Small animal endocrinopathies 3 Flashcards
Ketoacidosis
What findings may be expected on haematology in ketoacidosis?
- May be normal or stress leukogram
- Mature neutrophilia
- Left shift indicative of infection
- Heinz bodies in cats
Why might hypokalaemia occur in ketoacidosis?
Chronic PUPD = renal loss of K
Inadequate intake due to anorexia, GI losses due to V/D, insulin treatment drives potassium into cells
Why might hyperkalaemia occur in ketoacidosis?
- May move into extracellular location secondary to acidosis/lack of insulin/plasma hyperosmolarity
- Could reflect decreased urine output secondary to oluguric or anuric renal failure
What might urinalysis show in DKA?
- Dipstick shows acetone and acetoacetate (NB main one is BHB)
- Glucosuria, ketonuria
- Elevated USG
- Evidence of UTI
What management is required for a bright, happy ketonuric diabetic?
Does not need to be managed as a DKA - simply normal diabetic treatment
What factors need to be corrected in a DKA?
- Fluid deficits
- Perfusion
- Electrolyte abnormaliites
- Acidosis (via restoration of perfusion)
- Insulin and glucose
Outline the fluid therapy in a DKA
- Saline/Hartmann’s, IV
- Fluid bolus indicated
- Account for ongoing losses
- Monitor HR, pulse rate and peripheral pulse quality, RR and effort/crackles on ausc, MM colour and CRT, renal function via urine output
What are the signs of fluid overload?
- Shivering
- Nausea
- Vomiting
- Restlessness
- Tachypnoea
- Coughing
- Chemosis
What bolus of isotonic crystalloid fluids should be given in mild hypovolaemia?
10-20ml/kg over 30min to 1hr
What bolus of isotonic crystalloid fluids should be given in moderate hypovolaemia?
20-40ml/kg over 30 min to 1 hour
What bolus of isotonic crystalloid fluids should be given in marked hypovolaemia?
40-60ml/kg over 15 min to 1 hour
What degree of hypovolaemia would these clinical parameters suggest in a dog? HR: 130-150 MM: normal-pink CRT: rapid (<1s) Pulse amplitude: increased Metatarsal pulse: easily palpable
Mild hypovoalemia
What degree of hypovolaemia would these clinical parameters suggest in a dog? HR: 170-220 MM: grey, white or muddy CRT: prologed (>2s) Pulse amplitude: severely decreased Metatarsal pulse: absent
Severe
What degree of hypovolaemia would these clinical parameters suggest in a dog?
HR: 150-170
MM: pale pink
CRT: normal
Pulse amplitude: mild to moderate decreased
Metatarsal pulse: just palpable
Moderate
In what situation in a DKA crisis would fluid loss need to be corrected more rapidly?
PUPD, V/D, esp. if there is pre-ranl axotaemia
Once hypovolaemia in DKA crisis has been addressed, what fluid therapy is required?
Need to replace fluid deficit i.e % dehydration, replace in 12-24 hrs, sometimes replace half of deficit in first 4-6 hours. Need to also replace ongoing losses based on monitoring
What electrolyte may need to be supplemented in a DKA crisis and why?
Potassium - restoring renal perfusion leads to decreased serum K due to increased excretion, and correcting acidosis favours return of K+ into cells, as does insulin treatment
How should potassium be corrected in DKA crisis?
Supplement potassium in fluids
Explain the use of insulin in the treatment of DKA
- Rapid acting essential, “neutral” or “regular” for IV use
- Lots of protocols available
- No licensed animal preparation so use human
Give an example of an insulin protocol in the treatment of DKA
1: CRI soluble insulin. Add 25IU neutral insulin to 500ml bag 0.9% NaCl OR 2.5IU to a 50ml syringe. Infuse at 1ml/kg/hr until BG <15mmol/l. Then reduce insulin infusion rate to 0.5ml/kg/hr. Requires 2 bags 0 one for insulin and 1 for fluids +/- potassium (run at v different rates)
2: Initial dose 0.2IU/kg soluble insulin IM followed by 0.1IU/kg IM every 1 hour until BG <15mmol/l. Then 0.5IU/kg soluble insulin SC with subsequent adjusted doses q6h
What is required when using insulin in the treatment of DKA and why?
