Page 605 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 26 Tumors of the Endocrine System 583

DNA repair and cell cycle regulation were also down-regulated in used to identify small pancreatic tumors, but these approaches
the high-metastatic canine insulinomas. 381,390 In studies of poten- have yet to be significantly used in canine patients. 408–410 Con-
trast-enhanced ultrasound techniques are widely used in human
tial prognostic biomarkers for canine insulinoma, tumor size,
VetBooks.ir TNM stage, Ki67 index (a marker of proliferation), presence of medicine and are may be of value for the detection of pancre-
atic tumors in dogs. In this procedure, gas-filled microbubbles are
necrosis, nuclear atypia, and stromal fibrosis have all been iden-
tified as being predictive for DFI and/or ST, depending on the injected into the circulation and ultimately reach the vascular sup-
model used in analysis. 382,391 ply to the organ of interest, where they are detected on ultrasound
Canine insulinomas are most commonly reported in medium examination. 128 Because the microbubbles remain in the vascu-
and large breed dogs, particularly Labrador retrievers, golden lature, this technique is particularly valuable for assessing tissue
retrievers, German shepherd dogs, German short-haired pointers, blood supply and perfusion. Contrast-enhanced ultrasonography
Irish setters, boxers, and mixed breed dogs. Small breed dogs also has been described for the normal canine pancreas, 411–414 patients
can be affected; West Highland white terriers are overrepresented with pancreatitis, 415,416 and a small number of dogs with pancre-
in some reports. 379,385 Depending on the case series, the median atic tumors, 417,418 and the apparent safety and relative accessibility
reported age is 9 to 10 years, with a range of 3 to 15 years, and no of this technique indicate that its use very likely will increase. 128
sex predilection. 379,383–385,389,392 CT findings have been reported in a small number of dogs with
The clinical signs of insulinoma result from the effects of hypo- insulinoma. 407,419,420 In a study comparing ultrasound, CT, and
glycemia on the nervous system, which is termed neuroglycope- single-photon emission CT (SPECT), CT was found to be the
nia; these signs include weakness, ataxia, collapse, disorientation, most sensitive technique, identifying 10 of 14 confirmed primary
behavioral changes, and seizures. Catecholamine release stimu- insulinomas. However, CT also identified a significant number
lated by low blood glucose levels also may cause muscle tremors, of false positive metastatic lesions. 407 The results of SPECT with
1
shaking, anxiety, and hunger. Clinical signs can be present for 111 In-DTPA-D-Phe -octreotide have been reported in a total of
days to months and often are intermittent, episodic, or precipi- 19 dogs with insulinoma, with an overall sensitivity of 50% for
tated by fasting, exercise, excitement, or eating. Signs may be less detection and correct localization of the primary tumor. 388,407
pronounced with more chronic hypoglycemia, and patients can Enhanced CT techniques, such as dynamic CT or dual-phase
be clinically normal, with significantly low blood glucose levels. CT angiography, hold promise for greater sensitivity of detec-
Physical examination findings otherwise are unremarkable in tion of insulinomas in dogs, but large-scale studies have yet to be
most patients. A paraneoplastic peripheral neuropathy has been reported in the veterinary literature. 419–421 Somatostatin receptor
described in dogs with insulinoma. This is rare, although sub- scintigraphy (SRS) is an important imaging modality in humans
clinical neuropathies may be present and undetected. 393–397 Brain with pancreatic endocrine tumors, including insulinomas. Indium
lesions associated with hypoglycemia also have been reported in In-111 pentetreotide SRS has been reported in a total of six dogs
rare cases. 398,399 with insulinoma; positive results were reported in five cases,
The diagnosis of insulinoma is confirmed by documenting although an accurate anatomic localization was obtained only in
hypoglycemia (blood glucose <60 mg/dL) with a concurrent nor- one dog. 422,423 PET has been used in human patients to localize
mal or increased serum insulin concentration. In some cases it insulinomas when CT, MRI, and ultrasound are negative. 424 This
may be necessary to fast the patient, with careful monitoring, and modality has yet to be explored in canine insulinoma patients.
repeat blood glucose measurements every 30 to 60 minutes. Once Therapy for canine insulinoma involves acute and chronic
the blood glucose is less than 60 mg/dL, a serum sample should treatment of hypoglycemia and long-term management of the
be submitted for concurrent insulin measurement. The presence tumor. Acute treatment of hypoglycemia is accomplished through
of a normal or high serum insulin concentration in the face of administration of intravenous dextrose, often as a slow bolus, fol-
hypoglycemia is inappropriate and generally sufficient to confirm lowed by continuous rate infusion (CRI). This should be given
the diagnosis of insulinoma. This insulin-glucose pair should be with caution because this treatment can stimulate further unreg-
performed more than once if the initial sample provides equivocal ulated insulin secretion and worsened hypoglycemia. Glucagon
results. 400 The use of insulin:glucose or glucose:insulin ratios is infusion also has been safely and effectively used in the manage-
not recommended because these do not improve diagnostic accu- ment of hyperinsulinemic-hypoglycemic crises in a small number
racy. 401 Provocative testing is rarely used in veterinary medicine of dogs. 425,426
because of risks, expense, and poor sensitivity. 385,401 Serum fruc- Surgery is the recommended treatment for insulinoma in
tosamine and glycosylated hemoglobin concentrations also can dogs and is indicated in patients with hypoglycemia and inap-
be measured in dogs to support a suspicion of insulinoma. 402–405 propriately increased serum insulin concentrations, regardless
Concentrations of these glycosylated proteins would be expected of the results of abdominal imaging studies. 383–385,387,392 Ulti-
to be lower than normal in dogs with chronic hypoglycemia, mately, an exploratory laparotomy is necessary to evaluate the
although this is not necessarily pathognomonic for insulinoma. pancreas for the primary tumor and the remainder of the abdo-
Imaging studies often are used in the evaluation of insuli- men for metastatic disease. Most canine insulinomas are visible
noma patients, either to investigate other differential diagnoses or palpable at surgery, and tumors are identified in both lobes of
for hypoglycemia or for local and distant staging in preparation the pancreas with equal frequency. 375 Treatment before surgery
for surgical management. Thoracic and abdominal radiographs with corticosteroids may help improve blood glucose levels. 401
usually are unremarkable, 401 and abdominal ultrasonography, The patient should not have a long period of fasting, and some
although commonly performed, cannot be used to rule in or rule cases may require intravenous dextrose. 401 Conventionally the
out a diagnosis of insulinoma. This technique has been reported abdomen is explored via a ventral midline approach, although
to clearly identify and localize a pancreatic mass in less than 50% laparoscopic evaluation and partial pancreatectomy has been
of patients with insulinoma, 387,392,406,407 and it has low sensitivity reported. 427 A partial pancreatectomy of the affected portion of
and specificity for the detection of metastatic lesions. In human the pancreas and a margin of normal tissue is performed. This
medicine, endoscopic and intraoperative ultrasonography are can be performed by intracapsular dissection and ligation or