J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://www.jocmr.org

Original Article

Volume 16, Number 4, April 2024, pages 155-163

Biliary Tract Disorders and Associated Acute Complications in Patients With Acromegaly: A Single-Center Study

Figure 2. Biliary involvement in selected patients with acromegaly. BDs: biliary disorders; SAs: somatostatin analogs; LFU: lost to follow-up; GS: gallstone; DBD: dilation of the bile duct.

Figure 3. Dilation of common bile duct without the presence of obstruction on EUS. EUS: endoscopic ultrasonography.

Figure 4. ERCP showing choledochal lithiasis with dilation of common bile duct. ERCP: endoscopic retrograde cholangiopancreatography.

**Table 1.** Demographic, Clinical, Biochemical, and Imaging Characteristics of the Studied Population (n = 26)
Parameters	N (%)
BMI: body mass index; BP: blood pressure; GH: growth hormone; HbA1c: glycated hemoglobin; HDL-C: high-density lipoprotein-cholesterol; IGF-1: insulin-like growth factor 1; LDL-C: low-density lipoprotein-cholesterol; N: number of patients; TG: triglycerides. Limit ranges of IGF-1 level: 22 - 25 years: 105 - 311 ng/mL, 26 - 30 years: 98 - 290 ng/mL, 31 - 35 years: 87 - 278 ng/mL, 36 - 40 years: 80 - 271 ng/mL, 41 - 45 years: 75 - 249 ng/mL, 46 - 50 years: 64 - 236 ng/mL, 51 - 55 years: 55 - 234 ng/mL, 56 - 60 years: 48 - 241 ng/mL, 66 - 70 years: 32 - 226 ng/mL, 71 - 75 years: 24 - 218 ng/mL. GH levels were analyzed based on international limits: < 1.2 mIU/L.
Mean age at diagnosis of acromegaly (years)	49.6 ± 14
Sex distribution
Female	14 (53.8)
Male	12 (46.2)
Mean IGF-1 levels (ng/mL)	708 ± 252
Mean GH levels (mIU/L)	53 ± 83
Surgery	19 (73)
Medical treatment	16 (61.5)
Radiotherapy	3 (11.5)
Pituitary adenoma size
Macroadenoma	22 (84.6)
Microadenoma	4 (15.4)
BMI (kg/m²)	28.42 ± 3.7
Height	173.4 ± 13.3
BP
Systolic BP	130 ± 13.3
Diastolic BP	69 ± 7.4
Mean HbA1c	6.8 ± 1.3
TG	1.41 ± 0.63
LDL-C	1.12 ± 0.28
HDL-C	0.4 ± 0.14

Table 1. Demographic, Clinical, Biochemical, and Imaging Characteristics of the Studied Population (n = 26)

Parameters

N (%)

BMI: body mass index; BP: blood pressure; GH: growth hormone; HbA1c: glycated hemoglobin; HDL-C: high-density lipoprotein-cholesterol; IGF-1: insulin-like growth factor 1; LDL-C: low-density lipoprotein-cholesterol; N: number of patients; TG: triglycerides. Limit ranges of IGF-1 level: 22 - 25 years: 105 - 311 ng/mL, 26 - 30 years: 98 - 290 ng/mL, 31 - 35 years: 87 - 278 ng/mL, 36 - 40 years: 80 - 271 ng/mL, 41 - 45 years: 75 - 249 ng/mL, 46 - 50 years: 64 - 236 ng/mL, 51 - 55 years: 55 - 234 ng/mL, 56 - 60 years: 48 - 241 ng/mL, 66 - 70 years: 32 - 226 ng/mL, 71 - 75 years: 24 - 218 ng/mL. GH levels were analyzed based on international limits: < 1.2 mIU/L.

Mean age at diagnosis of acromegaly (years)

49.6 ± 14

Sex distribution

Female

14 (53.8)

Male

12 (46.2)

Mean IGF-1 levels (ng/mL)

708 ± 252

Mean GH levels (mIU/L)

53 ± 83

Surgery

19 (73)

Medical treatment

16 (61.5)

Radiotherapy

3 (11.5)

Pituitary adenoma size

Macroadenoma

22 (84.6)

Microadenoma

4 (15.4)

BMI (kg/m²)

28.42 ± 3.7

Height

173.4 ± 13.3

Systolic BP

130 ± 13.3

Diastolic BP

69 ± 7.4

Mean HbA1c

6.8 ± 1.3

1.41 ± 0.63

LDL-C

1.12 ± 0.28

HDL-C

0.4 ± 0.14

**Table 2.** Prevalence of Biliary Disorder at the Diagnosis of Acromegaly (n = 26) and During the Follow-Up (n = 19)
Parameters	N	%
GS: gallstone; N: number of patients.
Prevalence of dilation of bile duct
At diagnosis of acromegaly	5/26	19.2
After lanreotide treatment	1/16	6.2
Prevalence of GS at acromegaly diagnosis	2	7.7
Prevalence of GS after lanreotide treatment	3	18.7
Prevalence of gallbladder sludge after lanreotide treatment	2	12.5
Duration treatment at the onset of diagnosis of GS/sludge (months)	45	-

Table 2. Prevalence of Biliary Disorder at the Diagnosis of Acromegaly (n = 26) and During the Follow-Up (n = 19)

Parameters

GS: gallstone; N: number of patients.

