|
Hematocrit (%)
|
40.2±2.9
|
41.3±2.1
|
40.7±4.3
|
0.298
|
|
Platelet (K/mm3)
|
281±33
|
315±131
|
270±90
|
0.135
|
|
Glucose (mg/dL)
|
89.3±6.0 α,β
|
98.5±10.3
|
99.2±12.4
|
0.001
|
|
Blood urea nitrogen (mg/dL)
|
26.2±4.6 α
|
27.9±8.8
|
33.7±11.8
|
0.004
|
|
Creatinine (mg/dL)
|
0.58±0.08 α
|
0.61±0.12¥
|
0.92±0.87
|
0.013
|
|
Total Cholesterol (mg/dL)
|
201±32
|
202±36
|
194±54
|
0.496
|
|
Low density lipoprotein (mg/dL)
|
125±14
|
132±23
|
123±32
|
0.346
|
|
High density lipoprotein (mg/dL)
|
45.9±10.2
|
48.5±10.9
|
47.9±20.2
|
0.690
|
|
Triglyceride (mg/dL)
|
174±54
|
171±46
|
157±38
|
0.795
|
|
HbA1c (%)
|
5.41±0.24
|
5.58±0.44
|
5.65±0.21
|
0.006
|
|
hs-CRP (mg/L)
|
0.21±0.10α,β
|
0.43±0.34
|
0.47±0.38
|
0.001
|
|
Uric acid (mg/dL)
|
4.35±0.82 α
|
4.91±1.11
|
5.54±1.25
|
<0.001
|
|
Serum calcium (mg/dL)
|
9.2±0.35 α,β
|
10.7±0.55¥
|
11.4±0.88
|
<0.001
|
|
Urine calcium (mg/24 h)
|
37.7±7.4 α,β
|
188±103¥
|
375±183
|
<0.001
|
|
Serum phosphorus (mg/dL)
|
3.55±0.52 α,β
|
3.07±0.60¥
|
2.64±0.49
|
<0.001
|
|
Parathyroid hormone (pg/mL)
|
52.2±12.6 α,β
|
178.5±103¥
|
358.7±360.8
|
<0.001
|
|
25(OH) Vit D (ng/mL)
|
18.5±5.1
|
16.9±6.6
|
17.6±12.1
|
0.757
|
|
25(OH) Vit D<30 ng/mL n, (%)
|
21 (70%)
|
29 (85%)
|
24 (77%)
|
0.674
|
|
T scores in DEXA
|
—
|
−1.69±0.60
|
−2.19±0.86
|
0.008
|
|
T scores in DEXA< ̶ 2.5 n, (%)
|
—
|
3 (9%)
|
11 (36%)
|
0.014
|
The values were shown as mean±standard deviation or n (%), Group I=Control group,
Group II=Medical treatment group and Group III=Planed surgery group, 25(OH) Vit D:
25-hydroxyvitamine D, DEXA: dual x-ray absorptiometry; α=the significant association
between the Group I and Group III (p<0.05); β=the significant association between
the Group I and Group II (p<0.05)
¥=the significant association between the Group II and Group III p<0.05)
B-mode ultrasonography findings of study groups
When CC-IMT and IC-IMT measurements were compared between groups, there was no statistically
significant difference between the groups, but there was an increase in CC-IMT and
IC-IMT values from Group I to Group III ([Table 2]). The A-IMT value increased significantly from Group I to Group III and it was found
that A-IMT level was statistically significantly different among all study groups
([Table 2]).
Table 2 B-mode ultrasonography findings of study groups.
|
Variable
|
Group I
n=30
|
Group II
n=34
|
Group III
n=31
|
p
|
|
Common carotid IMT (mm)
|
0.74±0.08
|
0.75±0.14
|
0.81±0.15
|
0.079
|
|
Internal carotid IMT (mm)
|
0.64±0.09
|
0.68±0.17
|
0.71±0.16
|
0.169
|
|
Abdominal aort IMT (mm)
|
1.24±0.18 α,β
|
1.40±0.30 ¥
|
1.65±0.26
|
<0.001
|
The values were shown as mean±standard deviation , Group I=Control group, Group II=Medical
treatment group and Group III=Planed surgery group, IMT: Intima-media thickness α=the
significant association between the Group I and Group III (p<0.05); β=the significant
association between the Group I and Group II (p<0.05); ¥=the significant association
between the Group II and Group III p<0.05)
Multivariate logistic regression analysis for the detection of patients treated surgically
for primary hyperparathyroidism
In multivariate logistic regression analysis, it was found that A-IMT, phosphorus,
PTH, T scores in DEXA, serum and urine calcium levels independently determined the
patients to be treated surgically (p<0.05 and [Table 3]). According to this analysis, increased A-IMT (per 0.1), PTH (per 10 pg/mL), T scores
in DEXA (per 0.2), serum calcium (per 0.1 mg/dL), urinary calcium (per 10 mg/dL) and
decreased serum phosphorus (per 0.2 mg/dL) levels were found to increase the risk
of patients to undergo surgical treatment by 40.5%, 8.9%, 63.0%, 29.5%, 12.9% and
27.5% respectively ([Table 3])
Table 3 Variable regression analysis for the detection of patients treated surgically for
PHPT.
