Islet Cell Tumor in a Savannah Monitor (Varanus exanthematicus) Lisa M. Naples1, DVM, Jennifer N. Langan2,3, DVM, DACZM, Natalie D. Mylniczenko3, MS, DVM, DACZM, Rebecca Kagan4, DVM, DACVP, Kathleen Colegrove4, DVM, PhD, DACVP

1. Chicago Zoological and Aquatic Animal Residency Program, University of Illinois, College of Veterinary Medicine, Urbana, IL 61802, USA Current address for L. M. Naples: John G. Shedd Aquarium, 1200 S. Lake Shore Drive, Chicago, IL 60605, USA

2. University of Illinois, College of Veterinary Medicine, Urbana, IL 61802, USA Downloaded from http://meridian.allenpress.com/jhms/article-pdf/19/4/97/2208392/1529-9651-19_4_97.pdf by guest on 01 October 2021 3. Chicago Zoological Society, Brookfield Zoo, 3300 Golf Road, Brookfield, IL 60513, USA Current address for N. D. Mylniczenko: Disney’s Animal Kingdom, PO Box 10000, Lake Buena Vista, FL 32830, USA

4. University of Illinois, Zoological Pathology Program, Loyola University Medical Center, Building 101, Room 0745, 2160 South First Avenue, Maywood, IL 60153, USA Current address for R. Kagan: Wildlife Disease Labs, Zoological Society of San Diego, PO Box 120551, San Diego, CA 92112, USA

ABSTRACT: A 7.5-year-old captive born Savannah monitor, Varanus exanthematicus, presented with lethargy, anorexia, constipation, and narcolepsy-like behavior. Plasma biochemical analysis demonstrated mildly elevated liver enzymes, hypercalcemia, and hypoproteinemia. Coelomic ultrasound revealed multiple echolucent and rare echogenic round hepatic structures. Diagnostic coelioscopy was attempted but limited by anesthetic complications and varanid anatomy. Although it could not be confirmed during surgery, clinical signs and blood work supported hepatic disease. Because of progression and severity of clinical signs, the monitor was humanely euthanized. Further histopathologic evaluation revealed a pancreatic islet cell tumor with hepatic metastases and multifocal hepatic cholangiocarcinomas. Insulin immunoassay values were used post-mortem in this case and may be useful for diagnosis of insulinoma in reptiles. To the authors’ knowledge, this is the first report of a reptile with functional islet cell neoplasia that demonstrated clinical illness and elevated insulin levels.

KEY W ORDS: cholangiocarcinoma, insulinoma, islet cell tumor, neoplasia, Savannah monitor, Varanus exanthematicus.

INTRODUCTION This report describes a case of a metastatic islet cell tumor in a Savannah monitor, Varanus exanthematicus, and discusses The endocrine pancreas is composed of the islets of the challenges of diagnosing pancreatic disease in reptiles. Langerhans, which usually contain four cell types (alpha, beta, delta, and F cells) that each secrete unique hormones. CASE REPORT Dysfunction involving individual cell lines, as occurs with functional tumors, results in an imbalance of the particular A captive-born, 7.5-year-old, 3.42 kg male Savannah moni- hormones they secrete (Meleo and Caplan, 1999; Nelson, tor presented with lethargy, partial anorexia, and decreased 2000; Quesenberry and Rosenthal, 2004). Beta cell tumors, defecation, all of which occurred intermittently over a or insulinomas, result in the excess production of insulin two-month period. The monitor was housed alone in a and are commonly identified in ferrets (Nelson, 2000; 305 cm × 183 cm × 252 cm enclosure with an ambient tem- Quesenberry and Rosenthal, 2004), with less frequent perature of 26°C (78.8°F), basking temperature of 42°C reports in domestic carnivores and isolated cases in guinea (107.6°F), and a 66% relative humidity. An ultraviolet B pigs (Hawks et al., 1992; Kraihe, 2003; Vanneuel and (UVB) light (General Electric Lighting, Cleveland, OH) was Wilcock, 2005). Hematopoietic, hepatic, integumental, and mounted approximately 60 cm above the basking area. Two musculoskeletal tumors are the most commonly reported heat lamps (Zoo Med Laboratories, Inc., San Luis Obispo, neoplasms in the order Lacerta (Tocidlowski et al., 2001; CA) located approximately 60 cm above a 60 cm × 60 cm Hernandez-Divers and Garner, 2003; Gyimesi et al., 2005; concrete shelf were used to provide heat for 13 h per day, Sykes and Trupkiewicz, 2006), whereas neoplasms of the whereas the UVB light was provided 9 h daily. endocrine pancreas have rarely been documented in reptiles The initial physical examination was unremarkable, and (Harshbarger, 1976; Montali, 1980; Machotka, 1984; Frye, the animal was found to be in good body condition. A com- 1994; Garner et al., 2004; Sykes and Trupkiewicz, 2006). plete blood count (CBC) and plasma biochemical analysis

