tom tat tieng anh nghiên cứu biến đổi triệu chứng lâm sàng, hình thái, chức năng tuyến yên ở bệnh nhân u tuyến yên trước và sau điều trị bằng dao gamma quay

1
INTRODUCTION
Pituitary adenomas is a disease that has diversified clinical
symptoms. In 2007, Vietnam began to apply gamma knife
radiotherapy to treat brain tumors including patients with pituitary
tumors, but no reports have been released of the clinical and
subclinical changes after the treatment. In order to answer the above
issues, we conducted a study entitled "Research on the changes of
clinical symptoms, images and pituitary function in patients with
pituitary adenomas before and after treatment with rotating
gamma knife”
Objectives:
1. Describe clinical and sub-clinical characteristics of patients
with pituitary tumors
2. Assessment of clinical and subclinical changes in patients with
pituitary tumors before and after surgery.
Study Rationales:
Pituitary tumors account for 10-15% of intracranial tumors.
Radiographically applied gamma rays converge precisely at the
lesion and should be effective for treatment. Studies to evaluate
morphologic changes and pituitary function before and after
radiotherapy of patients with pituitary tumors are important to
contribute to the indications of the therapy as well as assessment of
radiation complications for treatment of pituitary tumors
New contribution of the Dissertation:
- Established indications in surgical patients who have not taken
all the tumors, recurrence after surgery or medical treatment failures
that can not be surgically removed and the tumor size is <40 mm.
- Evaluated the response time for both radiology and tumor
morphology.
- The study was able to assess the complications after surgery: less

complications, less impact on the surrounding brain organs, ensuring
the goal of preserving brain function.
Dissertation structure:
The dissertation has 121 pages, including: Introduction (2
pages), Chapter 1: Overview (32 pages), Chapter 2: Research
Object and Methods (21 pages), Chapter 3: Results (29 pages) ),
Chapter 4: Discussions (34 pages), Conclusions (2 pages),
Recommendations (1 page).
The dissertation has 120 references (Vietnamese: 17, English: 103).


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Chapter 1: AN OVERVIEW
1.1. Clinical and subclinical clinical manifestations, and
epidemiology of pituitary adenomas
1.1.1. Epidemiology of pituitary adenomas
+ Prevalence
In the United States, about 2500 cases of pituitary tumors are
diagnosed each year. In Western countries, the disease prevalence
was determined in almost all countries. In Vietnam, there are no
epidemiological studies on pituitary tumors
+ Age and Sex
Age: the average is from 38 to 50 years old
Sex: female / male ratio from 1.23 to 2.05.
1.1.2. Diagnosis of pituitary tumors
* Clinical symptoms caused by tumor compression:
- Headache, vomiting or nausea, eye and visual nerve damage
* Clinical symptoms of pituitary tumors associated with
hormone secretion disorders
- Menstrual irregularities, milk secretions, acromegaly, joint pain....

* Diagnosis based on biochemical markers
- Based on the concentration of pituitary hormones: PRL, GH,
TSH, ACTH, FSH, LH...
Magnetic resonance imaging (MRI)
Small pituitary tumor size less than 10mm:
Direct signs
- On T1W: Syndromes are usually expressed by hypointense
signals compared to the normal glandular structure.
- On T2W: isointense compared on normal glandular structure.
Pituitary tumor size more than 10mm:
Usually these tumors invade the pituitary cavity or down to the
sphenoid sinus.
* Histopathological diagnosis
Histopathological diagnosis is only performed when
specimens are collected.
1.3. Treatments for pituitary adenomas
1.3.1. Medical treatment
* Medical treatment of functioning pituitary adenomas
Drug medical treatment is the first choice for PRL, ACTH, GH,


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TSH hormone- released pituitary adenomas, and hypopituitarism
requiring hormone replacement therapy.
* Medical treatment of nonfunctioning pituitary adenomas
In order to rapidly reduce the pressure symptoms, reduce pressure
on visual interference and sinus cave ...
1.3.2. Surgical treatment
- Surgical indication
When tumor localization, neurological symptoms, nasal sphincter

leakage, hormone produced too much, biopsy to diagnose
pathological tissues.
1.3.3. Accelerated radiation therapy
Indications: tumors not elligible for surgery or surgical removal of
tumors is not exhausted, tumor recurrence after surgery, failure after
medical treatment without surgery
- Indications of radiotherapy:
- Malignancy, benign brain tumors and some cerebrovascular
diseasesU ác, u lành sọ não và một số bệnh lý mạch não
- Indications of radiation dose for brain tumors and some brain
diseases
Tumor
Volume of tumor
The largest dose (Gy)
diameter(mm)
(cm³)
12,5- 17,5
1,02- 2,81
24
20,0-27,5
4,19-10,9
18
3,0- 32,5
14,1-18,0
15
Chapter 2
OBJECTIVES AND RESEARCH METHODS
2.1. Research subjects
Study on 73 patients with pituiraty adonemas at the Center for
Nuclear Medicine and Oncology at Bach Mai Hospital, from January

2011 to January 2016.
2.2.1. Inclusion criteria
* Selection criteria
- Patients diagnosed with pituitary adenomas on MTI brain tumor
over 18 years old, tested for pituitary hormone.
- No acute, life-threatening illness
- Acceptance of study participation.