Carbohydrate source, exogenous insulin admin presents risk of hypoglycaemia (BG falls long before ketoacidosis resolves), animal may also be slow to start eating due to underlying trigger disease
Outline the provision of carbohydrate source in the treatment of DKA
- Supplementation of fluids with dextrose start when BG <15mmol/l (and reduce insulin), srtart 2.5% glucose infusion at 6-7ml/kg/hr
- Small vols of low fat food
What treatment is required once the BG is controlled in DKA and no further vomiting?
Start insulin therapy with longer acting insulin preparation e.g. Caninsulin
Other than fluids, insulin, potassium and CHO, what other treatments are indicated in DKA?
- treat underlying disease
- Analgesia (e.g. in pancreatitis esp., pain => inappetance)
- Anti-emetics (reduce fluid loss, encourage eating)
- Antibiotics (if awaiting culture and suspicious of UTI, also high risk of secondary infection)
What monitoring is required following a DKA?
- BG q1-2 hours
- K+ q4-6hrs
- Urine ketones
- PCV/total solids daily (dehydration status assessment)
What general conditions could the following clinical signs be indicative of in a puppy?
Mental dullness progressing to collapse, tachycardia, tremors, vocalisation, paresis/paralysis
- Neurological condition
- Hypoglycaemia
- Intoxication
- Liver disease
- Polycythermia
- Portosystemic shunt
- Dehydration
- Hypothermia
- Hypoadrenocorticism
- Parvo (and other infectious diseases)
At what BG level do clinical signs of hypoglycaemia usually occur?
2.5mmol/L
What are the potential consequences of hypoglycaemia?
- Neuronal damage
- Can progress to neuronal death (even if glycogen stores return to normal levels)
What conditions may the following clinical signs indicate in a cat?
Extreme lethargy, muscle twitches, unusual behaviour, loss of appetite, trembling, lack of coordination, blindness, unconsciousness
- Hypoglycaemia
- Hypoadrenocorticism
- Liver disease
- Neoplasia
- Sepsis
- Toxicosis
- Glycogen storage disease
- Polycythaemia
- Gastrointestinal disease
- Hypokalaemia
- Renal disease
- Neurological, or muscular
Compare the clinical signs of chronic vs. acute hypoglycaemia
Chronic adapt to low glucose so signs are inappropriately mild whereas in acute signs are usually severe
What factors should be taken into account when interpreting a hypoglycaemia in practice?
- Stress response in cats
- Septic hyperglycaemia can occur followed by a hypoglycaemic phase
- Incorrect tube choice
- Haemoconcetration falsely lowers blood glucose
What toxins lead to a hypoglycaemia?
- Xylitol
- Ethanol
- Beta-blockers
- Oleander extract
- Dried chicken pieces
What are the main mechanisms of hypoglycaemia?
- Excessive uptake of glucose by normal or neoplastic cells
- Impaired hepatic gluconeogenesis or glycogenolysis
- Malnutrition/starvation
- Deficiency in diabetogenic hormones
Give possible causes of excessive uptake of glucose by neoplastic cells
- Insulinoma
- Other non-beta cell neoplasms e.g. hepatomas and hepatic carcinomas
Explain how hypoglycaemia can occur due to neoplasms
Some can secrete insulin-like peptides and accelerate consumption of glucose by the tumour cells
Give examples of conditions that may lead to impaired hepatic gluconeogenesis or glycogenlysis
- Porto-systemic shunts
- Cirrhosis
Give an example of how deficiency in diabetogenic hormones can lead to hypoglycaemia
- Hypoadrenocorticism
- Causes increased uptake of glucose into cells and depletion from blood
- Impairs gluconeogensis and glucose production
Why might a diabetic animal present with low blood sugar?
- Overdose of insulin
- Sudden remission (cats)
- Anorexia
- Over exercising
- Systemic infectious diseases leading to lymphocytophilia
Why does xylitol intoxication lead to hypoglycaemia?
