Endocrine Flashcards
causes of diabetes mellitus
- destruction of beta cells in pancreas
(immune-mediated, pancreatitis, idiopathic) - insulin resistance leading to beta cell exhaustion
(obesity, concurrent disease, dioestrus)
clinical signs of diabetes mellitus
- concurrent disease
- diabetic ketoacidosis
- polyuria, polydipsia (secondary to glucosuria)
- cataracts
- polyphagia
- weight loss
diagnosis of diabetes
- glucosuria
- persistent hyperglycaemia
- fructosamine blood test (glycated proteins)
treatment of diabetes
- insulin
- diet
- exercise
- consistency
insulin treatment for diabetes
- vary in time of onset, max effect and duration of action
- ‘lente’ (intermediate acting) insulin is used most commonly
- neutral (short acting) insulin is used for diabetic ketoacidosis
insulin handling
- store in fridge
- replace bottles after 4 weeks
- invert to mix (allow foam to disperse)
- don’t shake
- vary injection site
- use red syringe for caninsulin
intact females and diabetes
- progesterone can be cause of insulin resistance
- entire females should be spayed
- consider algepristone if unable to spay
diabetes diet
- avoid simple sugars
- more complex carbohydrates and proteins
- increased fibre
- consistent timing, quantity and diet
- ad libitum feeding for grazers
initial stabilisation of newly diagnosed diabetic dog
- start at low insulin dose
- check blood glucose several times a day (blood glucose curve)
- monitor for hypoglycaemia
monitoring of newly diagnosed diabetic dog
- first recheck= 7-10 days
- next= 14 days
- 1 month
- continue every 3 months
- monitor clinical signs and for hypoglycaemia
clinical signs of hypoglycaemia
- lethargy
- reluctance to exercise
- collapse
- seizure
- BG <3mmol/L
- feed small meal or give glucose
urinalysis of diabetes patient
- usually mild amount of glucose before insulin admin
- no glucose >24hrs may indicate insulin overdose
- ketones may indicate poor glycaemic control
blood glucose curve
- feed and give insulin
- check BG levels every 2 hours until next feed and insulin injection
- create graph
- ensure BG is mainly below renal threshold (12mmol/L) and above 4mmol/L
- shows duration of action\
somogyi overswing
- rebound hyperglycaemia caused by physiologic response to hyperglycaemia
- BG<3.6mmol/L or drops quickly following insulin
long term consequences of diabetes
- cataract formation
- hypertension
- diabetes ketoacidosis
- diabetic nephropathy
diabetes in cats
- commonly non-insulin dependent
- increased insulin resistance
- plantigrade stance common
diagnosis of diabetes in cats
- fructosamine test more common
- stress hyperglycaemia is common so diagnosis is difficult
treatment of diabetes in cats
- diet (high protein, low carbs)
- weight loss in obese cats
- insulin (unpredictable response in cats)
diabetes ketoacidosis
- lack of insulin/insulin resistance prevents glucose from being transported into cells for respiration
- body used fats as energy source
- excessive fatty acid breakdown decreasing pH
clinical signs of diabetes in cats
- lethargy, collapse
- acetone odour on breath (pear drops)
- severe dehydration and hypovolaemia
management of the sick DKA
- restore water and electrolyte balance
- rapid and short acting insulin (neutral)
- correct acidosis
hypothalamic-pituitary-thyroidal axis
- hypothalamus secretes TRH
- pituitary gland is stimulated to produce TSH
- thyroid glands are stimulate to make T4, T3, rT3
- this negatively feedbacks to pituitary gland to produce less TSH and to hypothalamus to secrete less TRH
feline hyperthyroidism aetiology
- > 95% benign adenomatous hyperplasia/adenoma of thyroid tissues
- spontaneous secretion of thyroid hormones
- <5% adenocarcinoma
risk factors for feline hyperthyroidism
- middle-aged to elderly cats
- nutritional (iodine rich diet)
- environmental (flea sprays)
- genetic (siamese, himalayan cats)
clinical signs of hyperthyroidism
increased:
- metabolic rate, CO, HR, BP, GI motility, CNS activity
decreased:
- sleep, body weight
- palpably enlarged thyroid glands
- polyphagia, polyuria, polydipsia
handling the feline hyperthyroidism patient
- hands-off approach