Prevalence of dilation of bile duct

At diagnosis of acromegaly

5/26

19.2

After lanreotide treatment

1/16

6.2

Prevalence of GS at acromegaly diagnosis

7.7

Prevalence of GS after lanreotide treatment

18.7

Prevalence of gallbladder sludge after lanreotide treatment

12.5

Duration treatment at the onset of diagnosis of GS/sludge (months)

**Table 3.** Clinical, Biological, and Imaging Presentation of Cases With Acute Biliary Complications
	Case 1	Case 2	Case 3	Case 4
AC: acute complication; BMI: body mass index; CBD: common bile duct; CT: computed tomography; DB: direct bilirubin; ERCP: endoscopic retrograde cholangiopancreatography; EUS: endoscopic ultrasonography; GB: gallbladder; GGT: gamma-glutamyl transferase; GS: gallstone; IGF-1: insulin-like growth factor 1; MD: metabolic disorder; MRI: magnetic resonance imaging; NR: normal range; SA: somatostatin analog; TB: total bilirubin; ULN: upper limit of normal; US: ultrasound.
Age (years)	68	66	68	44
History of MD	Diabetes mellitus and hypertension	Diabetes mellitus	Diabetes mellitus and hypertension	None
BMI (kg/m²)	25.3	23	30	24
IGF-1 at diagnosis (ng/mL)	795	774	672	1,500
IGF-1 at the occurrence of AC (ng/mL)	389.9 (ULN: 1.9)	369 (ULN: 1.6)	299 (ULN: 1.3)	164 (NR)
Disease duration at the onset of the first symptoms (years)	24	21	19	7
The occurrence of cholelithiasis	After SA treatment	After SA treatment	Cholelithiasis at the diagnosis of acromegaly and before SA treatment	After SA treatment
AC-related symptoms	Sub jaundice, biliary colic	Atypical epigastralgia	Sub jaundice, biliary colic	Acute abdominal pain
Hepatic cytolysis	No	No	Yes	No
Biological cholestasis	TB: 24 mg/L; DB: 15 mg/L; GGT: 856 U/L	TB: 8 mg/L; DB: 3 mg/L; GGT: 36 U/L	TB: 117 mg/L; DB: 86 mg/L; GGT: 1,499 mg/L	TB: 35 mg/L; DB: 11 mg/L; GGT: 181 mg/L
Pancreatitis	No	No	No	No
Duration of treatment discontinuation before AC event	2 years	5 months	5 months	Occurrence of AC during SA treatment
Abdominal US	Microlithiasis of the GB; dilation of CBD (16 mm)	Dilation of CBD (13 mm)	Dilation of the bile ducts (12 mm)	Cholecystitis associated with biliary peritonitis (confirmed on abdominal CT scan)
Biliary MRI	-	Not made because of a metal hip prosthesis	Dilation of bile duct (13 mm)	-
EUS	-	Dilation of CBD (12 mm) with sludge and microlithiasis; microlithiasis of the GB	Dilation of CBD (14 mm); microlithiasis of the GB	-
ERCP	Choledochal lithiasis (Fig. 4); dilation of CBD (20 mm); GS; endoscopic biliary drainage with stone extraction	Dilation of the bile ducts with lithiasis in CBD; endoscopic biliary drainage	Dilation of the bile ducts (17 mm); endoscopic biliary drainage	-

Table 3. Clinical, Biological, and Imaging Presentation of Cases With Acute Biliary Complications

Case 1

Case 2

Case 3

Case 4

AC: acute complication; BMI: body mass index; CBD: common bile duct; CT: computed tomography; DB: direct bilirubin; ERCP: endoscopic retrograde cholangiopancreatography; EUS: endoscopic ultrasonography; GB: gallbladder; GGT: gamma-glutamyl transferase; GS: gallstone; IGF-1: insulin-like growth factor 1; MD: metabolic disorder; MRI: magnetic resonance imaging; NR: normal range; SA: somatostatin analog; TB: total bilirubin; ULN: upper limit of normal; US: ultrasound.

