Endocrinology Flashcards
What is the treatment of hypothyroidism?
Levothyroxine sodiu - drug of choice. Acts in the same way as endogenous thyroxine. It is converted to T3 in peripheral tissues, given orally usually once or twice daily. Start at maintenance dose but increase dose or frequency depending on clinical signs and TDM. Necessary to tailor to individual animal. Generally has good oral bioavailability in individuals may have reduced absorption. Half life of about 12-15 hours but individual animal variation. Thyrotoxicosis unusual.
What is hypothyroidism?
Primmarily a disease of dogs - lymphocytic thyroiditis, idiopathic atrophy. Diagnosis is based on clinical signs, serum haematology and biochemistry. measure bound and free T4 and also cTSH.
What is the difference between levothyroxine sodium tablets and levothyroxine sodium liquid?
Twice daily dosing often required for tablets. Therapeutic monitoring after 12 weeks, pre pill and 6 hours post pill (measure t3 and t4) required for Levothyroxine sodium. Liquid - once daily dosing, increased bioavailability vs tablets. Food decreases F value but can still give with food provided consistency. TDM 4-6 hours post treatment starting at 4 weeks.
What is liothyronine sodium?
Acts like endogenous T3 (triiodothyronine). It has a shorter duration of action and more rapidly metabolised. it is only used when there has been no or poor response to levothyroxine sodium. may be used to do a T3 suppression test in the diagnosis of equivocal hyperthyroidism in the cat.
What is hyperthyroidism?
Generally a condition of elderly cats. Usually associated with a benign adenoma of the thyroid gland leading to overproduction of thyroid hormones. Management/treatment - surgical removal of the thyroid, radioactive iodine treatment, drug therapy pre surgery or for long term management.
How do hyperthyroidism drugs work?
Prevent incorporation of thyroid peroxidase with thyroglovulin and therefore the production of T3 and T4. Most inhibit thyroid peroxidase - act as a preferential substrate, fail to get incorporation of iodide into the thyroglobulin molecule. Reduction in the production of T3 and T4. A number of drugs have been used - carbimazole, methimazole and proylthiouracil.
What is methimazole?
Licensed in the Uk for feline use. blocks thyroid peroxidase activity thus reducing levels of T3 and T4. The effects are reversible i.e control not cure. Can be used long term or prior to surgery (2-3 weeks). BID administration. Animals should be monitored every three weeks in terms of biochemistry, haematology and serum T4 levels for the first 4- months and thereafter every 3 months. Care especially in renal disease since GFR will b reduced. Especially at higher doses side effects not uncommon - but reversible. After oral absorption half life only 4-6 hours but may stay in the thyroid for about 20 hours. There is a great deal of variation in oral bioavailability and volume of distribution. It takes 1-3 weeks to see reduction in T4 levels. Preliminary work in transdermal administration, ease the problem of frequent oral dosing.
What is carbimazole?
Metabolised almost entirely to methimazole - appears to have fewer side effects than methimazole but not clear. Recently licensed for feline use in the UK - sustained release preparation for once daily dosing. half life 9 hours versus 5 hours for methimazole. Carbimazole less bitter. Do not crush or break tablets.
How is radioactive iodine used in hyperthyroidism?
131I is selectively taken up by the thyroid to be incorporated into thyroid hormone precursors. It emits beta and gamma radiation and so destroys the thyroid tissue. It is selective and not associated with damage to the surrounding tissue like the parathyroid. Special facilities and hospitalisation of the cat required post treatment as it is eliminated in faeces and urine.
What is hyperadrenocorticalism - cushings disease?
A relatively common endocrine abnormality in the dog. syndrome results from overproduction of cortisol and corticosterone from the adrenal gland. may be due to a pituitary adenoma or adrenal gland tumour. leeds to a large number of clinical signs and symptoms due to wide ranging effects of glucocorticoids.
How is trilostane used to treat hyperadrenocorticism?