Volume 19, No. 4, 2009 Journal of Herpetological Medicine and Surgery 97 Table 1. Complete blood cell counts and serum biochemical analyses from a Savannah monitor lizard with an Islet cell tumor. The blood samples were collected over a two month period.a

Test December 5 January 16 February 8 February 12 ISIS (SD)

WBC (103/UL) 2.8 4.5 8.4 3.5 5.1 (3.35)

HCT (%) 28 26 25 27 31.2 (6.1)

Glucose (mg/dL) 95 53 85 67 118 (17)

Uric acid (mg/dL) 8.9 6.6 6.3 8.3 6.7 (4.4)

Calcium (mg/dL) 16.5 26.2 20.5 16.5 14.6 (1.4)

Phosphorus (mg/dL) 2.5 2.8 2.3 2.3 4.6 (1.3) Downloaded from http://meridian.allenpress.com/jhms/article-pdf/19/4/97/2208392/1529-9651-19_4_97.pdf by guest on 01 October 2021 Sodium (mEq/L) 158 153 157 150 156 (4)

Potassium (mEq/L) 5 5.6 4.2 4.2 4.2 (0.7)

Chloride (mEq/L) 110 103 114 109 116 (7)

Cholesterol (mg/dL) 92 99 111 120 116 (56)

Total protein (gm/dL) 6.7 6.8 7 6.5 6.7 (1)

Albumin (gm/dL) 2.8 3 3 2.7 2.1 (0.4)

Aspartate aminotranferase (IU/L) 61 103 52 24 22 (20)

Alanine aminotranferase (IU/L) 45 36 118 43 70 (96)

Total bilirubin (mg/dL) 0.5 0.4 0.3 0.2 0.1 (0.1)

Alkaline phosphatase (IU/L) 30 41 39 35 147 (89)

Lactate dehydrogenase (IU/L) 952 NR 614 243 427 (89)

CPK (IU/L) >6,000 NR 2,425 1,057 764 (80)

Gamma glutamyltransfrase (IU/L) 12 14 9 9 7 (6)

Bile acids (umol/L)* 12.1 29 62 31.8 NA

NR = not registered, NA = no reference values are available for Savannah monitors. * Reference values for domestic canids and felids = <7 µmol/L (University of Miami, Comparative Pathology Laboratory, Miami, FL). Documented reptilian values = 7.5 ± 7.8 µmol/L and 33.3 ± 22 µmol/L pre- and post-prandial, respectively (McBride et al., 2006). a Values printed in bold represent values >2 SD from the ISIS (2002) reference range. were performed on blood collected from the ventral caudal throughout the clinical illness because of suspected hepatic tail vein. The CBC was within the reported reference range abnormalities. Unfortunately, no species-specific reference for a Savannah monitor, with mild changes in blood values were available for Savannah monitors. This animal’s biochemical values (Table 1). The monitor was returned to bile acid values were difficult to interpret, because they were its exhibit and received daily warm water soaks for 30– elevated compared with those of domestic mammals and 60 min to promote more regular bowel movements. Initially, some reptiles (Table 1) (McBride et al., 2006) but within the defecation rate improved and the animal’s appetite returned “normal” range described by Hernandez-Divers and Cooper to normal, although periodic self-limiting lethargy was still (2006). reported. To further evaluate the reported anorexia and decreased Within a month of the original presentation, the monitor bowel movements, the monitor lizard was sedated with became anorexic, severely lethargic, and had visible muscle intravenous propofol (6 mg/kg; Propoflo™, 10 mg/ml, atrophy. During physical examination, narcolepsy-like Abbott Laboratories, Chicago, IL), and contrast radio- behavior was observed, which included intermittent brief graphs were collected. The animal was intubated with a 2.5- catatonic episodes and rapid periods of arousal followed by mm endotracheal tube and maintained on 1.5% isoflurane a calm, flaccid, conscious state. No seizure-like activity (IsoFlo, Abbott Laboratories) in 100% oxygen at 1 L/min. was observed. Repeated serum biochemical abnormalities Gastrointestinal contrast radiography was performed were similar to those observed previously (Table 1). Serum after administration of 10 ml/kg of barium sulfate (LIQUID fasted bile acids were measured with each blood sampling E-Z-PAQUE®, 60% w/v, 41% w/w, E-Z-Em, Westbury, NY)

