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

CAUSE OF HYPOGLYCEMIA1. 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 glucagon3,5-3,2 mmol/l catecholamines3,1-2,7 mmol/l growth hormone2,8-2,6 mmol/l cortisol

neurogenic symptoms

neuroglycopenicsymptoms

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

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

Fasting test

0

1

2

3

4

5

6

7

Glu

cose

(mm

ol/l)

Before After0

20

40

60

80

100

IRI (

mU

/l)

Before After0

10

20

30

40

50

60

IRI/G

(mU

/mm

ol)

Before After

Positive: 100 % 91 % 98 %

Organic hyperinsulinism(3rd Department of Internal Medicine: 1980 – 2012)

Imaginating method Finding by surgery Positive Negative Confirmed Removed from positiveUS 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 findinga) localization (n=115) Head: 30 % Body: 28 % Tail: 42 %

b) histology Benign adenoma: 103 Malign carcinoma: 4 Uncertain biological activity: 5

Multiple microadenomatosis: 3

Algorithm of diagnosis in organic hyperinsulinismClinical suspition

Biochemical examination

Diagnosis confirmed Diagnosis unconfirmed

Topographic localisation

CT Angiography Endosonography

Localisation confirmed Localisation unconfirmed

Surgery

Insulinoma removed Insulinoma unremoved

Conservative treatment

TREA

TMEN

T

DIA

GN

OSI

S

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

Insulinoma Hypoglycemia factitiacaused by insulin

Hypoglycemia factitia caused by sulphonylurea

Plasma glucose ↓↓↓ ↓↓↓ ↓↓↓

Plasma insulin ↑ - ↑↑↑ ↑↑↑ ↑↑↑

Serum C-peptide ↑ - ↑↑ ↓ - ↓↓ ↑ - ↑↑

Plasma proinsulin

↑ - ↑↑ ↔ ↔

Sulphonylurea (urine)

negative negative positive

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

Collaboration

Surgery: Jan Šváb, Ladislav Krušina (†)Biochemistry: Jirina Hilgertová Marcela JarolímkováPathologist: Jaroslava DuškováMetabolic ward staff: Eva Kotrlíková Gustav Šindelka (†) Imaging: Josef Hořejš, Radan Keil