PRACTICAL GASTROENTEROLOGY • SEPTEMBER 2010 57

Adult Onset Nesidioblastosis: A Diagnostic Dilemma

INTRODUCTION

Nesidioblastosis is defined as diffuse proliferationof pancreatic islet cells budding from ductalepithelium.1 The term “nesidioblastosis,” intro-

duced by Laidlaw in 1938, is derived from Greek lan-guage “nesidia” stands for islets and “blastos” for germ.Adult-onset nesidioblastosis associated with hyperinsu-linemic hypoglycemia is a rare entity, with less than 75published cases till date.2 There have been only tworeported cases of nesidioblastosis in patients older thanour patient;3,4 and this is the first reported case of nesid-ioblastosis in a dialysis patient, which makes it unique.

CASE PRESENTATIONA 79-year-old African-American patient was admittedto a tertiary care hospital with altered mental status

secondary to hypoglycemia. Patient was hospitalized 3months prior with similar presentation and her symp-toms were attributed to dysphagia from deconditioningand a percutaneous endoscopic gastrostomy (PEG)tube was placed. However, the patient continued tohave hypoglycemic episodes despite placement ofPEG. As a result, a workup for organic cause of hypo-glycemia was initiated.

Laboratory results showed a C-peptide level of13.0 ng/ml (normal, 0.9–4.3 ng/ml), insulin level of 27IU/ml (normal, 1.4–14 IU/ml) and the urine sulphony-lurea screening test was negative. CT and MRI scansof the abdomen and pelvis did not reveal any tumors.This was followed by a complete body scan that wasalso unremarkable.

As a result, invasive tests were launched to findthe exact cause of hypoglycemia. ASVS (intra-Arterialcalcium Stimulation with Venous Sampling) test wasperformed by Interventional Radiology using fluo-roscopy. 0.025 mEq/kg of calcium was injected in thegastroduodenal artery, superior mesenteric artery andsplenic artery. Hepatic vein samples for insulin levels

A CASE REPORT

Dushyant Singh, MD, University of Missouri KansasCity School of Medicine, Kansas City, MO. ReetuSingh, MD, Shawnee Mission Medical Center,Shawnee Mission, KS.

by Dushyant Singh, Reetu Singh

Nesidioblastosis is a rare entity usually seen in the neonates. Our case is unique as thiswould be the only reported patient on dialysis and there are only 2 patients reported inthe literature that are older than our patient. Nesidioblastosis, while exceedingly rarein adult populations, should be considered in the differential diagnosis of severe hypo-glycemia. While extensive laboratory and imaging tests could not identify the pathol-ogy, ASVS test (intra-arterial calcium stimulation with venous sampling) played apivotal role in the diagnosis by localization of the pancreatic lesion. Nesidioblastosis canoften be unrecognized, and early identification and prompt treatment plays a criticalrole in the management of such patients.

PRACTICAL GASTROENTEROLOGY • SEPTEMBER 201058

A CASE REPORT

Adult Onset Nesidioblastosis

were drawn from each artery at baseline and afterinjection with calcium. There was a two-fold increasein insulin levels from gastroduodenal and splenic arter-ies after injection of calcium suggesting hyper-secre-tion of insulin from pancreas supplied by these arteries(Figure 1).

Based on ASVS test results, patient underwent aexploratory laparotomy and a successful distal pancre-atectomy with splenectomy was performed. Intraoper-ative ultrasound also failed to localize the lesion.

Post-operatively, patient had no further hypo-glycemic symptoms. Pathology showed islet cellshyperplasia (Figure 2A and B) with immunohistochem-ical staining positive for chromogranin (Figure 3A and B).

DISCUSSIONNesidioblastosis is usually seen in neonates.5 It is veryinfrequently described in adults as a cause of hypo-glycemia with less than 100 cases were published tilldate.2

In neonates, the pathogenesis is related to disrup-tion of normal relationship between blood glucose leveland insulin secretion due to dysfunction of adenosinetriphosphate (ATP) dependant potassium channel of thebeta-cells. In infants, mutation is seen in SUR1/Kir 6.2gene complex on chromosome 11p 14–15.7 In adults,no such relation to SUR1/Kir is found.

Clinically, patients with nesidioblastosis have neu-roglycopenic episodes exclusively after meal inges-tion. For diagnostic evaluation other causes of organichypoglycemia such as exogenous insulin ingestion,sulphoylurea use and insulinoma need to be ruled out

(Table 1). As mentioned above, patients with nesid-ioblastosis have post-prandial hypoglycemia, and neg-ative 72-hour fasts2 that helps to distinguishinsulinoma from nesidioblastosis.