98 Journal of Herpetological Medicine and Surgery Volume 19, No. 4, 2009 Downloaded from http://meridian.allenpress.com/jhms/article-pdf/19/4/97/2208392/1529-9651-19_4_97.pdf by guest on 01 October 2021

Figure 1. Ultrasonograph of a Savannah monitor lizard liver with metastatic islet cell tumors and cholangiocarcinoma. GB = gall bladder, CY = hepatic cyst, CC = cholangiocarcinoma.

by oral gavage. Serial radiographs were collected daily for hepatic cysts and enlarged bile ducts, respectively; addition- seven days until the contrast medium had passed through ally, liver echotexture was mottled in appearance with rare the gastrointestinal tract. No evidence of deficits, delayed hyperechoic foci (Fig. 1). transit time, or mass effect was observed. Several days later, the animal was anesthetized via The animal exhibited episodes of cataplexy-like behavior facemask with 5% isoflurane gas anesthesia, intubated each time it was handled. To further pursue suspected with a 2.5-mm endotracheal tube and maintained on 1.5% hepatic involvement, a coelomic ultrasound was performed isoflurane in 100% oxygen at 1 L/min, and an exploratory and revealed a single, 1 cm × 1 cm hypoechoic, round struc- coelioscopy performed to further evaluate the lizard. ture within the hepatic parenchyma adjacent to the gall Buprenorphine (0.02 mg/kg IM; Buprenex, 0.3 mg/ml, bladder. Bile ducts were subjectively normal, and renal Hospira, Inc., Lake Forest, IL) was administered presurgi- echotexture was bilaterally symmetrical with no significant cally for analgesia. The animal was positioned in left lateral abnormalities. recumbency, and the right paralumbar region was routinely Anorexia, constipation, and lethargy continued despite prepped. A 2-cm skin incision was made and the underlying supportive care, which included s-adenosylmethionine musculature and coelomic membranes were bluntly dis- (Denosyl®, Nutramax Laboratories, Edgewood, MD) sected to allow endoscopic evaluation of the caudal coelom. 30 mg/kg orally once daily and lactulose (Enulose, Actavis, A 2.7-mm rigid endoscope (Richard Wolf Medical Instru- Baltimore, MD) 0.5 ml/kg orally once daily. During the ments Corp., Vernon Hills, IL) was advanced into the physical examination being conducted two weeks after con- coelomic cavity. The renal parenchyma was diffusely pale, trast administration, the animal’s body was considered and gonadal appearance confirmed the monitor was male. underconditioned, and body weight had declined markedly The coelom contained yellow, slightly cloudy, fluid. Results to 2.84 kg (17% weight loss in 23 days). Cataplexy episodes of fluid analysis revealed an exudate with a total protein continued intermittently, although they increased in dura- of 50.0 g/L (5 g/dL), glucose of 4.1 mmol/L (73 mg/dL), spe- tion and frequency. Serum biochemical results were consis- cific gravity of 1.033, and pH of 8.0. Tissue samples were tent with further elevation of liver enzymes, bile acids, and collected from the kidney via biopsy forceps and were either calcium, with mild hypoglycemia (Table 1). Repeat ultraso- placed in 10% neutral buffered formalin for histopathologic nography of the liver revealed multiple hypoechoic round examination or submitted for aerobic culture and cytologic and tubular hepatic structures of varying size thought to be evaluation of impression smears.

Volume 19, No. 4, 2009 Journal of Herpetological Medicine and Surgery 99 Downloaded from http://meridian.allenpress.com/jhms/article-pdf/19/4/97/2208392/1529-9651-19_4_97.pdf by guest on 01 October 2021

Figure 2. Liver and pancreas resected from a Savannah monitor. Within the right lobe is a cholangiocarcinoma (solid white arrow). There are multiple insulinomas both within the right liver lobe and pancreas (dotted white arrows). In the left lobe, there are multiple, poorly demarcated hepatic cysts (white circle).

