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Case report of a guinea pig (Cavia porcellus) with a surgically treated

insulinoma

Miguel G. Agúndez LV , Carlos I. Velasco LV

PII: S1557-5063(20)30021-5
DOI: https://doi.org/10.1053/j.jepm.2020.02.014
Reference: JEPM 50285

To appear in: Journal of Exotic Pet Medicine

Please cite this article as: Miguel G. Agúndez LV , Carlos I. Velasco LV , Case report of a guinea
pig (Cavia porcellus) with a surgically treated insulinoma, Journal of Exotic Pet Medicine (2020), doi:
https://doi.org/10.1053/j.jepm.2020.02.014

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Highlights.

 Nodulectomy of an insulinoma in a guinea pig achieved clinical temporal

remission
 Insulinomas in guinea pigs can ossify and radiographs may aid in diagnosis
 Prednisolone and diazoxide could help manage insulinomas in guinea pigs
 Head tilt may occur frequently in guinea pigs with insulinoma

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Case Report

Case report of a guinea pig (Cavia porcellus) with a

surgically treated insulinoma

Miguel G. Agúndez, LV a* and Carlos I. Velasco, LV b

a
Centro Veterinario Madrid Exóticos. C/ Meléndez Valdés 17, 28015, Madrid, Spain.
* Correspondence: miguel.galego@gmail.com

b
Town & Country Veterinary Group, Milburn Street, Milburn Cottage, Aberdeen AB11
6SS, 01224 588770, ciglesiascsb@gmail.com.

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Abstract.

Background. Insulinomas in guinea pigs are poorly documented.

Case description. A 2.5-year-old female guinea pig presented with severe

hypoglycemia, head tilt, weakness, weight loss, hypothermia and a radiodense
abdominal structure. The serum insulin concentration was measured with unsatisfactory
results.

The animal was treated for acute hypoglycemia with clinical stabilization,
prednisolone, diazoxide and frequent syringe feeding, but severe hypoglycemia recurred
and an exploratory laparotomy was performed. Two pancreatic masses were located and
removed. The excised tissue was histologically diagnosed as insulinoma with osseous
metaplasia.

Four months postsurgery the same clinical signs and hypoglycemia recurred. Previous
medical treatment was prescribed; however, 20 days later the animal worsened and
euthanasia was elected.

Conclusions and case relevance. Nodulectomy of an insulinoma in a guinea pig can

achieve temporal remission of clinical signs. In guinea pigs with insulinoma head tilt
may occur frequently, X-rays may be helpful in revealing a pancreatic mass, and
treatment with prednisolone and diazoxide could help in disease management.

Keywords: guinea pig, hypoglycemia, insulinoma, ossification, surgery.

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Introduction.

Insulinomas are occasionally described in dogs, rarely reported in cats and considered
a common condition in ferrets. The overproduction of insulin by the neoplastic ß-cells
causes neuroglycopenia when compensatory mechanisms of glucose homeostasis fail to
compensate for the hypoglycemic effect of the insulin, impairing the brain metabolism.
Almost all clinical signs are caused by neuroglycopenia and elevated levels of
catecholamines[1, 2].

There are 4 previously reported cases of insulinoma in guinea pigs. Seric insulin was
measured successfully in one of them. None of the animals were treated surgically, and
the survival time after admission was less than 22 days in all 4 cases[3-5].

Case presentation.

A 2.5-year-old entire female tricolour American guinea pig (Cavia porcellus)

