Printer Friendly

Diabetes Mellitus With Concurrent Cerebellar Degeneration and Necrosis in a Domestic Goose (Anser anser domesticus).

Abstract: A 5-year-old sexually intact male Toulouse goose (Anser anser domesticus) was presented for ataxia, polyuria, and polydipsia. The goose was cachectic and exhibited head tremors. Results of plasma biochemical analysis and point-of-care glucometry revealed persistent hyperglycemia. Despite supportive care and oral glipizide, the goose died within 48 hours of presentation. Necropsy revealed severe pancreatic atrophy and fibrosis with regionally extensive cerebellar encephalomalacia and generalized Purkinje cell degeneration and necrosis. On a wet basis, hepatic zinc concentration was determined to be twice the reference interval by atomic absorption spectroscopy. Based on these findings, the pancreatic insufficiency with secondary diabetes mellitus was attributed to chronic zinc toxicosis. Despite birds' relative resistance to high blood glucose concentrations, prolonged hyperglycemia is suspected to have caused selective Purkinje cell degeneration and necrosis by glial activation, mitochondrial dysfunction, and glutamate toxicity, which resulted in the clinically observed motor deficits. This is consistent with experimental diabetic rat models. This case highlights the need for further investigation of the complex pathophysiology of diabetes mellitus in birds.

Key words: diabetes mellitus, hyperglycemia, neuropathy, pancreatitis, zinc, avian, goose, Anser anser domesticus

********** Clinical Report

An approximately 5-year-old sexually intact male Toulouse goose (Anser anser domesticus) was presented to the Zoological Medicine Service at the Louisiana State University Veterinary Teaching Hospital for ataxia, polyuria, polydipsia, weight loss, and difficulty lifting its head. The bird was housed with another goose, several domestic ducks, and chickens in a large outdoor pen with a coop for roosting at night and was fed commercial pelleted diets, cracked corn, and table scraps.

The bird was bright, alert, and responsive but was cachectic in spite of being polyphagic; it exhibited ataxia and head tremors, and had difficulty balancing while preening. The ventral plumage was soiled and droppings were profuse and watery, consistent with polyuria. Evaluation of a complete blood count of the goose revealed anemia (packed cell volume 30%; reference interval, 38%-58%), (1) while evaluation of plasma biochemical analysis indicated the bird was hyperglycemic (838 mg/dL; reference interval, 179-241 mg/dL) (2) and had an elevated creatine kinase level (3402 U/L; reference interval, 110-480 U/L). (2)

The recommended diagnostic and treatment plans included coelomic ultrasound, intravenous or intraosseous fluid therapy, parenteral insulin, and glucose curve, in addition to supportive care. These options were declined by the owners because of financial constraints and concerns about administering parenteral insulin at home. Consequently the treatments that were provided to the patient were fluid therapy (50 mL/kg SC q12h, Plasma-Lyte, Baxter Healthcare Corporation, Deerfield, IL, USA), supplemental feeding by gavage (60 mL PO ql2h, Emeraid Omnivore, Emeraid LLC, Cornell, IL, USA), and free access to water, cracked corn, and chick starter (Layena Chicken Feed, Nestle Purina PetCare Company, St. Louis, MO, USA). The next day, blood glucose levels were consistently too high to read on a point-of-care glucometer (AlphaTRAK 2, Abbott Laboratories, North Chicago, IL, USA). Because of persistent hyperglycemia, diabetes mellitus was suspected. Glipizide (1 mg/kg PO q12h, Sandoz Inc, Princeton, NJ, USA) therapy was initiated and administered once. The next morning, less than 48 hours after presentation, the goose was found dead and was submitted for postmortem examination.

At necropsy, the goose was severely emaciated (weight = 4.3 kg) with a prominent keel bone and generalized pectoral muscle atrophy. The pancreas was significantly atrophied and firm, measuring 2.5 x 0.5 x 0.4 cm (Fig 1). No gastrointestinal foreign bodies were identified. Qualitative fecal flotation results were negative for the presence of intestinal parasite ova or coccidian oocysts. Postfixation, longitudinal sectioning of the cerebellum revealed generalized attenuation of folia with a discrete, regionally extensive focus of malacia as indicated by softening and yellow discoloration of the neuropil (Fig 2). No other significant gross findings were observed.