UK licensed treatment for cushings disease - it Inhibits the enzyme 3- B hydroxysteroid dehydrogenase - inhibition is reversible. It reduces the production of cortisol and corticosterone. Does not consistently reduce aldosterone. Its oral bioavailability is improved with the presence of food. it has an active metabolite - ketotrilostane, elimination in the dog is not known. Close monitoring essential, given once daily, day 10 week 4 week 12 and every 3 months repeat ACTH stimulation test 4-6 hours post pill. Side effects - care with heart disease, vomiting, diarrhoea, pancreatitis, thromboembolism, adrenal necrosis, tablets should not be split.
What is mitotane?
Not available in the UK so imported on a special treatment certificate by applying to the VMD. Was the standard treatment prior to licensing of trilostane. If treatment with trilostane unsuccessful, mitotane may be used. related to DDT. Causes a selective destruction of the adrenal cortex zona fasciculata and zona reticularis. As it is a cytotoxic agent extreme care should be taken when handling and administering the drug. Induction phase and then maintenance phase. Daily treatment for about 7-14 days then once every 7-10 days. Generally mild side effects with lethargy vomiting diarrhoea. Occasionally get necrosis/destruction of the zona glomerulosa leading to addisonian crisis.
What is Addison’s disease?
Deficiency of mineralocorticoid and glucocorticoid production by the adrenal gland. Treatment involves mineralocorticoid and to a lesser extent glucocorticoid therapy. physiological replacement versus pharmacological effect. deficiency of adrenocortical steroid production. Mineralocorticoid and glucocorticoid deficiency. mostly in young female dogs. animals generally present collapsed, bradycardic, hyperkalaemic, hyponatraemic and dehydrated. Treated acutely with hydrocortisone, long term management with fludrocortisone.
What is DOCP?
Desoxycortisterone pivalate - available in US and canada - long acting analogue of DOCA. Given i/m approximately once every 25 days - tailor dose to individual animal.
Describe diabetes mellitus.
Insulin is produced by the B cells in the pancreas. there is extremely high interspecies sequence homology with porcine and canine insulin being identical. Type 1,2, and 3 diabetes mellitus all reflect an abnormality in glucose metabolism. type 1 is the most common in the dog. type 2 may be more important in the cat.
What are the functions of insulin?
Facilitates cellular uptake and metabolism of glucose, promotes synthesis of glycogen protein and fat, involved in the cellular uptake of ions such as K+.
What are the different types of insulin?
Short acting, intermediate, long acting. Insulin since it is a peptide hormone must be administered parenteraly. All preparations need to be stored between 2 to 8*. specialised syringed should be used. Insulin usually of bovine or porcine origin. Some of the human preparations are recombinant products.
Describe short acting insulin
Soluble insulin, neutral insulin
the only form of insulin that can be given Iv. may also be given im or sc. duration of activity when given i/v is about 2-4 hours. ideal for use in ketoacidotic emergencies- may b e administered as a constant rate infusion. can also be used in hyperkalaemia associated with UT obstruction.
Describe intermediate acting insulin
Onset of activity 1-2 hours; peak activity 6-12 hours, duration of effect 18-26 hours. often times are reduced in cats. Given s/c. Insulin Zinc suspension - mixture of 30% amorphous insulin zinc and 70% crystalline insulin zinc. Crystalline has a longer duration of action. Caninsulin is porcine origin (licensed).
Describe long acting insulin
onset of activity 4-6 hours, peak activity 14-24 hours, duration of effect 32-36 hours. Especally useful for cats where effect tends to be shortened vs the dog. Protamine zinc insulin - a bovine insulin administered s/c with slower release of insulin. Insulin glargine - new recombinant insulin, engineered to alter pharmacokinetic profile, acidic - ph4, don’t dilute or mix, injected s/c get micro precipitates to give relatively constant absorption profile. good results in cats where it is given twice daily in combination with a high protein low carb diet.
