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
Trang 1Pituitary adenomas is a disease that has diversified clinicalsymptoms In 2007, Vietnam began to apply gamma kniferadiotherapy to treat brain tumors including patients with pituitarytumors, but no reports have been released of the clinical andsubclinical 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”
New contribution of the Dissertation:
- Established indications in surgical patients who have not takenall the tumors, recurrence after surgery or medical treatment failuresthat can not be surgically removed and the tumor size is <40 mm
- Evaluated the response time for both radiology and tumormorphology
- 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 (2pages), Chapter 1: Overview (32 pages), Chapter 2: ResearchObject 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)
Trang 2Chapter 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 arediagnosed each year In Western countries, the disease prevalencewas determined in almost all countries In Vietnam, there are noepidemiological 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 hypointensesignals 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 thesphenoid sinus
* Medical treatment of functioning pituitary adenomas
Drug medical treatment is the first choice for PRL, ACTH, GH,
Trang 3TSH hormone- released pituitary adenomas, and hypopituitarismrequiring 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 sphincterleakage, hormone produced too much, biopsy to diagnosepathological tissues
1.3.3 Accelerated radiation therapy
Indications: tumors not elligible for surgery or surgical removal oftumors is not exhausted, tumor recurrence after surgery, failure aftermedical treatment without surgery
The largest dose (Gy)
Chapter 2 OBJECTIVES AND RESEARCH METHODS
- No acute, life-threatening illness
- Acceptance of study participation
Trang 4* 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 fromthe 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: birthcontrol 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: birthcontrol 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 visualinterference <3mm
+ 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
Trang 5- 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 monthspostoperative radiotherapy
Chapter 3 RESULTS 3.1 General characteristics of the study subjects
Table 3.1 Distribution of patients by age group and sex
Figure 3.1 Time from symptom onset to hospitalizationFrom 12-36 months comprised of 52,7%
Trang 6Table 3.3 Disease distribution by disease pattern
Disease pattern Quantity (n) Percentage %Nonfunctioning pituirity
Table 3.4 Reason for hospitalization
Clinical symptoms No of patients(n) Percentage%
Table 3.6 Distribution of clinical symptom due to tumor
compression
Symptom
Nonfunctioningpituirity adenomas(n=41)
Functioning pituirityadenomas
Trang 7Vomiting 3 7,3 1 3,1 <0,05 Percentage of patients with headache was relatively high (75,6%)
in Non-functioning pituirity adenomas and 56,2% in FunctioningPituirity adenomas patients
Table 3.7 Clinical manifestations of hormonal dysfunction in
functional pituirity adenomas
Symptom Functioning pituirity adenomas (n=32)
Table 3.8 Clinical features in the PRL released group
Table 3.9 Clinical characteristics of the GH- released group
Trang 8Hypertension 2 25,0
100% of the patients with acromegaly, headache and joint painwas 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
Indicator Quantity(n) Percentage (%) pABTA
Table 3.12 Characteristics of tumors on MRI
Characteristics Quantity (n) Percentage (%)Tumor border
Table 3.13 Invasive nature of the tumor in the study group
Characteristics Quantity (n) Percentage (%)Hardy Grade
Trang 9Stage C 8 11,0
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 sexHormone (n=4)Male Female (n=20) (n=24)Total PPRL (ng/ml) (min-max)Median 33,0-470,043,36 34,0-470,0106,66 33,0-470,081,22 < 0,01
LH (mU/ml) (min-max)Median 2,94-7,314,72 0,11-83,446,64 0,11-83,446,50 > 0,05FSH (mU/l) (min-max)Median 2,11-6,233,34 1,45-151,26,74 1,45-151,26,38 > 0,05ACTH
(pg/ml) (min-max)Median 11,92-98,6236,37 11,29-66,820,56 22,4711,29-98,62 < 0,05TSH (µU/l) (min-max)Median 1,25-3,411,73 1,08-100,02,04 1,08-100,02,04 > 0,05
GH (ng/ml) (min-max)Median 2,32-23,52,82 0,58-103,92,69 0,58-103,92,69 > 0,05Median PRL hormone level was very high, higher in women than
in men, the ACTH hormone in women is lower than men, thehormone LH, FSH, TSH, GH in male and female was equivalent
Table 3.16 Comparision of Median of selected hormon in
GH-released group by sex
Hormone (n=2)Male Female(n=6) (n=8)Total PPRL (ng/ml) (min-max)Median 5,31-33,019,15 9,44-76,0228,38 5,31-76,0226,43 > 0,05
