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==Description==

==Introduction==

[[Image:Islet cell tumour.jpg|right|thumb|100px|<small><center>Islet cell tumour (Image sourced from Bristol Biomed Image Archive with permission)</center></small>]]

[[Image:Islet cell tumour.jpg|right|thumb|100px|<small><center>Islet cell tumour (Image sourced from Bristol Biomed Image Archive with permission)</center></small>]]

'''Insulinomas''' are slow growing, well-encapsulated, functional tumours of the [[Pancreas - Anatomy & Physiology#Endocrine|beta cells]] of the pancreatic islets.  They secrete inappropriately high amounts of [[Pancreas - Anatomy & Physiology#Insulin|insulin]], irrespective of the serum glucose concentration.  They are often [[Neoplasia - Pathology#Classification|malignant]], with a high metastatic rate to regional [[Lymph Nodes - Pathology|lymph nodes]], [[Liver - Anatomy & Physiology|liver]] and omentum.  60% of insulinomas 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 islets.  They secrete inappropriately high amounts of [[Pancreas - Anatomy & Physiology#Insulin|insulin]], irrespective of the serum glucose concentration.  They are often malignant, with a high metastatic rate to regional lymph nodes, [[Liver - Anatomy & Physiology|liver]] and omentum.  60% of insulinomas are carcinomas, which are more likely to be endocrinologically active whereas the others are adenomas.

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 to insulin (such as glucagon, growth hormone, glucocorticoids and catecholamines) also contributes to the pathogenesis and clinical signs observed in animals with insulinoma.   

Blood glucose concentration is normally 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 to insulin (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 primarily to hypoglycaemia but the release of catecholamines during episodes of hypogylcaemia may be contributory:

The following signs are related primarily to '''hypoglycaemia''' but the release of catecholamines during episodes of hypogylcaemia may be contributory:

*'''Collapse'''

*'''Collapse'''

*'''Seizures'''

*'''Seizures'''

*'''Exercise intolerance'''

*'''Exercise intolerance'''

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.   

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:

A presumptive diagnosis can be made on the basis of '''Wipple's triad''', which refers to the presence of:

===Pathology===

===Pathology===

Collection and examination of a biopsy is needed for definitive confirmation of the diagnosis.  The following features may be identified:

Collection and examination of a biopsy 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.

*Usually single, or less often multiple, small (1-3cm) spherical nodules, yellow to dark red, in one or more lobes

 

*Histologically, small islets of acinar tissue are sometimes present within the neoplasm

Histologically, small islets of acinar tissue are sometimes present within the neoplasm.

*Pancreatic beta cells can readily be identified using immunocytochemistry

 

Pancreatic beta cells can readily be identified using immunocytochemistry.

===Diagnostic Imaging===

===Diagnostic Imaging===

A '''partial pancreatectomy''' is suitable for patients with a solitary tumour and any suspected metastases may be removed or biopsied during the procedure.  An intra-operative ultrasound scan can be performed if the mass is not evident when the pancreas has been exposed.  Possible post-operative complications include:

A '''partial pancreatectomy''' is suitable for patients with a solitary tumour and any suspected metastases may be removed or biopsied during the procedure.  An intra-operative ultrasound scan can be performed if the mass is not evident when the pancreas has been exposed.  Possible post-operative complications include:

*'''Persistent hypoglycaemia''', probably due to the presence of unidentified metastases.

*'''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.

*[[Pancreatitis|'''Pancreatitis]]''' or '''[[Diabetes Mellitus|Diabetes mellitus]]''' due to disruption to the pancreatic parenchyma during the procedure.

*'''Epilepsy''' and '''diffuse polyneuropathy''' due to chronic hypoglycaemia.

*'''Epilepsy''' and '''diffuse polyneuropathy''' due to chronic hypoglycaemia.

*'''Duodenal necrosis and perforation''' as the cranial pancreatico-duodenal artery may be disrupted when the right limb of the pancreas is dissected away from the duodenum.

*'''Duodenal necrosis and perforation''' as the cranial pancreatico-duodenal artery may be disrupted when the right limb of the pancreas is dissected away from the duodenum.

This is related to the WHO stage of the tumour at diagnosis.  An animal with a stage I and II neoplastic process could expect a median survival time of 18 months but this falls to only 6 months for an animal with stage III disease.  Patients which undergo surgery to remove an insulinoma have a better prognosis than those treated medically but the condition will recur invariably after surgical removal.  Those animals which show a recurrence of clinical signs after surgery may then be treated medically, an approach that produces a significant increase in median survival time (from approximately 2 years to 4 years).

This is related to the WHO stage of the tumour at diagnosis.  An animal with a stage I and II neoplastic process could expect a median survival time of 18 months but this falls to only 6 months for an animal with stage III disease.  Patients which undergo surgery to remove an insulinoma have a better prognosis than those treated medically but the condition will recur invariably after surgical removal.  Those animals which show a recurrence of clinical signs after surgery may then be treated medically, an approach that produces a significant increase in median survival time (from approximately 2 years to 4 years).

==References==

==References==

[[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:Pancreas_-_Hyperplastic_and_Neoplastic_Pathology]][[Category:Endocrine_System_-_Pathology]]

[[Category:Neoplasia]]

 

[[Category:To_Do_-_James]]

[[Category:Endocrine Diseases - Dog]][[Category:Neurological Diseases - Dog]][[Category:Pancreatic Diseases - Dog]]

[[Category:Cat]][[Category:Dog]]

[[Category:Endocrine Diseases - Cat]][[Category:Neurological Diseases - Cat]][[Category:Pancreatic Diseases - Cat]]

[[Category:To_Do_-_Review]]

[[Category:Expert_Review]]