What are oral hypoglycaemic agents?
The sulphonylureas and the biguanides. Probably of limited use in veterinary species. may be tried in cats. No way of discerning type 1 or type 2. Sulphonylurea derivatives - stimulate the pancreas to release insulin, increase the peripheral utilisation of insulin, glipizide is main agent used - inhibits ATP dependent K+ channels causing depolarisation and release of insulin. Kinetics based on human studies show good oral bioavailability with hepatic metabolism and renal excretion.
Which drugs are used in diabetes insipidus?
D insipidus results either from a reduced release of vasopressin from the posterior pituitary or a reduce insensitivity to vasopressin in the collecting tubules. DDAVP - desmopressin is a vasopressin analogue - used in central diabetes insipidus. Does not possess the vasoconstrictor properties. DDAVP increases the retention of water in the collecting duct by the renal tubule by acting on V2 receptors, also increases the production of Von willebrands factor. It may be administered in the conjunctival sac lasting up to 8 hours. Chlorpropamide is an oral hypoglycaemic drug thought to increase NACL reabsorption in the ascending loop of henle - needs ADH to be present - nephrogenic DI.
What are the thiazide diuretics?
Used in D insipidus. Eg chlorthiazide - site of action D.C. T inhibit Na+ and Cl- reabsorption - so loss of sodium and water in the DCT leads to hypovolaemia. more sodium and water are reabsorbed in the PCT. less urine in the loop of henle - less urine presented to collecting tubule. May induce hypokalaemia.
What are microsomal triglyceride transport protein inhibitors?
MTP and apoliprotein B are key lipid transfer pproteins. MTP required for the formation of apoB containig lipoproteins. Chylomicron formation from GI tract and VLDL formation by the liver. This occurs within the enterocytes and the liver in the ER. Inhibiition of MTPS results in lowering of cholesterol and triglyceride levels. REduction in absorption of dietary fat and increased faecal excretion of fat. Eg Dirlotapide - an MTP inhibitor, selective inhibition of intestinal MTP - fatty acds, monoglycerides and cholesterol in the enterocyte do not get assembled into chylomicrons. Fat filled enterocytes triggers release of anorectic peptides- satiety centres to reduce food intake. oral administration required for effect to be seen.
Describe the anatomy of the endocrine pancreas?
the pancreas lies in close association with the lesser curvature of the stomach and the duodenum. The exocrine component accounts for more than 90% of the total pancreatic mass, whereas the endocrine pancreas accounts for less than 10% and consists of several hundred thousand clusters of cells called the islets of langerhans. alpha cells - approx 25% of cells secrete glucagon. Beta cells - approx 60% - secrete insulin. Delta cells - approx 10% - secrete somatostatin. F cells - secrete Pancreatic polypeptide cells Beta cells occupy the centre of the islets while alpha and delta cells are situated at the periphery. Both glucagon and insulin are polypeptide hormones and they are responsible for maintaining blood glucose levels within a narrow range.
What is glycolysis?
The metabolism of glucose to provide energy as ATP
What is glycogenolysis?
the breakdown of glycogen to yield glucose
What is gluconeogenesis?
The formation of glucose from protein and fats.
What is glycogenesis?
The formation of glycogen from glucose.
What is insulin?
A small protein, consisting of an A andB petide chain held together by disulfide bonds. if the chains are split apart it loses its biological activity. porcine and canine insulins are identical while bovine differs from canine insulin by several amino acids. feline insulin is most closely related to bovine insulin. Insulin is produced in response to elevated blod glucose. the overall action of insulin is to promote nutrient uptake, utilisation and storage by tissues and thus lower the concentration of glucose in the circulation. Increased glucose uptake by peripheral cells; especially muscle, liver, fat, synthesis of glycogen in liver for storage, inhibition of glycoenolsys & gluconeogenesis (liver).
What is glucagon?