LH (mU/ml) (min-max)Median 2,86-4,503,68 3,02-11,605,82 2,86-11,64,79 > 0,05FSH (mU/l) (min-max)Median 1,60-3,582,59 4,55-59,06,25 1,60-59,05,59 > 0,05ACTH (pg/ml) (min-max)Median 20,73-98,659,67 10,92-39,522,46 10,92-98,6223,86 < 0,05TSH (µU/l) (min-max)Median 0,69-1,311,00 0,53-3,011,25 0,53-3,011,25 > 0,05
Trang 10GH (ng/ml) (min-max)Median 23,5-37,030,25 19,0-103,970,34 19,0-103,944,4 < 0,01Median GH levels in women are higher than men, ACTH inwomen is lower than men, PRL, LH, FSH, TSH hormones wereequivalent in males and females
Table 3.17 Comparision of median of hormon level in
nonfunctioning pituirity adenomas group by sex
(n=17) Female(n=24) (n=41)Total pPRL
(ng/ml) (min-max)Median 4,37-19,129,01 3,44-21,1410,92 3,44-21,1410,02 >0,05LH
(mU/ml)
Median
(min-max)
5,300,52-11,78
5,331,00-12,01
5,300,52-12,01 >0,05FSH
(mU/l) (min-max)Median 3,45-15,516,35 1,95-11,875,78 1,95-15,516,24 >0,05ACTH
(pg/ml)
Median
(min-max)
21,0210,82-54,92
20,881,00-45,93 1,00-54,9221,02 >0,05TSH
(µU/l) (min-max)Median 0,23-2,300,99 0,60-4,781,60 0,06-4,781,52 >0,05GH
(ng/ml)
Median
(min-max)
2,310,13-5,32
2,160,37-5,32
2,190,13-5,32 >0,05Median hormonal concentrations in the nonfunctioning pituirityadenomas group in men and women were similar
Figure 3.2 Correlation between tumor size and PRL level in
PRL-released patients
The tumor size was not significant correlated with hormonelevels PRL was positively correlated with tumor size and PRL levelwith r = 0.42, p = 0.04
3.3 Results of radiotherapy
Trang 113.3.1 General characteristics of the patients and radiation dose
Trang 12Table 3.20 Age and sex of the radiosurgery group
Indicators
Functionin
g pituirityadenomas(n=21)
Nonfunctionin
g pituirityadenomas(n=27)
Total(n=48)Age (year) 40,8±10,1 47,5±13,6 44,6±12,8
Discharge (day)
X± SD, (Min-max)
1,9 ±1,04(1-4)
2,1± 2,4(1-13)
2,0± 1,9(1-13)Follow-up after surgery
(month) X± SD,
(Min-max)
40,7± 9,7(24-56)
37,1± 11,8(12-63) 38,7±10,9
(12-63)Mean age was 44.6 ± 12.3 years, mean hospital stay was 2.0 ± 1.9days, mean follow-up was 38.7 ± 10.9 months
Table 3.21 Previous radiosurgery treatment
Previous radiosurgery
treatment
Radiosurgery treatment (n=48)Quantity (n) Percentage(%)
87,5% of the patients was treated before surgery
Table 3.22 Distribution of radiation dose
Group
Dose
(Gy)
FunctioningPituirityadenomas (n=21)
Non-functioningpituirityadenomas (n=27)
Total(n=48)Mean (X±
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
Trang 13Figure 3.3 Clinical symptoms before and after treatment in PRL groupSymptoms 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 adenomasgroup before and after treatment
Headache, Visual disorders, Memory loss reduced significantly after
12 months
Trang 143.3.3 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
Assessment point Functioning pituirityadenomas Nonfunctioning pituirityadenomas
Before surgery (0) 21 22,1±9,9 27 20,1±10,8After 6 months (1) 20 19,6±10,1 26 19,4±12,7After 12 months (2) 18 15,9±12,7 26 15,5±12,2After 24 months (3) 20 13,1±14,2 19 12,8±11,2After 36 months (4) 15 12,2±14,0 20 13,4±11,4
p P 0 -2,3,4<0,01P0-1<0,05 P0-2,3,4<0,01P0-1>0,05Mean tumor size decreases after 6, 12, 24 and 36 months in the group offunctioning pituirity adenomas The tumor size in the nonfunctioningpituirity adenomas group decreased significantly after 12 months
Figure 3.6 Tumor response assessed by the RECIST
Complete response (6.3%), partial response (41.7%), stabledisease (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 thehighest percentage of 62.5
Trang 15Figure 3.9 Tumor response by RECIST in the microadenoma and macroadenoma groups
Complete response was significantly higher in themicroadenoma group than in the macroadenoma group
Table 3.26 Response by tumor size according to RECIST following
radiotherapy
Response Cystic tumor(n=2) Solid tumor(n=34) Mixed tumor(n=12)
(n) Percentage% (n) Percentage% n Percentage%
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
Trang 16in Functioning Pituirity adenomas patients
+ Mean values of PRL and GH levels in Functioning Pituirityadenomas were decreased after surgery at 6, 12, 24 and 36 months aftersurgery
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 FunctioningPituirity adenomas before and after surgery were not significantlychanged
Figure 3.14 PRL and GH levels before and after surgery in functioning pituirity adenomas
Mean values of PRL, GH levels in non-functioning pituirityadenomas 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
Trang 17+ Mean values of hormone ACTH, LH, TSH, FFSH in functioning pituirity adenomas before and after surgery were notsignificantly changed.
non-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 6months
Trang 18Figure 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