|
Variable
|
Odds Ratio
|
95% Confidence Interval
|
p
|
|
Urine calcium (10 mg/24 h)
|
1.129
|
1.076 – 1.185
|
<0.001
|
|
Abdominal aort IMT (0.1 mm)
|
1.405
|
1.130 – 1.747
|
0.002
|
|
Serum phosphorus (0.2 mg/dL)
|
0.725
|
0.565 – 0.931
|
0.012
|
|
Parathyroid hormone (10 pg/mL)
|
1.089
|
1.002 – 1.184
|
0.045
|
|
Serum calcium (0.1 mg/dL)
|
1.295
|
1.024 – 1.638
|
0.031
|
|
T scores in DEXA (0.2)
|
1.630
|
1.050 – 2.529
|
0.029
|
DEXA: dual x-ray absorptiometry, IMT: Intima-media thickness
ROC analysis for the detection of patients treated surgically for primary hyperparathyroidism
In the ROC analysis, the area under the curve was 0.901, 0.874, 0.662, 0.836, 0.797
and 0.834 for urine calcium, serum calcium, T scores in DEXA, PTH, serum phosphorus
and A-IMT respectively (p<0.05, [Table 4]
and
[Fig. 3]). When the A-IMT and urine calcium cut-off values were taken as 1.5 mm and 400 mg/day,
respectively, it determines patients to undergo surgery with 80.6% sensitivity and
89.1% specificity, and 67.7% sensitivity and 100% specificity, respectively ([Table 4]). In group I, II and III, 4 (13%), 9 (27%) and 25 (80%) patients had A-IMT value≥1.5 mm
respectively. When the ROC curve analysis was performed to determine the group II
patients of A-IMT value between Group I and Group II, the area under ROC curve was
0.652 (CI 0.519 - 0.786, p=0.036), When the cut-off value was taken as 1.25 mm for
the A-IMT value, it was found that Group II was determined with 61% sensitivity and
70% specificity.
Fig. 3 The ROC curve of values for abdominal aortic intima-media thickness (IMT), serum
and urinary calcium levels for determining patients to be operated for primary hyperparathyroidism.
Table 4 ROC analysis for the detection of patients treated surgically for PHPT.
|
Variable
|
AUROC Curve
|
p
|
Cut-off
|
Sensitivity
|
Specificity
|
|
Urine calcium
|
0.901 (0.841 – 0.962)
|
<0.001
|
400 mg/day
300 mg/day
|
67.7%
80.6%
|
100%
84.4%
|
|
Serum calcium
|
0.874 (0.795 – 0.952)
|
<0.001
|
11.2 mg/dL
10.2 mg/dL
|
66.5%
90.3%
|
93.7%
71.9%
|
|
T ̶ scores in DEXA
|
0.662 (0.795 – 0.952)
|
0.025
|
−2.5–1.0
|
61.3%
93.5%
|
91.2%
67.6%
|
|
Parathyroid hormone
|
0.836 (0.758–0.915)
|
<0.001
|
170 pg/mL
110 pg/mL
|
77.4%
87.1%
|
79.7%
64.1%
|
|
Serum phosphorus
|
0.797 (0.702–0.892)
|
<0.001
|
3.0 mg/dL 2.5 mg/dL
|
87.1%
54.8%
|
73.4%
90.6%
|
|
Abdominal aort IMT
|
0.834 (0.743–0.925)
|
0.001
|
1.5 mm
1.3 mm
|
80.6%
90.3%
|
89.1%
60.9%
|
DEXA: dual x-ray absorptiometry, IMT: Intima-media thickness
Parameters associated with abdominal aortic intima-media thickness
Correlation analysis was performed between A-IMT and other demographic, clinical and
laboratory parameters ([Table 5]). Linear regression analysis was performed using parameters that correlated significantly
with A-IMT ([Table 5]). Serum and urinary calcium levels, and C-IMT were independently associated with
A-IMT ([Table 5]). The relationship between A-IMT and urinary calcium level is shown in [Fig. 4].
