Insulinoma 2012

30 years experience with diagnosis and treatment

Jan Škrha

3 rd Department of Internal Medicine, 1 st Faculty of Medicine, Charles University in Prague 27 th 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 3,8-3,6 mmol/l 3,5-3,2 mmol/l 3,1-2,7 mmol/l 2,8-2,6 mmol/l Hormone glucagon catecholamines growth hormone cortisol neurogenic symptoms neuroglycopenic symptoms

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

(3 rd Characteristics of the patients Departmrent of Internal Medicine: 1980 – 2012) Males / females Organic hyperinsulinism Functional hyperinsulinism (n = 125) (n = 30) 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/m 2 ) 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

7 100 60 6 50 80 5 40 60 4 30 3 40 20 2 20 10 1 0 Before After 0 0 Before After 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 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

Octreoscan

TREATMENT

a) surgical - by laparotomy - by laparoscopy b) conservative - regimen (diet, activity) - pharmacological (diazoxide, octreotide)

Enucleation

Resection (hemipancreatectomy)

INSULINOMA – RESULTS OF TREATMENT (3 rd Department of Internal Medicine, 1980-2012) 125 insulinomas / microadenomatosis 115 operated 10 conservatively in 104 removed (90 %) in 11 undiscovered 3 removed (by reoperation) 8 conservative 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

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

In differential diagnosis: HYPOGLYCEMIA FACTITIA

HYPOGLYCEMIA FACTITIA

Characteristic signs:

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suspicion on insulinoma

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uncertainty from clinical picture

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uncertainty from laboratory findings

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frequent relationship of the patient to health care providers Attention: IATROGENIC HYPOGLYCEMIA

Insulinoma vs hypoglycemia factitia Laboratory variable

Plasma glucose Plasma insulin Serum C-peptide Plasma proinsulin Sulphonylurea (urine)

Insulinoma Hypoglycemia factitia caused by insulin

↓↓↓ ↑ - ↑↑↑ ↑ - ↑↑ ↑ - ↑↑ negative ↓↓↓ ↑↑↑ ↓ - ↓↓ ↔ negative

Hypoglycemia factitia caused by sulphonylurea

↓↓↓ ↑↑↑ ↑ - ↑↑ ↔ positive

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