Endocrinology Flashcards
What is the aetiology of feline hyperthyroidism?
No evidence of auto-immune disease in cats
>95% benign adenomatous hyperplasia/adenoma of thyroid tissues
Spontaneous secretion of thyroid hormones, escaping control of hypothalamus and pituitary gland
2/3rds cases bilateral, 1/3rd cases unilateral
What are some potential causes of feline hyperthyroidism?
Nutritional factors (iodine levels, presence of goitrogens) Environmental factors (flea sprays, garden pesticides?) Genetic factors (Siamese/Himalayan cats 10x less likely to be hyperthyroid) Circulating factors (thyroid growth stimulating immunoglobulins)
What are some risk factors for developing feline hyperthyroidism?
Regular use of flea sprays/powders (3-4 fold increase in risk)
Indoor cats (4 fold increase)
Reported exposure to lawn herbicides/fertilisers/pesticides (3-5 fold increase)
Cats fed mainly canned food (3-4 fold increase)
What is the typical signalment for feline hyperthyroidism?
Middle-aged to elderly cats (mean = 10-13 years)
No sex predisposition
Signs vary from mild to severe depending on duration of disease/presence of concurrent diseases
What effect do thyroid hormones have in cats and what does this mean for hyperthyroid cats?
Increased: metabolic rate (skinny), CO (tachycardia), HR, BP (hypertensive), GI motility (V+/D+), CNS activity (altered mentation)
Decreased: sleep (more active), bodyweight (lose weight)
What are the major clinical signs of feline hyperthyroidism?
Palpable enlarged thyroid glands Weight loss Polyphagia Hyperactivity PUPD Tachycardia
What are some minor clinical signs of feline hyperthyroidism?
Lethargy Intermittent anorexia Voice changes Muscle weakness/tremors Congestive heart failure Heat intolerance Mild pyrexia Dyspnoea/tachypnoea
What is apathetic hyperthyroidism in cats?
Small percentage (<10%)
Lethargy, inappetence, weight loss, obtundation
Likely reflecting an underlying comorbidity, e.g. severe cardiac abnormalities often present
How do we handle feline hyperthyroid patients?
Cat-friendly Hands-off approach Put in quiet/dark room to calm Gabapentin (50mg once) 2hrs before travelling, oxygen therapy if required Acclimation period Monitoring RR (risk of heart failure)
How do we diagnose feline hyperthyroidism?
Compatible clinical signs
Screening tests
Confirmatory diagnostic test
What screening tests can we perform for feline hyperthyroidism?
Haematology
Biochemistry - elevated liver enzymes (mild-moderate), concurrent disease? chronic kidney disease?
Urinalysis - chronic kidney disease?
BP measurement
What is the confirmatory diagnostic test for feline hyperthyroidism?
Serum total thyroxine (T4) - gold standard
Elevated in most hyperthyroid cats (>50-60 nmol/L)
May fluctuate
Occasionally high-normal (early disease / non-thyroidal illness)
What are the general treatment options for feline hyperthyroidism?
Medical management - anti-thyroid drugs Iodine-restricted diet Surgery - thyroidectomy Radioactive iodine treatment Medical management should be tried first - stabilise prior to GA if surgery, assess renal function (CKD)
How do we use anti-thyroid drugs for feline hyperthyroid patients?
Methimazole BID (tablets, transdermal gel, oral liquids)
Slow-release carbimazole tablets SID
Normally euthyroid in <2-3 weeks - recheck 2-3 weeks after starting treatment, recheck CBC and biochem in first 3 months of treatment
What are the advantages of medical (anti-thyroid drug) management of feline hyperthyroidism?
Readily available Rapidly effective Inexpensive Practical No GA/hospitalisation
What are some disadvantages of medical (anti-thyroid drug) management of feline hyperthyroidism?
Lifelong
Long-term resistance
Compliance
Side effects
What side effects might we see from anti-thyroid drugs?
Minor, common, transient (10-20%) - e.g. vomiting, anorexia, lethargy
Major, rare, persistent (1-5%) - persistent GI signs, severe leukopenia/anaemia/thrombocytopenia, dermatitis (facial excoriation), hepatopathy, lymphadenomegaly, myasthenia gravis
STOP TREATMENT if major side effects!