Fig. 4 There was a significant correlation between urine calcium levels and abdominal aortic
intima-media thickness (IMT) in patients with primary hyperparathyroidism.
Table 5 The parameters associated with A-IMT and linear regression analysis for parameters
significantly correlated with A-IMT.
|
Variable
|
Univariate analyze
|
Multivariate analyze
|
|
p
|
r
|
p
|
β
|
|
Age (years)
|
0.010
|
0.264
|
0.177
|
0.148
|
|
Common carotid IMT (mm)
|
<0.001
|
0.473
|
<0.001
|
0.473
|
|
Internal carotid IMT (mm)
|
0.003
|
0.306
|
0.787
|
0.036
|
|
Blood urea nitrogen (mg/dL)
|
0.002
|
0.320
|
0.181
|
0.172
|
|
25-hydroxyvitamine D (ng/ml)
|
0.049
|
0.225
|
0.070
|
0.188
|
|
T scores in DEXA
|
0.046
|
−0.239
|
0.148
|
0.181
|
|
Parathyroid hormone (pg/ml)
|
0.008
|
0.269
|
0.065
|
0.192
|
|
Serum calcium (mg/dL)
|
<0.001
|
0.521
|
0.028
|
0.253
|
|
Urine calcium (mg/24 h)
|
<0.001
|
0.463
|
<0.001
|
0.390
|
IMT: Intima-media thickness, DEXA: dual x-ray absorptiometry * RAdjusted
2=0.433
Discussion
The main result of this study is that A-IMT is found to be significantly higher in
PHPT patients than in control group. Another striking finding is that with symptomatic
PHPT and asymptomatic PHPT who had surgery indications, had increased A-IMT than patients
with asymptomatic PHPT and had no surgery indications. In addition, we found that
serum and urine calcium levels were the most closely related parameters with A-IMT.
There are conflicting results in the literature regarding the increase of C-IMT in
patients with PHPT. C-IMT has been associated with an increase in PHPT patients [3]
[4]
[5]
[6], but especially in studies conducted in recent years, there is information that
there is no IMT increase in PHPT patients [7]
[8]
[9]
[10]
[11]. The most important reason for this is that patients are diagnosed in asymptomatic
or mild hypercalcemia periods of the disease with routine biochemical tests or diagnosed
incidentally, and because asymptomatic patients or patients without osteoporosis or
nephrolithiasis are treated early with medical and surgical treatments [13]
[17]. The reason for the lack of C-IMT increase in some studies may be that the patients
with PHPT may have diagnosed earlier and by early treatment of these patients, high
PTH and calcium levels could not affect IMT severely and for a long time. Furthermore,
in conducted studies, duration and severity of PHPT disease are different, and often
examining only single anatomic region (common or internal carotid IMT) may have caused
these different outcomes.
Abdominal A-IMT is affected by systemic diseases earlier than other vascular regions.
Therefore, A-IMT may be a sign of earlier involvement in PHPT patients. We have not
been able to find any studies investigating the relationship between A-IMT and PHPT
patients in literature. In our study, it was determined that A-IMT was increased without
a C-IMT increase in PHPT patients. We also evaluated patients with mild PHPT as well
as patients who went to surgery due to PHPT in our study. Previous studies of mild
PHPT patients have conflicting findings regarding elevated C-IMT [3]
[4] or non-elevated C-IMT [9]
[11]. In our study, C-IMT was similar to the control group in PHPT patients, but A-IMT
was found to be significantly higher in PHPT patients.
In some of the C-IMT assessments conducted in PHPT patients, C-IMT was found to be
increased in patients with CV risk factors (DM, HL, HT, obesity and smoking) but similar
to the control group in patients without these risk factors [5]
[9]. In very rare cases, there is information that C-IMT may increase even if there
isn’t a CV risk factors [3]
[4]. Patients with risk factors that could affect the IMT were not taken for this reason
and very careful attention was paid to this issue. In patients with PHPT who did not
have CV risk factors, we found that C-IMT value was similar to the control group in
accordance with most studies in the literature. However, this did not apply to A-IMT.
Two biochemical markers are important in PHPT patients for vascular involvement, which
are elevated serum calcium and PTH levels. In studies with IMT increase, these two
parameter increases were associated with IMT increase for physiopathology. However,
the relationship between C-IMT and serum calcium and PTH levels in PHPT patients also
has conflicting results. Some of these studies show a relationship between elevated
serum calcium and PTH levels and C-IMT [18]
[19]
[20]
[21] but there are many conflicting studies on that matter. [3]
[4]
[5]
[7]
[9]
[10]. Increased levels of calcium and PTH levels have been shown to negatively affect
vascular function, especially by impairing vasodilatation and increasing vessel stiffness.
