Weakness & Collapse in a Beagle

Ann Della Maggiore, DVM, and Richard Nelson, DVM, Diplomate ACVIM

Blue, a 10-year-old spayed female beagle, presented to the University of California William Prichard Veterinary Teaching Hospital to be evaluated for a 4-month history of episodic weakness and collapse.

HISTORY

The owner noted that Blue was lethargic and experiencing short episodes of weakness and collapse. No seizures or unconsciousness had been noted. The time between episodes of weakness and collapse was variable, ranging from weekly to once every 3 to 4 weeks. Blue would no longer go on walks further than a mile.

No change in water consumption, appetite, urination, or defecation had been noted. Blue’s food consisted of a senior dry kibble fed twice daily along with several treats per day; she had not had any incidences of vomiting or diarrhea. Blue was not currently receiving any medications.

PHYSICAL EXAMINATION

Blue was obese with a body condition score of 8 out of 9. Vitals were within normal limits. There were no murmurs or arrhythmias, masses or organomegaly, or muscle atrophy. Peripheral lymph nodes were < 1 cm.

LABORATORY ANALYSIS

The initial laboratory evaluation consisted of a CBC, serum biochemical profile, and urinalysis. The CBC and urinalysis were unremarkable. Serum biochemical profile results included (Table 1):

• Mild increase in hepatocellular enzymes—alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
• Normal alkaline phosphatase (ALP)
• Marked hypoglycemia.

DIFFERENTIAL DIAGNOSIS

Based on history, signalment, and physical examination (including body condition), the primary differential diagnoses for hypoglycemia and episodic weakness (Table 2) in this dog included:

• Insulin-secreting beta-cell tumor (insulinoma)
• Extrapancreatic neoplasia (eg, hepatoma, leiomyoma, leiomyosarcoma, lymphosarcoma, etc)
• Atypical hypoadrenocorticism (Addison’s disease).

ADDITIONAL DIAGNOSTICS

Serum Insulin Concentration

Serum insulin concentration, from the blood sample demonstrating hypoglycemia (35 mg/dL), was significantly increased (> 310 mcU/mL; reference interval, 5-20 mcU/mL) and consistent with a diagnosis of an insulin-secreting beta-cell tumor.

Diagnostic Imaging

Thoracic radiographs were taken to determine if metastatic lesions were present; there were no significant abnormalities.

Abdominal ultrasound revealed a markedly enlarged (1.5 cm) mesenteric lymph node in the right cranial abdomen near the caudal vena cava, which was consistent with a metastatic lesion, and a 0.5-cm hypoechoic nodule in the liver, which could represent metastatic disease or benign change. No definitive pancreatic nodules were identified (Figure 1).

Computed tomography (CT) was not performed.

SURGICAL TREATMENT

Surgical exploration of the abdomen found nodules in the right and left limbs of the pancreas. The nodule in the right limb was resected and the majority of the left limb of the pancreas was removed (Figure 2). Several mesenteric lymph nodes were enlarged and also removed (Figure 3).

Histopathology

Histopathology confirmed:

• Infiltrative beta cell carcinoma in the left limb of the pancreas (Figures 4 and 5)
• Metastatic beta cell carcinoma in the mesenteric lymph nodes.

Neoplastic cells in both the pancreas and mesenteric lymph node were strongly immunoreactive to antibodies against insulin, confirming insulin-secreting beta-cell carcinoma (Figure 6). No evidence of neoplasia was noted in the right limb of the pancreas or the hepatic biopsy.

Post Operative Recovery

Blue recovered from anesthesia without complications. Blood glucose measurements stabilized at 70 to 100 mg/dL while in the hospital post operatively. No specific medical therapy was started postoperatively except for routine postoperative care, including IV fluids, pain medication, antiemetics, and small frequent meals of a low-fat diet.

FOLLOW-UP

Blue was discharged 4 days after surgery. She was initially fed a low-fat food (to reduce risk of pancreatitis post operatively) three times a day until the 1-month recheck. A follow-up was recommended in 10 to 14 days for suture removal and to recheck her blood glucose.

Two-Week Recheck

At the 14-day recheck, Blue’s incision had healed nicely and blood glucose measurements were 66 and 71 mg/dL.

One-Month Recheck

At the 1-month recheck, Blue’s blood glucose, which was measured at home, ranged from 50 to 80 mg/dL, with occasional signs compatible with hypoglycemia. The owners noted that Blue had improved significantly since surgery, but recurrence of clinical signs with concurrent low blood glucose measurements confirmed metastatic disease containing functional islet cells that were probably producing insulin.

Blue’s food was switched to a diet with a moderate fat content, a mix of insoluble and soluble fiber, and limited simple sugars; she was fed 4 times a day.

Four-Month Recheck

At the 4-month recheck, most of Blue’s blood glucose measurements were approximately 50 mg/dL; however, her measurements were 70 to 80 mg/dL in the evenings. Blue was prescribed prednisone, 2.5 mg (0.16 mg/kg) PO Q 12 H, and fed 4 meals a day.

OUTCOME

Blue was last evaluated 21 months following surgery. She had measured blood glucose concentrations of 50 to 80 mg/dL and was being maintained on prednisone (2.5 mg PO Q 12 H), with minimal hypoglycemic complications.

ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; CT = computed tomography

References

1. Polton GA, White RN, Brearley MJ, et al. Improved survival in a retrospective cohort of 28 dogs with insulinoma. J Small Anim Pract 2007; 48:151-156.
2. Tobin RL, Nelson RW, Lucroy MD, et al. Outcome of the surgical versus medical treatment of dog with beta cell neoplasia: 39 cases (1990-1997). JAVMA 1999; 215(1):226-230.
3. Cohn LA, McCaw DL, Tate DJ, et al. Assessment of five portable blood glucose meters, a point of care analyzer, and color test strips for measurement of blood glucose concentration in dogs. JAVMA 2000; 216:198.
4. Robbern JH, Pollak YW, Matus RE, et al. Comparison of ultrasonagraphy, computed tomography, and single photon emission computed tomography for the detection and localization of canine insulinoma. J Vet Intern Med 2005; 19:15-22.
5. Feldman EC, Nelson RW. Beta cell neoplasia. Canine and Feline Endocrinology and Reproduction, 3rd ed. St. Louis: Saunders, 2004, pp 616-644.
6. Bryson ER, Snead EC, McMillian C, et al. Insulinoma in a dog with pre-existing insulin dependent diabetes mellitus. JAAHA 2007; 43:65-69.
7. Dunn JK, Bostock DE, Herrtage ME, et al. Insulin-secreting tumours of the canine pancreas: Clinical and pathological features of 11 cases. J Small Anim Pract 1993; 34:325.
8. Lurye JC, Behrend EN. Endocrine tumors. Vet Clin North Am Small Anim Pract 2001; 31:1083-1110.

Ann Della Maggiore, DVM, is currently finishing her small animal internal medicine residency at University of California – Davis School of Veterinary Medicine. She received her DVM from UC – Davis and completed an internship at Veterinary Medical and Surgical Group in Ventura, California.

Richard Nelson, DVM, Diplomate ACVIM, is a professor in the Department of Medicine and Epidemiology at University of California – Davis School of Veterinary Medicine. His teaching is focused on small animal endocrinology. Dr. Nelson received his DVM from University of Minnesota and completed a small animal internal medicine residency at UC – Davis.