Key words acromegaly - colonic polyps - growth hormone (GH) - colonoscopy - insulin-like growth
factor-1(IGF-1)
Introduction
Acromegaly is a chronic endocrine and metabolic disease accompanied by excessive
secretion of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) by
GH-secreting pituitary adenoma (GHPA) [1 ]
[2 ]. The increased mortality rate in acromegaly
results from cardiovascular and cerebrovascular diseases, respiratory complications,
and neoplastic complications such as colorectal cancer [3 ]
[4 ].
Colonic polyps and diverticula are typical digestive complications in acromegaly.
The
significantly increased risk of colonic polyps in patients with acromegaly compared
with the general population is well recognized [5 ]. The prevalence of colonic polyps in patients with acromegaly is
reported over a wide range from 7 to 76% [6 ]
[7 ]
[8 ]
[9 ],
while there is still a lack of epidemiological data from China. Most colorectal
cancers derive from an “adenomatous polyp-carcinoma sequence,” and
the process generally takes 10–15 years [10 ]. However, according to the current findings, the occurrence of
colorectal cancer in patients with acromegaly remains controversial. A nationwide
survey in Italy reported an overall standardized incidence ratio (SIR) for
colorectal cancer of 1.67 (95% CI: 1.07–2.58) [11 ]
[12 ].
At the same time, some population-based studies did not identify any significant
risk of colorectal cancer [13 ]. In patients
with acromegaly, a better understanding of digestive diseases, especially colonic
polyp developments, is critical for the early diagnosis of colorectal cancer and
associated clinical intervention.
To gain insights into the clinical characteristics and the associated factors of
colonic polyps in acromegaly, we collected and retrospectively analyzed the clinical
data of 86 patients with acromegaly who underwent a colonoscopy diagnosis at our
center. We also analyzed the prevalence, number, size, and site distribution of
colonic polyps and other clinical indicators and identified the associated risk
factors of colonic polyps in patients with acromegaly.
Materials and Methods
Patients
We retrospectively collected data of 181 patients with acromegaly followed at the
Second Affiliated Army Medical University (Xinqiao Hospital) from August 2015 to
July 2020. From these, we excluded 90 patients who did not undergo a colonoscopy
due to personal reasons or had no endoscopic data and five patients who
underwent a colonoscopy at other hospitals. Finally, 86 patients (44 males and
42 females) who underwent a colonoscopy at diagnosis were included in this
study. Acromegaly was diagnosed according to the criteria available at the time
of diagnosis as follows [14 ]
[15 ]: 1) evidence of clinical signs and
symptoms of the disease, 2) serum insulin-like growth factor I (IGF-I) levels
beyond the normal range for age- and sex-matched control individuals, and
elevated baseline growth hormone (GH) level, 3) maximally suppressed GH levels
(GHnadir) during a 75-g oral glucose load test (OGTT) were
>1 µg/L, and 4) evidence of a pituitary tumor on
imaging. No patient had a family history of colon cancer.
This study was approved by the Medical Ethics Committee of the Second Affiliated
Hospital of Army Medical University (No. 2021–035–01) and
registered in the Chinese Clinical Trial Registry (No. ChiCTR-1800017714). All
the participants provided written informed consent.
Data collection
Clinical data, including age, sex, height, weight, body mass index (BMI),
histological results, site distribution, size, and the number of polyps, were
collected. Blood samples were obtained after overnight fasting. Glucose
metabolic profiles were determined, including fasting blood glucose (FBG) and
glycosylated hemoglobin A1c (HbA1c) levels. The automatic biochemical analyzer
measured the creatinine (CREA) level, estimated the glomerular filtration rate
(EGFR), and measured the levels of uric acid (UA), urea, cholesterol (TC),
triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density
lipoprotein cholesterol (LDL-C). GH and IGF-1 levels were quantified by
chemiluminescent immunoassays. The outcome of the IGF-1 assay in each patient
was represented by the IGF-1 index (IGF-1×ULN): serum
IGF-1/upper limit of IGF-I for that age [9 ]. Each patient consumed a 75-g glucose beverage in 5 min, and blood
samples were collected before the start of the test (0 min) and 30, 60, 90, 120,
and 180 min after glucose intake. GHnadir levels during OGTT corresponded to
maximally suppressed GH levels during the 180 min-OGTT. The pituitary was imaged
with a 3T magnetic resonance imaging scanner with or without gadolinium-
diethylenetriamine pentaacetic acid (1.0 mmol/kg). The
anteroposterior diameter (AD), vertical diameter (VD), and transverse diameter
(TD), as well as the Knosp classifications of the GHPA, were evaluated by two
experienced radiologists using precision calipers. The GHPA volume was
calculated using the formula for approximating the volume of an ellipsoid:
π/6 × AD× VD × TD [16 ].