How can we feed an iodine-restricted diet to feline hyperthyroid patients?
E.g. Hills y/d Must be fed as sole food Can be euthyroid within 3 weeks Lifelong Less effective and not suitable for severely hyperthyroid cats
What considerations should we have pre-surgical management of feline hyperthyroidism?
Systemic effects of hyperthyroidism
Cardiac disease
Hypertension
Other diseases
Describe a thyroidectomy.
Stabilise with medical management prior to surgery
Removal of one or both thyroid glands
Preservation of parathyroid tissue to avoid post-op complications (hypocalcaemia)
Overall typically achieves euthyroidism in >90% of patients and within 24-48hrs
What are the advantages of a thyroidectomy for feline hyperthyroid patients?
Curative
Rapidly effective
Short hospitalisation period
What are some disadvantages of a thyroidectomy?
GA Skill Location Recurrence Cost Complications
What complications can we see post-thyroidectomy?
Damage to/removal of parathyroid tissue (post-op hypoparathyroidism)
Damage to recurrent laryngeal nerve (laryngeal paralysis - uncommon)
Damage to sympathetic trunk (Horner’s syndrome - uncommon)
Possible recurrence of disease if unilateral
Describe iatrogenic hypoparathyroidism.
Usually bilateral thyroidectomy
Usually transient - recovery of glands/restored function of ectopic tissues, weeks-months to recover
What are the clinical signs of iatrogenic hypoparathyroidism?
Within 2-3 days
Inappetence, weakness, tremors, ptyalism, pawing at face
Progressing to tetany, seizures, coma and death
Monitor serum calcium twice a day if bilateral surgery/concerned
What is the first step of treatment for iatrogenic hypoparathyroidism?
IV 10% calcium gluconate slowly (10-20mins)
Monitor with ECG for arrhythmia and bradycardia
Initial bolus followed by CRI IV
Avoid bicarbonate/lactate/phosphate-containing fluids - precipitate calcium
Subcut admin not recommended - causes skin sloughs
What is the second step of treatment for iatrogenic hypoparathyroidism?
Oral therapy as soon as possible (takes 1-3 days to work)
Calcium - elemental in divided doses, wean off IV drip
Oral vitamin D long-term
Gradually weaned off therapy if possible
Describe radioiodine treatment of feline hyperthyroidism.
Gold standard
Administered systemically but concentrated in thyroid
Beta particles cause local cell death
Gamma rays dangerous - cat isolated for 1-2 weeks
15 centres currently in UK
What are the advantages of radioiodine treatment for feline hyperthyroidism?
Gold standard Curative Simple procedure Higher doses to treat adenocarcinoma No GA Cost
What are the disadvantages of radioiodine treatment?
Limited availability Isolation period Irreversible May take some time to achieve euthyroid Very rarely causes iatrogenic hypothyroidism Cost
How are hyperthyroidism and chronic kidney disease linked?
HT may mask underlying CKD
Treatment may unmask CKD
Careful consideration before treatment
Medical management first before curative treatment of HT
Reassessment once euthyroid
Unmasking of mild azotaemia may not preclude definitive treatment
How should we monitor feline hyperthyroid patients?
Irrespective of treatment regime Recommend 6-mothly check-ups once stabilised Recurrence Hypertension CKS - urea-creatinine, BP, urinalysis
What is the prognosis for feline hyperthyroid patients?
Largely dependent on - severity/presence of concurrent disease, especially heart disease
Uncomplicated hyperthyroid cats have an excellent prognosis following curative treatment
What is canine thyroid neoplasia?
Carcinomas more common, adenomas usually incidental findings Usually large, solid, palpable mass Locally invasive +/- metastasise Most are euthyroid or hypothyroid Only 10% hyperthyroid
What are the clinical signs of canine thyroid neoplasia?
Average age 10yrs
Mass in ventral neck region
+/- cough/dyspnoea
How do we diagnose canine thyroid neoplasia?
Histopathology of mass (care - very vascular)
FNA often blood-contaminated so not diagnostic but may confirm thyroid origin
How do we treat canine thyroid neoplasia?
Surgical removal
Ideally followed by chemotherapy/radiation therapy - seek specialist advice
Radioactive iodine treatment - very high doses required for dogs so less used
What is the prognosis for canine thyroid neoplasia patients?
