Suspected congenital hyperinsulinism in a Shiba Inu dog

Abstract

A 3-month-old male intact Shiba Inu dog was evaluated for a seizure disorder initially deemed idiopathic in origin. Seizure frequency remained unchanged despite therapeutic serum phenobarbital concentration and use of levetiracetam. The dog was documented to be markedly hypoglycemic during a seizure episode on reevaluation at 6 months of age. Serum insulin concentrations during hypoglycemia were 41 U/μL (reference range, 10-29 U/μL). The dog was transitioned to 4 times per day feeding, diazoxide was started at 3.5 mg/kg PO q8h, and antiepileptic drugs were discontinued. No clinically relevant abnormalities were identified on bicavitary arterial and venous phase contrast computed tomographic imaging. The dog remained seizurefree and clinically normal at 3 years of age while receiving 5.5 mg/kg diazoxide PO q12h and twice daily feeding. Seizures later occurred approximately twice per year and after exertion, with or without vomiting of a diazoxide dose. Blood glucose curves and interstitial glucose monitoring were used to titrate diazoxide dose and dosing interval. Congenital hyperinsulinism is well recognized in people but has not been reported in veterinary medicine.

Juvenile hyperinsulinism in a Maine Coon kitten

“…In humans, a diagnosis of congenital hyperinsulinism entails demonstration of persistent hypoglycemic hyperinsulinism, exclusion of other causes, genetic testing and positron-emission tomography. 23 In the only other reported veterinary case, congenital hyperinsulinism was diagnosed in a 3-year-old Shiba Inu on the basis of persistent hypoglycemia, exclusion of other causes, and no findings on contrast CT, 12 similar to the diagnostic process in this case; however, histopathology was not performed as the dog responded well to therapy.…”

“… 9 The necropsy findings of possible islet hyperplasia with no neoplastic beta cells ruled out insulinoma and was considered strongly suggestive of congenital hyperinsulinism. 10 – 12 …”

“…9 The necropsy findings of possible islet hyperplasia with no neoplastic beta cells ruled out insulinoma and was considered strongly suggestive of congenital hyperinsulinism. [10][11][12] Peripheral neuropathy has been described as a consequence of insulinoma and chronic hypoglycemia in humans, dogs and cats. 10,13 It has been theorized that the neuropathy present in cases of insulinoma may result from metabolic derangements due to severe and prolonged hypoglycemia.…”

“…In 27-47% of humans, no genetic basis is found and the pathologic process is unknown. 12 Both focal and diffuse forms of hyperinsulinism have been described, with the focal forms characterized by a clonal expansion of beta cells that most often express mutations of the potassium genes ABCCC8/KCNJ1; these are often clinically more severe and drug resistant. 25 In the diffuse form, nuclear enlargement of beta cells is seen, often fourfold vs normal beta cells.…”