Histologically, pancreatic acini were largely replaced by abundant mature fibrous connective tissue with mild to moderate interstitial lymphoplasmacytic inflammation (Fig 3A). Remaining acinar cells were frequently degenerate, characterized by cytoplasmic vacuolation, shrunken angular cellular outlines, and regional depletion of zymogen granules. Pancreatic islets were multifocally degenerate, characterized by pale, swollen, lacy eosinophilic to clear vacuolated cytoplasm (Fig 3B). Pancreatic ducts were multifocally ectatic, containing a mixture of basophilic mucinous secretory product admixed with exfoliated epithelium and degenerative leukocytes. Ductular epithelium was segmentally denuded and necrotic, characterized by hypereosinophilic cytoplasm with pyknotic to karyorrhectic nuclei. Periductular connective tissues were infiltrated by a moderate number of lymphocytes and plasma cells, with fewer histiocytes. Cerebellar folia were globally attenuated with a focally extensive focus of encephalomalacia (Fig 4A). Within all folia, segmental loss, degeneration, and necrosis of Purkinje cells were evident (Fig 4B). The latter 2 features were characterized by clear discrete vacuoles and yellow granular periodic acid-Schiff-positive pigment within Purkinje cell perikarya, interpreted to be lipofuscin, or shrunken angular hypereosinophilic neurons (Fig 4B) with pyknotic nuclei. In areas of extensive Purkinje cell loss, neuropil contained accumulations of reactive astrocytes containing pale, swollen, vesicular nuclei (Bergmann's astrocytes) and the granular layer was markedly thinned and hypocellular. The focally extensive area of grossly discernible malacia was characterized by regional collapse of foliar architecture, with absence of stratification of cerebellar architecture (Fig 4A). Residual cerebellar grey matter within the area of encephalomalacia displayed generalized gliosis, numerous prominent reactive blood vessels, gitter cell infiltration, spongiosis, and dystrophic mineralization. Neighboring cerebellar white matter contained variable amounts of axonal spheroids indicative of axonal degeneration and spongiosis of the neuropil. No additional significant findings were observed; abnormalities within the fore- and midbrains were absent.

Results of pooled brain and heart samples tested for West Nile virus and pooled brain and pancreas samples tested for avian influenza and exotic Newcastle viruses were negative by reverse transcription-polymerase chain reaction. Hepatic vitamin E concentration was 27 [micro]g/g on a wet weight basis (in-house reference intervals, 15-40 [micro]g/g for chickens and 4-25 [micro]g/g for ducks, provided by Texas A&M Veterinary Medical Diagnostic Laboratory) determined by high-performance liquid chromatography. Flame atomic absorption spectroscopy performed on liver identified a hepatic zinc concentration slightly more than twice that of the in-house upper reference interval provided by the diagnostic laboratory (101 ppm on a wet weight basis, reference interval 25-50 ppm).

Morphologic diagnoses of the pancreas included severe, chronic pancreatic degeneration, atrophy, and fibrosis, with moderate lymphoplasmacytic pancreatitis and islet cell vacuolar degeneration. Morphologic diagnoses of the cerebellum included multifocal, subacute Purkinje cell degeneration, necrosis, with Bergmann's astrocytosis, granular cell atrophy, and chronic, locally extensive encephalomalacia with mineralization, gliosis, spongiosis, neovascularization, and gitter cell infiltration. These findings suggested the goose experienced zinc toxicosis with resultant pancreatic fibrosis and insufficiency resulting in diabetes mellitus, with cerebellar degeneration and necrosis attributed to persistent hyperglycemia.


The goose described in this report had pancreatic insufficiency and secondary diabetes mellitus associated with chronic zinc toxicosis. Prolonged hyperglycemia is suspected to have caused selective Purkinje cell degeneration and necrosis by glial activation, mitochondrial dysfunction, and glutamate toxicosis, which resulted in the clinically observed motor deficits, similar to central neuropathy and cerebellar lesions observed in diabetic mammals. The goose lived with a mixed flock of waterfowl in an outdoor pen without direct handling by the owners. Therefore, clinical disease signs were not identified until the owner caught and separated the bird from the rest of the flock after the onset of neurologic signs. The extreme emaciation and extent of pancreatic atrophy support chronic disease. In experimental models of diabetes mellitus, Toulouse geese that underwent subtotal pancreatectomy lost approximately 7% body weight per week, with few surviving past 6 weeks. (3)