Depends on size, local invasion, functional status and histological diagnosis (adenoma vs carcinoma)
Large, invasive masses at time of diagnosis - prognosis guarded to poor (6-24months with aggressive treatment)
Prognosis excellent following surgical removal of adenomas / good following removal of small, well-circumscribed carcinomas
Describe primary canine hypothyroidism.
At the level of the thyroid gland - most common form
Lymphocytic thyroiditis = destructive immune-mediated process, infiltration of lymphocytes/macrophages/plasma cells and replacement by fibrous connective tissue, clinical signs occur when 75% of gland is destroyed
OR
Thyroid atrophy = degenerative process with limited inflammation, progressive replacement by adipose and connective tissue, possibly end-stage lymphocytic thyroiditis
Describe secondary canine hypothyroidism.
Rare
Pituitary hypoplasia (congenital - disproportionate dwarfism) or dysfunction (acquired - neoplasia)
Most common cause is suppression of TSH secretion by exogenous glucocorticoid admin and hyperadrenocorticism
What is the signalment for canine hypothyroidism?
Mean age at diagnosis = 7 years
Breeds predisposed to lymphocytic thyroiditis tend to develop hypothyroidism sooner, e.g. English Setter/Golden Retriever/Rhodesian Ridgeback/Cocker Spaniel/Boxer
What are some clinical signs of canine hypothyroidism?
Decreased metabolic rate - weight gain, lethargy
Endocrine alopecia, rat-tail, hair in telogen phase (no regrowth)
Bitches - reproductive signs
Bradycardia
Neuromuscular disease - megaoesophagus, laryngeal paralysis, facial nerve paralysis (more likely concurrent disorders)
Association with myxoedema coma - mental dullness, weakness, hypothermia, hypotension
Ocular/GI signs
How can we diagnose canine hypothyroidism?
Appropriate history and clinical signs
Haematology and biochemistry
Specific thyroid testing - Total T4 (TT4), Canine TSH (cTSH), anti-thyroglobulin antibodies (TgABs)
What are we looking for on haem/biochem tests to diagnose canine hypothyroidism?
Mild non-regenerative anaemia (normocytic and normochromic)
Hypercholesterolaemia
Hypertriglyceridaemia
Hyperlipidaemia
Describe the Total T4 (TT4) test for diagnosing canine hypothyroidism.
Useful initial screening test - excellent sensitivity
Thyroglobulin antibodies can falsely increase TT4
T4 decreases with age/breed/non-thyroidal illness/drug therapy so poor specificity
Never use as single diagnostic test
Describe the canine TSH (cTSH) test for diagnosing canine hypothyroidism.
cTSH increased in hypothyroidism due to lack of negative feedback
Moderate sensitivity - low cTSH in central hypothyroidism/corticosteroid therapy
Good specificity - largely non-affected by non-thyroidal illness or drugs, but elevated in euthyroid dogs if recovery from non-thyroidal illness
Describe the anti-thyroglobulin antibodies (TgABs) test for diagnosing canine hypothyroidism.
No information about thyroid function
If positive, consistent with lymphocytic thyroiditis
Can be present long before hypothyroidism
How do we treat canine hypothyroidism?
Synthetic T4 - physiologic prohormone for active T3
Sodium levothyroxine 0.02mg/kg SID or divided BID
Absorption and metabolism vary between dogs
Bioavailability halved with food - consistency for admin and monitoring
In dogs with cardiac disease/diabetes mellitus/hypoadrenocorticism, start with 25% dose and titrate up
6-8 weeks before evaluating effect
Peak concentration = 3-5hrs post pill
Half-life = 9-15hrs
How do we monitor dogs post-treatment for canine hypothyroidism?
Clinical response
6-8 weeks after starting treatment / 2-4 weeks after altering dose
Measure TT4 - 6hrs post pill for SID and 4-6hrs for BID
Measure fT4 if chronic prednisolone admin
Measure cTSH
Aim = TT4 upper half of reference and TSH normal
What are the potential complications after treatment for canine hypothyroidism?
Thyrotoxicosis - rare, secondary to drug overdose
Clinical signs = panting, anxiety/aggression, PUPD, weight loss, polyphagia
Treatment = reduce dose/discontinuation
Myxoedema coma - rare
Treatment = supportive care, IV levothyroxine
What is the prognosis for canine hypothyroidism patients?
