Pancreatic Beta Cell Neoplasia

Chapter 35 Pancreatic Beta Cell Neoplasia

Nyssa J. Reine, Jennifer Bonczynski

Tumors of the beta cells of the pancreatic islets are functional tumors that secrete excessive amounts of insulin independent of normal regulatory mechanisms. Hyperinsulinism causes hypoglycemia and corresponding clinical signs. Consider beta cell neoplasia in the differential diagnosis of hypoglycemia in middle-aged and older dogs.

DIAGNOSIS

The diagnosis of an insulin-secreting beta cell tumor requires initial confirmation of hypoglycemia and then documentation of simultaneous, inappropriately high insulin secretion.

Signalment

Signalment is not always useful in differentiating insulinoma from other common causes of hypoglycemia (Table 35-2).

• Insulin-secreting tumors typically occur in the middle-aged or older dog, with an age range of 6 to 14 years.

• There is no apparent sex or breed predilection, although the Labrador retriever, German shepherd, Irish setter, golden retriever, collie, fox terrier, and standard poodle are commonly affected in our hospital.

• Islet cell neoplasia is rare in cats.

Physical Examination

The physical examination of dogs with insulin-secreting tumors is surprisingly unremarkable.

• Weight gain is evident in some dogs and is probably a result of the potent anabolic effects of insulin.

• Peripheral neuropathies have been reported in dogs with insulin-secreting tumors and may be manifested as proprioception deficits, depressed reflexes, and muscle atrophy.

Laboratory Studies

• The only consistent abnormality found on the hemogram, biochemical panel, and urinalysis is hypoglycemia.

• Hypoalbuminemia, hypophosphatemia, hypokalemia, and an increase in alkaline phosphatase and alanine aminotransferase have been reported, but these findings are considered nonspecific and not helpful in achieving a definitive diagnosis.

• A correlation has not been found between liver enzyme elevations and metastasis of the pancreatic tumor to the liver.

• A normal physical examination and lack of abnormalities other than hypoglycemia on hemogram, serum biochemical panel, and urinalysis strongly suggest beta cell neoplasia as the cause of the hypoglycemia. It is important to systematically eliminate other causes before pursuing a diagnosis of insulinoma (see Table 35-2).

Blood Glucose Assay

• Up to 98% of dogs with insulinoma reportedly present with hypoglycemia.

• Dogs with insulin-secreting tumors occasionally may have a normal blood glucose concentration on random testing. Such a finding does not eliminate intermittent hypoglycemia as a cause of episodic weakness or seizure activity.

• If hypoglycemia is not present on initial examination, fast the patient to induce hypoglycemia. Measure blood glucose hourly. Closely observe the patient for worsening of signs (i.e., seizures or collapse).

• Typically, point-of-care glucose monitors are adequate for glucose assessment. If such equipment is not available, separate serum from red blood cells immediately to minimize effects of red blood cell metabolism.

• A fast of 8 hours or less is usually successful in demonstrating hypoglycemia in most dogs with insulin-secreting tumors.

• Concurrent assessment of serum fructosamine level may provide supportive evidence of insulinoma. Patients with insulinoma should have a low serum fructosamine in the presence of normoglycemia. This has recently been reported in a dog with insulinoma without measurable hypoglycemia.

Ultrasonography

Abdominal ultrasonography can be used to identify the tumor in the region of the pancreas and to assess for potential metastatic lesions in the liver and surrounding structures; however, negative findings do not rule out an insulin-secreting tumor or the presence of metastasis.

• Pancreatic masses are reportedly identified in 27% to 93% of dogs.

• In one study, only 42% of the metastatic lesions found with ultrasonography were confirmed at surgery.

Insulin Secretion Measurement

Confirmation of an insulin-secreting neoplasm requires documentation of inappropriate insulin secretion during hypoglycemia. Measuring serum insulin concentration when the blood glucose is <60 mg/dl (<40 mg/dl using glucose reagent strips) usually establishes the diagnosis. A 4- to 8-hour fast may be required to obtain this level of hypoglycemia, but when the blood glucose concentration falls below 60 mg/dl, the simultaneous blood insulin concentration is interpreted as follows:

• Blood insulin is above normal (>120 pmol/L): An insulin-secreting neoplasm is likely.