Nesidioblastosis has been well established inpatients with gastric bypass surgery.8 Therefore, clini-cians need to be cautious in ascribing postprandialhypoglycemic symptoms to the dumping syndrome.8

Standard radiologic test like spiral CT, MRI, endo-scopic ultrasound may fail to localize any pancreatictumor and selective intra-arterial calcium-stimulationtest with venous sampling should be considered(ASVS). It is considered the best diagnostic test withsensitivity of approximately 100%. In this test, a rapidbolus of calcium gluconate is administered via acatheter in the celiac axis and the splenic, superiormesenteric, and gastroduodenal arteries. Blood sam-ples are obtained through a catheter in the right hepatic

Table 1. Differentiating features of various clinical scenarios with hyperinsulinsim.

PostprandialC-peptide Insulin Proinsulin Sulfonylurea Hypoglycemia 72-hour fast

Exogenous Insulin Normal High Low Absent Negative Negative

Sulfonylurea High High High Present Negative Negative

Insulinoma High High High Absent Negative Positive

Nesidioblastosis High High High Absent Positive Negative

Figure 1. Intra-arterial calcium stimulation with venous sam-pling shows a two-fold increase in insulin levels from gas-troduodenal and splenic arteries after injection of calcium.

Hepatic artery

Gastrodudenal artery

Superior mesenteric artery

Splenic arteryInsulinlevels

(IU/mL)

18

16

14

12

10

8

6

4

2

0

PRACTICAL GASTROENTEROLOGY • SEPTEMBER 2010 59

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Adult Onset Nesidioblastosis

vein before injection and at several intervals after theinjection. These blood samples are then tested for glu-cose, calcium, and insulin levels. An excessive insulinresponse from calcium stimulation in an artery sug-

gests the site of lesion. It can also be done intra-oper-atively to help the surgeon in ensuring proper tumorresection depending on the arterial distribution indicat-ing hyperfunction of the beta cells.

Figure 2A and B. Pathology slides of the pancreas showingislet cell hyperplasia.

Figure 3. Pathology slides of the pancreas showing positivestaining with chromogranin (A) and synaptophysin (B).

A A

B B

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Adult Onset Nesidioblastosis

On pathological slides, nesidioblastosis is charac-terized by diffuse hypertrophy of beta cell islets andislet-like cells budding off exocrine ducts, which stainpositive for chromogranin.

Pancreatic resection is the definitive treatment,however, the extent of surgical resection is still con-troversial.9 Most surgeons perform distal pancreatec-tomy; however, some have treated by 90–95%pancreatectomy.10 Near-total pancreatectomy is asso-ciated with insulin-dependant diabetes and also withexocrine pancreatic dysfunction.10 If surgery fails or iscounter-indicated, medication, such as diazoxide,6

sandostatin11 or verapamil, can be used.

CONCLUSIONNesidioblastosis, a rare entity, is one of the rare causesof hyperinsulinemic hypoglycemia in adults. It is a dis-ease usually described in neonates, but our 79-year-oldpatient had this unusual case of hypoglycemic eventsthat required extensive evaluation. Nesidioblastosiscan often be unrecognized, and early identification andprompt treatment plays a critical role in the manage-ment of such patients. n

References1. Laidlaw, GF et al. Nesidioblastoma, the islet tumor of the pan-

creas. Am J Pathol 1938; 14: 125-134.2. Raffel A, Anlauf M, Hosch SB, Krausch M et al, Hyperinsuline-

mic hypoglycemia due to adult nesidioblastosis in insulin-dependent diabetes. World J Gastroenterol. 2006 Nov 28;12(44):7221-4.

3. Walmsley D, Matheson NA et al. Nesidioblastosis in an elderly-patient. Diabet Med 1995; 12(6): 542-545.

4. Karnauchow PN. Nesidioblastosis in adults without insularhyperfunction. Am J Clin Pathol 1982; 78(4): 511-513.

5. De Lonlay DP, Poggy-Travert F et al. Clinical features of 52neonates with hyperinsulinism. N Engl J Med 1999; 340(5):1169-1175.

6. Harness JK, Geelhoed GW et al. Nesidioblastosis in adults: a sur-gical dilemma. Arch Surg 1981; 116(5): 575-580.

7. Sperling, MA. ATP-sensitive potassium channels—neonatal diabetes mellitus and beyond. New Engl J Med 2006; 355:507.

8. Service GJ, Thompson GB et al. Hyperinsulinemic hypoglycemiawith nesidioblastosis after gastric-bypass surgery. N Engl J Med2005; 353(3): 249-254.

9. Hirshberg B, Libutti SK et al. Blind distal pancreatectomy foroccult insulinoma, an inadvisable procedure. J Am Coll Surg2002 194 (6): 761-764.

10. WittelesRM, Strauss II FH et al. Adult-Onset nesidioblastosiscausing hypoglycemia: an important clinical entity and continu-ing treatment dilemma. Arch Surg 2001; 136(6): 656-663.

11. Mozell EJ, Woltering EA et al. Adult onset nesidioblastosis:response of glucose, insulin and secondary peptides to therapywith sandostatin. Am J Gastoenterol 1990; 85(2): 181-188.

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