weighing 0.76 kg [1.68 lb] was examined because in the last several months, it had
presented 6 episodes characterized by presumed neurological symptoms and anorexia of
1 or 2 days of duration, according to the owner. The animal recovered with frequent
syringe feedinga at home. The last episode occurred 24 h prior to the first visit to a
veterinary clinic specializing in exotic animal medicine and surgery. Frequent syringe
feedinga was administered by the owner, and at the time of the visit, the guinea pig was
apparently asymptomatic. Physical exams revealed hypothermia (36.5 ºC) and weight
loss. The diet of the guinea pig was hay, commercial pellets and green leaves of
vegetables, and always had food available. Hematology, blood biochemistry, urinalysis
and radiographs were performed. Relevant findings were severe hypoglycemia (23
mg/dL; reference interval, 89-287 mg/dL[6]) and a radiodense structure of 0.5 cm in
diameter centered in the cranial abdomen (Figure 1). Tympanic bullae were considered
normal on radiographs, but no other diagnostic test, such as a CT scan, was performed
to confirm this assumption. Frequent syringe feedinga was the only treatment
prescribed. Figure 2 summarizes the course of glycemia throughout this case.

Four days later, the guinea pig returned to the clinic, showing an intermittent right-
sided head tilt, weakness and anorexia of 24-h duration. Glycemia was checked with a
human glucometerb with a "LOW" result (< 20 mg/dL). A serum sample was sent to an
external laboratory to measure the insulin concentration by ELISA, which was below
the detection limit of the technique. An abdominal ultrasound showed two spherical
structures both located next to each other near the pyloric region; these structures were
surrounded by hyperechogenic capsules with moderate posterior acoustic shadowing
(Figure 3). The masses were diagnosed as presumptive insulinomas and were supposed
to correspond with the radiodense structure observed on radiographs 4 days prior. The
animal was hospitalized and administered an emergency treatment that consisted of
intravenous glucose 50% 1 mL/h for 3 h and then glucose 15% 3 mL/h during the rest
of the hospitalization. Additional treatment included dexamethasone c (1.5 mg/kg, IM) at
admission and diazoxided (15 mg/kg, OR, q 12 h). After 21 h, euglycemia (Figure 2)

4
and clinical improvement were observed, and consequently, the animal was discharged
with prednisolonee (1 mg/kg, OR, q 12 h) and diazoxide d (same dose).

During follow up examinations, on days 5, 7, 11 and 15 after the first exam, no

obvious clinical signs of disease were observed, and the guinea pig regained weight, but
the glycemia progressively decreased (Figure 2). On day 15 after the first exam syringe
feedinga every 4 - 6 h was added to the treatment to try to normalize blood glucose
levels.

On day 21 the guinea pig was examined again at the clinic after a clinical episode with
right-sided head tilt, weakness and anorexia, that resolved after increasing frequency of
syringe feeding at home. Glycemia was 21 mg/dL. An exploratory laparotomy was
scheduled to remove the suspected insulinoma. Two new blood samples were taken
before surgery, to measure the serum insulin concentration by chemiluminescence
immunoassay at two different laboratories. The results in both cases were below the
detection limit of the techniques.

Anesthesia was routinely performed for the exploratory laparotomy as follows: the
guinea pig was premedicated with midazolamf (1 mg/kg, IM), medetomidineg (0.08
mg/kg, IM) and methadone h (0.3 mg/kg, IM), anesthesia was maintained with isoflurane
1-2% in pure oxygen administered by a face mask. During the surgery, 15% glucose
fluid was administered intravenously via cephalic vein at 10 mL/kg/h. Two adjacent
masses were encountered in the pancreas (Figure 4), both very close to the
pancreaticoduodenal artery[7] and blunt dissection was successfully performed with
sterile cotton swabs. Hyperglycemia was observed immediately after nodulectomy, but
the day after surgery, the animal showed euglycemia and no clinical signs (Figure 2).
The day after surgery, the animal was discharged with meloxicami (0.3 mg/kg, OR, q 12
h), trimethoprim-sulfamethoxazolej (30 mg/kg, OR, q 12 h) and no gavage feeding. At
two and 6 days postsurgery the patient still showed no clinical signs and glycemia was
within normal range (Figure 2).

The biopsy of pancreatic tissue demonstrated a mass with features of a

neuroendocrine tumor. There were discrete glandular lobules intercalated with areas of
stromal bone metaplasia. Glands were tubules are rosettes of columnar cells in
monolayers supported by delicate fibrovascular stroma. The cells showed moderate
amounts of pale eosinophilic cytoplasm, oval nucleus with delicate chromatin, several
small nucleoli and no atypia. The clinical signs and histological findings were
compatible with an insulinoma with osseous metaplasia (Figure 5).