Glucagon has a major role in maintaining blood glucose levels by increasing the concentration i.e exactly the opposite of insulin. production is increased by low blood glucose or Excercise which results in initiating hepatic glycogenolysis, stimulating hepatic gluconeogenesis, stimulating breakdown of triglycerides in fat to provide fatty acids for fuel.
Describe type 1 diabetes mellitus
Insulin deficiency diabetes. associated with a total loss of beta cell function as occurs due to immune mediated disease, pancreatitis or irreversible beta cell exhaustion. This is the most common form of DM seen in dogs. affected animals have high resting blood glucose levels, low resting insulin and fail to secrete insulin in the presence of hyeprglycaemia. they are insulin dependent diabetics. almost all dogs diagnosed with DM will require insulin treatment for life. immune mediated disease is the usual cause of type I dm in humans. may occur in dogs.
Describe type 2 diabetes
Insulin resistance diabetes. patients have high resting blood glucose and normal/high levels of insulin, but this is insufficient for demand. most cases occur because of insulin resistance due to excess diabetogenic hormones or obesity. (progestagens, glucocorticoids, growth hormone, glucagon, adrenaline). PEripheral cell insulin receptors are less responsive to insulin, meaning ever higher insulin levels are required. initially as insulin secretion rises this keeps blood glucose levels normal. If the cause of insulin resistance is not removed, beta cell exhaustion results in a relative or lack of insulin. blood glucose rises and patients become type 1 insulin dependent diabetics. this is most common type of DM seen in cats. Associated with amyloid deposits around the islet cells in up to 90% of cases.
Describe the signalment for DM
Can occur in any breed. DM seen most freqently in middle aged dogs. Entire females are at increased risk due to prolonged high levels of progesterone during dioestrus. DM in keeshund puppies due to congenital aplasia of beta cells has been reorted. Twice as many males are affected as females in cats. usually middle age 10-13years. Burmese at increased risk.
What are the predisposing factors of diabetes mellitus?
Obesity, Progesterone, DM is more common in entire female dogs due to action of progesterone - growth hormone is stimulated from the mammary gland during dioestrus which induces insulin resistance. Glucocorticoids - inflammatory processes elevate glucocorticoids and inflammatory factors which will antagonise insulin. Growth hormone from pituitary adenomas, excessive catecholamines from pheochromocytomas of adrenal medulla and glucagon from glucagonomas of the islet alpha cells will antagonise insulin. Pancreatitis - chronic pancreatitis may lead to sufficient loss of endocrine tissue to result in DM.
Describe the altered metabolism and ketoacidosis with diabetes mellitus
Insulin deficiency results in a failure of glucose uptake by peripheral tissues leading to hyperglycaemia. the normal balance between insulin and glucagon is lost. predominance of glucagon permits uncontrolled glycogenolysis and gluconeogenesis, further increasing blood levels. Once the renal threshold for glucose is reached, hyperglycaemia induces glucosuria and osmotic diuresis, hence polyuria and compensatory polydipsia. Blood glucose cannot be taken up and used by cells for energy and remains in the circulation. the body mobilises proteins and adipose stores to release amino acids and fatty acids for gluconeogenesis. this leads to cachexia and weight loss. fatty acids from the circulation are oxidised to the ketones acetyle co A acetoacetate and beta hydrooxybutyrate in the liver. ketones are not used efficiently due to the lack of insulin and accumulate in the circulation leading to ketoacidosis. ketoacidosis has negative physiological effects including vomiting, anorexia, further osmotic diuresis, further electrolyte disturbances, dehydration and hypovolaemia. Polyphagia, polyuria, polydipsia, to weight loss, lethargy, anorexic, vomiting dehydrated and collapsed patient.
What is the usual history and clinical signs with diabetes mellitus?
Well or uncomplicated diabetes - polyphagia, polyuria and polydipsia. bright and active.