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* Criteria for selection of radiotherapy group
- Tumors not exhaustly removed after surgery
- Failure with medical treatment or relapse after surgery
- Old patients with no indication of intervention and anesthesia
- Patients do not agree to treat with other methods
- One tumor with the largest diameter <50mm, the distance from
the tumor to the visual interference ≥ 3mm
2.2.2. Exclusion criteria
* Exclusion criteria
- Patients do not accept to participate in the study.
- Severe status with non-evaluable clinical symptoms.
- Pregnant women and lactating women.
- Patients are using drugs that affect the results of the study: birth
control pills, corticosteroids, levothyroxine....
- Patients who are not examined and fully tested.
* Criteria for exclusion of radiographic group
- Patients who disagree radiosurgery.
- Severe status with non-evaluable clinical symptoms.
- Pregnant women and lactating women
- Patients are using drugs that affect the results of the study: birth

control pills, corticosteroids, levothyroxine....
- Patients who are not examined and fully tested.
- Patients do not adhere to regular examinations and monitoring.
- Maximum tumor diameter is ≥ 50mm, tumor distance to visual
interference <3mm.
2.2. Research Methods
2.2.1. Research design:
A cross-sectional descriptive study that combines longitudinal
monitoring, no control group.
2.2.2. Research procedures
+ Clinical examination before and after radiotherapy
+ Tests before and after radiation treatment at 6, 12, 24, 36 months.
* Prolactin, GH, FSH, LH, TSH, ACTH, Estradiol (for women),
testosterone (for men), blood cortisol, FT4 test
* Magnetic resonance imaging of the cerebral cortex
2.2.3. Radiotherapy
Indications of radiotherapy
Patient who met selection criteria:
- Postoperative pituitary tumors remained or recurrent
- Failure with medical treatment


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- Old patients with no indication of intervention and anesthesia
- Patient does not agree to other methods of treatment
- Tumor size <50mm, tumor distance to visual interference ≥ 3mm.
Surgical radiation dose: Dose by size, nature and location of the tumor.
Radiographic procedure
* Fixed patient head
* Simulated radiotherapy

* Treatment planning
* Determination of tumor volume
* Proposed treatment plan and switch to control room
* Proceeding with a rotating gamma knife
* Monitoring and evaluating results of 6, 12, 24 and 36 months
postoperative radiotherapy.
Chapter 3 RESULTS
3.1. General characteristics of the study subjects
Table 3.1. Distribution of patients by age group and sex
Female
Male
Total
Sex
Age group
n
%
n
%
n
%
18-30
11
15,1
1
1,4
12
16,4
31-45
22
30,1

9
12,3
31
42,5
46-60
14
19,2
7
9,6
21
28,8
>60
4
5,4
5
6,8
9
12,3
Total
51
69,9
22
30,1
73
100
Age mean
40,1±11,8
48,0±14,8
42,5±13,2
(min-max)

(18-66)
(21-78)
(18-78)
The mean age was 42.5 ± 13.2 years, the majority was 31-45 in
both sexes.

Figure 3.1. Time from symptom onset to hospitalization
From 12-36 months comprised of 52,7%.


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Table 3.3. Disease distribution by disease pattern
Disease pattern
Quantity (n)
Percentage %
Nonfunctioning pituirity
41
56,2
adenomas
32
43,8
PRL- released
15
20,5
3
4,1
Functioning GH- released
pituirity
ACTH- released
1

1,4
adenomas LH- released
1
1,4
FSH- released
1
1,4
Mix-released
11
15,0
Total
73
100
Table 3.3 showed 56,2% were nonfunctioning pituirity adenomas,
43% were functioning pituirity adenomas.
3.2. Clinical and sub-clinical characteristics of patients with
pituitary adenomas
3.2.1. Clinical features
Table 3.4. Reason for hospitalization
Clinical symptoms
No of patients(n)
Percentage%
Headache
41
56,2
Galactorrhea
5
6,8
Reduced sexual desire
1