- Xylitol leads to excessive insulin prod. (2.5-7x greater than for equal amount of glucose)
- Liver failure also described
Following ingestion of xylitol, what advice should be given to an owner?
- Bring into practice ASAP
- Rub jam/honey onto gums to minimise degree of hypoglycaemia (does not need to swallow)
Following ingestion of xylitol, what treatment should be provided once the animal is in the practice?
- Emetics/charcoal not recommended as too late
- Hepatoprotectants and dextrose supplementation administered
- Serial serum biochem performed from admission to 72 hrs post ingestion to monitor for acute hepatic failure
- Monitor BG until no longer hypoG., electrolytes e.g. K+ monitored
- Monitor phosphate
What electrolyte complications may occur following ingestion of xylitol?
- Can become hypokalaemic due to direct stimulation of pancreatic B cells
- Hyper, followed by hypophosphataemia may also occur
- A 10 year old FN cross breed is rushed in as an emergency. She has been slowing up on walks recently but has still been eating well. She has put on some weight in the last couple of months. Her owners assumed she has arthritis and the weight gain was due to reduced exercise.
She went out in the garden half an hour ago and her owners then found her outside having a seizure which seems to have stopped but she is still vacant, unable to stand and twitching. A vet nurse has checked her blood glucose which is 1.3mmol/l
How will you manage this situation and what will you do first?
- Low blood glucose (normal is 3.3-6.4mmol/l), need to administer glucose
- Provide fluids
- Determine potential causes e.g ingestion of toxin
What concentration of glucose should be administed to a hypoglycaemic patient and why?
- 5% solution (50mls of 50% glucse in 500ml normal saline)
- High conc. of glucose into peripheral vein can lead to vein irritation or thrombophlebitis
- High glucose conc. increases risk of infection
Give examples of non-islet cell secreting tumours that have been associated with hypoglycaemia
- Hepatocellular carcinoma
- Leiomyoma
- Leiomyosarcoma
- Haemagiosarcoma
- Multiple myeloma
- Renal adenocarcinoma
- Hepatoma
What blood tube should be used when suspicious of hypoglycaemia?
Fluoride oxalate - stops metabolism of glucose
Outline a diagnostic plan for an animal with hypoglycaemia
- Double check blood glucose, esp. if dealyed separation/analysis
- Check on in-house glucometer
- Evaluate haematology physical exam, biochem, CBC, urinalysis to identify underlying cause
- +/- specific tests to rule in/out cause
- Bile acids, diagnostic imaging where needed
What is an insulinoma?
A tumour rising from beta-cells of the pancreas and secreting excessive insulin
Describe the metastasis of insulinomas
- Usually malignant and almost always metastasise
- To liver, local LNs, omentum
What breeds of dog are predisposed to insulinomas?
- GSD
- Boxer
- Poodle
- Collie
- Fox terrier
Describe the clinical signs of an insulinoma?
Typically episodic, not continuous level of secretion at all times, usually increase in severity and present 1-6months before diagnosis
How is an insulinoma diagnosed?
- Ultrasonography to identify pancreatic mass
- NB too small to detect in most cases - dependent on equipment and operator
- MRI and CT
- Look for metastases to determine treatment outcome (surgical or not)
Describe the typical structure of an insulinoma
- Equal frequency in left and right lobes
- 15% of dogs have multiple nodules
If no tumour identified, some recommend removal of 50% or more of pancreas
What is a key post-operative complication with insulinomas?
Pancreatitis
Describe the medical treatment of insulinomas
- Prednisolone 0.2-0.5mg/kg BID: inhibitory to insulin, but can lead to hyperglycaemia, hyperadrenocorticism, iatrogenic hypoadrenocorticism, liver damage
- Diazoxide: inhibits pancreatic beta- cell insulin production, enhances hepatic glycogenolysis and gluconeogenesis, inhibits glucose uptake in peripheral tissue
- Chemo difficult and rare due to side effects
describe the dietary managemet of an insulinoma
- Frequent complex CHO meals (GI diets0
- Feed at least q4-8hrs
- complex carbs reduce stimulation of insulinoma due to slow release of glucose (avoid spike in glucose leading to insulin release)
- High fibre good but not for underweight dogs
- Diabetic diet may be good BUT high fat anf so have high risk of overfeeding leading to obesity
What is the prognosis for an insulinoma?