Ketoacidotic diabetics - depression, anorexia, vomiting, dehydration. PUPD for some time previous presentation. Initially animals are obese but most patients lose weight as condition advances. clinical signs often observed following a recent oestrus and the history may indicate transient pupd following previous oestrous. early signs of pdpu and polyphagia often go unnoticed in outdoor cats. may also exhibit a plantigrade stance due to peripheral neuropathy. ddx - diabetes insipidus, psychogenic polydipsia, hyperadrenocorticism, hypoadrenocorticism, CRF, pyometra, hyperthyroidism.
How is diagnosis of DM in dogs made?
Documenting appropriate clinical signs, persistent fasting blood glucose of greater than 14mmmol with glucosuria. hyperglycaemia can be as high as 35mmol. presence of ketones in urine also supports diagnosis. Moderate hyperglycaemia of up to around 16mmol can occur rapidly due to stress. Recheck in 4 hours or the following day if hospitalised.
Describe how the measurement of fructosamine may help with interpretation of a moderately high blood glucose?
Fructosamine is produced by the irreversible glycosylation of albumin iin proportion to the surrounding glucose levels. its half life is around 1-2 weeks so levels give an indication of the average blood glucose level over that time span. Levels are used to primarily monitor diabetic control in response to treatment in both dogs and cats and also to aid differentiation of stress hyperglycaemia from DM in cats.
What is glycosylated haemoglobin?
produced in a similar manner to fructosamine but the half life is considerably longer. not routinely used as veterinary assays not commercially available. most common complication of DM is bacterial cystitis due to glucosuria and an impaired immune system. This may be missed due to the PUPD and a lack of an adequate inflammatory immune response. Every newly diagnosed diabetic should have a urine sediment exam and culture performed in addition to routine analysis.
What are the complications associated with untreated or poorly controlled DM?
bacterial cystitis
Formation of cataracts
retinopathy
peripheral neuropathy - weakness and plantigrade stance
Recurrent bacterial infections - urinary tract, skin, dental)
Life threatening diabetic ketoacidosis.
Describe how insulin and diet is used to manage uncomplicated diabetes mellitus?
Twice daily insulin to stabilise adequately. once daily insulin regimes can be tried if it is impossible for the owner to give twice daily injections. May be necessary to use a longer acting insulin if caninsulin fails to stabilise the patient due to its short duration of action. Caninsulin is given at 12 hourly intervals. A meal should be fed at the time of each injection, contanining 30-50% of the daily requirement. some patients need additional small meals between injections to avoid hypglycaemic episodes. providing dry food free choice for non greedy eaters will help avoid this. feed the same amount at the same times every day and avoid titbits. Reduce weight. water must always be freely available. Patients monitored by checking blood glucose. glucometers readily available and cheap to buy. At revisit carry out blood glucose curve and adjust insulin dose accordingly. Aim to maintain blood glucose between 5-11 however many diabetics will remain well with good quality of life despite not achieving this level of control. Intact bitches should be spayed during anoestrus.
Describe how blood glucose curves should be performed
By having the owner feed and inject their dog at home as per their normal routine and then bringing them straight to the surgery. A period of 5-7 days should be allowed before assessing the response to a change in insulin. Some dogs may always have an erratic response when hospitalised.
Describe what excercise regime should be used with diabetes mellitus?
Diabetics should be encouraged to exercise regularly and there is no reason to restrict it. however consistency is important. large fluctuations in amount of exercise from day to day may result in instability of blood glucose levels or hypoglycaemic episodes. Advise owners to take a sugary snack or oral glucose gel with them on walks.
How is uncomplicated diabetes mellitus managed in cats?
Many cats have reversible DM. All cats will require twice daily insulin if caninsulin is used. the shorter duration of action means that often even this is inadequate and three times dosing or longer acting preparation is required. Cats should retain their usual feeding schedule if possible. should be allowed free choice food if not overweight. weight reduction is vital if overweight. Blood glucose curves difficult due to stress hyperglycaemia. Moitor carefully for remission of DM and taper dose gradually. Glipizide is a sulphonylurea which stimulates insulin secretion and therefore its action depends ont he presence of functioning beta cells. this added strain on beta cells will decrease chances of achieving remission of DM. Acarbose impairs glucose absorption from the nitestine but must be given with food.