1,4
Visual disorders
16
21,9
Acromegaly
3
4,1
RLKN
7
8,2
Polyuria
1
1,4
Total
73
100
Patients admitted to the hospital for headache accounted for the
highest percentage 56.2%, Reduced sexual desire and polyuria
accounted for a low percentage 1.4%.
Table 3.6. Distribution of clinical symptom due to tumor compression
Nonfunctioning
Functioning pituirity
pituirity adenomas
adenomas
(n=41)
(n=32)
Symptom
p
Quantity Percentage% Quantity Percentage%
(n)

(n)
Headache
31
75,6
18
56,2
<0,05
Visual
10
24,4
6
18,8
<0,05
disorders
Memory loss
14
34,1
7
21,8
<0,05
Vomiting
3
7,3
1
3,1
<0,05


7
Percentage of patients with headache was relatively high (75,6%)

in Non-functioning pituirity adenomas and 56,2% in Functioning
Pituirity adenomas patients.
Table 3.7. Clinical manifestations of hormonal dysfunction in
functional pituirity adenomas
Functioning pituirity adenomas (n=32)
Symptom
No of patients (n)
Percentage%
Galactorrhea
15
46,9
Reduced sexual desire
6
18,8
Acromegaly
8
25,0
Arthralgia
4
12,5
Polyurea
1
3,2
Menstrual disorder
14
43,4
Milk secretion (46,9%), Menstrual disorder (43,4%),
acromegaly 25,0%, other symptoms were less.
Table 3.8. Clinical features in the PRL released group
Symptom

PRL released tumor (n=24)
No of patients (n)
Percentage%
Headache
13
54,2
Visual disorders
3
12,5
Galactorrhea
15
62,5
Reduced sexual desire
5
20,8
Memory loss
5
20,8
Infertility
3
12,5
Menstrual disorder
12
50,0
Headache and Milk secretion were found in 54,2% and 62,5%,
Menstrual disorder was 50,0%.
Table 3.9. Clinical characteristics of the GH- released group
Symptom
GH released group (n=8)

No of patients(n)
Percentage%
Headache
5
62,5
Visual disorders
1
12,5
Acromegaly
8
100
Arthralgia
4
50,0
Diabetes
1
12,5
Hypertension
2
25,0


8
100% of the patients with acromegaly, headache and joint pain
was 62,5% and 50%. Hypertension (25,0%), Diabetes (12,5%).
3.2.2. Subclinical features of pituitary tumors
Table 3.10. Tumor size characteristics of studied patients
Quantity Percentage
p
Indicator

(n)
(%)
ABTA
Microadenoma
19
26,0
classification
<0,05
74,0
Macroadenoma
54
(n=73)
<10mm
19
26,0
Group
classification
10-30mm
42
57,6
(n=73)
>30mm
12
16,5
Tumor size mean (X ± SD mm)
18,0±10,9
(n=73)
The mean tumor size was 18.0 ± 10.9 mm, the percentage of
macroadenoma was significantly higher than that of the
microadenoma

Table 3.12. Characteristics of tumors on MRI
Quantity (n) Percentage (%)
Characteristics
Clear
32
43,8
Tumor border
(n=73)
Not clear
41
56,2
6
8,2
Cystic
Tumor structure
Solid
51
69,9
(n=73)
Mixed
16
21,9
Tumors with clear boundary accounted for 43.8%, solid tumors
accounted the highest percentage, cystic tumor accounted for a low
percentage
Table 3.13. Invasive nature of the tumor in the study group
Characteristics
Grade I
Grade II
Hardy Grade

(n=73)
Grade III
Grade IV
Stage A
Stage B
Hardy Stage
(n=73)
Stage C
Stage D

Quantity (n)
19
23
19
12
19
42
8
4

Percentage (%)
26,0
31,5
26,0
16,5
26,0
57,5
11,0
5,5

9
Tumor grade II accounted for the highest proportion (31,5%),
Tumor grade IV was not significant (16,5%).
Tumor stage B accounted for the highest proportion 57,5%, Stage
D was the lowest 5,5%.
Table 3.15. Comparision of Median of selected hormone in PRL
released patients by sex
Female
(n=20)
Median
106,66
43,36
(min-max)
34,033,0-470,0
470,0
Median
4,72
6,64
(min-max) 2,94-7,31 0,11-83,44
Median
3,34
6,74
(min-max) 2,11-6,23 1,45-151,2
Median
36,37
20,56
(min-max) 11,92-98,62 11,29-66,8
Median
2,04

1,73
(min-max)
1,081,25-3,41
100,0
Median
2,69
2,82
(min-max)
0,582,32-23,5
103,9

Hormone
PRL (ng/ml)
LH (mU/ml)
FSH (mU/l)
ACTH
(pg/ml)
TSH (µU/l)
GH (ng/ml)

