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*[[Adenoma|Adenomas]] and [[Carcinoma|carcinomas]] deerived from beta cells
*[[Adenoma|Adenomas]] and [[Carcinoma|carcinomas]] deerived from beta cells
**Neurologic signs - stupor, confusion, coma, seizures, peripheral neuropathy may also develop
**Neurologic signs - stupor, confusion, coma, seizures, peripheral neuropathy may also develop
'''Insulinomas''' are slow growing, well-encapsulated, functional tumours of the [[Pancreas - Anatomy & Physiology#Endocrine|beta cells]] of the pancreatic islet cells. They secrete inappropriately high amount of [[Pancreas - Anatomy & Physiology#Insulin|insulin]], irrespective of the serum glucose level. They are predominantly [[Neoplasia - Pathology#Classification|malignant]] (90% of canine insulinomas), with a high metastatic rate to regional [[Lymph Nodes - Pathology|lymph nodes]], [[Liver - Anatomy & Physiology|liver]] and omentum. 60% of isulinomas are [[Neoplasia - Pathology#Nomenclature|carcinomas]], which are more likely to be endocrinologically active whereas the others are [[Neoplasia - Pathology#Nomenclature|adenomas]].
'''Insulinomas''' are slow growing, well-encapsulated, functional tumours of the [[Pancreas - Anatomy & Physiology#Endocrine|beta cells]] of the pancreatic islet cells. They secrete inappropriately high amount of [[Pancreas - Anatomy & Physiology#Insulin|insulin]], irrespective of the serum glucose level. They are predominantly [[Neoplasia - Pathology#Classification|malignant]] (90% of canine insulinomas), with a high metastatic rate to regional [[Lymph Nodes - Pathology|lymph nodes]], [[Liver - Anatomy & Physiology|liver]] and omentum. 60% of isulinomas are [[Neoplasia - Pathology#Nomenclature|carcinomas]], which are more likely to be endocrinologically active whereas the others are [[Neoplasia - Pathology#Nomenclature|adenomas]].
Blood glucose concentration is maintained within a narrow range
Blood glucose concentration is maintained within a narrow homeostatic range because several tissues are able to use only glucose as an energetic substrate. These tissues are particularly affected by the hypoglycaemia which occurs with hyperinsulinaemia and they include neurones, blood cells, renal medullary cells and fibroblasts in healing wounds. The release of hormones antagonistic hormones (such as glucagon, growth hormone, glucocorticoids and catecholamines) also contributes to the pathogenesis and clinical signs observed in animals with insulinoma.
==Signalment==
==Signalment==
==Diagnosis==
==Diagnosis==
===Clinical Signs===
===Clinical Signs===
The following signs are related to hypoglycaemia:
The following signs are related primarily to hypoglycaemia but the release of catecholamines during episodes of hypogylcaemia may be contributory:
*collapse
*'''Collapse'''
*seizures
*'''Seizures'''
*muscle tremor
*'''Muscle tremors and weakness'''
*'''Ataxia'''
*ataxia
*'''Lethargy and depression'''
*lethagy and depression
*'''Exercise intolerance'''
*exercise intolerance
These signs may be intermittent at the beginning of the disease, but they become more often with time. In between hypoglycaemic episodes, the animals are generally normal. A presumptive diagnosis can be made on the demonstration of the Wipple's triad. This includes the presence of clinical signs associated with hypoglycaemia, fasting hypoglycaemia and amelioration of clinical signs with the administration of glucose. Insulinoma should always be considered when clinical signs are associated with exercise, fasting, excitement or feeding.
These signs may be intermittent early in the course of the disease, but they become more frequent and sustained with time. In between hypoglycaemic episodes, the animals often appear to be normal. Hypoglycaemic episodes may occur shortly after feeding (as insulin secretion is stimulated) or a long time after feeding (as the animal cannot maintain its blood glucose in the acceptable range) and they may also be associated with exercise or excitement.
A presumptive diagnosis can be made on the basis of '''Wipple's triad''', which refers to the presence of:
*Clinical signs associated with hypoglycaemia
*Fasting hypoglycaemia
*Amelioration of clinical signs with the administration of glucose
===Laboratory Tests===
===Laboratory Tests===
====Biochemistry====
====Biochemistry====
*Hypoglycemia
*'''Hypoglycaemia''' which should be a persistent finding during fasting.
*'''Serum ALT and ALK''' are often elevated but the significance of these findings is not known.
====Other Tests====
====Other Tests====
*A tentative diagnosis can be made if an inappropriately high serum insulin level in the presence of a hypoglycaemia is shown.
*'''Serum insulin concentration''' is usually elevated in the face of profound hypoglycaemia, with an '''insulin: glucose ratio''' of >4.2 considered to be diagnostic for insulinoma.
*'''Serum fructosamine levels''' can also be assessed to gauge whether the animal has been persistently hypoglycaemic over the previous 2-3 weeks. A level <250-350 umol/l is suggestive of insulinoma
===Histopathology===
===Histopathology===
This is needed for confirmation the diagnosis.