• Blood insulin is in the high-normal range (60–120 pmol/L): An insulin-secreting tumor is possible.

• Blood insulin is in the low-normal range (30–60 pmol/L): An insulin-secreting tumor has not been confirmed.

• Blood insulin in the low-normal range with hypoglycemia can be associated with non-islet cell tumors as well as insulin-secreting tumors. This is an indication for further diagnostics, includ-ing repeating the blood glucose and insulin determinations.

• Blood insulin is in the below-normal range (<30 pmol/L): Insulinopenia has been documented, and an insulin-secreting tumor has been ruled out.

MEDICAL TREATMENT FOR ACUTE HYPOGLYCEMIC CRISIS

The acute onset of clinical signs of hypoglycemia (see Table 35-1) typically occurs in the dog in the home environment or immediately postoperatively in the dog with an inoperable tumor or metastases. Therapy depends on the severity of clinical signs and the location of the dog or cat (i.e., home or hospital).

• In the hospital, administer 50% dextrose solution (1 ml/kg) slowly IV until clinical signs are controlled.

• If the dog is home, instruct the owner to rub a sugar-containing solution (e.g., Karo syrup) on the buccal mucosa until clinical signs are controlled.

• Dogs and cats with hypoglycemia should respond to the administration of glucose in 30 to 120 seconds.

Avoid overstimulation of the tumor when administering dextrose IV. Overzealous administration of dextrose can stimulate the tumor to release excessive amounts of insulin into the circulation and cause severe rebound hypoglycemia. A vicious cycle that is difficult to break may ultimately result in persistent seizures and eventually death.

• The goal of therapy is to control the clinical signs, not correct hypoglycemia, through the judicious administration of dextrose.

• Administer small amounts of dextrose slowly rather than large boluses rapidly to minimize stimulation of the tumor.

• IV dextrose supplementation should be replaced by frequent feedings as soon as possible.

• Constant rate infusion of glucagon has been used to successfully manage acute hyperinsulinemic-hypoglycemic crisis in a dog with insulinoma.

Seizures

Occasionally, seizures will persist despite normalization of blood glucose concentration. This may indicate the presence of cerebral edema or rarely the presence of a permanent cerebral lesion (i.e., necrosis). If intractable seizures due to hypoglycemia develop, take the following actions:

• Discontinue bolus injections of dextrose.

• Begin continuous IV infusion of 2.5% to 5.0% dextrose solution that is 1½ to 2 times the maintenance rate (90–120 ml/kg/day).

• Consider mannitol (0.5 g/kg IV) if signs of cerebral edema are present (i.e., anisocoria).

• Consider the addition of rapid acting glucocorticoids (i.e., dexamethasone sodium phosphate).

• Administer the somatostatin analog SMS 201-995 (octreotide; Sandostatin, Sandoz), 10 to 40 mg q8–12h SC, to decrease insulin secretion by the tumor.

• Anti-convulsants may be needed if seizures persist (i.e., phenobarbital; see Chapter 127).

SURGICAL TREATMENT

Surgical Anatomy

The pancreas consists of the right lobe, left lobe, and the body.

Right Lobe

The right lobe is located in the mesoduodenum adjacent to the descending duodenum. The proximal portion of the right lobe is intimately associated with the duodenum (Fig. 35-1). The proximal half of the right limb is supplied by the cranial pancreaticoduodenal artery, which is the terminal branch of the hepatic artery. The distal half of the right limb is supplied by the caudal pancreaticoduodenal artery, which is a branch of the cranial mesenteric artery. Damage to the pancreaticoduodenal vessels may result in avascular necrosis of the duodenum.

Figure 35-1 Anatomy and blood supply of the right and left lobes of the pancreas.

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Tags: Saunders Manual of Small Animal Practice

Aug 27, 2016 | Posted by admin in SMALL ANIMAL | Comments Off

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