Experienced gastroenterologists performed colonoscopies in acromegalic patients
after careful bowel preparation with a 2 L dose of polyethylene glycol
electrolyte-based solution (Shenzhen Wanhe Pharmaceutical Co., Ltd., Shenzhen,
China). All colonic polyps on colonoscopy were recorded and, if possible,
removed for histological examination. Age was divided into four groups with a
categorical variable as ≤39, 40–49, 50–59, and
≥60 years. The site distribution of polyps was defined as the right
colon (the cecum, ascending colon, and hepatic flexure), the left colon (the
splenic flexure, descending colon, sigmoid colon, and rectum), and the whole
colon (both the right colon and the left colon) [10 ]. All colonic polyps detected at colonoscopy were grouped
according to size (≤0.5, 0.6–0.9, and ≥1.0 cm)
depending on endoscopic measurement by the diameter of open biopsy forceps [17 ]. The number of polyps was divided into
a categorical variable (single or multiple (≥2)).
Statistical analysis
Analyses were conducted by R studio (version 1.3.1093). The Shapiro-Wilk W test
verified the normality of the variable distribution; variable distribution was
considered normal if P ≥0.05. According to the distribution,
variables were described either as means±standard deviation or medians
with interquartile ranges. For normally distributed variables, we used an
independent samples t -test to compare variables between two groups,
whereas one-way ANOVA, followed by Tukey’s multiple comparison test, was
used to compare variables among three or more groups. For non-normally
distributed variables, the Mann-Whitney U test was used to compare variables
between two groups, whereas the Kruskal-Wallis test, followed by pairwise
comparisons using the best-worst scaling all-pairs test, was used for multiple
subgroups. The relationships between variables were examined using
Spearman’s correlation analysis. Univariate and multivariate logistic
regression analyses were performed to assess the associations of the variables
with the diagnosis. A nomogram was created using the predictors from the
multivariate analysis to relate the risk of polyp occurrence. The tests were
considered statistically significant at P <0.05.
Results
Clinical features of acromegalic patients with colonic polyps
A total of 86 acromegalic patients (mean age, 43.53±11.78 years; sex,
48.8% females) who underwent complete colonoscopy at our hospitals were
included in this study. Of the 86 patients, 35 (18 females, 17 males) had one or
more polyps, with a higher prevalence (40.7%) than a general Asian
population (17.6–23.9%) of comparable age [17 ]
[18 ]
[19 ]
[20 ]. The prevalence of polyps increased
with age, reaching a peak at ≥60 years. The prevalence rates of polyps
in acromegalic patients aged ≤39, 40–49, 50–59, and
≥60 years were 30, 32, 50, and 77.8%, respectively ([Fig. 1 ]). Of the 35 patients, 13 (37.2
%) and 22 (62.8%) had a single polyp and multiple polyps,
respectively. The mean diameter of the polyps in most cases was ≤5 mm
(71.4%), and the maximum diameter was ≥10 mm. With respect to
the distributions of colonic polyps at different sites, four (11.4%)
patients had polyps in the right colon, 19 (54.3%) had polyps in the
left colon, and 12 (34.3%) had polyps in the whole colon. Colonic polyps
were more frequently detected in the sigmoid colon and rectum. In addition, only
five cases of colonic polyps were examined by biopsy, and all of them were
histologically confirmed to be adenomas. Furthermore, 21 patients had
hemorrhoids, and one had chronic colitis. No patient had colorectal carcinoma
([Table 1 ]).
Fig. 1 Association between age (years) and prevalence of polyps
(%). Age was parsed into a categorical variable with four
groups: ≤39, 40–49, 50–59, and ≥60
years. Prevalence (%) of polyposis is presented according to
Renehan et al. [30 ], Matano et al.
