Polyneuropathy related to insulinoma in a dog

What is an insulinoma

An insulinoma is a malignant pancreatic tumor that inappropriately secretes excessive insulin, resulting in severe hypoglycemia.  They are functional neuroendocrine tumors that originate in the beta cells of the islets of Langerhans, they tend to be very aggressive and relapse locally as well as metastasize. Any breed of dog can be affected, but large breeds tend to be overrepresented with no sex predilection.

Clinical presentation

Most affected dogs do not have abnormalities on physical examination, and early clinical signs related to the disease can be sporadic and vague. It’s true that neurologically what you will typically see will be the changes related to hypoglycemia: weakness and collapsing episodes or seizures. These signs might be related to exercise or around food: Hypoglycemia is secondary to exercise or fasting but also after excess insulin release after eating.

Although typical neuro signs of hypoglycemia are weakness and seizures, with insulinoma, on some rare occasions like on this case a what it’s believed to be a paraneoplastic polyneuropathy can develop.

Description of the video

Here we can see a 6 years old German Shepherd presented for a progressive few weeks of difficulties walking and collapsing. On this video you can see the combination of the weakness and the paresis. This case presents an ambulatory tetra paresis, worst on the hind limbs. he collapses, he’s weak. However, we have normal proprioception with inconsistent hind limb withdrawal and absent patellar reflex.

Very important on this video we don’t see ataxia, we don’t see incoordination, just the difficulties walking and the collapse: see how he tumbles on the front limbs? These insulinoma polyneuropathies are extremely difficult, because you might have the combination of Central and Peripheral nervous system disease: You might have seizures (CNS) but then reduced spinal reflexes (peripheral nervous system)

Diagnosis of insulinoma
Blood Glucose:  A simple low blood glucose level should make us concern. DO NOT ignore a low glucose level EVER! From this low glucose we might think on the possibility of increase insulin release.
Insulin-to-Glucose Ratio: This test capitalizes on the lack of response to physiologic negative feedback inhibitory loops that decrease insulin secretion when the glucose is low. A positive insulin-to-glucose ratio demonstrates an inappropriately elevated insulin level in the setting of hypoglycemia. So you need to do this test on the same blood where you found the hypoglycemia.

Imaging: Thoracic radiography and abdominal ultrasound are recommended to assess for the presence of a possible pancreatic mass and associated metastatic disease (eg, lymph nodes, liver, lungs). Conventional computed tomography (CT) with contrast has an improved sensitivity of 71% for pancreatic lesions

Diagnosis of the polyneuropathy related to insulinoma

A polyneuropathy will present with weakness, paresis and reduced spinal reflexes. The difficult part on these cases is that your neurological examination and localization could be very complicated as this could localize multifocal: you can have the peripheral and central nervous system affected.

To prove that indeed the nerves are not working properly, electrodiagnosis will be needed. You will see a reduction in amplitude and/or velocity of nerve conduction (as you can see on the video) and abnormal spontaneous muscle activity  when performing the EMG.

Treatment of insulinoma

Surgical removal of the tumor provides the best chance for relief of clinical signs and the best survival times. Moreover, allows complete staging via biopsy of regional lymph nodes and liver to determine the extent of suspected metastatic disease.

Medical management of insulinoma is possible in patients that are not good surgical candidates, don’t want to do surgery, or that have persistent hypoglycemia after surgery (if the tumor can’t be removed completely). This approach includes dietary management as well as medications, such as prednisone, diazoxide,
and octreotide.

What is the prognosis for recovery

Insulinomas can be aggressive tumors…and on top of that…little is known about the paraneoplastic signs. The prognosis of recovery of the polyneuropathy after surgical removal is unknow. Some dogs might improve a bit after starting steroids, but medical treatment won’t provide a long-term recovery.

A paraneoplastic syndrome is a a set of signs that develop distant to a cancer in the body . We believe this is due to the production of chemical signaling molecules (such as hormones and cytokines)  by tumor cells or by an immune response against the tumor. The paraneoplastic signs are not related to the mass effect or the local presence of cancer cells but satellites effects. In certain occasions the paraneoplastic signs might appear even before the local signs of cancer.