Endocrinology Flashcards
what is the most common endocrine condition in cats?
feline hyperthyroidism
why is feline hyperthyroidism recognised with increasing frequency?
awareness of the disease
cats living longer
becoming more common?
what is the aetiology of feline hyperthyroidism?
no evidence of autoimmune disease
mostly benign adenomatous hyperplasia/adenoma of thyroid tissues
is feline hyperthyroidism usually bilateral or unilateral?
2/3rds bilateral
what is ectopic thyroid tissue?
functional thyroid tissue found elsewhere - usually mediastinum
what are the potential factors contributing to feline hyperthyroidism?
nutritional factors (iodine levels, goitrogens)
environmental factors (flea sprays, garden pesticides)
genetic factors (some breed dispositions)
circulating factors (thyroid growth stimulating immunoglobulins)
what are the risk factors for developing feline hyperthyroidism?
regular use of flea sprays/powders
indoor cats
primarily canned food diet
exposure to lawn herbicides/fertilisers/pesticides
what signalment more commonly presents with feline hyperthyroidism?
middle aged-elderly cats (10-23 years)
no sex predilection
what is increased in the body due to feline hyperthyroidism?
metabolic rate cardiac output heart rate blood pressure GI motility CNS activity
what is reduced due to feline hyperthyroidism?
sleep
body weight
what are the major clinical signs of feline hyperthyroidism?
palpable enlarged thyroid glands weight loss polyphagia hyperactivity PUPD tachycardia
what are the minor clinical signs of feline hyperthyroidism?
lethargy intermittent anorexia voice changes muscle weakness/tremors congestive heart failure heat intolerance mild pyrexia dyspnoea/tachhypnoea
what are the signs of apathetic hyperthyroidism?
lethargy, inappetence, weight loss, obtundation
small percentage, likely reflecting an underlying comorbidity
which comorbidity often accompanies apathetic hyperthyroidism?
severe cardiac abnormalities
how should cats with feline hyperthyroidism be handled?
cat-friendly, hands-off approach
put in quiet room to calm
oxygen therapy, sedation (gabapentin) if required
acclimatisation period
monitor RR
what is required for diagnosis of feline hyperthyroidism?
compatible clinical signs
positive screening tests
serum total thyroxine test
how do we feel for enlargement of the thyroid gland?
feel the neck up to the larynx from the level of the thoracic inlet
what screening tests are used for diagnosis of feline hyperthyroidism?
haematology
biochemistry (elevated liver enzymes, concurrent disease?)
urinalysis (CKD?)
blood pressure measurement
what ocular feature can accompany severe feline hyperthyroidism?
retinal detachment due to acute hypertensive crisis
what is the gold standard test for feline hyperthyroidism?
serum total thyroxine (TT4) test - elevated in most hyperthyroid cats but may fluctuate
what TT4 value is considered feline hyperthyroidism?
> 50-60nmol/L
why might TT4 present as high-normal in feline hyperthyroidism?
early disease
non-thyroidal illness can affect T4
what are the treatment options for feline hyperthyroidism?
anti-thyroid drugs
iodine-restricted diet
thyroidectomy
radioactive iodine treatment
why should medical management be tried for feline hyperthyroidism first?
to assess renal function when patient is euthyroid before undertaking irreversible treatment
to stabilise the patient prior to anaesthesia if surgery is planned
how do anti-thyroid drugs work?
block production of T4 by the thyroid gland
what anti-thyroid drugs are available?
methimazole - BID tablets/transdermal gel/oral liquid
slow-release carbimazole tablets SID (rapidly converted to methimazole)
how long does it take for antithyroid drugs to work?
normally euthyroid in <2-3 weeks - recheck TT4 2-3 weeks after starting treatment
what are the advantages of anti-thyroid drugs?
readily available rapidly effective inexpensive practical no GA/hospitalisation
what are the drawbacks of anti-thyroid drugs?
life-long
long-term resistance
must be good compliance
side effects
what are the minor/common/transient side effects of anti-thyroid drugs?
vomiting
anorexia
lethargy
what are the major/rare/persistent side effects of anti-thyroid drugs?