Male
(n=4)

Total
(n=24)

P

81,22
33,0-470,0

< 0,01

6,50
0,11-83,44
6,38
1,45-151,2
22,47
11,29-98,62

> 0,05
> 0,05
< 0,05

2,04
1,08-100,0

> 0,05

2,69
0,58-103,9

> 0,05

Median PRL hormone level was very high, higher in women than
in men, the ACTH hormone in women is lower than men, the
hormone LH, FSH, TSH, GH in male and female was equivalent.
Table 3.16. Comparision of Median of selected hormon in GHreleased group by sex
Hormone
PRL (ng/ml)

LH (mU/ml)
FSH (mU/l)

Male
(n=2)

Female
Total
(n=6)
(n=8)
Median
28,38
26,43
19,15
(min-max)
9,445,31-76,02
5,31-33,0
76,02
Median
3,68
5,82
4,79
(min-max) 2,86-4,50 3,02-11,60 2,86-11,6
Median
2,59
6,25
5,59
(min-max) 1,60-3,58 4,55-59,0 1,60-59,0

P

> 0,05
> 0,05
> 0,05


10
Median
59,67
23,86
22,46
ACTH (pg/ml) (min-max) 20,7310,9210,92-39,5
98,6
98,62
Median
1,00
1,25
1,25
TSH (µU/l)
(min-max) 0,69-1,31 0,53-3,01 0,53-3,01
Median
30,25
70,34
44,4
GH (ng/ml)
(min-max) 23,5-37,0 19,0-103,9 19,0-103,9

< 0,05
> 0,05
< 0,01

Median GH levels in women are higher than men, ACTH in
women is lower than men, PRL, LH, FSH, TSH hormones were
equivalent in males and females
Table 3.17. Comparision of median of hormon level in
nonfunctioning pituirity adenomas group by sex
Hormone
PRL
(ng/ml)
LH
(mU/ml)
FSH
(mU/l)
ACTH
(pg/ml)
TSH
(µU/l)
GH
(ng/ml)

Median
(min-max)
Median
(min-max)
Median
(min-max)
Median
(min-max)
Median
(min-max)
Median

(min-max)

Male
(n=17)
9,01
4,37-19,12
5,30
0,52-11,78
6,35
3,45-15,51
21,02
10,8254,92
0,99
0,23-2,30
2,31
0,13-5,32

Female
(n=24)
10,92
3,44-21,14
5,33
1,00-12,01
5,78
1,95-11,87

Total
(n=41)
10,02
3,44-21,14

5,30
0,52-12,01
6,24
1,95-15,51

20,88
1,00-45,93

21,02
1,00-54,92

1,60
0,60-4,78
2,16
0,37-5,32

1,52
0,06-4,78
2,19
0,13-5,32

p
>0,05
>0,05
>0,05
>0,05
>0,05
>0,05

Median hormonal concentrations in the nonfunctioning pituirity

adenomas group in men and women were similar.

Figure 3.2. Correlation between tumor size and PRL level in
PRL-released patients


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The tumor size was not significant correlated with hormone
levels. PRL was positively correlated with tumor size and PRL level
with r = 0.42, p = 0.04
3.3. Results of radiotherapy
3.3.1. General characteristics of the patients and radiation dose


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Table 3.20. Age and sex of the radiosurgery group
Functioning Nonfunctioning
pituirity
pituirity
Total
Indicators
adenomas
adenomas
(n=48)
(n=21)
(n=27)
Age (year)
40,8±10,1
47,5±13,6
44,6±12,8

Ratio Female/Male
17/4
15/12
32/16
Discharge (day)
1,9 ±1,04
2,1± 2,4
2,0± 1,9
X± SD, (Min-max)
(1-4)
(1-13)
(1-13)
Follow-up after surgery
40,7± 9,7
37,1± 11,8
38,7±10,9
(month) X± SD, (Min-max)
(24-56)
(12-63)
(12-63)
Mean age was 44.6 ± 12.3 years, mean hospital stay was 2.0 ± 1.9
days, mean follow-up was 38.7 ± 10.9 months
Table 3.21. Previous radiosurgery treatment
Radiosurgery treatment (n=48)
Previous radiosurgery
Percentage
treatment
Quantity (n)
(%)
No treatment

6
12,5
Medical treatment
29
60,4
Surgical treatment
7
14,6
Medical + Surgical treatment
6
12,5
Total
48
100
87,5% of the patients was treated before surgery
Table 3.22. Distribution of radiation dose
Group
Functioning
Non-functioning
Total
Dose
Pituirity
pituirity
(n=48)
(Gy)
adenomas (n=21) adenomas (n=27)
Mean ( X ± SD)
14,05 ± 2,89
13,20 ± 1,36
13,61 ± 2,18