- consider gabapentin 2hrs before travel
- quiet, dark room
- give time to acclimatise in consult, nursing room
diagnosis of feline hyperthyroidism
- compatible clinical signs
- screening tests
- confirmatory tests
screening tests for feline hyperthyroidism
- haematology
- biochemistry (elevated liver enzymes)
- look for concurrent disease (chronic kidney disease)
- urinalysis (look for concurrent disease)
- BP measurement
confirmatory diagnostic test for feline hyperthyroidism
- serum total thyroxine (TT4)
- false negatives are possible (can fluctuate over 24hr day, can be falsely low in patients with concurrent disease)
treatments for feline hyperthyroidism
- anti-thyroid drugs
- iodine restricted diet
- surgery
- radioactive iodine
anti-thyroid drugs for hyperthyroidism
- block production of T3 and T4
- methimazole BID (tablet, gel, liquid)
- carbimazole
- must be given whole, once a day
- converts to methimazole
- care with handling if pregnant
- regulates thyroid within 2-3 weeks
advantages of anti-thyroid drugs
- readily available
- effective
- inexpensive
- practical (bioavailable)
- no GA or hospitalisation
disadvantages of anti-thyroid drugs
- lifelong (expensive)
- long-term resistance
- compliance
- side effects
side effects of anti-thyroid drugs
- vomiting, anorexia, lethargy (10-20%)
- GI irritant, leukopenia, anaemia, dermatitis, hepatopathy, myasthenia gravis
iodine-restricted diet for feline hyperthyroidism
- starves the thyroid of iodine which is needed to make hormones
- euthyroid within 3 weeks
- less effective, not suitable for severely hyperthyroid cats
- life long
thyroidectomy
- increased surgical risks due to systemic effects of hyperthyroidism (cardiac disease, hypertension)
- stabilise medically prior to surgery
- excision of thyroid adenoma
- preservation of parathyroid tissue
- euthyroidism in >90% patients
advantages of thyroidectomy
- curative
- rapidly effective
- short hospitalisation period
disadvantages of thyroidectomy
- GA risks
- cost
- complications
- depends of location of adenoma
- recurrence
complications of thyroidectomy
- damage to parathyroid tissue (post-op hypoparathyroidism)
- damage to recurrent laryngeal nerve
- damage to sympathetic nerve (horner’s syndrome)
- possible recurrence
Iatrogenic hypoparathyroidism
- associated with bilateral thyroidectomy
- removal of parathyroid glands prevents TTH production which causes hypocalcaemia
clinical signs of iatrogenic hypoparathyroidism
- inappetence
- weakness, tremors
- hypersalivation
monitor serum calcium BID if bilateral thyroidectomy
Iatrogenic hypoparathyroidism treatment
- hospitalisation
- IV 10% calcium gluconate
- avoid bicarbonate, lactate, phosphate fluids as precipitates calcium
- ECG to monitor for arrythmia and bradycardia
radioiodine treatment for feline hyperthyroidism
- only available in specialist centres
- single injection of radioactive iodine IV
- administered systemically but concentrated in thyroid as it rapidly takes up iodine to make thyroid hormones
- beta particles can cause local cell death
- cat needs to be isolated for 1-2 weeks
- most ideal treatment
advantages of radioactive iodine therapy
- curative
- simple procedure
- no GA, minimally invasive
- can treat carcinoma
disadvantages of radioactive iodine therapy
- limited availability
- isolation treatment
- irreversible
- may take time to achieve euthyroid
- high initial cost (cheaper long term)
monitoring of feline hyperthyroid patient
- 6 monthly check-ups once stabilised
- recurrence (history, clinical signs, blood test)
- hypertension
- chronic kidney disease (urinalysis, urea- creatinine)
hyperthyroidism and chronic kidney disease
- hyperthyroidism may mask underlying CKD, treatment will uncover CKD
- consider medical management before curative treatment
canine thyroid neoplasia
- carcinomas are far more common
- large, solid, palpable mass on neck
- only 10% hyperthyroid (most euthyroid)
- surgical removal and chemotherapy
- prognosis is poor (6-24 months with aggressive treatment)
canine hypothyroidism clinical signs
- most commonly caused by atrophy or immune mediated destruction of thyroid