[42 ], Yamamoto et al. [43 ], and this study.
Table 1 Clinical characteristics of the study patients with
acromegaly.
Total number of patients (n=86)
Patients without polyps (n=51)
Patients with polyps (n=35)
P- value
Age (years)
43.53±11.78
40.63±11.58
47.77±10.88
0.005*
Sex, female, n (%)
42 (49)
24 (47)
18 (51)
0.858
BMI (Kg/m2)
26.1±3.05
25.96±3.05
26.31±3.09
0.602
GHPA Volumes (cm³)
2.47 (1.15, 6.44)
2.2 (1.17, 4.87)
3.19 (1.15, 7.31)
0.305
Basal GH levels (µg/L)
18.3 (8.08, 34.5)
17.8 (5.94, 29.8)
19.3 (9.7, 52.5)
0.153
GHnadir levels during OGTT (µg/L)
12.1 (5.24, 30.9)
12 (4.41, 25.2)
13 (6.54, 40.85)
0.18
Basal IGF-1 levels (ng/mL)
762.56±259.66
733.73±259.89
804.57 ±2 57.24
0.215
IGF-1×ULN
2.53 (1.94, 3.01)
2.22 (1.79, 2.88)
2.73 (2.1, 3.2)
0.03*
FBG (mmol/L)
5.07 (4.4, 5.96)
4.95 (4.38, 5.82)
5.33 (4.54, 6.29)
0.34
Hemorrhoids, n (%)
21(24)
7(20)
14(27)
0.403
Hypertension, n (%)
24 (28)
15 (29)
9 (26)
0.896
Diabetes mellitus, n (%)
0.708
normal
25 (29)
14 (27)
11 (31)
IGT
39 (45)
25 (49)
14 (40)
DM
22 (26)
12 (24)
10 (29)
Data are shown as mean±standard deviation for variables of normal
distribution and median with the interquartile range
(25–75%) for skewed variables. BMI: body mass index;
GHPA Volumes: growth hormone (GH)-secreting pituitary adenoma volumes;
GH: growth hormone; GHnadir levels during OGTT: the maximal suppression
of GH levels during 180-OGTT; IGF-1: insulin-like growth factor-1; ULN:
upper limit of normal; IGT: impaired glucose tolerance; DM: diabetes
mellitus. P value for patients without polyps vs. patients with
polyps, *P <0.05
At diagnosis, 79 (92%) patients had pituitary macroadenoma, 3
(3%) patients had pituitary microadenoma, and 4 (5%) patients
had no data on the pituitary tumor diameter. Hypertension and impaired glucose
metabolism (diabetes mellitus and impaired glucose tolerance) were separately
diagnosed in 24 (28%) and 47 (55%) patients ([Table 1 ]).
Characteristics of colonic polyps associated with hormone levels
Patients with acromegaly and having colonic polyps were older and had higher
insulin-like growth factor-1 × upper limit of normal (IGF-1×ULN)
levels than those without colonic polyps (P =0.005 and
P =0.03, respectively, [Table
1 ]). No significant differences were found between acromegaly patients
with or without colonic polyps regarding sex, BMI, FBG levels, dyslipidemia,
hypertension, diabetes mellitus, GHPA volumes, Knosp classifications, UA levels,
GH levels, GHnadir levels during OGTT, and IGF-1 levels ([Table 1 ] and Supplementary Table
1 ). Although GH and GHnadir levels during OGTT were similar in acromegaly
patients with or without colonic polyps, GHPA volumes and IGF-1 levels tended to
be higher in those with polyps, but the differences between the two groups were
not statistically significant ([Table
1 ]). As shown in [Table 2 ], with
respect to the distribution of polyps at different sites, GH levels and GHnadir
levels during OGTT in patients with polyps in the right colon were higher than
in those with polyps in the whole colon and the left colon. Interestingly,
compared with polyp diameters >5 mm, GH levels were
significantly higher in patients with polyp diameters ≤5 mm
(P =0.031, [Table 2 ]).
Apart from the BMI (P =0.013), we did not identify relevant
clinical indicators between the two groups with single polyps and multiple
polyps ([Table 2 ]). GHPA volumes, IGF-1
levels, and IGF-1× ULN levels were similar among subjects with
distribution at different sites, sizes, and the number of polyps.