Visualization of the hepatic tissue was obscured by the remaining liver was diffusely tan and slightly friable. The post-hepatic membrane. Further evaluation of the coelomic pancreas contained multiple 0.5–1.0 cm diameter white to cavity proved difficult because of the coelomic effusion and tan, nodular masses, similar to those observed in the liver the location of the coelioscopic incision. The monitor was (Fig. 2). The kidneys were diffusely dark green and had a difficult to maintain under a surgical plane of anesthesia, slightly irregular surface. A complete tissue set was fixed in and the procedure was terminated before evaluation of the 10% neutral buffered formalin, routinely processed for liver was possible. The skin incision was closed with 3-0 histology, sectioned at 5 µm, and stained with hematoxylin polydioxanone (PDSII, Ethicon, Somerville, NJ) suture in a and eosin. horizontal mattress pattern. Postoperative treatment Histopathologically, the pancreatic and the soft, tan included buprenorphine at 0.02 mg/kg IM every 12 h for hepatic masses were expansile, well demarcated, partially to 3 days, lactated Ringers solution (Hospira, Lake Forest, IL) nonencapsulated and composed of lobules and packets of at 30 ml/kg every 24 h for 3 days, warm water soaks for 1 h polygonal neoplastic cells surrounded by a moderately dense every 24 h for 10 days, and long-acting ceftiofur (Excede, fibrovascular stroma. Some lobules had central large vascu- 200 mg/ml, Pfizer, New York, NY) at 6.6 mg/kg SC every lar channels and there was peripheral and perivascular pali- 5 days. The monitor’s clinical signs continued to worsen sading of neoplastic cells. Mitotic figures were infrequent, following surgery; therefore, the animal was euthanized with an average of one per high power field. The masses because of a significant decline in its quality of life and poor were morphologically consistent with pancreatic islet cell prognosis. tumors (Fig. 3). Within the unaffected pancreas, there was During the gross necropsy examination, the parenchyma diffuse exocrine cell atrophy and zymogen granule deple- of all hepatic lobes contained several, 1–4 cm diameter, soft, tion. The hepatic masses corresponding to the firm masses tan, nodular masses, some of which bulged from the capsu- observed grossly were infiltrative and characterized by lar surface. Several masses were firm, white, and had slightly numerous, widely spaced tubules of neoplastic epithelial depressed firm, tan centers. Within the left lobe there was a cells embedde d within an abundant dense collagenous 4-cm diameter cystic mass adjacent to a solid 1-cm diameter tissue. Neoplastic cells were cuboidal and had distinct mass (Fig. 2). The cyst was filled with colorless fluid. The cell borders. Mitotic figures were rare. These masses were

100 Journal of Herpetological Medicine and Surgery Volume 19, No. 4, 2009 Downloaded from http://meridian.allenpress.com/jhms/article-pdf/19/4/97/2208392/1529-9651-19_4_97.pdf by guest on 01 October 2021

Figure 3. Histopathologic examination of a pancreatic islet cell tumor. Packets of polygonal neoplastic cells surrounded by a moderately dense fibrovascular stroma. There is peripheral and perivascular palisading of neoplastic cells.

morphologically characteristic of cholangiocarcinomas from this monitor from a period during which the animal (Fig. 4). Additional findings in the liver included hepatic was considered healthy and later when the animal was clini- lipidosis and canalicular bile stasis, which were likely a cally ill. Five additional plasma samples from unrelated consequence of anorexia and hepatic neoplasia. Savannah monitor lizards were submitted for comparison. Immunohistochemistry (IHC) using a monoclonal anti- All but one sample measured a low value of serum insulin body directed against insulin (MU029-UC, clone HB125, (<2 µIU/ml; Cornell University, no reference values avail- BioGenex, San Ramon, CA) was attempted on affected able). The one exception was the sample collected from the pancreas to help confirm insulin secretion by the neoplastic animal described in this case during the time it was clinically cells. Unfortunately, the antibody did not cross-react with ill; the insulin result was four times greater (8.78 µIU/ml) monitor islet cells, and IHC could not confirm insulin than any other sample (Table 2). production from the Varanus pancreatic tissue. Additional histologic findings included vacuolation of DISCUSSION cerebral and cerebellar white matter and reactive astrocyto- sis with scattered Alzheimer type II astrocytes. Similar Attempts at IHC staining to identify the cell line of the lesions are noted in domestic species with hepatic encepha- tumor failed to further classify the islet cell neoplasm in this lopathy (Summers et al., 1995). Moderate membranous case. The endocrine pancreas of the Savannah monitor glomerulonephritis and renal interstitial fibrosis were lizard has a predominance of alpha cells; thus, a gluca- observed in both biopsy and necropsy kidney samples. gonoma may have been expected (Miller, 1960). However, Because of the pathologic findings, serum insulin levels retrospective evaluation of the Savannah monitor lizard’s were retrospectively evaluated. Banked, frozen plasma serum insulin levels in comparison to clinically normal samples were submitted for serum insulin immunoassays monitors supports a presumptive diagnosis of beta cell (Cornell University, Ithaca, NY). Plasma was submitted tumor (insulinoma). Histopathology is the only way to

