Insulinoma 2012
30 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
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
Hypoglycemia and activation of
contraregulatory hormones
Glucose
Hormone
3,8-3,6 mmol/l
3,5-3,2 mmol/l
3,1-2,7 mmol/l
2,8-2,6 mmol/l
glucagon
catecholamines
growth hormone
cortisol
neurogenic
symptoms
neuroglycopenic
symptoms
HYPOGLYCEMIC SYMPTOMS
1) neurogenic:
(adrenergic)
sweatting, palpitations, tachycardia,
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
Characteristics of the patients
(3rd Departmrent of Internal Medicine: 1980 – 2012)
Males / females
Age (yrs)
Organic
Functional
hyperinsulinism
hyperinsulinism
(n = 125)
(n = 30)
32 / 93 (~ 75 % women)
7 / 21
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
(mm Hg)
diastolic
134 ± 17
125 ± 15
(55 % normal)
79 ± 10
78 ± 6
Fasting test
100
7
60
6
50
4
3
IRI/G (mU/mmol)
5
IRI (mU/l)
Glucose (mmol/l)
80
60
40
40
30
20
2
20
10
1
0
Before
Positive:
After
100 %
0
Before
After
91 %
0
Before
After
98 %
Organic hyperinsulinism
(3rd Department of Internal Medicine: 1980 – 2012)
Imaginating method
Positive
Negative
Finding by surgery
Confirmed
from positive
Removed
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
Octreoscan
TREATMENT
a) surgical
- by laparotomy
- by laparoscopy
b) conservative
- regimen (diet, activity)
- pharmacological
(diazoxide, octreotide)
Enucleation
Resection (hemipancreatectomy)
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 %)
Histology
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
DIAGNOSIS
Algorithm of diagnosis in organic hyperinsulinism
Clinical suspition
Biochemical examination
Diagnosis confirmed
Diagnosis unconfirmed
Topographic localisation
TREATMENT
CT Angiography Endosonography
Localisation confirmed
Localisation unconfirmed
Surgery
Insulinoma removed
Insulinoma unremoved
Conservative treatment
In differential diagnosis:
HYPOGLYCEMIA FACTITIA
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
Insulinoma vs hypoglycemia factitia
Laboratory
variable
Plasma glucose
Insulinoma Hypoglycemia
Hypoglycemia
factitia
factitia
caused by insulin caused
by sulphonylurea
↓↓↓
↓↓↓
↓↓↓
Plasma insulin
↑ - ↑↑↑
↑↑↑
↑↑↑
↓ - ↓↓
↑ - ↑↑
↑ - ↑↑
↔
↔
negative
negative
positive
Serum C-peptide ↑ - ↑↑
Plasma
proinsulin
Sulphonylurea
(urine)
Conclusions for clinical practice
Hypoglycemia is deleterious for organism
and is life threatening
• 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)
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