Table 2 Clinical characteristics of acromegalic patients with
polyps.
The site distribution of polyps
a
The size of polyps
The number of polyps
Right colon (n=4)
Left colon (n=19)
Whole colon (n=12)
≤5 mm (n=25)
>5 mm (n=10)
P value
Single polyp (n=13)
Multiple polyps (n=22)
P- value
Age (years)
49.25±13
44.58±10.47
52.33±9.95
47±11.43
49.7±9.62
0.486
43.23±11.73
50.45±9.62
0.056
Sex (Female), n (%)
4 (100)
8 (42)
6 (50)
13 (52)
5 (50)
1
7 (54)
11 (50)
1
BMI (kg/m2)
27.09±3.74
26.19±3.56
26.24±2.19
25.95±3.42
27.2±1.91
0.182
24.66±3.25
27.28±2.6
0.013*
GHPA volumes (cm³)
4.83 (3.55, 5.88)
3.48 (1.3, 12.63)
1.83 (0.96, 6.91)
3.48 (1.25, 6.75)
2.22 (0.54, 8.81)
0.615
3.59 (1.81, 7.46)
2.95 (1.05, 6.86)
0.366
Basal GH levels (µg/L)
127.5 (70.33, 189.5)
17 (13.05, 33.95)
11.95 (7.8, 33.08)
26.6 (14.5, 61.4)
9.7 (8.08, 19.1)
0.031*
35.3 (14, 82)
16.45 (8.2, 27.57)
0.142
GHnadir levels during OGTT (µg/L)
73.9 (44.7, 111.1)
12.4 (8.59, 37.2)
8.75 (5.02, 24.25)
21.2 (8.76, 48)
8.7 (4.52, 12.32)
0.05
21.2 (10.3, 48)
11.25 (4.43, 28.23)
0.124
Basal IGF-1 (ng/mL)
731.75±261.15
869±267.81
726.83±229.95
802.56±271.42
809.6±231.27
0.939
808.54±247.11
802.23±268.75
0.945
IGF-1×ULN
2.92 (1.84, 3.93)
2.83 (2.22, 3.2)
2.59 (2.36, 2.97)
2.84±1.05
2.94±0.85
0.773
2.72 (2.08, 3.16)
2.78 (2.42, 3.22)
0.585
Hypertension, n (%)
1 (25)
1 (5)
7 (58)
6 (24)
3 (30)
0.694
1 (8)
8 (36)
0.109
DM, n (%)
0.33
0.455
normal
0 (0)
11 (58)
3 (25)
12 (48)
2 (20)
6 (46)
8 (36)
IGT
0 (0)
6 (32)
4 (33)
6 (24)
4 (40)
2 (15)
8 (36)
DM
4 (100)
2 (11)
5 (42)
7 (28)
4 (40)
5 (38)
6 (27)
Data are shown as mean±SD for variables of normal distribution
and median with the interquartile range (25–75%) for
skewed variables. BMI: body mass index; GHPA volumes: growth hormone
(GH)-secreting pituitary adenoma volumes; GH: growth hormone; GHnadir
levels during OGTT: the maximal suppression of GH levels during
180-OGTT; IGF-1: insulin-like growth factor-1; ULN: upper limit of
normal; DM: diabetes mellitus; IGT: impaired glucose tolerance; SD:
standard deviation. a: Considering only four patients with polyps in the
right colon may lead to unreliable statistical results, we only made
statistical description in the site distribution of polyps subgroups.
*: P<0.05.
In addition, hypertension and diabetes mellitus maybe have an association with
the distribution of polyps at different sites ([Table 2 ]). However, FBG and HbA1c levels did not differ with respect
to the three different site of the distribution of polyps (Supplementary
Table 2 ). Next, to investigate the effect of IGF-1×ULN in
acromegaly patients with polyps, we further divided the subjects into
IGF-1×ULN-quantile subgroups (Q1 to Q4) according to the
IGF-1×ULN level (Supplementary Table 3 ). Age, GH levels, and
GHnadir levels during OGTT were significantly higher in acromegaly patients with
the highest IGF-1×ULN levels than those with the lowest
IGF-1×ULN levels in the first quantile (P <0.05 for Q1 vs.