Min
11
12
11
Max
22
16
22
p
>0,05
Average radiation dose: 13,61±2,18Gy (11-22Gy).
3.3.2. Clinical response after surgery
3.3.2.2 Clinical response in PRL functioning pituirity adenomas
group


13

Figure 3.3. Clinical symptoms before and after treatment in PRL group
Symptoms of headache, galactorrhea, menstrual disorders,
infertility over time as compared to before treatment.
3.3.2.2 Clinical response in GH functioning pituirity adenomas group

Figure 3.4. Clinical symptom of GH increasement before and after
treatment
100% of the patients with acromegaly at any assement timepoints.
3.3.2.2 Clinical response in non functioning pituirity adenomas group

Figure 3.5. Clinical symptoms in nonfunctioning pituirity adenomas
group before and after treatment

Headache, Visual disorders, Memory loss reduced significantly after
12 months


14
3.3.3. Response by tumor imaging after surgery
Table 3.25. Comparision of the average size of tumors before and
after surgery in functioning pituirity adenomas and nonfunctioning
pituirity adenomas
Functioning pituirity Nonfunctioning pituirity
adenomas
adenomas
Assessment point
n
n
( X ± SD)
( X ± SD)
Before surgery (0)
21
22,1±9,9
27
20,1±10,8
After 6 months (1) 20
19,6±10,1
26
19,4±12,7
After 12 months (2) 18
15,9±12,7
26
15,5±12,2

After 24 months (3) 20
13,1±14,2
19
12,8±11,2
After 36 months (4) 15
12,2±14,0
20
13,4±11,4
P0-1<0,05
P0-1>0,05
p
P 0 -2,3,4<0,01
P0-2,3,4<0,01
Mean tumor size decreases after 6, 12, 24 and 36 months in the group of
functioning pituirity adenomas. The tumor size in the nonfunctioning
pituirity adenomas group decreased significantly after 12 months.

Figure 3.6. Tumor response assessed by the RECIST
Complete response (6.3%), partial response (41.7%), stable
disease (43.8%), progressive disease (8.3%).

Figure 3.7. Tumor response by RECIST criteria in the PRL secretory
group and GH secretory group
GH released patients with partial response accounted for the
highest percentage of 62.5


15

Figure 3.9. Tumor response by RECIST in the microadenoma and

macroadenoma groups
Complete response was significantly higher in the
microadenoma group than in the macroadenoma group
Table 3.26. Response by tumor size according to RECIST following
radiotherapy
Cystic tumor
Solid tumor
Mixed tumor
(n=2)
(n=34)
(n=12)
Response
(n) Percentage% (n) Percentage% n Percentage%
Complete
0
0
3
8,9
0
0
Partial
1
50
13
38,2
6
50,0
Stable
0
0

17
50
4
33,3
Progressive 1
50
1
2,9
2
16,7
Total
2
100
34
100
12
100
Solid tumor with stable disease response was high (41.2%).
Mixed tumor with partial response accounted for 50.0%.
3.3.4. Responses in hormone levels after surgery
3.3.4.1. Change in hormone levels before and after treatment at 6,
12, 24 and 36 months

Figure 3.12. PRL hormone levels, mean GH before and after surgery
in Functioning Pituirity adenomas patients


16
+ Mean values of PRL and GH levels in Functioning Pituirity
adenomas were decreased after surgery at 6, 12, 24 and 36 months after

surgery.

Figure 3.13. Concentrations of ACTH, LH, TSH, FSH before and
after surgery in Functioning Pituirity adenomas.
Mean values of hormone ACTH, LH, TSH, FFSH in Functioning
Pituirity adenomas before and after surgery were not significantly
changed.

Figure 3.14. PRL and GH levels before and after surgery in nonfunctioning pituirity adenomas
Mean values of PRL, GH levels in non-functioning pituirity
adenomas before and after surgery were not significantly changed.

Figure 3.15. Concentration of ACTH, LH, TSH, FSH before and after
surgery in Non-functioning pituirity adenomas
+ Mean values of hormone ACTH, LH, TSH, FFSH in non-


17
functioning pituirity adenomas before and after surgery were not
significantly changed.

Figure 3.16. PRL hormone levels, mean GH before and after
surgery in the PRL group
PRL levels in PRL secretory patients decreased rapidly after 6
months

EMBED Excel.Chart.8 \s

Figure 3.17. Levels of hormone ACTH, LH, TSH,
FSH before and after surgery in the PRL released

patients
ACTH, LH, TSH, FFSH in the PRL before and after radiotherapy
were not significantly changed.
3.3.4.2. Responses in hormone levels before and after treatment at 6,
12, 24 and 36 months.