According to the owner, the guinea pig had normal activity for four months after
surgery; then it had an episode with anorexia, neurologic signs and hypoglycemia (37
mg/dL). Additional diagnostic tests were declined, and the previous medical treatment
was prescribed. Twenty days later, the animal worsened, and euthanasia was elected
(177 days after the first consultation). Necropsy was not allowed.

Discussion and Conclusions.

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 The guinea pig of this case report presented clinical signs and hypoglycemia that
shows longer remission time with medical and surgical treatment compared to previous
reported cases treated medically[3-5]. The presence of two pancreatic masses with a
histological appearance of neuroendocrine tumor and the clinical signs were compatible
with insulinomas.

In reported cases of guinea pigs with insulinomas and in the present case report severe
hypoglycemia was observed as the main clinical finding. Other clinical findings
included head tilt (4/5)[3-5], lateral recumbency, weight loss, weakness, hemiparesis,
ataxia, seizures and abdominal distention. Head tilt has been rarely reported in dogs and
ferrets with insulinoma[2,8], but it should be considered a possible sign of insulinoma in
guinea pigs.

In the present case report serum insulin concentration was attempted in three
laboratories with no results. More studies are needed to validate a technique to measure
the concentration of serum insulin in guinea pigs.

The animal showed no adverse effect attributable to medical therapy, but there is
sparse literature in the use of prednisolone and diazoxide in pet guinea pigs with
insulinoma[5] and it is advisable to perform health checks during similar treatment
regimes. Immunosuppression could be the most important potential side effect. It is
unclear whether steroid-related immunosuppression should be expected as a
consequence of the dosage administered. Although guinea pigs and rabbits have been
historically considered steroid-sensitive species, there is limited clinical evidence that
support this assumption. However periodic monitoring (e.g. CBC and biochemistry),
should be recommended in any species undergoing long-term steroid treatment.

In the 4 cases of insulinomas previously described in guinea pigs, the longest survival
time was 22 days after admission[3-5]. Only one of these 4 guinea pigs was treated
(diazoxide) and died at 21 days[5]. The survival time in this report was 177 days, the
longest recorded in a guinea pig with insulinoma.

Only two cases of insulinomas with osseous metaplasia have been reported
previously, in a dog[9] and a guinea pig[3]. Including the present case, two out of five
reported cases of insulinoma in guinea pigs presented osseous metaplasia as detected by
X-rays and histopathological examination. Due to the limited number of cases it is
difficult to establish if insulinomas in guinea pigs are more prone to osseous metaplasia,
but X-ray examination is recommended in cases of guinea pigs showing hypoglycemia.

In summary, insulinomas appear infrequent in guinea pigs, reported cases usually

show hypoglycemia and head tilt, and X-rays and ultrasounds may be helpful in
revealing a pancreatic mass. Surgical treatment may provide longer survival time than
medical treatment alone.

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Footnotes.

a. Critical care for herbivores, Oxbow, USA.

b. One Touch Ultra Easy, LifeScan, USA.
c. Rapidexon, Fatro Ibérica, Spain.
d. Proglicem, MSD, Germany.
e. Estilsona Gotas, Laboratorios ERN, Spain.
f. Midazolam, Normon Laboratories, Spain.
g. Domtor, Esteve Laboratories, Spain.
h. Metasedin, Esteve Laboratories, Spain.
i. Metacam, Boehringer Ingelheim, Spain.
j. Septrin Pediátrico suspensión, UCB Pharma, Spain.

Funding: This research did not receive any specific grant from funding agencies in the
public, commercial, or not-for-profit sectors.