Treatment was limited to supportive care and oral glipizide. Glipizide is a sulfonylurea drug that increases endogenous insulin secretion by interacting with sulfonylurea receptors or by inhibiting potassium channels on pancreatic beta cells. Studies of tolbutamide, another sulfonylurea, show that it can increase blood insulin concentrations in normal chickens and decrease blood glucose concentrations even in pancreatectomized chickens. (4)

The role of the endocrine pancreas in maintaining euglycemia in birds is not fully understood. Parenteral exogenous insulin has been reported to be of partial therapeutic use in some cases of diabetic psittacine birds (5-7) and to have no effect in others. (8) In experimental models, partially pancreatectomized Toulouse geese were non-insulin responsive or became insulin resistant within several weeks. (9) This may be a result of differences in sensitivity amongst avian species to commercially available insulins, which are mammalian in origin, or to differences in glycemic control between mammals and birds. With respect to mammals, birds have higher glucagon and lower insulin concentrations in both pancreatic tissue and blood. (10) Therefore, unlike in mammals, glucagon may play a more important role than insulin in glucose homeostasis in birds.

Zinc toxicosis was diagnosed postmortem by observing a twofold increase in hepatic zinc levels. Zinc interferes with normal exocrine pancreatic function and has been found to lead to atrophy and degeneration of the pancreas. (11,12) Chronic exposure to high zinc levels is required for homeostatic mechanisms to fail and for zinc concentrations to surpass reference intervals. (13) Because zinc has a short half-life (1.5 days), (14) the postmortem hepatic concentration is likely significantly less than the initial exposure. In experimentally induced zinc toxicosis in cockatiels (Nymphicus hollandicus), neurologic signs were not reported. (15) In a retrospective study of ducks with zinc toxicosis, all clinical signs, including weakness and inappropriate mentation, resolved with removal of zinc-laden ingesta. (16) Neither study reported postmortem lesions in the central nervous system.

Pancreatitis also has been documented to result from experimental avian influenza virus infections in turkeys (Meleagris gallopavo) (17) and from a naturally occurring herpesvirus infection in a cockatiel. (18) Results of antemortem hemogram and blood smear analysis and postmortem gross and histologic examinations and ancillary tests did not suggest any infectious process.

Diabetes mellitus was diagnosed based on persistent hyperglycemia. Ideally, glucosuria would have been identified, although glucose can be difficult to measure in the urine of birds because of contamination by feces and urates. Clinical reports of diabetes mellitus in birds are restricted to single cases. Polyphagia, emaciation, polyuria, and polydipsia are commonly reported clinical signs of diabetic birds while signs of central neuropathy have not been reported or observed. (5-8) No evidence of systemic or CNS infection was observed grossly or microscopically, and vitamin E deficiency was ruled out by quantifying hepatic concentrations. The neurologic signs observed, including intention tremors, ataxia, and loss of balance, were consistent with cerebellar disease. Clinical signs were not consistent with peripheral neuropathy nor were gross or histologic lesions present on the sections of sciatic nerves and plexi examined.

The pathophysiology of diabetic neuropathy has not been fully elucidated. Chronic exposure to high glucose concentrations leads to the nonenzymatic glycation of lipids and proteins by the Maillard reaction, resulting in activated glycation end-products (AGEs). Experimental studies in Wistar rats have shown that AGEs cause oxidative stress and cell death in the brain. (19) Cerebellar degeneration is characterized by astrocytosis and hypertrophy of Bergmann's glial cells due to reduced glutamate transportation (19) and necrosis and loss of Purkinje cells due to mitochondrial dysfunction. (20) These changes lead to changes in cognitive behavior and motor function. Many bird species are tolerant of blood glucose concentrations above the reference intervals for most mammals. Hyperglycemic birds do produce Maillard reaction end-products such as fructosamine. (7) However, the production of AGEs has not been documented, nor do birds exhibit signs associated with oxidative damage at resting glucose concentrations that would be pathologic for many mammals. (21,22) Mitochondria in the brain of healthy pigeons (iColumba livia) have been shown to produce lower levels of reactive oxygen species than those of mammals (23) and hummingbirds (Calypte anna, Calypte costae, Archilochus colubris) have been shown not to produce AGEs in spite of blood glucose concentrations exceeding 800 mg/dL. (21) Birds also have higher concentrations of antioxidants such as superoxide dismutase and glutathione peroxidase in tissues (23) and uric acid in blood. (24,25) Despite these protective mechanisms, this case illustrates that in some birds chronic diabetic hyperglycemia may lead to central neuropathy and cerebellar lesions similar to those in diabetic mammals. This case highlights the need for further investigation of the complex pathophysiology of diabetes mellitus in birds.