- decreased metabolic rate (weight gain, lethargy, inactivity)
- alopecia, rat-tail and ‘tragic’ facial expression
- neuro, repro, cardiac signs are less common
diagnosis of canine hypothyroidism
- compatible clinical signs
- haematology and biochemistry
- confirmatory tests
- low T4, high TSH
- anti-thyroglobulin antibodies
total T4 (TT4) test
- useful initial screening test, excellent sensitivity
- thyroglobulin antibodies can falsely increase TT4
- TT4 decreases with age, breed, non-thyroidal illness and drug therapy
- not recommended as single diagnostic test
Canine TSH (cTSH)
- increased in hypothyroidism due to lack of negative feedback
- good specificity: largely non-affected by non-thyroidal illness or drugs
Anti-thyroglobulin antibodies
- if positive, consistent with immune mediated destruction of thyroid gland
- only recognises one path of development of hypothyroidism
- can be present long before hypothyroidism
- provides no information about thyroid function
treatment of canine hypothyroidism
- synthetic T4
- available in tablet and liquid forms
- bioavailability is halved with food
- try give on empty stomach
monitoring of hypothyroidism patient
- clinical response (weight loss, higher activity levels, less dermatological symptoms)
- check up 6-8 weeks after treatment start
- measure TT4 6hrs post pill (SID) or 4-6hrs post pill (BID)
- measure cTSH
canine hypoadrenocorticism (addison’s disease)
- suspected to be due to immune mediated destruction of adrenal cortex
- results in loss of production of cortisol and aldosterone
lack of cortisol: weakness, vomiting, diarrhoea, anorexia (esp when stressed)
lack of aldosterone:
aldosterone
- acts on cells in the late distal tubule and collecting tubule
- stimuli of aldosterone production: hyperkalaemia, increased angiostensin II
- action of aldosterone: reabsorption of NaCl and H2O
- secretes K+ and H+
clinical signs of canine hypoadrenocorticism
- polydipsia and polyuria
- addisonian crisis:
- collapse, severe dehydration, hypovolaemia, pre-renal azotaemia, cardiac arrhythmias due to hyperkalaemia
screening tests for hypoadrenocorticism
- haematology (absence of leukogram)
- biochemistry (hyperkalaemia, hyponatraemia, hypercalcaemia, hypoglycaemia
- urinalysis (variably concentrated)
- basal cortisol (test to exclude disease)
- > 55nmol/L (addison’s is unlikely)
- <55nmol/L ACTH stimulation test indicated
confirmation tests of hypoadrenocorticism
ACTH stimulation test
1. collect serum for baseline cortisol measurement
2. inject 5mcg/kg of ACTH IV (synacthen)
3. collect serum 1hr post ACTH admin
diagnosis= pre and post ACTH cortisol concentrations below 20nmol/l
treatment of canine hypoadrenocorticism (addisonis crisis)
- manage hypovolaemia (fluid boluses)
- hydrocortisone or dexamethasone IV
- sudden correction of hyponatraemia can cause brain oedema
- treat hypoglycaemia, hyperkalaemia if necessary
- long term treatment
long-term therapy of canine hypoadrenocorticism
glucocorticoid (prednisolone):
- trial and error dosage to limit clinical signs of polyphagia, polyuria, polydipsia, weight gain
- increase dose if lethargy, vomiting, diarrhoea
mineralocorticoid:
- desoxycortone pivalate (zycortal)
monitoring of canine hypoadrenocorticism patient
- ask for evidence of lethargy, vomiting, diarrhoea
- blood testing for mineralocorticoid needs:
- measure Na/K 10-14 days after DOCP injection (peak effect)
- measure Na/K 25-30 days after DOCP injection (duration of effect)
good prognosis but will need lifelong treatment
hyperadrenocorticism
- Cushing’s disease
- due to excessive production of cortisol as a consequence of pituitary or adrenal tumours
3 causes: pituitary dependent, adrenal dependent, iatrogenic (excessive and sustained steroid admin)
pituitary dependent hyperadrenocorticism
- most common cause of cushing’s (85%)
- adenoma of pars distalis of pituitary gland
- results in the overproduction of ACTH which stimulates overproduction of cortisol
- 10-20% can grow large (macroadenoma), causing neuro signs
adrenal dependent hyperadrenocorticism
- adenomas/carcinomas causing excess cortisol production