Volume 19, No. 4, 2009 Journal of Herpetological Medicine and Surgery 101 Downloaded from http://meridian.allenpress.com/jhms/article-pdf/19/4/97/2208392/1529-9651-19_4_97.pdf by guest on 01 October 2021

Figure 4. Histopathologic examination of a hepatic cholangiocarcinoma. Widely spaced tubules of neoplastic cuboidal epithelial cells (black arrow) embedded within dense collagenous tissue.

definitively diagnose insulinoma (Nelson, 1995; Caplan A presumptive diagnosis of insulinoma based on clinical et al., 1996; Meleo and Caplan, 1999; Tobin et al., 1999). signs can be difficult in any species. In this case, vague In this monitor, a coelomic exploratory surgery, rather clinical signs, including lethargy, anorexia, weight loss, and than a caudal coelioscopic approach, would have provided musculoskeletal degeneration, were observed. Although better visual assessment of internal organs as well as these signs have been associated with islet cell tumors improved sample collection opportunities and possibly a in canids (Nelson, 2000) and ferrets (Quesenberry and diagnosis earlier in the course of the disease. The severity Rosenthal, 2004), they are not specific to this disease of the monitor’s clinical signs and concerns about poor process. Antemortem diagnosis has not been reported in recovery and incisional healing led the authors to elect coe- reptiles, and descriptions of tumor functionality vary (Frye, et al lioscopy over exploratory surgery. The approach was based 1994; Garner ., 2004); thus, clinical manifestations of insulinomas in reptiles are unknown. Among mammalian on iguanid anatomical literature (Hernandez-Divers et al., species, clinical signs typically develop episodically second- 2007) but did not provide adequate hepatic or pancreatic ary to hypoglycemia (Nelson, 1995; Nelson, 2000; Quesen- visualization in this varanid species. Regardless of entry berry and Rosenthal, 2004). For this animal, however, location, visualization and pancreatic biopsy are likely to episodic clinical abnormalities did not always correlate with be more challenging than in iguanid lizards, because islet a hypoglycemic state. In ferrets, serial fasted serum samples cell tissue in monitor lizards is concentrated in the distal are sometimes necessary to accurately measure glucose in region of the dorsal pancreatic lobe adjacent to the spleen insulinoma patients, and this may also apply to reptiles. (Miller, 1962; Moscona, 1990). Further investigation of Additionally, reptiles may possess lower serum glucose more appropriate coelioscopy sites or less invasive diagnos- thresholds than do domestic mammals for neuroglucopeni a- tic techniques to evaluate lizard pancreatic abnormalities associated clinical signs such as seizures. In one study, would be of significant value. lizards given synthetic insulin were observed to have loss of