Describe how you should treat a diabetic ketoacidosis?
History is usually short onset, diagnosis can be confirmed by presence of ketonuria or ketonaemia. consider the placement of an IV line. A baseline electrolyte panel, total proteiin, blood gases, haematology and urinalysis should be obtained. Asess degree of dehydration. calculate fluid deficit - give fluids. monitor urine output. start insulin therapy. Adjust potassium in IV fluids as necessary. Hypophosphataemia coon following treatment of DKA and can cause haemolytic anaemia. Patients may be hyper or hyponatraemic at presentation. IV sodium bicarbonate to correct acidosis should be used with great caution and only if blood gas analysis is available. Once blood glucose level has been maintained between 10 and 15 mmol for at least 12 hours the ketone levels are falling and electrolyte levels are normalised, patient should be much brighter and keen to et.
What are the most common instabilities during DM
The most frequent complication is hypoglycaemic crisis. Signs of hypoglycaemia include anxiety, muscle tremors, ataxia, collapse, convulsions, coma and death. IF these signs occur and the patient is conscious then feed a high glucose food/drink/gel. The majoirity of problems are not due to complex hormonal interactions but the failures in the routine home management.
What is an insulin induced hypoglycaemia?
Somogyi effect, rapid decline in blood gucose followed by rebound hyperglycaemia due to counter regulatory response. these animals willl be hyperglycaemic most of the day and the hypoglycaemia may be very transient so patients apear as if they have insulin resistance unless a very detailed blood glucose curve is examined. Suspect this if control was initially good but has deteriorated despite increasing blood glucose level.
What sort of nutrition should be used in dogs with DM
avoid semi moist foods which are high in sugars. the aim is to ensure food is available or in digestive tract during periods of high insulin concentrations. if dogs are not greedy eaters providing dry food free choice will help avoid hypoglycaemic episodes. some clinicians prefer giving insulin before food, some after food and some at the same time. Giving insulin after the dog has eaten is the safetst option to avoid risk of hypoglycaemia should the dog not eat. Some dogs will not eat well until insulin is given and blood glucose falls to stimulate appetite. For dogs on once daily insulin provide 25-30% of daily ration at time of injection and the remainder at peak of insulin action 6-8 hours later. For dogs on twice daily provide 50% at each injection. Some dogs may need a snack 6-8 hours after each injection to alleviate hunger.
Which feeding regime should be used in cats with DM?
Allow cats to adhere to their usual feeding schedule whenever possible most cats eat small frequent meals and having free choice food available will help avoid hypoglycaemic episodes. otherwise feed the ration split to as many meals as is practicable and at leas two meals given at the time of the insulin injections. Automatic feeders may be useful.
How much carbohydrate and protein should be given in diets for animals with DM?
The diet should not contain large amounts of simple sugars which will cause post prandial surges in blood glucose levels. calories should be provided by complex carbohydrates (Starch) and high quality protein. in dogs, rice based diets may result in higher postprandial glucose than those with sorghum or barley. in cats, high protein diets more closely mimc the natural diet than high carbohydrate does. thus diets with increased protein content and restricted quantities of fat and especially carbohydrate decreases postprandial hyperglycaemia and may improve insulin sensitivity even to the point where diabetic remission occurs.
How much fibre should be given in diabetic dogs?
Diabetic diets often have high fibre but evidence from studies have shown a marked individual variation in the glycaemic responses of dogs to increased fibre i.e not a consistent improvement in postprandial hyperglycaemia. high fibre diets are not suitable for thin diabetic dogs. In cats only very high glucose diets produce post prandial hyperglycaemia ad so fibre would appear to be even less important.
