Transcript New Developments in Treatment of Insulinoma

New Developments in
Treatment of Insulinoma
By
Deborah Cottrell DVM
westendanimal.com
Insulinoma Overview
• Incidence in older ferrets may be close to 50%
• May be related to diet, but this is still speculation
• MEN 1 syndrome known to be hereditary in
people
• Article by May Van Dahm: Results of a Four Year
Study on Light Sensitivity in Ferrets
Insulinoma Overview
• Early warnings: drooling, staring into space,
ataxia, muscle twitching
• Progressing to screaming, seizuring, and death if
untreated
• Unlike dogs, most are benign, but almost always
multiple and recurring
• Timing of symptoms not related to food intake,
since insulinomas secrete large amounts insulin in
unpredictable cycles
Diagnosis
• Fast ferret four hours if possible, no more
than six
• Fasting blood glucose of less than 70 mg/dl
is pretty diagnostic
• Insulin/glucose ratio probably not necessary
• Radiographs to rule out gastric foreign body
as cause
Easy Blood Draw Technique
Foreign Bodies
• Can lower blood glucose if they don’t completely
occlude pylorus or small intestine and cause
classic symptoms of blockage.
Standard Treatments
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Surgical treatment: nodulectomy
Surgical treatment: partial pancreatectomy
Medical treatment: Prednisolone
Medical treatment: Diazoxide
Combining surgical and medical treatment
can buy another two years of quality life
Nodulectomy
• Advantage: Quick and easy
• Disadvantage: Less time without symptoms
Partial Pancreatectomy
• Advantage: Longer time without symptoms
• Disadvantages: Can create diabetes,
occasionally permanently
• Cannot remove right lobe near pylorus due
to presence of bile duct
Pancreatic Duct/Bile Duct
Medical Treatment
• Prednisone or Prednisolone
Body converts prednisone to prednisolone
Ferrets can tolerate high doses
Mobilizes carb stores to raise glucose level
• Diazoxide
Also well-tolerated, but efficacy is erratic
Expensive
Investigative Treatments
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Verapamil/Amlodipine
Streptozotocin
Doxorubicin (Adriamycin)
Octreotide
Verapamil/Amlodipine
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Based on one case report in human
Unknown efficacy in animals
Normally used for hypertension
Verapamil is anti-arrhythmic
Amlodipine is calcium channel blocker
Streptozotocin
• Specifically toxic to pancreatic beta cells
• May be carcinogenic
• Originally an antibiotic derived from the
microorganism Streptomyces achromogenes
• Not tested in ferrets
• Dog data two studies with mixed results
• Dosed at 500 mg/m2 every three weeks
Streptozotocin Warning
• Recent anecdotal evidence and small
numbers of trial cases have shown this drug
to be very toxic to ferrets at the previously
recommended dose. If you wish to try it, it
is suggested you use 200 mg/m2
Doxorubicin (Adriamycin)
• Dose used in ferrets much lower than people—
humans=60 mg/m2; ferrets=5 mg/m2
• Dog dose for insulinoma=30mg/m2
• Dose of 1 mg per ferret given IV every three
weeks for four treatments
• Few side effects at this dose
• Consider increasing dose to increase effectiveness
Octreotide
• Analog of somatostatin, a natural hormone
• Once daily dose of 50 micrograms
subcutaneously was used in both humans
and dogs
• Results extremely encouraging
• Efficacy in ferrets not well-known, but
appears safe and well tolerated
• Cost is $15-20 per 50 mcg vial
Alternative/Complementary
Treatments
• Glucosamine: warnings exist about
diabetics taking it, because it has potential
to raise blood sugar. May be helpful, and
also relieve mild arthritis
• Brewer’s yeast: Chromium may help, but
evidence is conflicting.
• Xiao Yao San: Widely used in TCM, but I
found NO evidence.
Drug Doses
• Pred: start at 0.25 mg/lb p.o. sid. Go up to 2 mg/lb bid with
few problems
• Diazoxide: start at 5 mg/lb p.o. bid. Go up to 15 mg/lb bid
with few problems
• Streptozotocin: extrapolate from dog dose of 500 mg/m2 iv
• Adriamycin: 30 mg/m2 iv standard dose
• Doxorubicin: 1 mg iv standard dose
• Verapamil: 1 mg/kg p.o. bid
• Amlodipine: 0.1 mg/kg p.o. bid
• Octreotide: 1-2 mcg/kg subQ bid-tid
References
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Eastman RC, Come SE, Strewler GJ, Gorden P, Kahn CR. Adriamycin
Therapy for Advanced Insulinoma. J Clin Endocrinol Metab. 1977
Jan;44(1):142-8.
Dobson J and Gorman T. Cancer Chemotherapy in Small Animal Practice.
Blackwell Scientific Publications. 1993, p 20.
Shimada A, Morita T, Ikeda N, Torii S, Haruna A. Hypoglycemic Brain
Lesions in a Dog with Insulinoma. J Comp Pathol 2000 Jan; 122 (1):67-71.
Moertel CG, Lavin PT, Hahn RG. Phase II Trial of Doxorubicin Therapy for
Advanced Islet Cell Carcinoma. Cancer Treat Rep. 1982 Jul;66(7);1567-9.
Dutton M. Case Studies of Doxorubicin for the Treatment of Ferret Insulinoma
(12 Cases). Exotic Mammal Medicine & Surgery 2004 May; 2.1.
Caplan ER, Peterson ME, Mullen HS, Quesenberry KE, Rosenthal KL, Hoefer
HL, Moroff SD. Diagnosis and Treatment of Insulin-secreting Pancreatic Islet
Cell Tumors in Ferrets: 57 cases (1986-1994). J Am Vet Med Assoc. 1996 Nov
15;209(10);1741-5.
References
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Igaz P, Igaz I, Racz K, Tulassay Z. Hereditary Tumors of the Endocrine
Pancreas. Orv Hetil. 2006 Feb 5;147(5):195-200.
Robben JH, vad den Brom WE, Mol JA, van Haeften TW, Rijnberk A. Effect
of Octreotide on Plasma Concentrations of Glucose, Insulin, Glucagon,
Growth Hormone, and Cortisol in Healthy Dogs and Dogs with Insulinoma.
Res Vet Sci. 2006 Feb;80(1):25-32.
Kishakawa H, Okada Y, Hirose A, Tanikawa T, Kanda K, Tanaka Y. Successful
Treatment of Insulinoma by a Single Daily Dose of Octreotide in Two Elderly
Female Patients. Endocr J. 2006 Feb;53(1):79-85.
Weiss CA, Williams BH, Scott MV. Insulinoma in the Ferret: Clinical
Findings and Treatment Comparison of 66 Cases. J Am Anim Hosp Assoc.
1998 Nov-Dec;34(6):471-5.
Bell R, Mooney CT, Mansfield CS, Jones BR. Treatment of Insulinoma in a
Springer Spaniel with Streptozotocin. J Small Anim Prac. 2005
May;46(5):247-50.
References
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Owecki M, Sowinski J. Successful Pharmacological Treatment of
Hyperinsulinemic Hypoglycemia with Verapamil and Amlodipine-Case
Report. Pol Merkuriusz Lek. 2005 Aug;19(110):196-8.
Eatwell K. Two Unusual Tumors in a Ferret (Mustela putorius furo). J Small
Anim Prac. 2004 Sept;45(9);454-9.
Van Dahm M. Results of a 4 Year Study on Light Sensitivity in Ferrets.