18

Figure 3.18. Hormonal response in Functioning Pituirity
adenomas patients
Percentage of patients with hormone returned to normal after
6 months reached 20%, increasing after treatment

Figure 3.19. Hormone response in PRL group
Percentage of patients with hormone returned to normal after 6
months reached 18.8%, increasing gradually after treatment


19

Figure 3.20. Response in hormones in the GH
secretion group
Percentage of patients with hormone returned to normal after 6
months reached 12.5%, increasing gradually after treatment.
3.3.5. Postoperative complications
Table 3.27. Complications after radiotherapy
Tumor
group
Complication

Insomnia
Headache
Dry mouth
Anesthesia
Hair loss
Dermatitis
Cerebral edema

Nonfunctioning
pituirity adenomas
(n=27)
n
8
6
7
13
3
2
1

%
29,6
22,2
26
48,1
11,1
7,4
3,7

Functioning

pituirity
adenomas
(n=21)
n
%
6
28,6
4
19,0
7
33,0
10
47,6
4
19,0
1
4,8
2
9,5

Total
(n=48)
n
14
10
14
23
7
3
3

%
29,2
20,8
29,2
47,9
14,6
6,2
6,2

The most common symptom was anesthesia with 47.9%,
insomnia and dry mouth accounted for 29.2%, headache was 20.8%.
Table 3.28. Relation of radiographic complications to dosing
Dose (Gy)
Dose group
Dose group
P
Symptom
<14Gy
≥ 14Gy
(n=48)
n
%
n
%
Insomnia
8
16,7
6
12,5

>0,05
Headache
4
8,3
6
12,5
>0,05
Dry mouth
4
8,3
10
20,8
<0,05


20
Anesthesia
13
27,1
10
20,8
>0,5
Dry mouth in the dose group ≥14Gy have higher proportion
compared to the dose <14Gy.
Table 3.29. Percentage of hypopituitarism following radiotherapy
Tumor group
hypopituitarism
Reduced ACTH
Reduced TSH
Reduced LH

Total

Nonfunctioning
pituirity adenomas
(n=27)
n
2
0
0
2

%
7,4
0
0
7,4

Functioning
pituirity
adenomas
(n=21)
n
%
2
9,5
1
4,7
1
4,7
4

19,0

Total
(n=48)
n
4
1
1
6

%
8,3
2,1
2,1
12,5

Percentage of hypopituitarism following radiotherapy was 12,5%
Chapter 4 DISCUSSION
4.1. General characteristics of the research subjects
4.1.1. Age and gender
Study subjects comprised of 73 patients with more females
(69.9%) compared to males (30.1%), average age 42.5 ± 13.2 years
old, a majority of the patients in between 31-60 years old).
4.1.4. Duration of the disease
Percentage of patients with disease duration from 12 to 36 months
accounted for 52.7%.
4.1.5. Reason for hospitalization
Reason for hospitalization is mainly due to headache 56.2% (table 3.4).
Other reasons included headaches 37.3% and reduced vision 48.2%.
4.2. Clinical and subclinical features of patients with pituitary

adenomas.
4.2.1. Clinical features of pituitary adenomas
* Symptom due to tumor compression
Headache is the most common, accounted for 67.1%, consistent
with Guadalupe's (66%). Vommitting was low (5.5%). Visual
disorders (21.9%). This was lower than the findings in Ly Ngoc Lien
study (92.8%).
* Clinical characteristics of PRL secretory group
Table 3.8 showed that menstrual disorders and Galactorrhea
accounted for a high percentage (50% and 62.5%). Nguyen Duc Anh
study revealed that milk secretion accounted for 44.9%, and


21
according to Omar, amenorrhea was 70%.
* Clinical characteristics of GH secretory group
The results of table 3.9 show that 100% have acromegaly. This is
consistent with Arafah (> 98%), Joint Pain (50%). Hypertension 25%,
diabetes 12.5%, according to Melmed study, diabetes and hypertension
accounted for 25% and 30% respectively.
* Clinical characteristics of nonfunctioning pituirity adenomas group
Results in table 3.6 showed typical symptoms: Headache (75.6%),
Visual disorders (24.4%), Memory loss (34.1%). According to Maria
study, Headache (68.3%), Visual disorders (74%) Visual disorders
were higher due to larger tumor size
4.2.2. Subclinical features of pituitary adenomas
* Magnetic resonance imaging of pituitary tumor (MRI)
+ Tumor size
The mean tumor size was 18.0 ± 10.9 mm, 74% macroadenoma
and 26% microadenoma. Nguyen Thanh Xuan study showed 89.5%