Peter M. DiGeronimo, VMD, MSc, Nicholas A. Crossland, DVM, Dipi ACVP, Angela Jugan, DVM, Javier G. Nevarez, DVM, PhD, Dipi ACZM, Dipi ECZM (Herpetology), Thomas N. Tully, Jr., MS, DVM, Dipi ABVP (Avian), Dipi ECZM (Avian), and Dawn E. Evans, DVM, Dipi ACVP

From the Departments of Clinical Sciences (DiGeronimo, Jugan, Nevarez, Tully) and Pathobiological Sciences (Crossland, Evans). Louisiana State University School of Veterinary Medicine, Skip Bertman Drive. Baton Rouge, LA 70803, USA; and the Louisiana Animal Disease Diagnostic Laboratory. Baton Rouge, LA 70803, USA (Evans). Present address (DiGeronimo): MJR Veterinary Hospital. School of Veterinary Medicine, University of Pennsylvania, 3900 Spruce Street, Philadelphia, PA 19104. USA; (Crossland): National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02215. USA.


(1.) Campbell TW, Smith SA, Zimmerman KL. Hematology of waterfowl and raptors. In: Weiss DJ, Wardrop KJ, eds. Schalm's Veterinary Hematology. 6th ed. Ames, IA: Blackwell Publishing; 2010:978-979.

(2.) Johnson-Delaney CA, Harrison LR, eds. Exotic Companion Medicine Handbook for Veterinarians. Lake Worth, FL: Wingers Publishing; 1996.

(3.) Karmann H, Mialhe P. Glucose, insulin and glucagon in the diabetic goose. Horm Metab Res. 1976;8(6):419-426.

(4.) Seki Y, Sato K, Ohtsu H, Akiba Y. Persistent hypoglycemia is induced by tolbutamide administration in broiler chickens fed a low-carbohydrate diet. Domest Anim Endocrinol. 2001 ;20(2); 109-122.

(5.) Bartlett SL, Bailey R, Baitchman E. Diagnosis and management of diabetes mellitus in a Bali mynah (Leucopsar rothschildi). J Avian Med Surg. 2016; 30(2): 146-151.

(6.) Desmarchelier M, Langlois 1. Diabetes mellitus in a nanday conure (Nandayus nenday). J Avian Med Surg. 2008;22(3):246-254.

(7.) Gancz AY, Wellehan JFX, Boutette J, et al. Diabetes mellitus concurrent with hepatic haemosiderosis in two macaws (Ara severa, Ara militaris). Avian Pathol. 2007;36(4):331-336.

(8.) Pilny AA, Luong R. Diabetes mellitus in a chestnut-fronted macaw (Ara severa). J Avian Med Surg. 2005; 19(4):297-302.

(9.) Karmann H, Mialhe P. Progressive loss of sensitivity of the A cell to insulin in geese made diabetic by subtotal pancreatectomy. Horm Metab Res. 1982; 14(9):452-458.

(10.) Braun EJ, Sweazea KL. Glucose regulation in birds. Comp Biochem Physiol B Biochem Mol Biol. 2008; 151(1); 1-9.

(11.) Sileo L, Beyer WN, Mateo R. Pancreatitis in wild zinc-poisoned waterfowl. Avian Pathol. 2003;32(6): 655-660.

(12.) Carreira V, Gadsden BJ, Harrison TM, et al. Pancreatic atrophy due to zinc toxicosis in two African ostriches (Struthio camelus). J Zoo Wildl Med. 2011 ;42(4)304-308.

(13.) Stahl JL, Greger JL, Cook ME. Zinc, copper and iron utilization by chicks fed various concentrations of zinc. Br Poult Sci. 1989;30(1): 123-134.

(14.) Oh SH, Nakaue H, Deagen JT, et al. Accumulation and depletion of zinc in chick tissue metallothioneins. J Nutr. 1979; 109(10); 1720-1729.

(15.) Howard BR. Health risks of housing small psittacines in galvanized wire mesh cages. J Am Vet Med Assoc. 1992;200(11): 1667-1674.