- Guarded
- 66-75% of dogs survive >6mo before intractable hypoG develops
- Surgery survival: median 381 days
- Medical survival: median 74 days
What are the potential thyroid abnormalities that may lead to feline hyperthyroidism and compare their prevalence?
- Multinodular adenomatous hyperplasia (95% of cases)
- Thyroid carcinoma (3%)
Describe the histopathological appearance of a hyperactive thyroid
Similar to toxic nodular goitre seen in people
What are potential causes for feline hyperthyroidism?
Largely unknown,, diet suggested (canned food, dietary fish/soy), flea products, indoor lifestyle, cat litter
- Immunological
- Genetics
What breed of cats do not get hyperthyroidism?
Siamese
Describe the potential tissue abnormalitites in multinodular adenomatous hyperplasia of the thyroid gland
- Bilateral in 70% of cases, rest are unilateral (contralateral gland atrophy)
- Ectopic thyroid tissue seen in 3-5% of cats (cranial mediastinum, neck)
What are the main roles of thyroid hormones?
- Thermoregulation
- Carbohydrate protein, lipid metabolism
- Interaction with CNS (increased sympathetic drive)
Describe the relationship between clinical signs and T4 levels in hyperthyroidism
- Individual variation in ability to cope with excess
- T4 alone does not predict clinical signs
What is the typical signalment for hyperthyrodism?
- Older cat (average 13yo, range 4-20)
- DSH and DLH most common
- Males and females equally affected
What conditions would be differentials with the following presentation?
- 15yo MN DSH, weight loss, good appetite, good activity, PUPD, dull fur, diarrhoea, tachycardia 250bpm, poor BCS, muscle loss
- Hyperthyroidism
- CKD (PD, weight loss, vomiting)
- Diabetes
- GI lymphoma, IBD (polyphagia, weight loss, V/D)
- Primary liver disease (weight loss, V/D)
- Hypertrophic cardiomyopathy (tachycardia, murmur, arrhythmia)
What beahvioural changes can be associated with hyperthyroidism in cats?
- Restlessness/hyperactivity
- Short fuse
- Vocalisation
- Mouth breathing
- Tachypnoea
What cardiovascular signs are commonly associated with feline hyperthyroidism?
- Tachycardia >240bpm
- Murmur
- Gallop rhythm
- Premature beats
Describe atypical/apathetic hyperthyroidism
- Much less common
- Anorexia, weakness, lethargy, weight loss
What electrolyte should be checked specifically if suspicious of atypical hyperthyroidism?
Potassium should always be checked in weak cats - hypokalaemia may be complication that adds to weakness seen
What aspects of a physical examination are particularly important in a case of suspected feline hyperthyroidism?
- Kidneys (size, shape, texture)
- GI tract: thickness of walls, LNs palpable/enlarged, abdominal fluid, mass lesions
Explain the significance of haematology and biochemistry when working up a case of suspected feline hyperthyroidism
- RUle in or out other differentials
- Does not rule in hyperthyroidism
- Often normal, mild increase in PCV not uncommon
- treatment may cause problems that can be identified on haematology so it is useful to have ref.
What may be found in a hyperthyroid cat on haematology?
Neutrophilia, lymphopaenia, eosinopaenia, monocytopaenia
What is the significance of urinalysis when working up a case of suspected feline hyperthyroidism?
- Rule out diabetes, does not rule in hyperT
- 12-22% of cats have UTI and often asymptomatic
- Glucosuria may occur as a result of stress hyperglycaemia
What may be seen on biochem in case of suspected hyperthyroidism in the cat?
- MIld-mod increase in 1 or more liver enzymes (ALT usually <500IU/L)
- Urea and creatinine
- Phosphate increased in 20% of cases
- Stress hyperglycaemia
What may lead to normal creatinine in a hyperthyroid cat?
