May 2025

In this VETgirl online veterinary continuing education blog, Dr. Amy Kaplan, cVMA, DACVECC, MRCVS reviews canine insulinoma, including how to recognize the clinical signs, what diagnostics you need (STAT red top!), how to treat, and what the overall prognosis is. Insulinomas are a rare and tricky-to-diagnose pancreatic tumor in dogs, but knowing when to have this on your differential list can help you catch them early and improve patient outcomes.

Canine Insulinoma: Recognition, Diagnosis & Treatment

By Dr. Amy Kaplan-Zattler, cVMA, DACVECC, MRCVS
VETgirl CE Program Manager

Insulinomas are small – generally < 2.5 cm in diameter – and more often found in the right or left limbs of the pancreas as opposed to the body of the pancreas. These are functional tumors, meaning they overproduce insulin resulting in hypoglycemia. Due to an impaired negative feedback mechanism, neoplastic pancreatic beta cells fail to suppress insulin release in response to falling glucose levels, thus exacerbating the hypoglycemia.

What Signalment Develops Canine Insulinoma?

Generally, it’s the older (> 9 years of age), larger breed dogs that we see with insulinoma including:


However, small breeds such as West Highland White Terriers, Chihuahuas and Yorkies are also at risk. This author has diagnosed insulinomas (confirmed on histopathology) in a variety of middle-aged (e.g. 6-8 year old) smaller breed dogs (e.g. Chihuahua mix, French Bulldog), so it’s important to keep this differential in your sights even for small dogs of middle to advanced age.

Clues Owners Might Notice

The early signs of insulinomas are vague and nonspecific. A common early complaint from owners is “My dog is acting ‘spacy’ and ‘lost’.” Symptoms can be episodic – usually triggered by exercise or fasting – and between episodes, dogs act totally fine! So, owners may disregard these infrequent, mild episodes and not bring their dogs in for a check-up until the frequency or severity of symptoms gets worse. As insulin production increases – possibly due to tumor growth, metastasis, or chronicity of neuroglycopenia (low glucose levels in the brain) –  we start to see more severe symptoms.

 

Variability of Neurologic Signs

Now, you may wonder “Why do some dogs wag their tail with a blood glucose (BG) of 40 mg/dL (2.2 mmol/L) and others develop seizures?” The degree of neurologic impairment does not directly correlate with a specific blood glucose level. Individual responses will vary due to the following:

  • magnitude of BG change
  • speed of BG change
  • duration of hypoglycemia

With gradual or mild BG changes, as seen in episodic hypoglycemia, clinical signs tend be subtle behavioral changes (e.g. confusion, weakness) and often resolve as BG normalizes. These dogs may present with normal or low-normal BG, but more commonly, they will be hypoglycemic, which can be confirmed by running a quick BG on your handheld glucometer or in-house analyzer.  Reminder –  anemia falsely elevates BG on handheld glucometers (e.g., Alphatrak®). On the other end of this spectrum, rapid, severe or persistent drops in BG can lead to more serious neurologic issues like tremors or seizures.

How do we Diagnose Insulinomas in Dogs?

First, we have to make sure we keep this differential on our radar for any dog presenting with subtle or episodic behavior changes. For emergency doctors, we might more commonly see these patients for seizures – so be sure to keep a glucometer handy when triaging those seizure patients!
Next, we investigate whether the patient fulfills Whipple’s triad:

    1. Hypoglycemia
    2. Exhibits clinical signs related to hypoglycemia
    3. Demonstrates resolution of these clinical signs upon restoration of blood glucose levels (usually through IV dextrose or feeding)

However, Whipple’s triad isn’t specific to insulinomas. Other differentials need to be ruled out, such as insulin-like growth factor-secreting tumors (e.g., hepatocellular carcinoma, leiomyosarcoma, lymphoma), sepsis, hypoadrenocorticism, portosystemic shunts, liver failure, toxicants (e.g., xylitol, blue-green algae, SGLT2 inhibitors), exogenous insulin overdose, glycogen storage disease, and lab error. Some of these differentials can be ruled out with basic bloodwork (e.g., CBC, biochemistry panel, urinalysis), possibly a cortisol level to rule out hypoadrenocorticism, and, if no other causes are identified, a blood sample can be submitted to a veterinary diagnostic laboratory for an insulin-to-glucose ratio (IGR). An elevated IGR indicates an excess in insulin (resulting from overproduction and impaired negative feedback on insulin production).

Image courtesy of Dr. Heidi Fay

This test is performed during periods of hypoglycemia and BEFORE administration of dextrose supplementation. What that means to you? YOU MUST REMEMBER to fill that extra red top tube BEFORE giving a dextrose bolus or starting a dextrose CRI!

 

Gold standard imaging for insulinomas is a contrast-enhanced CT scan to localize the tumor, check for metastasis, and help assign a TNM stage (TNM stands for tumor, node, and metastasis). Abdominal ultrasound may be more easily accessible and affordable, but is less reliable, identifying only about 1/3 of insulinomas. Ultrasound is still recommended for obtaining FNAs or biopsies of hepatic lesions or abdominal LN enlargements from local spread of insulinomas. Remember to also get a 3-view met check of the chest.

Labrador retriever in CT. Photo courtesy of Amanda M. Shelby.