persistent GI signs
blood dyscrasias (severe leukopenia/anaemia/thrombocytopenia)
dermatitis (facial excoriation)
hepatopathy
lymphadenomegaly
myasthenia gravis
stop treatment if any of these occur!
what diet is available for managing feline hyperthyroidism?
iodine-restricted
Hills y/d
what are the drawbacks of feeding an iodine-restricted diet?
must be fed as sole food (strictly)
life-long
less effective and not suitable for severely hyperthyroid cats
what are the pre-surgical considerations for feline hyperthyroidism?
systemic effects of hyperthyroidism
cardiac disease
hypertension
other disease
what is a thyroidectomy?
removal of one/both thyroid glands
what must great care be taken during thyroidectomy surgery?
preservation of parathyroid tissue to avoid post-operative complications (hypocalcaemia)
how long does thyroidectomy take to work?
typically achieves euthyroidism in >90% patients in 24-48 hours
what are the advantages of thyroidectomy?
curative
rapidly effective
short hospitalisation period
what are the drawback of thyroidectomy?
GA and great skill required location recurrence cost complications
what are the complications associated with thyroidectomy surgery?
damage to/removal of parathyroid tissue (post-operative hypoparathyroidism)
damage to the recurrent laryngeal nerve
damage to sympathetic trunk (horners syndrome)
possible recurrence of disease (if unilateral)
what condition commonly occurs due to bilateral thyroidectomy?
iatrogenic hypoparathyroidism - usually transient, weeks-months to recover
what are the clinical signs of iatrogenic hypoparathyroidism?
inappetence weakness tremors ptyalism pawing at face
progressing to tetany, seizures, death
monitor serum calcium twice a day of bilateral surgery or if concerned
what is the treatment for iatrogenic hypoparathyroidism?
IV 1-% calcium gluconate slowly (10-20 mins)
oral therapy ASAP - elemental calcium in divided doses while weaning off IV drip PLUS oral vitamin D long-term
how should you monitor patients during hypoparathyroidism treatment?
monitor with ECG for arrhythmia and bradycardia
what fluids should be avoided when administering IV calcium for hypoparathyroidism?
bicarbonate, lactate or phosphate-containing fluids –> precipitate calcium
why can’t calcium gluconate be administered subcut?
can cause skin sloughs
what is the gold standard for treating feline hyperthyroidism?
radioiodine treatment
how is radioiodine treatment carried out?
administered systemically but concentrated in thyroid
cat isolated for 1-2 weeks - gamma rays dangerous
what are the advantages of radioactive iodine treatment?
gold standard
curative
simple procedure
higher doses can treat adenocarcinoma
no GA
lower cost (compared to lifelong antithyroid drugs)
what are the drawbacks of radioactive iodine treatment?
cost
limited availability
isolation period
irreversible
may take some time to achieve euthyroid
iatrogenic hypothyroidism (rare)
how are feline hyperthyroidism and CKD linked?
feline hyperthyroidism may mask underlying CKD –> treatment may unmask CKD
usually only change by maximum one IRIS stage
how often should we monitor cats with feline hyperthyroidism? what are we monitoring for?
6-monthly check-ups once stabilised, regardless of treatment regime
checking for recurrence, hypertension, CKD (urea, creatinine, BP, urinalysis)
what is the prognosis for feline hyperthyroidism?
largely dependent on severity/presence of concurrent disease (especially heart disease)
uncomplicated hyperthyroid cats have an excellent prognosis following curative treatment
what are the characteristics of canine thyroid neoplasia?
carcinomas common, adenomas usually incidental findings
usually large, solid, palpable mass at level of thyroid gland
does canine thyroid neoplasia result in hyperthyroidism?
no - usually euthyroid or hypothyroid
10% hyperthyroid
what are the clinical signs of canine thyroid neoplasia?
average age 10 years
mass in ventral region of neck
+/- cough/dyspnoea
how is canine thyroid neoplasia diagnosed?
histopathology of the mass - FNA often blood contaminated but may confirm thyroid origin
care as very vascular
what treatments are available for canine thyroid neoplasia?