Good - adult dogs with primary hypothyroidism
Guarded - secondary hypothyroidism
What is the prognosis for canine hypothyroidism patients?
Good - adult dogs with primary hypothyroidism
Guarded - secondary hypothyroidism
What is the alternative name for primary canine hypoadrenocorticism?
Addison’s disease
Describe primary hypoadrenocorticism.
Most common
Lack of glucocorticoids and mineralocorticoids
Atypical hypoadrenocorticism = lack of glucocorticoids but normal mineralocorticoids
Suspected immune-mediated destruction of adrenal cortex
Describe secondary canine hypoadrenocorticism.
Central cause - neoplasia, inflammation, infection, infarct, iatrogenic
Only glucocorticoid deficiency as aldosterone secretion is regulated by RAAS
Neurological signs
What are the clinical features of Addison’s disease?
Typically young/middle-aged female dogs
Breed disposition e.g. Standard Poodles/Bearded Collies/Nova Scotia Duck Toller/Great Dane
Often vague, waxing and waning history
Lack of cortisol = weakness, vomiting, diarrhoea, anorexia (esp. at times of stress)
Lack of aldosterone (not in atypical cases) = PUPD due to low Na
How does an Addisonian crisis present?
Collapse, severe dehydration and hypovolaemia, pre-renal azotaemia and cardiac arrhythmias due to hyperkalaemia (bradycardia)
Emergency!
How do we diagnose Addison’s disease (hypoadrenocorticism)?
Compatible history and clinical signs Haematology Biochemistry Urinalysis Basal cortisol ACTH stimulation test
What would we expect to see on haematology tests with canine hypoadrenocorticism?
Non-regenerative anaemia
Absent stress leukogram - decreased neutrophils, increased lymphocytes/eosinophils
What would we expect to see on biochemistry tests with canine hypoadrenocorticism?
Hyperkalaemia and hyponatraemia - due to lack of mineralocorticoids
Hypercalcaemia
Pre-renal azotaemia - due to hypovolaemia and dehydration
Acidaemia
Hypoglycaemia - due to lack of glucocorticoids
Increased liver enzymes - due to poor perfusion
Decreased albumin and cholesterol - due to GI insult (lack of glucocorticoids)
What would we expect to see on urinalysis with canine hypoadrenocorticism?
Variable USG - due to low Na and high Ca
What is the basal cortisol test for canine hypoadrenocorticism?
Screening test to EXCLUDE disease
>55nmol/L - Addison’s disease UNLIKELY
<55nmol/L - do an ACTH stimulation test
Describe the ACTH stimulation test for canine hypoadrenocorticism.
Exogenous glucocorticoid will cross react (except dexamethasone)
Previous glucocorticoid treatment will suppress adrenal production of cortisol
Usually both pre- and post-ACTH cortisol concentrations below 20nmol/L
How do we do an ACTH stimulation test?
Cortisol before and 1h post-ACTH admin
Collect serum for basal cortisol concentration
Inject 5mcg/kg of ACTH IV
Collect second serum sample 60min after
How do we treat an Addisonian crisis?
IV fluids (0.9% NaCl) - shock doses (60-90ml/kg)
Hydrocortisone/dexamethasone IV (CRI possible)
Hyponatraemia can cause brain oedema - slow correction <0.5nmol/L/hr
Treatment of hypoglycaemia and hyperkalaemia if necessary - glucose and/or insulin, calcium gluconate
What is the long-term glucocorticoid therapy for canine hypoadrenocorticism?
Most commonly prednisolone > fludrocortisone
0.5mg/kg PO q13hr tapered down to 0.1-0.2mg/kg PO q12-24hr
Trial and error dosage to limit clinical signs of polyphagia, PUPD, weight gain
Increase dose if lethargy of V+/D+
Double dose if stressful event
What is the long-term mineralocorticoid therapy for canine hypoadrenocorticism?
Desocycortone pivalate (DOCP) - Zycortal > fludrocortisone (able to manage need for GC separately from MC requirement) Textbook dose = 2.2mg/kg SC q25d Now starting dose at 1.5mg/kg SC
How do we monitor canine hypoadrenocorticism patients once they have begun treatment?
