Case presentation Endocrine module Jacques le Roux Jacques le Roux 20/04/ /04/2012

Clinical picture 34 year male (security worker) 34 year male (security worker) Presenting with spontaneous hypoglycemia episodes from 2010 Presenting with spontaneous hypoglycemia episodes from 2010 Admitted after a hypoglycemic attack which resulted in neurological symptoms that ranged from confusion to loss of concious/coma or convulsions Admitted after a hypoglycemic attack which resulted in neurological symptoms that ranged from confusion to loss of concious/coma or convulsions No ETOH use. No smoker. No ETOH use. No smoker. No sulphonylurea overdose (not known diabetic) No sulphonylurea overdose (not known diabetic)

Special investigations Random glucose 2 low Random glucose 2 low Insuline levels normal, C-peptide normal Insuline levels normal, C-peptide normal Amylase normal Amylase normal TFT normal, Calsium levels normal TFT normal, Calsium levels normal ESR 59, CRP < 1, FBC normal ESR 59, CRP < 1, FBC normal Renal function normal Renal function normal Newly diagnosed RVD + Newly diagnosed RVD + No TB tests done No TB tests done

Imaging CXR CXR Abdominal sonar Abdominal sonar CT chest and abdomen CT chest and abdomen Octreotide scan Octreotide scan

CXR

Sonar

CT ARTERIAL PORTO-VENOUS

Octreotide scan

Differential diagnosis 1) Functional Islet cell tumor of the pancreas / Insulinoma [ small hypervascular pancreas lesion on the art phase, hypoglycemia] – classic 2) NH Lymphoma / AIDS related lymphoma (mediastianl LN present, pancreas lesion not hypovascular) (mediastianl LN present, pancreas lesion not hypovascular) - will first consider infective cause for mediastinal LN’s - will first consider infective cause for mediastinal LN’s - mets not likely from insulinoma (no large lesion,no calcifications,no liver lesions,no peripancreatic LN’s) - mets not likely from insulinoma (no large lesion,no calcifications,no liver lesions,no peripancreatic LN’s) 3) Metastatic pancreatic lesion (no primary visible, kidneys normal) 4) Paraganglioma (not correct location) 5) Other pancreas pathology,example pancreatitis (normal S-amylase)

ISLET CELL TUMORS Part of MEN I MEN It is autosomal dominant conditions Characterized by 2 or more tumors (adenomas) in endocrine organs These organs come from the neural ridge These tumors, also called Apudomas, contain neuro-endocrine cells (APUD or Kulchitsky cells) – they produce diff. hormones Associated with hyperfunction and can be malignant Can occur alone (sporadic)

FEATURES OF MEN 1 (WERMER SYNDROME) A) MAJOR DISEASE COMPONENTS = PPP 1) Parathyroid – hyperplasia or adenomas – 95% (common) 2) Pancreatic islet cell tumor – 40% 3) Ant. Pituitary tumor – 30% B)ASSOCIATED TUMORS 1) Facial angiofibroma – 90%(common) 2) Adrenal cortical tumor – 40% 3) Foregut carcinoid – 3% e.g. thymus, bronchus, stomach - Colon polyps, thymoma

Usually functional, small and multiple adenomas In order of frequency 1) INSULINOMAS Hypoglycemia 10% Occur with gastrinomas 10% Malignant 2) GASTRINOMAS Associated with Zollinger Ellison Syndrome: (Presents with PU and diffuse stomach wall thickening) and multiple duod. microgastrinomas 60% Can be become malignant 3) GLUCAGONOMAS DM and glossitis 80% Malignant 4) VIPOMA (Vasoactive intest peptide) WDHA syndrome (watery diarrhea, hypokalemia, achlorhydrin) 60% malignant 5) SOMATOSTATINOMA DM (block insulin) 80 % malignant

IMAGING - Choice 1) CT = MRI Hypervascular – CE + Signs of malignancy (must do follow up) Large tumor Ca⁺⁺ Hypervasc. mets to liver 2)NM Octreoscan ¹¹¹ indium Is somatostatin receptor. scan - Blocks insulin and growth hormone

SONAR eg. Transabdominal – Low sensitivity ( 70%) or Endoscopic – nearly 100% sensitivity, but invasive Intraoperative Islet cell tumors are hypoechoic masses Endoscopic a) in duod wall b) In pancreatic body Intraoperative c) in pancreatic body

Hypoecchoic lesion in pancreas on sonar

CT – 80% sensitive Most widely used for localization, local spread and liver involvement Hypervascular – will enhance (art phase) Large tumors and calcifications suggest malignancy A - insulinoma B - non functional islet cell tumor A B

MRI – Greater sensitivity than CT for small adenomas SOLITARY ADENOMA (PANCREAS) a) T₁ – low signal b) T₂ Fat-saturated – high signal c) T₁ with contrast – enhance MULTIPLE ADENOMAS (PANCREAS) d) T₂ high signal lesions

Nuclear medicine SRS (Somatostatin receptor scintigraphy) Some islet cell tumors have these receptors It is a whole body technique Use indium gastrinomas will show increase uptake PET Currently insufficient evidence for routine use (tumors have low metabolic rate)

PANCREATIC ANGIOGRAPHY If no functional tumor is detected do: Art stimulation with Ca⁺⁺ (will cause secretion of hormones – catheter into splenic art and do venous sampling with catheter into R hepatic vein and will get rise in hormone concentration

Octreotide scan with islet cell tumor and liver mets- high uptake

Thickened gastric wall – gastrinoma with Zollinger Ellison

Patient with prolactinoma – MEN 1 associated with multiple pancreas islet cell tumors, usually non functional

Further management Patient must be followed up, lesions may become malignant (6 months initially) Patient must be followed up, lesions may become malignant (6 months initially) Exclude other features of MEN1 (PPP, colon polyps,thymoma,carsinoid) – NM, colonoscopy / imaging,MRI brain, bloodtests (HPT, Calsium) Exclude other features of MEN1 (PPP, colon polyps,thymoma,carsinoid) – NM, colonoscopy / imaging,MRI brain, bloodtests (HPT, Calsium) Family screening Family screening * For this case - Mediastinoscopy with biopsy to determine cause of mediastinal pathology ? Infective/ ? malignant

REFERENCES 1. Brandt W E, Helms C A. Fundamentals Of Diagnostic Radiology 3 rd ed. Phicadelphia: Lippincott, 2006: , Adam A. Grainger and Allison's Diagnostic Radiology. Churchill Livingstone, 2008: Dähnert W. Radiology Review Manual 6th ed. Lippincott, 2007: Scarsbrook A F. Multiple Endocrine Neoplasia. Radiographics 2006; 26: Lewis R. Pancreatic Endocrine Tumors : Radiological Clinicopathologic Correlation. Radiographics 2010; 30 :