(16.) Zdziarski JM, Mattix M, Bush RM, Montali RJ. Zinc toxicosis in diving ducks. J Zoo Wildl Med. 1994;25(3):438-445.

(17.) Cavicchioli L, Zappulli V, Beffagna G, et al. Histopathological and immunohistochemical study of exocrine and endocrine pancreatic lesions in avian influenza A experimentally infected turkeys showing evidence of pancreatic regeneration. Avian Pathol. 2015;44(6);498-508.

(18.) Phalen DN, Falcon M, Tomaszewski EK. Endocrine pancreatic insufficiency secondary to chronic herpesvirus pancreatitis in a cockatiel (Nymphicus hollandicus). J Avian Med Surg. 2007;21 (2): 140-145.

(19.) Nagayach A, Patro N, Patro I. Experimentally induced diabetes causes glial activation, glutamate toxicity and cellular damage leading to changes in motor function. Front Cell Neurosci. 2014;8:1-15.

(20.) Yang S, Xia C, Li S, et al. Mitochondrial dysfunction driven by the LRRK2-mediated pathway is associated with loss of Purkinje cells and motor coordination deficits in diabetic rat model. Cell Death Dis. 2014;5:e1217.

(21.) Beuchat CA, Chong CR. Hyperglycemia in hummingbirds and its consequences for hemoglobin glycation. Comp Biochem Physiol A Mol Integr Physiol. 1998; 120(3):409-416.

(22.) Guha B, Ghosh A. Diabetes and avian resistance. Curr Sci. 1992;62(8):564-568.

(23.) Ku H, Sohal RS. Comparison of mitochondrial prooxidant generation and anti-oxidant defenses between rat and pigeon; possible basis of variation in longevity and metabolic potential. Mech Ageing Dev. 1993;72(1):67-76.

(24.) Klandorf H. Probert IL, Iqbal M. In the defence against hyperglycemia: an avian strategy. World's Poult Sci J. 1999;55:251-268.

(25.) Stinefelt B. Leonard SS, Blemings KP, et al. Free radical scavenging, DNA protection, and inhibition of lipid peroxidation mediated by uric acid. Ann Clin Lab Sci. 2005;35(1):37-45.

Caption: Figure 1. The pancreas (*) from a 5-year-old Toulouse goose exhibiting neurologic signs and hyperglycemia is severely shrunken and firm and is replaced by mature fibrous connective tissue measuring 2.5 x 0.5 x 0.4 cm (bar = 2.5 cm).

Caption: Figure 2. Longitudinal section through the cerebellum of the goose described in Figure 1. The cerebellar folia are diffusely attenuated, with focally extensive malacia characterized by softening and yellow discoloration of neuropil (*) (bar = 2 mm).

Caption: Figure 3. Photomicrograph of affected pancreas from the goose described in Figure 1 (hematoxylin and eosin stain). (A) Pancreatic acini are regionally replaced by mature fibrous connective tissue, with moderate lymphoplasmacytic inflammation (*). Remaining pancreatic lobules are atrophic and degenerative (bar = 200 [micro]m). (B) Pancreatic islet cells are undergoing vacuolar degeneration characterized by severe cytoplasmic swelling and pallor (*) (bar = 20 [micro]m).

Caption: Figure 4. Photomicrograph of the cerebellum of the goose described in Figure 1 (hematoxylin and eosin). (A) A cerebellar folium is regionally collapsed and dissociated with loss of normal stratification consistent with encephalomalacia (arrow) (Scale bar = 350 [micro]m). (B) Multiple neighboring Purkinje cells are segmentally necrotic, indicated by the presence of shrunken, angular, and hypereosinophilic nuclei (*) (Scale bar = 50 [micro]m).
COPYRIGHT 2018 Association of Avian Veterinarians
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2018 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Title Annotation:Clinical Report
Author:DiGeronimo, Peter M.; Crossland, Nicholas A.; Jugan, Angela; Nevarez, Javier G.; Tully, Thomas N., J
Publication:Journal of Avian Medicine and Surgery
Article Type:Report
Date:Jun 1, 2018
Previous Article:A Retrospective Study of Horner Syndrome in Australian Wild Birds, 2010-2016.
Next Article:T-cell Thymic Lymphoma With Proventricular Metastasis in a Florida Scrub Jay (Aphelocoma coerulescens).

Terms of use | Privacy policy | Copyright © 2022 Farlex, Inc. | Feedback | For webmasters |