surgical removal followed by chemotherapy/radiation therapy
radioactive iodine treatment (high doses required)
what is the prognosis for canine thyroid neoplasia?
depends on size, local invasion, functional status and histological diagnosis (adenoma vs carcinoma)
what does thy thyroid gland produce?
active thyroid hormones
thyroxine (T4)
triiodothyronine (T3)
what are the thyroid hormones produced from?
from tyrosine amino acids and action of thyroid peroxidase (TPO) - oxidation of iodine
which thyroid hormone is secreted in higher amounts
mostly T4, small amount of T3
how much T4 is bound to proteins?
> 99%
which type of T4 is biologically active?
unbound/free t4 is biologically active and exerts a negative feedback on TSH production
what is the most common form of hypothyroidism?
primary hypothyroidism
what are the 2 causes of primary hypothyroidism in dogs?
lymphocytic thyroiditis
thyroid atrophy
what is lymphocytic thyroiditis?
destructive immune-mediated process - infiltration of lymphocytes, macrophages and plasma cells and replacement by fibrous connective tissue
clinical signs occur when 75% of the gland is destroyed
what is thyroid atrophy?
degenerative process with limited inflammation
progressive replacement by adipose and connective tissue
possibly end-stage lymphocytic thyroiditis
what is secondary hypothyroidism?
rare
pituitary hypoplasia (congenital - disproportionate dwarfism)
or
dysfunction (acquired - neoplasia)
what signalment predisposes hypothyroidism?
mean age at diagnosis is 7y
breed dispositions: english setter, golden retriever, rhodesian ridgeback, cocker spaniel, boxer
what are the metabolic signs of hypothyroidism?
decreased metabolic rate - weight gain, lethargy, inactivity
what are the dermatologic signs of hypothyroidism in dogs?
endocrine alopecia (symmetrical, non-pruritic)
rat-tail (hair loss at tail tip)
tragic facial expression due to myxoedema
hair in telogen phase - poor hair growth after clipping
what are the reproductive signs of hypothyroidism?
persistent anoestrus
weak/silent oestrus
prolonged oestral bleeding
inappropriate lactation
no effect on male reproductive system
what are the cardiac signs of hypothyroidism?
bradycardia
association with atrial fibrillation and DCM
what are the neuromuscular signs of hypothyroidism?
megaoesophagus
laryngeal paralysis
facial nerve paralysis
peripheral vestibular syndrome
(more likely concurrent disorders than causal effect)
what is the association between hypothyroidism and myxoedema coma?
what are the symptoms of a myxoedema coma?
life-threatening consequence of hypothyroidism
profound mental dullness, weakness, hypothermia, bradycardia and hypotension
what are the ocular signs of hypothyroidism?
corneal lipid deposits (via hyperlipidaemia), ulceration, uveitis
what are the GI signs of hypothyroidism?
diarrhoea due to SIBO
constipation due to decreased peristalsis
how is hypothyroidism diagnosed?
appropriate history and clinical signs
haematology and biochemistry markers
specific thyroid testing
what haematology/biochemistry abnormalities are used in diagnosis of hypothyroidism?
mild non-regenerative anaemia (normocytic and normochromic)
hypercholesterolaemia
hypertriglyceridaemia
what hormone abnormalities would you expect to see in a hypothyroid dog?
low T4
high TSH
(low T4 = no negative feedback on pituitary gland production of TSH)
which thyroid tests are performed in diagnosing hypothyroidism?
total T4 (TT4) canine TSH (cTSH)
why is total T4 a useful screening test for hypothyroidism?
has excellent sensitivity
what are the limitations of using TT4 as a diagnostic test?
thyroglobulin antibodies can falsely increase TT4
poor specificity - TT4 decreases naturally with ages/breed/non-thyroidal illness and drug therapy
how sensitive is the canine TSH test?
moderate sensitivity - low cTSH in central hypothyroidism or corticosteroid therapy
how specific is the canine TSH test?