of macroadenoma
+ Characterization of tumors on magnetic resonance imaging
Solid structure accounts for a high percentage (69.9%) of low
percentage of cysts (8.2%). This is consistent with 85.9% of solid
structure and 8% of cysts in Nguyen Thanh Xuan study.
+ Evaluation of tumor invasion
Table 3.14 showed Grade II by Hardy classification was the
highest (31.5%), Grade 4 was the lowest (16.5%), Stage B was the
highest (57.5%), and Stage C and D low (16.5%). The lowest was
Ly Ngoc Lien III cervicalage (34.9%), phase B (37.2%), stage C
and D (32.5%). According to Maria invasive on MRI was 83.8%.
* Characteristics of hormone levels in pituitary adenomas
Phù hợp với Santiago u tiết PRL percentage cao nhất (90%) sau đến
u tiết GH, ACTH, u tiết TSH percentage thấp nhất. Results in table 3.15
showed median PRL hormone levels were significantly higher in women
than men. The hormone levels LH, TSH, FSH, ACTH and GH were
similar in both sexes. This is consistent with Santiagov results that
showed the highest percentage of PRL- released tumor (90%) followed
by GH, ACTH, and TSH was the lowest.
* Characteristics of hormone levels in PRL and GH secretory group
The concentration of PRL, GH is very high. According to
Zbigniew, patients with PRL secretion and PRL levels were


22
significantly elevated.
* Characteristics of hormone levels in nonfunctioning pituirity
adenomas
Median PRL, GH, ACTH, LH, FSH and TSH hormone level are
similar in both sex. This is consistent with study results of Le Thanh

Huyen that showed average hormone levels in patients with nonfunctioning pituitary adenomas in the normal range due to the limited
number of patients with hypopituitarism
* The correlation between tumor size and selected pituitary
hormone levels
The PRL group had a positive correlation between tumor size and
PRL with r = 0.42, p = 0.04. According to Kosuke, non-functional
pituirity adenomas patients showed a significant negative correlation
between tumor size and PRL (r = -0.36), the larger size of the tumor, the
possibility of hypopituitarism is higher.
4.3. Results of radiographic interventions in patients with pituitary
adenomas
4.3.1. General characteristics of the intervention group
* History of interventions before surgery
87.5% of the patients had been treated before radiation, findings of
our study is consistent with El-Shehaby study of radiotherapy that
showed 50% failure after surgery.
* Discharge time and follow-up time after surgery
Results in table 3.21 showed discharge time was 2.0 ± 1.9 days,
consistent with Nguyen Quang Hung results to show discharge time of 3
days. 38.7 months follow-up time is consistent with Raef study to
follow-up patient for 28 months (12-84 months).
* Dose distribution and correlation between dosing and some
tumor characteristics
Table 2.23 and 3.24 showed the mean dose of radiation was 13.61 ±
2.18 Gy, lower than that of Wan (22.2 Gy) because of the higher tumor
size in our study.
4.3.2. Clinical changes in pituitary tumors before and after surgery
* Clinical change after radiotherapy of PRL secretory group
Figure 3.3 showed headache, milk secrection was reduced
statistically significant at 12 months, and the infertility decreased

slowly after 24 months. According to Tanaka (2010), clinical
improvement was 63.6%.
* Clinical change after radiotherapy of GH secretory group


23
Percentage of patients with acromegaly 100% did not decrease,
only decreased in degree of hypertrophy. This was lower than
findings in Raine’s study with clinical improvement was 60% after
12-24 months due to higher doses than in our study, doses ranging
from 18-22 Gy.
* Clinical change after radiotherapy in nonfunctional pituirity
adenomas
Headache, Visual disorders, Memory loss decreased significantly
after 12 months. Guadalupe study showed headache preoperative 66%,
Visual disorders 87.2% and after surgery, these were reduced to 9.7%
and 31% respectively.
4.3.3. Changes in tumor size in patients with pituitary tumors
before and after surgery
* Transformation of postoperative tumor size
The size of tumors decreased with time. Results at 6, 12, 24 and 36
months showed significant difference. 100% of patients do not
responsed if the tumor size> 40mm. The result consistent with Frederic's
study that showed 50% patients with reduction in tumor size after
surgery. Castro study showed tumor <30mm responsed with 98%.
* Tumor transformation in functional pituirity adenomas after
radiotherapy
The tumor size was significantly reduced at 6 months with p <0.05. This
is consistent with Raef study that show the percentage of patient who can
control of tumor size in PRL, GH, ACTH was 96%, 90% and 100%

respectively.
* Changes in tumor size in non-functioning pituirity adenomas
after surgery
The tumor size was reduced statistically significant at 12, 24 and 36
months with p <0.01. This is consistent with Zbigniew study to show
100% of the patients controlled tumor size after 3 years.
4.3.4. Changes in pre and postoperative hormone levels in patients
with pituitary tumors
Average concentration of PRL, GH decreased over time, statistically
significant after 6 months, the hormone ACTH, LH, TSH, FSH difference
did not change significantly. Raef study showed hormone stability in 63%,
significantly reduced after 12 months.
* Changes in some pituitary hormones before and after surgery in
the PRL and GH secretion groups
Figure 3.19 and 3.20 showed percentage of patients with PRL