102 Journal of Herpetological Medicine and Surgery Volume 19, No. 4, 2009 Table 2. Comparative table of serum insulin results and serum insulinomas have been described with episodic mentation glucose values from Savannah monitor lizards. Samples labeled abnormalities similar to the episodes observed with this with numbers 1–5 are banked serum samples from other Savan- monitor, but the confounding hepatic disease makes it nah monitor lizards in the Brookfield Zoo collection. Samples difficult to elucidate the specific etiology of this behavior 6 and 7 were both collected from the monitor lizard described (Rosenthal and Quesenberry, 2004). in this case report, with number 7 having been collected during Hypoglycemia in canids and ferrets at levels <40 mg/dL clinical manifestation of a pancreatic islet cell neoplasm. and 60 mg/dL, respectively (Quesenberry and Rosenthal, Normalized means and standard deviations for serum insulin 2004), in addition to elevated insulin levels, support a analytes are based on information from Cornell University presumptive diagnosis of insulinoma. This monitor’s mild (Ithaca, NY). Reference ranges have not been established for hypoglycemia, although possibly associated with hepatic Varanus exanthematicus. disease, still warrants inclusion of pancreatic disease in a list of differential diagnoses. Insulin resistance, environmental Varanus Serum insulin factors, and altered metabolic rates could explain the lack of exanthematicus concentration Serum a severe hypoglycemia (Miller and Wurster, 1956; Miller, sample (μIU/mL)a glucose 1961). Based on this report, chronic cases of mild hypo- glycemia with an unknown etiology may warrant further Downloaded from http://meridian.allenpress.com/jhms/article-pdf/19/4/97/2208392/1529-9651-19_4_97.pdf by guest on 01 October 2021 1 <2 6.94 mmol/L investigation by measuring insulin levels. 125 mg/dL In mammals, serum insulin immunoassays (Nelson, 1995; Meleo and Caplan, 1999; Quesenberry and Rosenthal, 2004) 2 <2 8.72 mmol/L are used to diagnose insulinomas where hypoglycemia is 157 mg/dL absent or to rule out other etiologies for hypoglycemia (Nelson, 1995; Steiner and Bruyette, 1996; Meleo and 3 <2 4.55 mmol/L Caplan, 1999; Quesenberry and Rosenthal, 2004). Because 82 mg/dL serum glucose is a less reliable marker of pancreatic pathol- 4 <2 8.83 mmol/L ogy in reptiles, insulin immunoassays may be of more diagnostic use for reptiles (Miller, 1961). To the authors’ 159 mg/dL knowledge, these tests have not been used for diagnosis of 5 <2 1.33 mmol/L insulinomas in reptiles, and serum-insulin reference values 24 mg/dL have not been established for any reptile species. It is specu- lated that, because of a high affinity for human insulin 6 <2 6.77 mmol/L receptors, reptilian serum insulin will sufficiently react with 122 mg/dL mammalian assays to prove useful (Conlon et al., 1997). In one study, radioimmunoassay values correlated well with 7 8.78 4.72 mmol/L hyperglycemia in a bearded dragon (Pogona vitticeps) 85 mg/dL (Griswold, 2001). A study measuring immunoreactive insulin-like content in Savannah monitor lizards suffering a Units based on reported interpretation from Cornell University (Ithaca, from starvation found a reduction in insulin levels within NY). pancreatic tissue (Godet et al., 1984). The monitor in the present report was anorexic at the time of testing; therefore, lower insulin levels might be expected. However, the oppo- site was found with a four-fold increase compared to other muscle coordination, trembling, and convulsive and coma- samples evaluated. In addition, another monitor in the col- tose states, regardless of blood glucose levels (Miller and lection with hypoglycemia secondary to severe liver disease Wurster, 1956). Therefore, insulin levels rather than glucose did not demonstrate an elevation in serum insulin levels. In levels may regulate the development of clinical signs. mammalian species, insulinomas are commonly confirmed Although the neurological signs observed in this monitor when hypoglycemia persists in the face of increasing or may have been associated with serum insulin levels, signifi- nondeclining insulin concentrations (Quesenberry and cant hepatic disease and a resultant hepatic encephalopathy Rosenthal, 2004). Antemortem use of this test would have cannot be discounted. Thus, a connection between neuro- supported a presumptive diagnosis of an insulinoma but logic clinical signs and insulinoma cannot definitively be would not have identified the concurrent hepatic neoplastic deduced from this case. disease identified via histopathology. Exploratory surgery One of the more interesting clinical signs was the narco- and biopsy would have been the most likely diagnostic lepsy-like episodes observed during the physical examina- procedures that could have identified concurrent pancreatic tion. Narcolepsy is described as a nonprogressive disease of and hepatic neoplasms in this case. the central nervous system causing excessive drowsiness, Although early diagnosis and treatment of insulinomas occasional sleep-attacks, and cataplexy (sudden loss of in ferrets have shown increased survival and disease-free muscle tone) (Tonokura et al., 2007). It has been reported in intervals (Weis et al., 1998), overall prognosis for this moni- domestic large and small animal species but not in reptiles tor was grave because of the multiple neoplasias identified. (Strain et al., 1984; Lunn et al., 1993; Peck et al., 2001; White However, identification of diagnostic tools to rule out and De Lahunta, 2001; Tonokura et al., 2007). The etiology pancreatic disease would be beneficial in the management of of narcolepsy is debatable, and varies among species. Genet- similar challenging reptile cases. Further useful studies ics, hypocretin peptide deficiency, trauma, and infection include a comprehensive account of individual reptile have been implicated (Tonokura et al., 2007). Ferrets with species’ endocrine function, identification of normal reptile