[7]
[8]
[22]. In the study conducted by Lumachi et al. [9], it was reported that there is no relation between serum calcium and PTH levels
and C-IMT and therefore serum calcium level is not correlated with carotid atherosclerosis
development. The study by Luigi et al. [18] showed an independent relationship between urinary calcium level and C-IMT. In our
study, both serum and urinary calcium levels and A-IMT increase were closely and independently
related to each other. PTH levels were associated with A-IMT but this relationship
was not independent. Our study supports the findings of the study conducted by Luigi
et al. In addition, urinary calcium level and A-IMT value in our study was found to
be independent determination of who underwent surgery, as well as serum phosphorus
and PTH levels. These two findings suggested that serum calcium as well as urine calcium
may be important for following PHPT patients.
In the literature, there is no data on abdominal-IMT increase or variability in PHPT
patients, recently, Pep et al. [23], for the first time, found that the frequency and severity of abdominal aortic calcification
with lateral abdominal radiographic thinning in the postmenopausal PHPT patients was
greater in the control group. It was also reported that serum PTH level correlated
with calcification in the same study and this finding could be correlated with CV
risk in PHPT patients. In our study, a different and more objective assessment of
vascular involvement, the abdominal-IMT assessment was performed in the same anatomic
region,and higher A-IMT was detected in PHPT patients, similar to the previous study.
However, in our study, the relationship between increased A-IMT and other CV risk
factors in PHPT patients was not assessed, patients with risk factors were excluded
because they had an effect on the A-IMT value.
In PHPT patients, matrix metallopeptidase-9 is upregulated, and in addition to that,
PTH enhances the genes in fat tissue and inflammation [24]. Chronic hypercalcemia has been shown to stimulate calcium accumulation in the IMT
layer of the artery [19], and increased levels of PTH enhance collagen superimposition and re-organization
in smooth muscle cells [25], in addition to increased production of atherosclerotic parameters from endothelial
cells [26]. These changes lead to an increase in HT and atherosclerotic process in patients
with PHPT. Atherosclerosis begins to develop as fatty streaks in childhood and can
be detected early by sensitive imaging methods [27]. Because atherosclerosis develops first in the distal abdominal aorta, A-IMT measurement
with new high-resolution USG devices in adult patients can be used to detect early
atherosclerosis development [12]. We hypothesized that increased serum calcium and PTH levels in patients with PHPT
may show an earlier increase in abdominal A-IMT than C-IMT, and thus it is maybe more
useful to use A-IMT instead of C-IMT. For this reason, we received A-IMT measurements
from the abdominal aorta of our patients. In our study, histopathological vascular
tissue examination was not carried out, but physiopathologic changes described in
patients with PHPT were clearly explained. An increase in A-IMT in patients with PHPT
is more prominent and significant than an increase in C-IMT. In addition, serum and
urinary calcium levels are closely and independently associated with A-IMT.
There are some important limitations in this study. First of all, the number of patients
gathered for the study is limited. Patients were not followed up and there was no
data about efficacy in the effect of the treatment on the IMT. In addition, since
the presentation of the association of A-IMT in patients with PHPT is the first of
its kind in the literature, it is necessary to support the existing data with a study
with more participants.
In our study only 8 patients has renal stone history, there is no skeletal fragility,
coronary artery disease, stroke, and other advanced stage PHPT organ involvement.
In our study, the reason for the lower renal stone in the PHPT patient group compared
to the previous studies was thought to be due to the relatively younger patient group
without cardiovascular risk factors. Therefore, A-IMT was not evaluated in this group
of patients.Patients with CV risk factors are not included in the study in order to
clearly visualize the effect of PHPT patients on IMT. For this reason, it is necessary
to carry out studies on patients with these risk factors. It has been reported that
CV mortality and morbidity are high in patients with PHPT and high PTH [28]. However, our study did not evaluate the prognosis of the disease.
Conclusions
While C-IMT is not significantly increased in PHPT patients, A-IMT is increased and
A-IMT is more useful than C-IMT in showing vascular organ involvement in relatively
early years of PHPT. A part of the renal USG, a routine examination for nephrolithiasis
in PHPT patients, should be the A-IMT measurement, which is a very close neighbor,
and the A-IMT value should be reported in the conclusion part of the renal USG. Measurement
of A-IMT is a cheap, easy, reproducible and noninvasive parameter that can be used
to detect IMT increase, which is an early finding of vascular involvement in patients
with PHPT .