Are Insulinomas Treatable?

Ideally, complete removal with surgery (e.g., enucleation, partial pancreatectomy) is recommended and has been shown to prolong life expectancy by a few years. However, at the time of diagnosis, metastasis is present in about ½ of cases, resulting in a reduction in life expectancy even if the primary tumor is surgically removed.

Medical management involves maintaining adequate glucose levels through medications, feeding adjustments, and exercise restriction.  Diazoxide and glucocorticoids (i.e. prednisolone) are the primary medications used to reduce the frequency and severity of hypoglycemia. Diazoxide is a benzothiadiazine approved by the FDA for treatment of hyperinsulinism in people. It raises blood glucose levels by binding to the ATP-sensitive potassium (KATP) channels on pancreatic beta cells, causing excessive polarization, preventing their ability to release insulin. Additionally, diazoxide enhances hepatic glucose production while reducing hepatic glucose uptake. Side effects of diazoxide are not commonly seen in dogs, but may include anorexia, vomiting, and ptyalism. Glucocorticoids such as prednisone and prednisolone elevate blood glucose levels by increasing insulin resistance in skeletal muscle and adipose tissue, reducing glucose uptake, stimulating hepatic gluconeogenesis, and promoting glucagon secretion from pancreatic alpha cells. Streptozocin and octreotide are no longer routinely recommended for treating canine insulinoma due to their limited proven efficacy and potential adverse effects in dogs. Meals should be small and fed frequently – up to 4-6 meals per day – with a diet high in protein, fat, and complex carbohydrates, but low in simple carbohydrates to minimize glucose spikes that can trigger additional insulin release. Exercise should be restricted to short leash-walks to minimize glucose requirements.

Treating the Hypoglycemic Canine Insulinoma Patient

As hypoglycemia can be life-threatening, it requires prompt identification and treatment. Again, a red top tube should be collected for insulin levels PRIOR to dextrose supplementation to send out for an IGR level. Conscious dogs can be fed, while more clinically affected patients should be promptly treated with 50% dextrose (1 mL/kg diluted 1:4 with saline, IV), given over several minutes to avoid sudden spikes in blood glucose that can trigger additional insulin secretion and rebound hypoglycemia. For patients in status epilepticus, prompt therapy is warranted – immediate IV catheter placement, bolus of 50% dextrose diluted, followed immediately by a CRI (typically of 5% dextrose, and slowly weaned to 2.5% dextrose supplementation as needed); rarely, in severe cases, persistent seizure activity after normalization of BG may require administration of benzodiazepines (e.g., midazolam, diazepam) and additional anti-epileptic medications. (When in doubt, don’t forget to frequently check that BG!) Not sure how to calculate a dextrose CRI–check out this quick video HERE!

Video 1. Insulinoma patient with persistent focal and generalized seizures despite BG normalization as a result of chronic neuroglycopenia. A 1 mL/kg bolus of dextrose (diluted; IV) raised the patient’s BG from 45 mg/dL (2.5 mmol/L) to 288 mg/dL (15.5 mmol/L), but seizure activity continued as shown here. Video courtesy of Dr. Amy Kaplan.

Video 2. Same patient after treatment with 0.5 mg/kg midazolam IV. Video courtesy of Dr. Amy Kaplan.

While feedings and IV dextrose provide temporary relief, they can also trigger further insulin release from the tumor. Glucagon is another option for raising BG without stimulating insulin release, though it’s not always accessible or affordable. Low-dose dexmedetomidine (1 mcg/kg) can also help inhibit insulin release and is often included in anesthesia protocols for insulinoma patients.

What’s the Prognosis for Canine Insulinoma?

If metastasis is present, the prognosis is guarded. With medical management alone, median survival is just 4 months (range 0-8 months) However, in dogs without detectable metastasis, surgical resection can lead to a good quality of life, with a life expectancy of 1 to 3 years (median 2.5 years), and some cases surviving up to 5 years post-surgery. When in doubt, pet owners must be educated on the importance of medical vs. surgical management, clinical signs to monitor for, and related prognosis for treatment of canine insulinoma.

Abbreviations:

BG: blood glucose
CBC: cell blood count
CRI: constant rate infusion
CT: computed tomography (i.e., cat scan)
FNA: fine needle aspirate
IGR: insulin to glucose ratio
IV: intravenous
LN: lymph node
TNM: tumor, node, metastasis (staging)

Resources:

  1. Buishand FO. Current Trends in Diagnosis, Treatment and Prognosis of Canine Insulinoma. Vet Sci. 29;9(10):540.
  2. Datte K, Guillaumin J, Barrett S, et al. Retrospective evaluation of the use of glucagon infusion as adjunctive therapy for hypoglycemia in dogs: 9 cases (2005-2014). J Vet Emerg Crit Care. 2016;26(6):775-781.
  3. Green R, Musulin SE, Baja AJ, et al. Case report: Low dose dexmedetomidine infusion for the management of hypoglycemia in a dog with an insulinoma. Front Vet Sci. 2023;10:1161002. Published 2023 Apr 6.
  4. Ryan D, Pérez-Accino J, Gonçalves R, et al. Clinical findings, neurological manifestations and survival of dogs with insulinoma: 116 cases (2009-2020). J Small Anim Pract. 2021;62(7):531-539.

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