By Elisabeth Simone-Freilicher, DVM, DABVP (Avian practice)
Insulinomas are insulin-secreting tumors of the pancreatic beta cells. Unlike in dogs, these are usually benign functional tumors, although metastasis can occur rarely. Insulinomas have been reported in ferrets from two- to seven-years-old. There is no predilection due to sex. Current thinking is that high carbohydrate diets can overstimulate the pancreas, possibly contributing to the development of insulinoma, and there is very likely a strong genetic predisposition as well.
History of the patient can vary depending on how attentive the owner is. Many ferrets seem to gradually adjust to a lower blood glucose, and a fragile homeostasis may often be maintained until the glucose dips too low or an inciting event such as an illness tips the balance. The aware owner may notice that the ferret is subdued or sluggish first thing in the morning, but then seems better later in the day. The ferret may sleep more, or even have intermittent bouts of ataxia. Often the owner will attribute these signs to “aging” and not seek medical attention. The owner may not even think to mention these behaviors on history, but careful questioning can elicitthe information. Nausea, ptyalism, vomiting or gagging, or pawing at the mouth may also be described.
Physical examination findings can vary from a ferret which is subdued but alert (often with a somewhat obtunded aspect) to a hypothermic ferret which is lethargic, tremoring, or even actively seizuring. Bradycardia is usually present. The ferret may look normal otherwise, or signs of other illnesses such as adrenal gland disease may be concomitantly present.
Diagnostic blood glucose levels have been reported as below 40 mg/dL in some references, and below 60 mg/dL in others. I find that ferrets can have individual responses to blood sugars in the 40-60 mg/dL range. I have seen some ferrets alert and active at a blood glucose level of 42 mg/dL, and other ferrets cold, sluggish, and bradycardic at 58 mg/dL. Generally, if a ferret is symptomatic (either on physical examination or historically) and has a blood glucose level below 60 mg/dL, treatment is indicated as ferrets are very tolerant of treatment, and leaving a ferret with an untreated insulinoma can result in fatal hypoglycemia. Seizuring, tremoring, depressed, or poorly responsive patients should be hospitalized until blood sugar can be stabilized. Although IV dextrose may be needed, this should be kept to lowest concentration needed, as this will further stimulate insulin release and may actually drive the blood glucose lower. Oral sugars should be avoided as they will be even more insulin-stimulating then intravenous administration.
Blood glucose at intake can be highly variable, depending on when (and what) the ferret last ate. Many ferret owners are aware of the more obvious signs of hypoglycemia, and will give their ferrets a sugary liquid (or rub it on their gums) as an emergency treatment prior to presentation to the clinic. This can result in a falsely normal blood glucose measurement. A more definitive test is a timed 3-hour fast prior to sampling. Bloodwork to help identify or rule-out other underlying systemic disease is recommended, as underlying disease may be the inciting factor which led to destabilization of the ferret and the onset of more obvious clinical signs.
Imaging is usually not very helpful in detecting insulinomas, as the lesions are usually very small ‑ only a few millimeters or so. Very high quality ultrasonography and a skilled ultrasonographer can sometimes detect subtle changes, but in my experience, this is rare.
There is controversy regarding whether surgical or medical management is the best treatment for insulinomas in ferrets. Surgery is preferred in humans and dogs, and is considered the treatment of choice to stop or slow progression of the disease in ferrets. Surgery is associated with longer survival times (1.25-1.8 years vs. 0.5-1.5 years with medical management alone). However, several studies have shown that more than half the ferrets with nodulectomies or partial pancreatectomies will have recurrence of clinical signs in less than one year, and a small number will not achieve euglycemia post-operatively. Once informed of this, many owners decline surgical intervention in favor of medical management. In my experience, surgical intervention tends to be performed more often in ferrets which are not able to be stabilized medically, or have other known surgical diseases such as adrenal gland disease.
Principles of long-term medical treatment of the stable patient include prednisolone or prednisone (either is appropriate in ferrets) 0.5-1.5 mg/kg PO BID. Steroids should be titrated to the lowest dose needed to maintain euglycemia, as disease progression often necessitates incremental dose increases over time. An alcohol-free formulation is strongly recommended, since, similar to cats, ferrets find the taste and smell of alcohol so objectionable that the owner may find it impossible to reliably treat their pet. A 3-hour fasting blood glucose should be performed approximately three weeks after beginning medication as the ferret’s system stabilizes, and the dose adjusted as needed. Fasting blood glucoses should be checked every 3 months thereafter, or sooner if clinical signs recur. Famotidine is an appropriate adjunct to long-term steroid administration, particularly as ferrets are prone to ulcer-inducing Helicobacter mustelae, and it has been theorized that they experience increased gastric acid production with insulinomas.
If prednisone is insufficient to maintain glycemic control, diazoxide may be added to the treatment regimen, with the same monitoring parameters. Often the prednisone dose can be decreased if the diazoxide is successful. In addition, a low carbohydrate diet is recommended ‑ sugary treats should be discontinued and high protein meals should be offered. If the ferret is not seen to eat several times per day, supplemental high protein syringe-feeding should be performed.
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