Difference between revisions of "Insulinoma"

Revision as of 10:17, 22 August 2009

Signalment

More common in dogs than cats
Middle-aged to older dogs
No sex predilection
Breed predisposition, more common in medium to large-breed dogs:
- Irish Setter
- German Shepherd
- Labrador Retriever
- Standard Poodle
- Boxer

Description

Insulinomas are well slow growing, encapsulated, functional tumours of the beta cells of the pancreatic islet cells, They secrete inaappropriately high amount of insulin irrespective of the serum glucose level. They are predominantly malignant (90% of canine isulinomas), with a high metastatic rate to regional lymph nodes, liver and omentum. 60% of isulinomas are carcinomas, which are more likely to be endocrinologically active, the others being adenomas.

Diagnosis

Clinical Signs

The following signs are attributal to hypoglycaemia:

collapse
muscle tremor
muscle weakness
ataxia
mentally dull and disorientated

These sigs may be intermittent at the beginning of the disease, but this becomes progressively more often. In between hypoglycaemic episodes, the animals are normal. A presumptive diagnosis can be made on the demonstration of the Wipple's triad. This includes presence of clinical signs associated with hypoglycaemia, fasting hypoglycaemia and amelioration of clinical signs with the admistration of glucose. Insulinoma should be considered especially when clinical signs are associated with exercise, extended fasting or after feeding.

Laboratory Tests

Biochemistry

Hypoglycemia

Other Tests

A tentative diagnosis can be made if inappropriately high serum insulin level in the presence of hypoglycaemia is shown.

Histopathology

This is needed to confirm the diagnosis.

Diagnostic Imaging

Radiography

A thoracic radiograph may be used to identify any pulmonary metastases, but this is uncommon.

Ultrasonography

Occasionally, it may be possible to visualise the location of the tumour on the pancreas. However, this may not be possible if the tumous is too small. Metastases to lymph nodes and liver can sometimes be revealed.

Treatment

Medical

This is more suitable to 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 a simple carbohydrate content.
Exercise restriction.
Prednisolone to increase hepatic glucose prodection and decrease cellular glucose uptake.
Diazoxide, an oral hyperglycaemic drug, to inhibit pancreatic insulin secretion and tissue glucose uptake

Surgery

A partial pancreatectomy is suitable for patients with a solitary tumour, provided there is no metastasis. Complications such as persistent hypoglycaemia, pancreatitis, diabetes mellitus, epilepsy and diffuse polyneuropathy can occur.

Prognosis

This is dependent on the WHO staging of the tumour. A stage I and II can expect a median survival time of 18 months whereas it is only 6 months for a stage III. Patients suitable for surgical excision has better prognosis than those treated medically.

References

Ettinger, S.J. and Feldman, E. C. (2000) Textbook of Veterinary Internal Medicine Diseases of the Dog and Cat Volume 2 (Fifth Edition) W.B. Saunders Company.
Fossum, T. W. et. al. (2007) Small Animal Surgery (Third Edition) Mosby Elsevier
Nelson, R.W. and Couto, C.G. (2009) Small Animal Internal Medicine (Fourth Edition) Mosby Elsevier.
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 [1]