Ask for evidence of lethargy, V+/D+ (signs that would prompt increase in glucocorticoids)
Blood test for mineralocorticoids - measure Na/K ratio 10-14 days after DOCP admin (peak of DOCP effect) to determine next mg/kg dose and 25-30 days after DOCP admin (duration of DOCP effect)
What is the prognosis for canine hypoadrenocorticism patients?
Good if well managed - lifelong medication
May need additional glucocorticoids at times of stress
Monitor dogs with atypical Addison’s for development of mineralocorticoid deficiency
What is the other name for canine hyperadrenocorticism and why does it occur?
Cushing’s disease
Occurs due to excessive production of cortisol as a consequence of pituitary or adrenal tumours
What are the three forms of Cushing’s disease?
Pituitary-dependent hyperadrenocorticism (PDH)
Adrenal-dependent hyperadrenocorticism (ADH)
Iatrogenic (admin of glucocorticoids)
Describe pituitary-dependent hyperadrenocorticism (PDH).
Most common form Adenoma of pars distalis Overproduction of ACTH, loss of negative feedback Bilateral adrenal hyperplasia Breed disposition - Dachshunds, Poodles, small Terriers No sex predisposition Mid to old-aged dogs (median 7-9yrs) Rarely macroadenoma - causes CNS signs
Describe adrenal-dependent hyperadrenocorticism (ADH).
Less common form
Adenomas/carcinomas
Excess cortisol, suppression of ACTH production
Atrophy of contralateral gland
Females more predisposed
More frequently large breeds (50% cases > 20kg)
Describe iatrogenic hyperadrenocorticism.
Due to chronic admin of glucocorticoids
Suppression of CRH and ACTH production
Bilateral adrenal atrophy
What are the clinical signs of canine hyperadrenocorticism?
Abdominal distension Hepatomegaly Lethargy/exercise intolerance Panting PUPD Polyphagia Skin changes/alopecia
What are the potential complications of Cushing’s disease?
Progression of major signs Diabetes mellitus from insulin resistance Pulmonary thromboembolism Neurological signs - obtundation/blindness/seizure Pancreatitis Secondary infections - pyoderma/UTI Hypertension Glomerulopathy and proteinuria
How can we diagnose Cushing’s disease?
Screening tests - haem, biochem, urinalysis
Tests of HPA axis - ACTH stimulation test, low dose dexamethasone suppresssion test (LDDST), urine cortisol : creatinine ratio
No single test is 100% diagnostic
Define sensitivity.
Probability of a positive result if the patient is affected
High sensitivity - negative result = rule out disease
Define specificity.
Probability of a negative result if the patient is not affected
High specificity - positive result = rule in disease
What would haematology show in a Cushing’s patient?
Mild erythrocytosis/thrombocytosis
Stress/steroid leukogram - increased neutrophils and/or monocytes, decreased eosinophils and/or lymphocytes
What would biochemistry show in a Cushing’s patient?
Increased ALKP - 5 to 40 times upper end of reference
Increased ALT
Hypercholesterolaemia, hypertriglyceridaemia due to lipolysis
Hyperglycaemia due to insulin antagonism
Increased bile acids
What would urinalysis show in a Cushing’s patient?
Variable USG
Dilute urine +/- proteinuria +/- glycosuria
+/- UTI
Urolithiasis - calcium oxalate crystals
What considerations should we have before running HPA axis tests to diagnose canine hyperadrenocorticism?
Essential that some historical/clinical signs are apparent before pursuing diagnosis
No recent steroid administration
How do we use the ACTH stimulation test to diagnose canine hyperadrenocorticism?
More specific but less sensitive than LDDST - be aware of false negatives, but less affected by non-adrenal illness
Good first line test
Does not distinguish PDH from ADH
Useful for iatrogenic disease
Often used for monitoring response to treatment
How do we carry out a low dose dexamethasone suppression test (LDDST)?
Collect serum for basal cortisol concentration
Inject 0.01mg/kg IV dexamethasone
Collect serum sample 4 and 8hrs after injection
How can we use the LDDST to diagnose canine hyperadrenocorticism?
