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Insulinoma 201230 years experience with diagnosis and
treatment
Jan Škrha
3rd Department of Internal Medicine,
1st Faculty of Medicine,
Charles University in Prague
27th Symposium of the Federation of the International Danube-Symposia
of Diabetes Mellitus, Budapest, 28-30th June, 2012
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CAUSE OF HYPOGLYCEMIA
1. According to pathogenesis
a) decreased glucose production - lack of contraregulatory hormones
- liver or kidney disease, alcohol
b) increased glucose utilisation
- exogenously caused (DM treatment)
- endogenously caused (insulinoma)
2. According to timing of the food ingestion
a) fasting hypoglycemia (!!!)
b) random hypoglycemia during the day
- reactive (functional), postoperative
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Hypoglycemia and activation of contraregulatory hormones
Glucose Hormone
3,8-3,6 mmol/l glucagon3,5-3,2 mmol/l catecholamines3,1-2,7 mmol/l growth hormone2,8-2,6 mmol/l cortisol
neurogenic symptoms
neuroglycopenicsymptoms
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HYPOGLYCEMIC SYMPTOMS
1) neurogenic: sweatting, palpitations, tachycardia,
(adrenergic) anxiety, tremor
2) neuroglycopenic:
a) neurologic: confusion,headache, blurred vision,
diplopy, dysarthria, decreased abbility
to concentrate, impaired speech and
consciousness, cramps, epilepsy
b) psychiatric: unusual hesitation, temper changes
(depression, euphory)
impaired thinking
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Characteristics of the patients(3rd Departmrent of Internal Medicine: 1980 – 2012)
Organic Functional
hyperinsulinism hyperinsulinism
(n = 125) (n = 30)
Males / females 32 / 93 (~ 75 % women) 7 / 21
Age (yrs) 52 ± 17 27 ± 5
Duration of the disease (yrs) 3 (0,1 – 25) 1 (0,5 – 2)
BMI (kg/m2) 28,2 ± 5,3 (32 % normal) 24,3 ± 2,9
Blood pressure – systolic 134 ± 17 125 ± 15
(mm Hg) (55 % normal)
diastolic 79 ± 10 78 ± 6
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Fasting test
0
1
2
3
4
5
6
7
Glu
cose
(m
mo
l/l)
Before After0
20
40
60
80
100
IRI
(mU
/l)
Before After0
10
20
30
40
50
60
IRI/G
(m
U/m
mo
l)
Before After
Positive: 100 % 91 % 98 %
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Organic hyperinsulinism(3rd Department of Internal Medicine: 1980 – 2012)
Imaginating method Finding by surgery
Positive Negative Confirmed Removed
from positive
US 4 (8 %) 47 (92 %) 2 (50 %) 45 (88 %)
EU 41 (84 %) 8 (16 %) 33 (83 %) 45 (94 %)
CT 27 (30 %) 64 (70 %) 22 (85 %) 86 (95 %)
AG 39 (43 %) 52 (57 %) 25 (64 %) 89 (94 %)
Localised ~ 70 % of insulinomas before operation
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Octreoscan
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TREATMENT
a) surgical - by laparotomy - by laparoscopy
b) conservative - regimen (diet, activity) - pharmacological (diazoxide, octreotide)
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Enucleation
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Resection (hemipancreatectomy)
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INSULINOMA – RESULTS OF TREATMENT
(3rd Department of Internal Medicine, 1980-2012) 125 insulinomas / microadenomatosis
115 operated 10 conservatively
in 104 removed (90 %) in 11 undiscovered
3 removed 8 conservative (by reoperation)
Surgical success: 93 %
Agreement with preoperative examination : 64 of 81 (79 %)
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Histology
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Surgical and histological finding
a) localization (n=115) Head: 30 % Body: 28 % Tail: 42 %
b) histology Benign adenoma: 103 Malign carcinoma: 4 Uncertain biological activity: 5
Multiple microadenomatosis: 3
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Algorithm of diagnosis in organic hyperinsulinism
Clinical suspition
Biochemical examination
Diagnosis confirmed Diagnosis unconfirmed
Topographic localisation
CT Angiography Endosonography
Localisation confirmed Localisation unconfirmed
Surgery
Insulinoma removed Insulinoma unremoved
Conservative treatment
TR
EA
TM
EN
T
DIA
GN
OS
IS
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In differential diagnosis:
HYPOGLYCEMIA FACTITIA
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HYPOGLYCEMIA FACTITIA
Characteristic signs:
- suspicion on insulinoma
- uncertainty from clinical picture
- uncertainty from laboratory findings
- frequent relationship of the patient to
health care providers
Attention: IATROGENIC HYPOGLYCEMIA
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Insulinoma vs hypoglycemia factitia
Laboratory variable
Insulinoma Hypoglycemia factitiacaused by insulin
Hypoglycemia factitia caused by sulphonylurea
Plasma glucose ↓↓↓ ↓↓↓ ↓↓↓
Plasma insulin ↑ - ↑↑↑ ↑↑↑ ↑↑↑
Serum C-peptide ↑ - ↑↑ ↓ - ↓↓ ↑ - ↑↑
Plasma proinsulin
↑ - ↑↑ ↔ ↔
Sulphonylurea (urine)
negative negative positive
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Conclusions for clinical practice
• to analyse symptoms (history !)• to confirm hypoglycemia• to elucidate cause of hypoglycemia
(confirm diagnosis)• to realize reliable treatment strategy
removing hypoglycemia (related to diagnosis and clinical state of
the patient)
Hypoglycemia is deleterious for organism and is life threatening
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Collaboration
Surgery: Jan Šváb, Ladislav Krušina (†)
Biochemistry: Jirina Hilgertová
Marcela Jarolímková
Pathologist: Jaroslava Dušková
Metabolic ward staff: Eva Kotrlíková
Gustav Šindelka (†)
Imaging: Josef Hořejš, Radan Keil