@@ Line 1: / Line 1: @@
-{{OpenPagesTop}}
+{{unfinished}}
-==Introduction==
+{{dog}}
-[[Image:Islet cell tumour.jpg|right|thumb|100px|<small><center>Islet cell tumour (Image sourced from Bristol Biomed Image Archive with permission)</center></small>]]
+{{cat}}
-'''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 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==
-Insulinomas occur most commonly in middle-aged or older dogs of the larger breeds.  There is no sex predilection and the condition occurs less commonly in cats.  Older cattle may rarely develop insulin-secreting tumours.
+*More common in dogs than cats
+*Middle-aged to older dogs
+*No sex predilection
+*Breed predisposition, more common in medium to large-breed dogs:
+**Irish Setter
+**German Shepherd
+**Labrador Retriever
+**Standard Poodle
+**Boxer
+==Description==
+Insulinomas are well slow growing, encapsulated, functional tumours of the beta cells of the pancreatic islet cells,  They secrete inaappropriately high amount of insulin irrespective of the serum glucose level.  They are predominantly malignant (90% of canine isulinomas), with a high metastatic rate to regional lymph nodes, liver and omentum.  60% of isulinomas are carcinomas, which are more likely to be endocrinologically active, the others being adenomas.
 ==Diagnosis==
 ===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 attributal to hypoglycaemia:
-*'''Collapse'''
+*collapse
-*'''Seizures'''
+*muscle tremor
-*'''Muscle tremors and weakness'''
+*muscle weakness
-*'''Ataxia'''
+*ataxia
-*'''Lethargy and depression'''
+*mentally dull and disorientated
-*'''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 sigs may be intermittent at the beginning of the disease, but this becomes progressively more often.  In between hypoglycaemic episodes, the animals are normal.  A presumptive diagnosis can be made on the demonstration of the Wipple's triad.  This includes presence of clinical signs associated with hypoglycaemia, fasting hypoglycaemia and amelioration of clinical signs with the admistration of glucose.  Insulinoma should be considered especially when clinical signs are associated with exercise, extended fasting or after feeding.
-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===
 ====Biochemistry====
-*'''Hypoglycaemia''' which should be a persistent finding during fasting.
+*Hypoglycemia
-*'''Serum ALT and ALK''' are often elevated but the significance of these findings is not known.
 ====Other Tests====
-*'''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.
+*A tentative diagnosis can be made if inappropriately high serum insulin level in the presence of hypoglycaemia is shown.
-*'''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
-===Pathology===
-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.
-Histologically, small islets of acinar tissue are sometimes present within the neoplasm.
+===Histopathology===
+This is needed to confirm the diagnosis.
-Pancreatic beta cells can readily be identified using immunocytochemistry.
 ===Diagnostic Imaging===
 ====Radiography====
-Thoracic radiographs may be used to identify any pulmonary metastases, but it is uncommon for insulinomas to metastasise to the lungs.
+A thoracic radiograph may be used to identify any pulmonary metastases, but this is uncommon.
 ====Ultrasonography====
-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.
+Occasionally, it may be possible to visualise the location of the tumour on the pancreas.  However, this may not be possible if the tumous is too small.  Metastases to lymph nodes and liver can sometimes be revealed.
 ==Treatment==
-===Emergency Stabilisation===
+===Medical===
-In the event of a hypoglycaemic episode, a bolus of 50% dextrose solution should be given immediately by the intra-venous route.  Glucose syrup can also be rubbed onto the gums of an affected animal or a meal could be provided and this approach may reduce the risk of rebound hypoglycaemia encountered with administration of 50% dextrose solution.  Intra-venous fluid therapy can then be maintained using 2.5% dextrose solution.
+This is more suitable to 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 a simple carbohydrate content.
+*Exercise restriction.
+*Prednisolone to increase hepatic glucose prodection and decrease cellular glucose uptake.
+*Diazoxide, an oral hyperglycaemic drug, to inhibit pancreatic insulin secretion and tissue glucose uptake
-===Medical Management===
+===Surgery===
-This is suitable for patients in which surgery has been declined or when clinical signs recur after surgical treatment due to the presence of metastases.  A suitable regime would include:
+A partial pancreatectomy is suitable for patients with a solitary tumour, provided there is no metastasis.  Complications such as persistent hypoglycaemia, pancreatitis, diabetes mellitus, epilepsy and diffuse polyneuropathy can occur.
-*'''Small and frequent meals''' (3-6 times/day) of with high fat and protein content and some complex carbohydrate.
-*'''Exercise restriction'''.
-*[[Steroids|'''Glucocorticoids''']] such as prednisolone prescribed to increase hepatic gluconeogenesis and to decrease cellular glucose uptake.
-*'''Diazoxide''', an oral hyperglycaemic drug, used to inhibit pancreatic insulin secretion and tissue glucose uptake.
-*'''Octreotide''', a somatostatin analogue which reduces the synthesis of insulin but which is rarely used for management of insulinomas.
-===Surgical Management===
-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.
-*[[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.
-*'''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.
 ==Prognosis==
-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 dependent on the WHO staging of the tumour.  A stage I and II can expect a median survival time of 18 months whereas it is only 6 months for a stage III.  Patients suitable for surgical excision has better prognosis than those treated medically.
-{{Learning
-|Vetstream = [https://www.vetstream.com/felis/Content/Disease/dis02122.asp Insulinoma]
-|literature search = [http://www.cabdirect.org/search.html?rowId=1&options1=AND&q1=Insulinoma&occuring1=title&rowId=2&options2=AND&q2=&occuring2=freetext&rowId=3&options3=AND&q3=&occuring3=freetext&x=44&y=8&publishedstart=yyyy&publishedend=yyyy&calendarInput=yyyy-mm-dd&la=any&it=any&show=all Insulinoma publications]
-}}
 ==References==
@@ Line 82: / Line 71: @@
 *Nelson, R.W. and Couto, C.G. (2009) '''Small Animal Internal Medicine (Fourth Edition)''' ''Mosby Elsevier''.
 *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]
-{{review}}
-{{OpenPages}}
-[[Category:Pancreas_-_Hyperplastic_and_Neoplastic_Pathology]][[Category:Endocrine_System_-_Pathology]]
-[[Category:Neoplasia]][[Category:Pancreas_-_Hyperplastic_and_Neoplastic_Pathology]][[Category:Endocrine_System_-_Pathology]]
-[[Category:Endocrine Diseases - Dog]][[Category:Neurological Diseases - Dog]][[Category:Pancreatic Diseases - Dog]]
-[[Category:Endocrine Diseases - Cat]][[Category:Neurological Diseases - Cat]][[Category:Pancreatic Diseases - Cat]]
-[[Category:Expert_Review]]