Q4). Compared to patients with lower IGF-1×ULN levels in the second
quantile, UA levels were significantly higher in patients with the highest
IGF-1×ULN levels (P <0.05 for Q2 vs. Q4). Notably, the
IGF-1×ULN-quartile subgroups differed with respect to acromegaly
patients with or without colonic polyps, GHPA volumes groups, and IGF-1 levels
(P <0.05, Supplementary Table 3 ).
Prognostic model for colonic polyps in acromegaly patients
In univariate analysis of acromegaly patients, age, especially 60 years and
older, and the IGF-1×ULN level could predict polyp occurrence, as shown
in Table 4. Furthermore, in multivariate analysis, these variables showed that
GHPA volumes (OR: 1.09, 95% CI: 1.01–1.20;
P =0.039) and IGF-1×ULN Q2 levels (OR: 6.51, 95%
CI: 1.20–44.60; P =0.038) were independently associated
with polyp occurrence ([Table 3 ]).
IGF-1×ULN Q3 and IGF-1×ULN Q4 cloud also are independent risk
predictors, although no significant difference was found. Thus, univariate and
multivariate analyses revealed that GHPA volumes and IGF-1×ULN levels
could be independent risk factors for polyps in acromegaly patients. In
addition, a nomogram for predicting acromegalic patients with polyp risk was
constructed using the variables ([Fig.
2 ]). According to the prognostic model, for evaluating the risk of colonic
polyps, a woman with a GHPA volume of 3.0 cm³ and an IGF-1×ULN
level of 3.5 was predicted to have an 85% probability of polyps.
Fig. 2 Constructed colonic polyp incidence risk nomogram. The
colonic polyp risk was constructed with the features, including GHPA
volume and IGF-1× ULN. GHPA volume: growth hormone
(GH)-secreting pituitary adenoma volume; IGF-1: insulin-like growth
factor-1; ULN: upper limit of normal. For example, a woman had a GHPA
volume of 3.0 cm3 and an IGF-1×ULN level of 3.5. To
use the nomogram, the points are located on each variable axis (GHPA
volume axis and IGF-1×ULN level axis) and draw the red line
vertically up to the Points axis to determine the corresponding points
for each variable. The point for GHPA volume points was 65, and the
IGF-1×ULN level was 50. The sum (115) of these points (GHPA
volume points and IGF-1×ULN level points) is located on the
Total Points axis, and a red dotted line is drawn downward to the polyp
risk prediction axis to determine the possibility of having polyps,
which was approximately 85% in this case.
Table 3 Univariate and multivariable logistic regression
analysis of associations between clinical and biochemical variables
and polyps in patients with acromegaly.
Univariate analysis
Multivariate analysis
OR (CI 95%)
P- value
OR (CI 95%)
P- value
Age
1.06 (1.02, 1.11)
0.007
1.05 (0.99, 1.12)
0.11
sex
1.19 (0.50, 2.84)
0.691
–
–
Height
0.02 (0.00, 2.03)
0.102
0.03 (0.00, 16.03)
0.286
Weights
0.98 (0.94, 1.02)
0.397
–
–
BMI
1.04 (0.90, 1.20)
0.597
–
–
GHPA volumes
1.06 (0.99, 1.15)
0.136
1.09 (1.01, 1.20)
0.039
Basal GH levels
1.00 (1.00, 1.01)
0.278
–
–
GHnadir levels during OGTT
1.00 (1.00, 1.01)
0.22
–
–
Basal IGF-1 levels
1.00 (1.00, 1.00)
0.216
–
–
IGF-1×ULN
1.65 (1.04, 2.75)
0.04
1.47 (0.88, 2.55)
0.151
FBG
1.07 (0.86, 1.34)
0.548
–
–
TG
0.84 (0.50, 1.10)
0.394
–
–
TC
0.77 (0.49, 1.10)
0.21
–
–
HDL
1.96 (0.33, 12.46)
0.459
–
–
LDL
0.89 (0.47, 1.64)
0.71
–
–
UA
1.00 (1.00, 1.01)
0.702
–
–
Age groups
0.011
≤39
1
1
40–50
1.10 (0.34, 3.48)
0.873
–
–
50–60
2.33 (0.75, 7.53)
0.147
–
–
>60
8.17 (1.61, 62.58)
0.019
–
–
IGF-1×ULN quartile
0.015
Q1
1
1
Q2
5.45 (1.34, 28.54)
0.026
6.51 (1.20, 44.60)
0.038
Q3
5.00 (1.24, 25.93)
0.033
5.82 (0.71, 55.33)
0.106
Q4
7.20 (1.80, 37.50)
0.009
10.52 (0.42, 300.62)
0.152
OR, odd ratio; CI, confidence interval. BMI: body mass index; GHPA
volumes: growth hormone (GH)-secreting pituitary adenoma volumes; GH:
growth hormone; GHnadir levels during OGTT: the maximal suppression of
GH levels during 180-OGTT; FBG: fasting blood glucose; IGF-1:
insulin-like growth factor-1; ULN: upper limit of normal; OGTT: oral
glucose tolerance test; TG: triglycerides; TC: total cholesterol; LDL:
low-density lipoprotein cholesterol; HDL: high-density lipoprotein
cholesterol; UA: uric acid; SD: standard deviation.