How much fat should be given to diabetic dogs?
Fats only need to be specifically restricted in dogs which are overweight or those with a history of chronic pancreatitis. diabetes may occur secondary to chronic pancreatitis and diabetes may be a risk factor for pancreatitis so evaluate patients for pancreatic disease and restrict fat content of diet when appropriate.
What is carnitine?
Carnitine plays a key role in fatty acid metabolism. supplemental carnitine promotes fatty acid oxidation over protein catabolism for energy mobilisation and so may protect against muscle wastage in diabetic dogs and cats. carnitine may be beneficial in cats undergoing weight loss due to protection against hepatic lipidosis. it has also been shown to promote weight loss in cats undergoing caloric restriction.
What are the risk factors for developing obesity?
Genetics and breeds - labs, golden retrievers, pugs, chihuahuas, spaniels. Neutering and age - unnetured cats and dogs generally weigh less. Neutering appears to result in a decrease in metablic rate. Oestrogen also inhibits lipogenesis (fat production) and this decreases in female animals after spaying. with spaying - lean body mass declines causing a decrease in total daily energy expenditure. Diet and feeding - highly palatable diets most important exogenous factor influencing obesity in companion animals. Feeding of table scraps and treats. Hypothyroidism lowers metabolic rate and orthoaedic disease impairs ability to excercise, decreasing energy expenditure.
How can overweight dogs be managed?
A balanced proprietary diet should be fed, these are generally low fat and high fibre with moderate carbohydrate levels. Carnitine, supplementary vitamins etc are likely to be added. Calculate energy requirement based on ideal body weight and feed 60-65% of this for weight loss. Wet diets may give higher satiety than dry diets. n diabetic animals monitor insulin dosage carefully as the requirement may drop with weight reduction. Talk to owners about eliminating or reducing treats. Advise what to use as low calorie treat. Advise on weight loss exercise programme.
Describe how obesity in cats can be managed?
Do not over restrict food to encourage rapid weight loss in cats as they are prone to developing hepatic lipidosis if severely energy restricted. A low carbohydrate balanced proprietary diet will be most effective and most likely to reduce insulin requirement in diabetic animals. Calculate energy requirements based on ideal body weight and feed 70% of this amount for weight loss. wet diets may give higher satiety than dry diets. monitor insulin dosage carefully as requirement may drop quickly and significantly. advise on how to increase the cats activity levels. If this fails after several months consider switching to a more calorie restricted diet which will have higher carbohydrate and higher fibre content
What is an insulinoma?
Insulinomas are functional tumours of the beta cells secreting insulin. they are rare in dogs and extremely rare in cats. they occur more often in ferrets. high insulin levels are responsible for profound hypoglycaemia which causes the clinical signs. More often reported in larger breeds such as GSD, irish setter, boxer, poodles, collies. Middle age dogs. During normal fasting blood glucose is maintained by glycogenolysis for approx 24 hours. therafter hepatic glucogenesis is required. Excessive insulin from an insulinoma promotes rapid uptake of circulating glucose by tissues and inhibits glycogenolysis and Gluconeogenesis and so hypoglycaemia develops. An attempt is made by counter regulatory hormones including GH, cortisol and catecholamines to reverse the fall in blood glucose but is not efective.
What are the clinical signs of an insulinoma?
The brain is dependent on glucose and very sensitive to hypoglycaemia. this results in a neuroglycopaenic response: trembling, anxiety, weakness, ataxia, disorientation, seizures, coma and death. Clinical signs vary due to degree of hypoglycaemia and the speed with which it develops. Signs may be episodic and are most frequent during fasting and improve on feeding. Typically patients will exhibit weakness, excercise intolerance, behavioural changes, ataxia followed by collapse and seizures. Most patients are polyphagic.