Age (years)

History of MD

Diabetes mellitus and hypertension

Diabetes mellitus

Diabetes mellitus and hypertension

None

BMI (kg/m²)

25.3

IGF-1 at diagnosis (ng/mL)

795

774

672

1,500

IGF-1 at the occurrence of AC (ng/mL)

389.9 (ULN: 1.9)

369 (ULN: 1.6)

299 (ULN: 1.3)

164 (NR)

Disease duration at the onset of the first symptoms (years)

The occurrence of cholelithiasis

After SA treatment

Cholelithiasis at the diagnosis of acromegaly and before SA treatment

After SA treatment

AC-related symptoms

Sub jaundice, biliary colic

Atypical epigastralgia

Sub jaundice, biliary colic

Acute abdominal pain

Hepatic cytolysis

Yes

Biological cholestasis

TB: 24 mg/L; DB: 15 mg/L; GGT: 856 U/L

TB: 8 mg/L; DB: 3 mg/L; GGT: 36 U/L

TB: 117 mg/L; DB: 86 mg/L; GGT: 1,499 mg/L

TB: 35 mg/L; DB: 11 mg/L; GGT: 181 mg/L

Pancreatitis

Duration of treatment discontinuation before AC event

2 years

5 months

Occurrence of AC during SA treatment

Abdominal US

Microlithiasis of the GB; dilation of CBD (16 mm)

Dilation of CBD (13 mm)

Dilation of the bile ducts (12 mm)

Cholecystitis associated with biliary peritonitis (confirmed on abdominal CT scan)

Biliary MRI

Not made because of a metal hip prosthesis

Dilation of bile duct (13 mm)

EUS

Dilation of CBD (12 mm) with sludge and microlithiasis; microlithiasis of the GB

Dilation of CBD (14 mm); microlithiasis of the GB

ERCP

Choledochal lithiasis (Fig. 4); dilation of CBD (20 mm); GS; endoscopic biliary drainage with stone extraction

Dilation of the bile ducts with lithiasis in CBD; endoscopic biliary drainage

Dilation of the bile ducts (17 mm); endoscopic biliary drainage

**Table 4.** Associated Factors to Biliary Abnormalities Occurrence in Patients With Acromegaly
Studied parameters	P-value (r)
^aDilation of the bile duct without detected obstruction on abdominal US, MRI, EUS. *Statistically significant values (P < 0.05). The r represents the Pearson correlation coefficient. BMI: body mass index; GH: growth hormone; IGF-1: insulin-like growth factor 1.
Age ≥ 50 years	0.48 (r = 0.28)	0.64 (r = 0.128)	0.16 (r = 0.35)
Sex	0.48 (r = 0.28)	0.64 (r = 0.128)	0.015 (r = 0.54)*
BMI	0.67 (r = -0.093)	0.5 (r = -0.18)	0.7 (r = -0.17)
Disease duration	0.06 (r = 0.003)	0.5 (r = 0.15)	0.014 (r = 0.3)*
Postoperative IGF-1 levels	-	0.38 (r = -0.28)	-
Preoperative IGF-1 levels	0.84 (r = -0.071)	0.041 (r = 0.429)*	0.038 (r = 0.23)*
Preoperative GH levels	1 (r = -0.131)	0.63 (r = 0.54)	0.44 (r = -0.39)
Preoperative adenoma volume	0.59 (r = -0.12)	0.41 (r = 0.219)	0.34 (r = -0.216)
Dyslipidemia	0.017 (r = 0.47)*	0.018 (r = 0.48)*	0.18 (r = 0.34)
Diabetes	1 (r = -0.012)	0.155 (r = -0.339)	0.37 (r = -0.21)
Lanreotide treatment duration > 2 years	-	0.005 (r = 0.7)*	-

Table 4. Associated Factors to Biliary Abnormalities Occurrence in Patients With Acromegaly

Studied parameters

P-value (r)

Cholelithiasis at the time of acromegaly diagnosis

Cholelithiasis after medical treatment

Dilation of the bile ducts^a

^aDilation of the bile duct without detected obstruction on abdominal US, MRI, EUS. *Statistically significant values (P < 0.05). The r represents the Pearson correlation coefficient. BMI: body mass index; GH: growth hormone; IGF-1: insulin-like growth factor 1.

Age ≥ 50 years

0.48 (r = 0.28)

0.64 (r = 0.128)

0.16 (r = 0.35)

Sex

0.48 (r = 0.28)

0.64 (r = 0.128)

0.015 (r = 0.54)*

BMI

0.67 (r = -0.093)

0.5 (r = -0.18)

0.7 (r = -0.17)

Disease duration

0.06 (r = 0.003)

0.5 (r = 0.15)

0.014 (r = 0.3)*

Postoperative IGF-1 levels

0.38 (r = -0.28)

Preoperative IGF-1 levels

0.84 (r = -0.071)

0.041 (r = 0.429)*

0.038 (r = 0.23)*

Preoperative GH levels

1 (r = -0.131)

0.63 (r = 0.54)

0.44 (r = -0.39)

Preoperative adenoma volume

0.59 (r = -0.12)

0.41 (r = 0.219)

0.34 (r = -0.216)

Dyslipidemia

0.017 (r = 0.47)*

0.018 (r = 0.48)*

0.18 (r = 0.34)

Diabetes

1 (r = -0.012)

0.155 (r = -0.339)

0.37 (r = -0.21)

Lanreotide treatment duration > 2 years

0.005 (r = 0.7)*