This is needed for definitive confirmation of the diagnosis. The following features may be identified:
*Usually single, or less often multiple, small (1-3cm) spherical nodules, yellow to dark red, in one or more lobes
*Small islets of acinar tissue are sometimes present within the neoplasm
===Diagnostic Imaging===
===Diagnostic Imaging===
====Radiography====
====Radiography====
Thoracic radiographs may be used to identify any pulmonary metastases, but it is uncommon for insulinomas to metastasise to the lungs.
====Ultrasonography====
====Ultrasonography====
Occasionally, it may be possible to visualise the location of the tumour on the [[Pancreas - Anatomy & Physiology|pancreas]]. However, this may not always be possible, especially if the tumour is too small. Metastases to [[Lymph Nodes - Anatomy & Physiology|lymph nodes]] and [[Liver - Anatomy & Physiology|liver]] can sometimes be seen.
Occasionally, it may be possible to visualise the location of the neoplasm on the [[Pancreas - Anatomy & Physiology|pancreas]] as a hypoechoic nodule. However, this may not always be possible, especially if the tumour is very small. Metastases to [[Lymph Nodes - Anatomy & Physiology|lymph nodes]] and [[Liver - Anatomy & Physiology|liver]] can sometimes be identified but suspected hepatic metastases should always be biopsied.
==Treatment==
==Treatment==
===Emergency===
===Emergency Stabilisation===
*In the event of a hypoglycaemic episode, a dextrose bolus should be given immdediately.
*In the event of a hypoglycaemic episode, a dextrose bolus should be given immdediately.
*This should be followed by intravenous fluid therapy with 2.5% dextrose.
*This should be followed by intravenous fluid therapy with 2.5% dextrose.
===Medical===
===Medical===
This is more suitable for patients in which surgery has been declined or when surgery is inappropriate or fails due to the presence of metastasis.
This is more suitable for patients in which surgery has been declined or when surgery is inappropriate or fails due to the presence of metastasis.
*Small and frequent meals (3-6 times/day) of complex carbohydrate content.
*'''Small and frequent meals''' (3-6 times/day) of with high fat and protein content and some complex carbohydrate.
*Exercise restriction.
*'''Exercise restriction'''.
*[[Steroids|Glucocorticoid]] such as prednisolone to increase hepatic glucose production and decrease cellular glucose uptake.
*[[Steroids|'''Glucocorticoids''']] such as prednisolone may be prescribed to increase hepatic gluconeogenesis and to decrease cellular glucose uptake.
*Diazoxide, an oral hyperglycaemic drug, to inhibit pancreatic insulin secretion and tissue glucose uptake.
*'''Diazoxide''', an oral hyperglycaemic drug, may be used to inhibit pancreatic insulin secretion and tissue glucose uptake.
===Surgery===
===Surgery===
A partial pancreatectomy is suitable for patients with a solitary tumour, provided there is no metastasis. Complications such as persistent hypoglycaemia, [[Pancreatitis - Dog and Cat|pancreatitis]], diabetes mellitus, epilepsy and diffuse polyneuropathy can occur.
A '''partial pancreatectomy''' is suitable for patients with a solitary tumour and any suspected metastases may be removed or biopsied at the same time. Possible post-operative complication include:
*'''Persistent hypoglycaemia''', probably due to the presence of unidentified metastases
*[[Pancreatitis - Dog and Cat|'''Pancreatitis]]''' or '''Diabetes mellitus''' due to disruption to the pancreatic parenchyma during the procedure
*'''Epilepsy''' and '''diffuse polyneuropathy''' due to chronic hypoglycaemia
==Prognosis==
==Prognosis==
*Polton, G. A., White, R. N., Brearley, M. J. and Eastwood, J. M. (2007) '''Improved survival in a retrospective cohort of 28 dogs with insulinoma''' ''Journal of Small Animal Practice'' 48:151-156 [http://www3.interscience.wiley.com/cgi-bin/fulltext/117961667/PDFSTART]
*Polton, G. A., White, R. N., Brearley, M. J. and Eastwood, J. M. (2007) '''Improved survival in a retrospective cohort of 28 dogs with insulinoma''' ''Journal of Small Animal Practice'' 48:151-156 [http://www3.interscience.wiley.com/cgi-bin/fulltext/117961667/PDFSTART]
[[Category:Pancreas_-_Hyperplastic_and_Neoplastic_Pathology]][[Category:Endocrine_System_-_Pathology]]
[[Category:Pancreas_-_Hyperplastic_and_Neoplastic_Pathology]][[Category:Endocrine_System_-_Pathology]]
[[Category:Neoplasia]][[Category:Pancreas_-_Hyperplastic_and_Neoplastic_Pathology]][[Category:Endocrine_System_-_Pathology]]
[[Category:Neoplasia]]
[[Category:Neoplasia]]
[[Category:To_Do_-_James]]
[[Category:To_Do_-_James]]
[[Category:Cat]][[Category:Dog]]
[[Category:Cat]][[Category:Dog]]