What are the ddx for hypoglycaemia and how can insulinoma be diagnosed?
hunting dog, toy dog or neonatal hypoglycaemia, prolonged starvation, infections, glycogen storage diseases, hepatic insufficiency, hypoadrenocorticism, sepsis, toxins, extrahepatic producing tumours, panhypopituitarism. Tumours usually difficult to detect even with imaging. Diagnosis relies on laboratory testing. normal fasted insulin levels are less than 20uU/ml but resting values alone are not a reliable indicator of insulinoma. simultaneous glucose and insulin levels are required. In practice this means hospitalising the patient for fasting and serial blood glucose estimations 2 hourly under close observation. The aim is to document hyperinsulinaemia in the presence of hypoglycaemia. This is the diagnosis for insulinoma.
What is the treatment of choice for insulinoma?
Surgery. unfortunately the tumour has usually metastasised at the time of diagnosis so usually only gives remission for several months or even a few years but the prognosis remains guared. prior to surgery feed several small meals daily and give prednisolone to antagonise insulin. During surgery administer IV glucose saline and closely monitor blood glucose. Palpate and remove all detectable pancreatic nodules.
What are the medical management options for if surgery is not possible or relapse occurs?
small frequent meals throughout the day to reduce risk of hypoglycaemic episodes. Avoid simple sugars which may provoke insulin release and provide calories with complex carbohydates protein and fat. Prednisolone good for management. Diazocide increase slowly from smallest dose to satisfactory response. this drug inhibits insulin secretion by blocking calcium entry into beta cells. It also increases hepatic gluconeogenesis, glycogenolysis and peripheral uptake of glucose b y tissue cells. Ocreotide - only work where there are somatostatin receptrs expressed on the neoplastic cells.
What is a gastrinoma?
A rare neuroendocrine gastrin secreting tuour in the pancreas reported in middle aged dogs and cats. Clinical signs relate to overproduction of gastric acid, with vomiting anorexia, diarrhoea, gastroduodenal and oesophageal ulceration and perforation, haematemesis, haematology and serum biochemistry abnormalities. Diagnosis based on demonstrating elevated fasting gastrin levels and diagnostic imaging of the pancreas for insulinoma. Treament is surgical removing any pancreatic nodules, debulking metastases and repairing and gastrointestinal ulcers.Medical treatment with antacids and gastroprotectants, omeprazle, sucralfate, misoprostol, ocreotide. Poor prognosis.
What is a glucagonoma?
A rare neuroendocringe glucagon secreting tumour of the islet alpha cells only. only around 20 cases reported. clinical signs - inappetance, lethargy, lymphadenopathy and diarrhoea, skin lesiosn with erythema, crusting and ulceration and secondary skin infections, most dogs have hyperglycaemia and often overt diabetis mellitus. glucagon assays are not readily available so premortem diagnosis is based on clinical sgns. diagnostic imaging of the pancreas. Surgical removal for treatment or for medical treatment; insulin therapy, amino acid suupplementation, antibiotics for skin infection.
Describe the anatomy and physiology of the adrenal gland?
The adrenal glands are paired with one at the cranial pole of each kidney and embedded in an island of fat, they are retroperitoneal. Each is composed of cortex and medulla. The cortex surrounds the medulla and produces aldosterone from zona glomerulosa, cortisol from the zona fasciculata and zona reticularis and sex hormones from the zona reticularis. The adrenal medulla secretes adrenaline and noradrenaline from chromaffin cells.
How is cortisol secretion regulated?
By the hypothalamic pituitary adrenal axis. Stress and illness override this normal negative feedback control which normally maintains plasma ACTH and cortisol levels and high concentrations of these hormones result.
What effects do glucocorticoids have on metabolism?
During stress or starvation cortisol increases and thus maintains normal blood glucose concentration via mobilisation of amino acids from muscle and fatty acids from adipose tissue for energy substrates and hepatic gluconeogenesis and inhibition of glucose and amino acid uptake in muscle and adipose tissue by antagonism of insulin action.