More sensitive but less specific than ATCH stimulation test - be careful false positives, and affected by non-adrenal illness
Should not be used as sole diagnostic test
Can distinguish PDH from ADH
Not useful for iatrogenic disease
How do we use the urine cortisol : creatinine ratio to diagnose Cushing’s disease?
Highly sensitive, not very specific - false positives common
Urine sample collected at home - 2 pooled morning samples, several days after ‘stressful event’
Useful to EXCLUDE hyperadrenocorticism, i.e. normal results = Cushing’s very unlikely
What tests can we do to distinguish between PDH and ADH in Cushing’s disease?
Low dose dexamethasone suppression test (LDDST)
High dose dexamethasone suppression test (HDDST)
Imaging
Endogenous ACTH concentration
How can we use abdominal ultrasound to distinguish between PDH and ADH?
PDH = symmetrical adrenal glands, enlarged or normal ADH = asymmetrical adrenal glands
How can we use CT / MRI to distinguish between PDH and ADH?
Evaluate pituitary gland and adrenal glands
90% of PDH have a brain mass
Micro/macroadenoma
How can we use endogenous ACTH concentration to distinguish between ADH and PDH?
PDH = ACTH >45pm/ml
ADH = undetectable (low) ACTH
Concentrations between 10 and 45ph/ml are unhelpful for diagnostics
What considerations should we have before treating canine hyperadrenocorticism?
Difficult diagnosis to make in some cases
Only treat if very high index of suspicions - history, clinical signs, haem/biochem, specific testing
Progressive disease - may need to wait and re-test
Treatment is expensive
How can we medically treat pituitary-dependent hyperadrenocorticism?
Trilostane, 1-2mg/kg PO SID or half PO BID
Give with food
Monitoring - clinical signs + ACTH stimulation test or pre-pill cortisol
Side effects uncommon but life-threatening - GI signs, hypoadrenocorticism, adrenal necrosis
How can we surgically treat pituitary-dependent hyperadrenocorticism?
Hypophysectomy - complete surgical removal of pituitary gland, accessed via soft palate
Only available potential curative treatment option for dogs with PDH
Around 75% experience long-term cure, 70% 3-year survival
Increased pituitary tumour size associated with higher mortality and incidence of residual disease/relapse
After surgery, lifelong hormonal supplementation with glucocorticoids and thyroxine
How can we use radiation therapy to treat pituitary-dependent hyperadrenocorticism?
May be effective in reducing size of macroadenomas or eliminating neurologic signs
Reduction in secretion of ACTH variable so often concurrent treatment with trilostane required
Good choice for large pituitary macroadenomas
Delayed improvement in clinical signs can occur
How can we surgically treat adrenal-dependent hyperadrenocorticism?
Adrenalectomy
Need work-up before operation
Complications include haemorrhage, hypertension, acute hypercortisolaemia, hypoaldosteronism, wound breakdown
How can we medically treat adrenal-dependent hyperadrenocorticism?
Generally more resistant to therapy
Trilostane
Used pre-surgery
What general considerations should we have when treating canine hyperadrenocorticism?
May unmask other underlying diseases
Reduced cortisol can cause pituitary lesions to expand - CNS signs
What is the prognosis for canine hyperadrenocorticism?
PDH = depends on age/overall health/owner commitment, mean survival following diagnosis approx. 30 months ADH = mean survival following successful surgery 36 months, dogs with metastatic disease usually die/euthanised within 12 months
What are the clinical signs of feline hyperadrenocorticism?
Insulin resistant diabetes mellitus Cachexia Fragile skin syndrome - care with handling! Alopecia No increase in ALP
How can we diagnose feline hyperadrenocorticism?
High dose dexamethasone suppression test (HDDST) - 0.1mg/kg IV
AND
ACTH stimulation test with post-sample at 60 and 90mins after injection
How can we treat feline hyperadrenocorticism?
Treatment is difficult
Adrenalectomy if adrenal mass
No reliable medical treatment for PDH - some success with trilostane
Hypophysectomy/bilateral adrenalectomy has been described in literature
What is the prognosis for feline hyperadrenocorticism?
Guarded to poor
Worse than in dogs
What are the possible causes of canine diabetes mellitus?