Declaration of interest: none

7
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[1] Goutal CM, Brugmann BL, Ryan KA. Insulinoma in dogs: a review. J Am Anim
Hosp Assoc 2012;48:151-163. https://doi.org/10.5326/JAAHA-MS-5745
[2] Schoeman JP. Insulin-secreting tumors. In: Ettinger SJ, Feldman EC, Côté E,
editors. Textbook of veterinary internal medicine, 8 th ed, Missouri: Elsevier; 2017, p.
1762-1767.
[3] Facher A, Veit C. Case Report: Insulinoma in a guinea pig. [German] Fallbericht:
Ein Insulinom beim Meerschweinchen. Kleintiermedizin 2000;3:337-338.
[4] Vannevel JY, Wilcock B. Insulinoma in 2 guinea pigs (Cavia porcellus). Can Vet J
2005;46:339–341.
[5] Hess L, Ravich M, Reavill D. Diagnosis and treatment of an insulinoma in a guinea
pig (Cavia porcellus). J Am Vet Med Assoc 2013;242:522-526.
https://doi.org/10.2460/javma.242.4.522
[6] Quesenberry KE, Donnelly TM, Mans C. Biology, Husbandry, and Clinical
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Ferrets, Rabbits and Rodents. Clinical Medicine and Surgery, 3 rd ed, Missouri: Elsevier;
2012, p. 279-294. https://doi.org/10.1016/b978-1-4160-6621-7.00022-1
[7] Shively MJ, Stump JE. The systemic arterial pattern of the guinea pig: the abdomen.
Anat Rec 1975;182:355-66. https://doi.org/10.1002/ar.1091820309
[8] 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;10:1741-1745.
[9] Pieczarka EM, Russell DS, Santangelo KS, Aeffner F, Burkhard MJ. Osseous
metaplasia within a canine insulinoma. Vet Clin Pathol 2014;43:89-93.
https://doi.org/10.1111/vcp.12117

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Captions.

Figure 1. Left lateral survey radiograph of a 2.5-year-old guinea pig with insulinoma.
Note the radiodense structure, presumably an insulinoma, that is observed centered on
the cranial abdomen.

Figure 2. Twenty-seven-day glucose curve during the diagnosis and treatment of an

insulinoma in a guinea pig.

Figure 3. Ultrasonographic image of a 2.5-year-old guinea pig with insulinoma. Two

spherical structures next to each other and both near the pyloric region, which were
surrounded by hyperechogenic capsules with moderate posterior acoustic shadowing,
were observed. These structures were considered insulinomas.

Figure 4. Exploratory laparotomy in a guinea pig. One of the two excised masses is
observed in the pancreas and indicated by the forceps, the histological analysis after
nodulectomy confirmed that it was an insulinoma. Stomach and spleen are also
observed.

Figure 5. Histologic appearance of a beta-cell tumor insulinoma surgically excised in a

2,5-year-old female guinea pig. (A) Metaplasia of the pancreatic tissue with formation
of trabecular bone (a), cells of the islets of Langerhans arranged in cords (b) and (B)
healthy pancreatic tissue for comparison (c) are observed. A: H&E stain; bar = 50 µm.
B: H&E stain; bar = 100 µm.

9
10
 492
GLUCEMY mg/ml

365

189
155
127 132
86
61
23 31 29 21
0

1 4* 4** 5 7 11 15 21 21† 21†† 22 24 27

DAYS

*Emergency treatment with intravenous glucose 50% 1 ml/h for 3 hours and then glucose 15% during the rest of the admission, one dose of dexamethasone 1,5 mg/kg
intramuscular, and diazoxide 15 mg/kg per os q12h
**The guinea pig was discharged with prednisolone 1 mg/kg per os q12h, diazoxide 15 mg/kg per os q12h and frequent syringe feeding.
†Intraoperative measurement of glucose, 5 minutes post-nodulectomy.
††Measurement of glucose 3 hours post-nodulectomy.
Blue circles: glucose value outside the reference interval (89-287 mg/dL)1.
Orange circles: euglycemia.
Note: all glucose values, except the day 1, were obtained with a glucometer (One Touch ultra mini, Johnson and Johnson) employing whole blood.

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