- leads to negative feedback of production of ACTH of pituitary gland
- one adrenal gland enlarged due to tumour, the other adrenal gland atrophied due to suppression of ACTH production
common clinical signs of cushing’s disease
- dermatological signs (skin thinning, alopecia)
- excessive panting
- polyuria, polydipsia, polyphagia
- pendulous (loose) abdomen
screening tests for hyperadrenocorticism
- haematology, biochemistry, urinalysis
- ACTH stimulation test
- no confirmatory test available
- need to keep animal stress free to prevent increases in cortisol levels unrelated to cushings
haematology findings as indicators for cushing’s
- mild erythrocytosis (elevated RBCs)
- mild thrombocytosis (elevated platelets)
- stress/steroid leukogram
- increased neutrophils, monocytes
- decreased eosinophils, lymphocytes
biochemistry findings as indicators of cushings
- increase in ALKP
- increased ALT
- hypercholesterolaemia, hypertriglyceridemia due to lipolysis
- hyperglycaemia due to insulin antagonism
- increased bile acids
urinalysis findings as indicators of cushings
- dilute urine <1.015 USG (cortisol inhibits ADH)
- proteinuria, glycosuria (prolonged steroids can damage kidneys)
- urolithiasis
test of HPA axis for hyperadrenocorticism
- essential that some clinical signs are apparent before pursuing a diagnosis
- no recent steroid admin (minimise chance of false positives)
- LDDST, ACTH stim, cortisol:creatinine ratio
sensitivity definition
probability of a positive result if the patient is affected
sensitivity definition
probability of a positive result if the patient is affected
- Sn N out: high sensitivity, negative result, rule out
specificity definition
probability of a negative result if the patient is not affected
- Sp P in: high specificity, positive result, rule in
ACTH stimulation test for cushings
- cortisol before and 1hr post ACTH admin
- collect serum for basal cortisol concentration
- inject %mcg/kg of ACTH IV
- collect second serum sample 1hr after
advantages and disadvantages of ACTH stimulation test
- more specific but less sensitive than LDDST
- good first line test (positive result can indicate cushings)
- doesn’t distinguish PDH from ADH (types of cushings)
- used for monitoring response to treatment
low dose dexamethasone suppression test (LDDST)
- collect serum for basal cortisol concentration
- inject 0.01mg/kg IV dexamethasone
- collect serum sample 4 and 8 hours after injection
LDDST test findings to indicate cushings
- normal dog= cortisol conc decreases over the 8hrs (dex injection inhibits CRH secretion from hypothalamus)
- some pituitary dependant dog= cortisol decreases till 4hrs then rises
- adrenal and pituitary dependant dog= flat line response
advantages and disadvantages of LDDST test
- more sensitive but less specific than ACTH stimulation test
- affected by non-adrenal illness
- shouldn’t be used as sole diagnostic test
- can distinguish PDH from ADH
urine cortisol:creatinine ratio
- highly sensitive, not very specific
- false positives common
- urine sample collected at home, not after stressful event (low stress)
- pooled samples
tests to differentiate PDH from ADH
- LDDST
- HDDST (high dose dexamethasone)
- most pituitary dependant cases have V shape cortisol concentration trend
- imaging
- adrenal glands in ADH are asymmetrical
treatment of cushings
- medical
- trilostane
- surgery
- hypophysectomy for PDH
- adrenalectomy for ADH
- radiation therapy
trilostane as treatment of cushings
- give with food SID or BID
- monitor through clinical signs or ACTH stim test
hypophysectomy as treatment for pituitary dependant hyperadrenocorticism
- complete removal of pituitary gland
- 75% canine patients experience long-term cure
- life long hormonal supplementation after surgery
adrenalectomy as treatment for adrenal dependant hyperadrenocorticism
- can cause haemorrhage, iatrogenic hypoadrenocorticism
radiation therapy as treatment for cushings
- reduces the size of macroadenomas to help eliminate neurological signs
- reduction of ACTH is variable so often concurrent treatment with trilostane is needed