Destruction of pancreatic beta cells - genetics / immune-mediated pancreatic damage / pancreatitis / idiopathic
Immune resistance leading to beta cell exhaustion - obesity / concurrent disease e.g. pancreatitis or endocrinopathy / dioestrus / drugs
What is the typical signalment for canine diabetes mellitus?
Middle-aged/older dogs
More commonly female
Breed disposition i.e. Australian Terrier, Schnauzer, Bichon
What are the clinical signs of canine diabetes mellitus?
PUPD secondary to glycosuria Polyphagia and weight loss Cataracts Diabetes ketoacidosis - vomiting, collapse, dehydration Concurrent disease
How can we diagnose canine diabetes mellitus?
Glycosuria and persistent hyperglycaemia
Fructosamine - average of glycaemia of previous 2-3 weeks, should be interpreted in correlation with clinical signs
How can we treat canine diabetes mellitus?
Insulin
Diet
Exercise
Consistency and commitment
What are the types of insulin available?
Intermediate acting e.g. Caninsulin - porcine origin
Long acting e.g. PZI - recombinant human insulin / Glargine - synthetic insulin
How should we handle and store insulin?
Store in fridge/avoid extremes of temperature
Replace bottles after 4 weeks
Invert to mix - let any foam disperse then gently roll
Appropriate syringes
Vary injection site
What should we do with intact diabetic females?
Should be spayed, especially in dioestrus
1-3 days after starting insulin
Progesterone is a cause of insulin resistance
If not possible to spay, use aglepristone
What is the ideal composition of food for diabetic dogs?
Diabetic brand
Should not contain simple sugars to minimise post-prandial hyperglycaemia
Calories provided by complex carbohydrates and proteins
Increased fibre content (not in thin dogs)
Thin dogs - feed calorie-dense, lower fibre maintenance diet
Picky dogs - feed whatever they are used to
What feeding schedule should diabetic dogs be on?
Consistent timing, quantity and type of diet
Twice daily injections - feed half daily requirement at time of each injection
Once daily injections - feed 1/3-1/2 at time of injection and remainder 8hrs later
Ad lib feeding for grazers
How can we initially stabilise a healthy, newly diagnosed diabetic dog?
At home if possible Stabilisation can take weeks to months Start 0.25-0.5U/kg SC BID (low dose) Check blood glucose several times over first day in practice (q2-3hrs) - avoid hypoglycaemia The goal is not perfect control!
How do we monitor a healthy, newly diagnosed diabetic dog?
Clinical signs - PUPD, polyphagia, weight loss
If no clinical signs, check for hypoglycaemia - lethargy, reluctance to exercise, collapse, seizure
First recheck at 7-10 days, then 14 days later, 1 month and every 3 months if well controlled
Why do we use blood glucose curves in diabetic dogs?
Important if poor glycaemic control to make rational adjustments of insulin therapy
Do not use alone to make management changes
How do we carry out a blood glucose curve?
Serial blood glucose - taken in the ear every 2hrs and then every hour close to the nadir
Continuous glucose monitoring - measured interstitial blood glucose, freestyle libre
Important to asses nadir and duration of action
How can we use urinalysis to monitor diabetic dogs?
Usually mild amount of glucose in the urine
Especially before insulin admin
No glucose > 24hrs may indicate insulin overdose
Ketones may indicate poor glycaemic control
What are some potential complications of insulin therapy?
Hypoglycaemia
Somogyi overswing
Short duration of action - switch to long acting insulin BID
Prolonged duration of action - switch to long action insulin SID or short acting
What are some potential long-term complications for diabetic dogs?
Hypoglycaemia Cataract formation - common Diabetic neuropathy - uncommon Diabetic nephropathy - uncommon Hypertension Diabetic ketoacidosis
What is the prognosis for diabetic dogs?
Good if well managed with committed owners
Mean survival time 3-5yrs
What are some risk factors for feline diabetes mellitus?
Old age Obesity Male Indoor Breed disposition - Burmese, Maine Coon, Russian Blue, Siamese
What are the possible causes for feline diabetes mellitus?
Insulin resistance - genetically determined, obesity?
Reduced insulin secretion - beta cell damage
Why might a cat develop insulin resistance?
Obesity
Inflammatory/infectious disease - pancreatitis, UTI, CKD, dental disease, enteropathy
Endocrinopathies - hyperthyroidism, acromegaly, hypercortisolism
How is feline pre-DM defined?