Discussion
Several population-based studies have indicated a 0.9 to 2.4% incidence of
colon cancer in patients with acromegaly [12 ]
[21 ]
[22 ]. However, the risk of colon cancer in
acromegaly is still controversial. Colonoscopy screening for early detection can
reduce mortality due to colorectal cancer by the removal of pre-existing adenomatous
polyps. In this study, we ascertained a high prevalence of colonic polyps of
40.7% in acromegalic patients. IGF-1×ULN levels were higher in
patients with polyps than in those without polyps. GHPA volumes and
IGF-1×ULN levels were independent risk factors for polyps.
Colonic polyps have a high prevalence in acromegaly patients; the overall prevalence
of colonic polyps in this study was 40.7%. The prevalence of colonic polyps
in the acromegaly population is significantly higher than in the general Asian
population. In the non-acromegaly population, the prevalence of polyps ranged from
17.6 to 23.9% [17 ]
[18 ]
[19 ]
[20 ]. The prevalence of colonic
polyps also varies in different acromegalic populations. One of the largest datasets
from 14 centers across Europe indicated a 13% prevalence of polyps in a
fourth of acromegaly patients (820/3173) who had a colonoscopy [23 ]. Furthermore, the prevalence of polyps in
patients with acromegaly was 32% in an Italian single-center study [24 ]. In contrast, the French national registry
data reported that the prevalence of colonic polyps ranged from 27% to
55% [22 ]. The different prevalence of
colonic polyps in populations may be because of differences in genetic
predisposition, environmental backgrounds, and lifestyle (including dietary habits).
In our study, the prevalence of multiple polyps was 62.8% compared to
earlier reports by Bogazzi (50%) [9 ]
and Colao (72.1%) [8 ]. A colonic polyp
diameter >10 mm is generally considered a high risk of colorectal
carcinoma and is thought to take more than ten years to develop. A recent study
reported a frequency of 15.2% for polyps ≥10 mm, and five
patients were detected with colorectal cancer [25 ]. However, in our study, the maximum diameter of colonic polyps was
<10 mm, and most colonic polyps were in their early stages
≤5 mm (71.4%), which may explain why no colorectal cancer
was detected.
We found a significant association between polyp occurrence and hormone levels. In
detail, IGF-1×ULN levels in patients with polyps were higher in than those
without polyps, consistent with previous findings [22 ]. Although GH and GHnadir levels during OGTT were similar in patients
with or without colonic polyps, IGF-1 levels and GHPA volumes tended to be higher
in
those with polyps. Nevertheless, few studies have consistently suggested that IGF-1
levels are significantly related to polyp prevalence [24 ]
[26 ].
This study also indicated that GH and Ghnadir levels during OGTT were higher in
patients with polyps with a diameter ≤5 mm in the right colon.
However, limited by a small amount of data, our results need to be confirmed in a
larger prospective study. As a result, we hypothesize that GH levels may play
different roles in different stages of polyp development. The findings in patients
with acromegaly suggest a higher prevalence of polyps in the left colon, similar to
Battistone et al. [27 ]. In the general
population, the site distribution of polyps was detected mainly in the left colon
[17 ]
[28 ], although several studies also observed polyps in the cecum and the
ascending colon [29 ]
[30 ]
[31 ].