24
hormone levels controlled were 18.8%, 35.7%, 33.3% and 46.2%
respectively. For GH hormones, these were 12.5%, 28.6%, 42.9%.
Raef found that 60% of patients had controlled GH levels at 12-24
months postoperatively
* Changes in some pituitary hormones before and after surgery in
the group of functioning pituirity adenomas
Percentage of patients with hormones in the normal range increased
over time, after 6, 12, 24 and 36 months, the respective percentages were
20%, 27.8%, 30% and 40%. In accordance with the study of Yazdani
that showed hormone ACTH, GH, PRL were controlled in 70%, 73%
and 67% of the patients
* Changes in some pituitary hormones before and after surgery in

the group of nonfunctioning pituirity adenomas
Results in figure 3.14 and 3.15 showed PRL, GH, ACTH, LH, FSH
and TSH hormones of patients with non-functioning pituitary adenoma
prior to treatment compared to 6, 12, 24 and 36 months postoperative;
these hormones were either reduced or remain unchanged. Raef study
showed 70% patients with ACTH hormone level within the normal
range. Thus, rotary gamma radiation has been shown to control hormone
levels in both functional pituirity adenomas and non-functioning pituirity
adenomas.
4.3.5. Postoperative complications
Headache, anorexia, and insomnia were associated with low rates of
both functional pituitary adenomas and non-functional pituitary adenomas.
This was consistent with Nguyen Quang Hung findings of complications:
loss of appetite, headache, cerebral edema and dry mouth. Pituitary
insufficiency (12.5%), Feigl G.C study showed pituitary insufficiency
ranged from 8.7 to 34.8%. According to Jason, the pituitary insufficiency
rate was 21%. Thus, radiotherapy is one of the methods with low
complication rates
CONCLUSION
1. Some clinical and subclinical features in patients with pituitary
adenomas
Clinical:
The mean age was 42.5 ± 13.2 years, the age of radiographic group
was 44.6 ± 12.8 years. Female / male ratio was 51/22. Functioning
pituirity adenomas accounted for 43.8% and nonfunctioning pituirity
adenomas (56,2%). PRL secretion (20.5%), GH secretion (4.1%), mixed


25
secretion (15.0%). PRL: Headache (54.2%), Galactorrhea (62.5%), GH

secretion: acromegaly (100%), joint pain (50%), headache (62.5%). In
non-functioning pituirity adenomas: headache (75.6%), visual disorders
(34.1%).
Subclinical
- High levels of PRL and GH hormones, TSH, FSH and LH
hormones in normal range, ACTH hormone levels decreased. ACTH in
functional pituirity adenomas group decreased compared to nonfunctioning pituirity adenomas.
- Average tumor size: 18.0 ± 10.9 mm, solid tumor structure
(69.9%), mixed (21.9%), cyst (8.2%). On MRI: Grade II had the
highest percentage of 31.5%, phase B had the highest percentage of
57.5%
- There was a positive correlation between tumor size and PRL levels
in the PRL group with r = 0.42, p = 0.04.
2. Radiographic intervention results
- Short discharge time: 2.0 ± 1.9 days. Postoperative follow-up: 38.7
± 10.9 months. Clinical symptoms tended to decrease over time, with a
statistically significant decrease after 12 months, unchanged in
acromegaly percentage. Size of tumors was reduced statistically
significant after 12, 24 and 36 months. Hormone response: after 6, 12,
24 and 36 months the percentage of patients in normal range increased in
functioning pituirity adenomas, PRL secretion group and GH secretion
group.
- Pituitary insufficiency complication was found in 12.5%, other
complications are mild and transient.
- Radiotherapy is a minimally invasive intervention for patients with
pituitary tumors that improves clinical and laboratory outcomes for
patients after failure with other methods such as surgery, medical
therapy, and with relatively few complication.
RECOMMENDATIONS
Radiotherapy should be used for patients with pituitary tumors who

undergo surgery but with tumors remained, recurrence after surgery or
medical treatment failures that can not be surgery and tumor size ≤
40mm. This is a time-consuming treatment, results in long-lasting, less
complications, less impact on the surrounding brain areas and ensuring
the goal of preserving the cranial nerve function.