Impaired fasting glucose - rarely documented due to stress hyperglycaemia
BG consistently > 6.5mmol/L
How is feline subclinical DM defined?
BG > 10mmol/L and < 16mmol/L (renal threshold) persistently
Benefit from low carbohydrate diet, weight loss and possible insulin sensitisers
How is feline overt DM defined?
Hyperglycaemia - BG > 16mmol/L
Increased fructosamide (not stress-related)
Glycosuria
What are the clinical signs of feline diabetes mellitus?
PUPD, weight loss, polyphagia, DKA
Peripheral neuropathy (DM > 5yrs)
Cataracts - rare
How do we diagnose feline diabetes mellitus?
Hyperglycaemia and glycosuria
Fructosamine - mean BG over the last week, use with history and clinical signs to differentiate stress hyperglycaemia from diabetes mellitus
How can we treat feline diabetes mellitus?
Insulin
Diet
Exercise
Consistency and commitment
What insulin is available for feline DM patients?
Prozinc - protamine zinc human recombinant insulin, licensed for cats
Caninsulin - similar to dogs but cats are notoriously unpredictable in their response
Glargine insulin - only used in UK under cascade when licensed products fail
How are oral hypoglycaemic drugs used to manage feline DM?
Glipizide - increases insulin secretion
Useful if owner declines insulin
With diabetic diet
What is the typical composition of the diet for a feline diabetes mellitus patient?
Wet High fibre less useful than in dogs High protein Low carbohydrate Reliable intake
How effective is diet management in feline DM patients?
Resolution of DM in 30% cats - major difference compared to dogs!
Reduction in insulin dose in 50% of cats
How is feline acromegaly defined?
Excessive growth hormone production - more commonly from benign tumour of pituitary gland
Growth hormone inhibits action of insulin at target tissues leading to insulin resistance
What are the clinical signs of feline acromegaly?
Insulin-resistance diabetes mellitus (usually)
Weight gain despite poor diabetic control
Organomegaly
Prognathia inferior (protrusion of mandible)
Increased interdental spacing
Prominent facial features e.g. broad head
Stertor
How do we diagnose feline acromegaly?
Increased serum insulin-like growth factor 1 (IGF-1) concentration (> 1000ng/ml) - marker for growth hormone production
Presence of pituitary mass on intracranial imaging (CT/MRI)
Definitive diagnosis - histopathology of pituitary tumour
How can we treat feline acromegaly?
Hypophysectomy - diabetic remission up to 85%, lifelong supplementation with oral levothyroxine and corticosteroids, mortality rate 14%
Radiation therapy - variable response, any positive effect can be slow in onset
What is the cause of diabetic ketoacidosis?
Serious complication of diabetes mellitus
Significant concurrent diseases e.g. heart failure, pancreatitis, sepsis
Increased production of glucoregulatory hormones - glucagon, epinephrine, cortisol and growth hormone
In DM, lack of insulin allows glucogenic effects of these stress hormones to be unopposed in liver/muscle/adipose tissue - excessive free fatty acid breakdown, excessive ketone formation
What are the clinical signs of diabetic ketoacidosis?
PUPD, polyphagia, weight loss (may be unnoticed by owner)
Systemic signs e.g. lethargy, anorexia, vomiting
Worsening ketosis and acidosis
Additional signs of concurrent disease e.g. pancreatitis may be present
Strong odour of acetone on the breath (‘pear drops’)
Severe dehydration and hypovolaemia
What is the aim of DKA treatment?
Restore water and electrolyte balance (sodium, potassium, phosphorous)
Provide adequate insulin to ‘switch-off’ ketone production (neutral insulin)
Correct acidosis
Identify any underlying disease
What supportive therapy can we provide to diabetic ketoacidosis patients?
Analgesia
Feeding - appetite stimulant (mirtazapine), anti-nausea drug (maropitant), NO/O-tube?
Careful monitoring - hyperglycaemia usually improves in 12-24hrs, ketosis takes 48-72hrs
What is the prognosis for diabetic ketoacidosis patients?
Challenging to treat, often underlying disease
25% die or are euthanised
Referral?
With careful treatment, some could become happy healthy diabetics
Cats can even enter DM remission after DKA