Low muscle mass
What is the consequence of identifying azotaemia in a hyperthyroid cat?
- Hyperthyroid cats have increased GFR
- Azotaemia at time of diagnosis carries poor prognosis
What USG should a cat usually have if it is “only” hyperthyroid (i.e. no concurrent renal disease)?
> 1.035
What tests can be used to diagnose hyperthyroidism in cats?
- tT4
- TSH
- T3 suppression test
Describe the interpretation of a total T4 test
- Low end of ref. range: not hyperT
- Over ref. range: hyperT
- High end of ref. range: possibly hyperT (daily fluctuations may mean sampling at low point in the day
Describe the specificity and sensitivity of the tT4 test
Both good, but not perfect
Why might a falsely negative tT4 result occur?
- Daily fluctuations
- Early disease
- Abnormal tT4 suppression into ref. range by non-thyroidal illness
When suspicious of a falsely negative tT4, what would be a logical approach?
Repeat blood sample at a different time of day in 2-3 weeks or sooner
What interpretation is most likely in a case of a cat presented with weight loss, good appetite, diarrhoea, low t$ and high fT4?
NOT hyperthyroid - tT4 consistent with non-thyroidal illness, and some cats with concurrent illness have high fT4
Explain the use of a TSH test to diagnose hyperthyroidism in a cat
- No cat specific assays, canine used
- Hyperthyroid cats should have very low/undetectable TSH
- A value alone is not useful, but measurable serum TSH rules out hyperthyroidism
- Use in combination with T4
Describe the use of a T3 suppression test to diagnose hyperthyroidism in a cat
- Rarely needed
- used for differentiating mild hyperthyroid cats from euthyroid cats
- Oral T3 given for 3 days
- Normal cats: -ve feedback suppresses TRH and TSH leading to reduced T4
What result would be expected on a T3 suppression test on a hyperthyroid cat?
Loss of -ve feedback, no suppression of T4 compared with basal
In a case where you are highly suspicious of hyperthyroidism but cannot diagnose it on any tests, what would be a sensible approach
- Review patient history, physical exam, all tests results
- Consider additional tests to look for non-thyroidal illness (diagnostic imaging, urine culture)
- Speak to clin. path lab about dynamic testing (TRH stim test)
- Refer for possible scintigraphy
What aspects of hyperthyroidism can hide concurrent CKD?
Increased catecholamines, metabolic rate and cardiac output lead to increased GFR
What is a potential complication of hyperthyroid treatment?
- Can reveal occult renal disease
- Sudden drop in GFR with treatment can cause or worsen azotaemia
- Reversible treatment may be preferred
What treatment should be used if develop hypertension during hyperthyroid treatment?
Amlodipine
Describe the relationship between hyperthyroidism and heart disease
Thyrotoxic cardiomyopathy can occur, managed by treating hyperthyroid state
What are the options for treating hyperthyroidism in the cat?
- Medical management
- Dietary management
- Thyroidectomy
- Radioactive iodine
What drugs are used in the treatment of hyperthyroidism? How are these administered?
- Methimazole
- Carbimazole (metabolised to methimazole)
- Oral, methimazole BID, carbimazole SID
What is the mechanism of action of the drugs used to treat hyperthyroidism?
Interfere with the synthesis of thyroid hormones
In what way are the drugs used to treat hyperthyroidism related?
Carbimazole is a precursor to methimazole, metabolised in the body - reaction to one means cannot use the other either
How should the dosage of hyperthyroid medication be adjusted?
Are aiming to achieve tT4 in lower half of reference range, titrate according to clinical response and tT4 results
What are the advantages of the hyperthyroidism medications available?
- Quick,
- Licensed, reversible
- Good for pre-op stabiliastion
- Dose titration possible
- Cheap
- Relaitvely safe
What are the disadvantages of hyperthyroidism medications available?
- Life long treatment and monitoring required
- Compliance issues
- Side effects can be severe
What are the mild side effects of hyperthyroid medication?
- Lethargy
- Vimiting
- Anorexia
- Eosinophilia, leukopaenia, lymphocytosis