Additionally, the acromegaly patients with multiple polyps had higher BMI than those
with single polyps. Compared to patients without polyps, those with polyps were
older. Simultaneously, the prevalence of colonic polyps increased significantly with
age ≥50 years (>50%). Bogazzi [9 ] and Parolin [24 ] also reported similar trends in polyp prevalence in ≥50 years
old patients. Although the recent guidelines recommend the initiation of colonoscopy
screening at 50 years of age for the average-risk non-acromegaly population [32 ]
[33 ],
this may be inadequate for patients with acromegaly. A few guidelines suggest that
the initial colonoscopy should be performed at the age of 40 years for early
detection of precancerous polyps in acromegaly [31 ]
[34 ]
[35 ]. We observed that several patients younger
than 40 years had colonic polyps. Similarly, Terzolo et al. reported that younger
acromegaly patients had a higher risk of colonic neoplasia than the age-matched
controls [7 ]. Therefore, as per recent
guidelines, colonoscopic surveillance should be performed at the time of diagnosis
of acromegaly [36 ]
[37 ]
[38 ]
[39 ].
GHPA volumes may be a reliable predictor for polyp occurrence in acromegaly.
According to univariate analysis and clinical parameters, the final diagnostic model
was decided using age, height, GHPA volumes, and IGF-1×ULN levels. To our
knowledge, this is the first study to report that GHPA volume (OR: 1.09, 95%
CI: 1.01–1.20; P =0.039) is an independent risk factor for
colonic polyp occurrence. However, GHPA volumes did not differ significantly between
patients with or without polyps. We speculate that the larger GHPA volumes indicate
long-term and uncontrolled secretion of GH and IGF-1, contributing to the higher
risk of polyp occurrence. Meanwhile, we found that the IGF-1×ULN level (OR:
6.51, 95% CI: 1.20–44.60; P =0.038) is a predictor for
polyp occurrence, similar to the results of Gonzalez [26 ]. Therefore, we established a polyp risk
prediction model based on GHPA volumes and IGF-1×ULN levels. For example, a
man with a GHPA volume of 2.0 cm³ and an IGF-1×ULN level of 4.0 has
an approximately 80% probability of polyp occurrence.
In this study, standard intestinal preparation alone resulted in inadequate
intestinal cleansing in most patients with acromegaly, seriously affecting the
detection of colonoscopy (data not shown). Previous studies have suggested two
consecutive bowel preparations or an increased dose of PEG solution for patients
with acromegaly [40 ], with a significantly
prolonged time required to reach the cecum during colonoscopy [41 ].
We acknowledge several limitations in our study. First, this study was conducted on
a
relatively small number of patients, with no control group. Second, this was a
retrospective analysis, and it was not possible to avoid selectivity bias. Third,
most polyps with a diameter >5 mm were not examined by biopsy.
Further long-term prospective studies involving patients with acromegaly may
determine whether colonic polyps have a similar tendency to develop into colon
cancer as in the general population.
In conclusion, we confirmed the high prevalence of colonic polyps in patients with
acromegaly. Older age and multiple polyps, usually occurring in the left colon, were
the clinical features of acromegaly patients with colonic polyps. In addition, GHPA
volumes and IGF-1×ULN levels might predict the occurrence of colonic polyp
in the population with acromegaly.
Ethics Statement: This study was approved by the Medical Ethics Committee of
The Second Affiliated Hospital of Army Medical University.
Informed consent: Informed consent was obtained from all individual
participants included in the study.
Author Contributions
GLP, PH, and YLZ: data acquisition; RFS and LZ: analyzed MRI data; YYZ, JYB, and GLP:
assessed colonoscopy data; GLP, XL, and RFS: statistical analysis of data and
drafted the manuscript; LZ, MYL, YLZ and WXL: interpreted the data, contributed to
the methods, and performed the laboratory analyses; ML, HTZ, and ZS: revised the
manuscript; RFS and ML: obtained the study funding and supervised the study. All
authors read and approved the manuscript for publication.