Volume 19, No. 4, 2009 Journal of Herpetological Medicine and Surgery 103 serum bile acid values, and the application of insulin Machotka SV. 1984. Neoplasia in reptiles. In Hoff GL, Frye immunoassay values in reptile medicine. FL, Jacobson ER (eds): Diseases of Amphibians and Reptiles. Plenum Press, New York, NY:519–580. Acknowledgments: The authors would like to thank the McBride M, Hernandez-Divers SJ, Koch T, Bush S, Latimer Chicago Zoological Society’s Brookfield Zoo; with special KS, Wilson H, Hernandez-Divers SM, Stedman NL. 2006. thanks to the veterinary services and animal helper staff; Preliminary evaluation of pre- and post-prandial 3a-hydroxy and Dr. Jackie Zdziarski. bile acids in the green iguana, Iguana iguana. J Herp Med Surg, 16(4):129–134. LITERATURE CITED Meleo KA, Caplan ER. 1999. Treatment of insulinoma in the dog, cat and ferret. In Bonagura JD (ed): Current Veterinary Caplan ER, Peterson ME, Mullen HS, Quesenberry KE, Therapy XIII. W. B. Saunders, Philadelphia, PA:357–361. Rosenthal KL, Hoefer HL, Moroff SD. 1996. Diagnosis and Miller MR. 1960. Pancreatic islet histology and carbohydrate treatment of insulin-secreting pancreatic islet cell tumors in metabolism in amphibians and reptiles. Diabetes, 9(4): ferrets: 57 cases (1986–1994). J Am Vet Med Assoc, 318–323. 209(10):1741–1745. Miller MR. 1961. Carbohydrate metabolism in amphibians Conlon JM, Secor SM, Adrian TE, Mynarcik DC, Whittaker and reptiles. In Martin AW (ed): Comparative Physiology Downloaded from http://meridian.allenpress.com/jhms/article-pdf/19/4/97/2208392/1529-9651-19_4_97.pdf by guest on 01 October 2021 J. 1997. Purification and characterization of islet hormones of Carbohydrate Metabolism in Heterothermic Animals. (insulin, glucagon, pancreatic polypeptide, and somatostat in) University of Washington Press, Seattle, WA:125–147. from the Burmese python, Python molurus. Regul Pept, Miller MR. 1962. Observations on the comparative histology 71(3):191–198. of the reptilian pancreatic islet. Gen Comp Endocrinol, Frye FL. 1994. Diagnosis and surgical treatment of reptile 2:407–414. neoplasia with a compilation of cases: 1966–93. In Vivo, Miller MR, Wurster DH. 1956. Studies on the blood glucose 8(5):885–892. and pancreatic islets of lizards. Endocrinology, 63:114–120. Garner MM, Hernandez-Divers SM, Raymond JT. 2004. Montali RJ. 1980. An overview of tumors in zoo animals. Reptile neoplasia: a retrospective study of case submission In Montali RJ and Magaki G (eds): The Comparative to a specialty diagnostic service. Vet Clin Exot Anim, Pathology of Zoo Animals. Smithsonian Institution Press, 7(3):653–671. Washington, DC:531–542. Moscona AA. 1990. Anatomy of the pancreas and Langerhans Godet R, Mattei X, Dupe-Godet M. 1984. Alterations of islets in snakes and lizards. Ann Rec, 227:232–244. endocrine pancreas B cells in a Sahelian reptile (Varanus Nelson RW. 1995. Insulin-secreting islet cell neoplasia. In exanthematicus) during starvation. J Morphol, 180(3): Ettinger SJ, Feldman EC (eds): Textbook of Veterinary 173–180. Internal Medicine. 4th ed. W. B. Saunders, Philadelphia, Griswold WG. 2001. Hepatocellular carcinoma with associated PA:1501–1509. hyperglycemia in an inland bearded dragon, Pogona Nelson RW. 2000. Insulin-secreting islet cell neoplasia. In vitticeps. Proc ARAV, 227–231. Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Gyimesi ZS, Garner MM, Burns RB, Nichols DK, Brannian Internal Medicine. 15th ed. W. B. Saunders, Philadelphia, RE, Raymond JT, Poonacha KB, Kennedy M. 2005. High PA:1429–1438. incidence of lymphoid neoplasia in a colony of Egyptian Peck KE, Hines MT, Mealey KL, Mealey RH. 2001. Pharma- spiny-tailed lizards (Uromastyx aegyptius). J Zoo Wild Med, cokinetics of imipramine in narcoleptic horses. Am J Vet 36(1):103–110. Res, 62(5):783–786. Harshbarger JC. 1976. Activities Report Registry of Tumors in Quesenberry KE, Rosenthal KL. 2004. Endocrine diseases. Lower Animals, 1975 supplement. Smithsonian Institute In Quesenberry KE, Carpenter JW (eds): Ferrets, Rabbits, Press, Washington, DC. and Rodents: Clinical Medicine and Surgery. 2nd ed. W. B. Hawks D, Peterson ME, Hawkins KL, Rosebury WS. 1992. Saunders, Philadelphia, PA:79–90. Insulin secreting pancreatic (islet cell) carcinoma in a cat. Steiner JM, Bruyette DS. 1996. Canine insulinoma. Comp J Am Vet Med Assoc, 6:193–196. Cont Educ Pract Vet, 18:13–23. Hernandez-Divers SJ, Cooper JE. 2006. Hepatic lipidosis. Strain GM, Olcott BM, Archer RM, McClintock BK. 1984. In Mader DR (ed): Reptile Medicine and Surgery. 2nd ed. Narcolepsy in a Brahaman bull. J Am Vet Med Assoc, Elsevier, St. Louis, MO:806–813. 185(5):538–541. Hernandez-Divers SJ, Stahl SJ, McBride M, Stedman NL. Summers BA, Cummings JF, DeLahunta A. 1995. Degenera- 2007. Evaluation of an endoscopic liver biopsy technique in tive diseases of the central nervous system. In Summers BA, green iguanas. J Am Vet Med Assoc, 230(12):1849–1853. Cummings JF, DeLahunta A (eds): Veterinary Neuropathol- Hernandez-Divers SM, Garner MM. 2003. Neoplasia of ogy. Mosby, St. Louis, MO:208–249. reptiles with an emphasis on lizards. Vet Clin Exot Anim, Sykes JM, Trupkiewicz JG. 2006. Reptile neoplasia at the 6(1):251–273. Philadelphia Zoological Garden, 1901–2002. J Zoo Wild International Species Inventory System (ISIS). 2002. Apple Med, 37(1):11–19. Valley, MN. http://www.isis.org. Accessed 2007 December. Tobin RL, Nelson RW, Lucroy MD, Wooldridge JD, Feld- Krajhe AC. 2003. Hypoglycemia and irreversible neurologic man EC. 1999. Outcome of surgical versus medical treatment complications in a cat with insulinoma. J Am Vet Med Assoc, of dogs with beta cell neoplasia: 39 cases (1990–1997). J Am 223:812–814. Vet Med Assoc, 215(2):226–230. Lunn DP, Cuddon PA, Shaftoe S, Archer RM. 1993. Familial Tocidlowski ME, McNamara PL, Wojcieszn JW. 2001. occurrence of narcolepsy in miniature horses. Equine Vet J, Myeloygenous leukemia in a bearded dragon (Acanthodraco 25(6):483–787. vitticeps). J Zoo Wild Med, 32:90–95.

104 Journal of Herpetological Medicine and Surgery Volume 19, No. 4, 2009 Tonokura M, Fujita K, Nishino S. 2007. Review of pathophys- Weis CA, Williams BH, Scott MV. 1998. Insulinoma in the iology and clinical management of narcolepsy in dogs. Vet ferret: clinical findings and treatment comparisons in 66 Rec, 161(11):375–380. cases. J Am Anim Hosp Assoc, 34(6):471–475. Vanneuel JY, Wilcock B. 2005. Insulinoma in 2 guinea pigs White EC, De Lahunta A. 2001. Narcolepsy in a ram lamb. Vet (Cavia porcellus). Can Vet J, 46:339–341. Rec, 149:156–157. Downloaded from http://meridian.allenpress.com/jhms/article-pdf/19/4/97/2208392/1529-9651-19_4_97.pdf by guest on 01 October 2021

Volume 19, No. 4, 2009 Journal of Herpetological Medicine and Surgery 105