Good specificity - largely non affected by NTI or drugs
will be elevated in euthyroid dogs in recovery from NTI
how is hypothyroidism treated?
synthetic T4 (physiologic prohormone for active T3) in the form of sodium levothyroxine SID or divided BID
how does pairing with food affect the bioavailability of sodium levothyroxine?
halved with food
how should you dose sodium levothyroxine in dogs with cardiac disease, diabetes mellitus, or hypoadrenocorticism?
start with 25% of dose and titrate up
how long should Sodium levothyroxine be given before evaluating its effect?
6-8 weeks
how long does it take Sodium levothyroxine to reach peak concentration?
3-5 hours post-pill
what is the half-life of Sodium levothyroxine?
9-15 hours (affects dosing intervals)
what products are available to administer sodium levothyroxine?
soloxine - tablets
thyforon - flavoured tablets
leventa - liquid formulation
how often should you monitor dogs with hypothyroidism?
6-8 weeks after starting treatment or 2-4 weeks after altering dose
what are the aims of hypothyroidism treatment?
TT4 upper half of the reference value
TSH normal value
how common is iatrogenic thyrotoxicosis?
rarely cause hyperthyroidism with treatment for hypothyroidism
what are the potential complications of hypothyroidism treatment?
thyrotoxicosis (rare) - secondary to drug overdose myxoedema coma (rare)
what are the clinical signs of thyrotoxicosis?
panting anxiety/aggression PUPD weight loss polyphagia
what is the treatment for thyrotoxicosis?
reduce dose/discontinuation of treatment
what is the treatment for a myxoedema coma?
supportive care
IV levothyroxine
antibiotics if sepsis
what is the prognosis for hypothyroidism?
good for adult dogs with primary hypothyroidism
guarded for secondary hypothyroidism
what are the main 2 parts of the adrenal glands? what does each produce?
medulla (catecholamines)
cortex (mineralocorticoids/glucocorticoids/sex hormones)
what type of molecule is aldosterone?
mineralocorticoid (steroid hormone)
where is aldosterone produced?
adrenal cortex
where is the major renal tubular site of aldosterone action?
principal cells in the last distal tubule and collecting tubule
what is the action(s) of aldosterone?
reabsorption of NaCl and H2O
secretion of K+ and H+
more important for K+ regulation than Na+ regulation
what are the most important stimuli for aldosterone production?
hyperkalaemia
increased angiotensin II
what other name is given to primary hypoadrenocorticism?
addison’s disease
what happens in primary hypoadrenocorticism?
lack of aldosterone secretion by the adrenal cortex, resulting in hyperkalaemia, hyponatremia and hypocalcaemia
what is secondary hypoadrenocorticism?
Secondary hypoadrenocorticism refers to a central (anterior pituitary) deficiency of ACTH, resulting in isolated glucocorticoid insufficiency
what is atypical hypoadrenocorticism?
lack of glucocorticoids but normal mineralocorticoids
what causes primary hypoadrenocorticism?
suspected immune-mediated destruction of the adrenal cortex
what causes secondary hypoadrenocorticism?
central (anterior pituitary) cause - neoplasia, inflammation, infection, infarct, iatrogenic
what secretion is affected in secondary hypoadrenocorticism?
only glucocorticoid deficiency as aldosterone secretion is regulated by RAAS
what secretion is affected in primary hypoadrenocorticism?
lack of glucocorticoids and mineralocorticoids
which dogs are more prone to developing hypoadrenocorticism?
typically young/middle-aged female dogs
breeds: standard poodles, bearded collie, nova scotia duck toller, great dane
what are the symptoms of a lack of cortisol in hypoadrenocorticism?
weakness, vomiting, diarrhoea, anorexia
especially at times of stress
what are the symptoms of lack of aldosterone?
polyuria and polydipsia (due to low Na)
what type of molecule is cortisol?
glucocorticoid (steroid hormone)
what are the symptoms of an addisonian crisis?
collapse
severe dehydration and hypovolaemia
pre-renal azotemia
cardiac arrhythmias due to hyperkalaemia (bradycardia)
how do you diagnose primary hypoadrenocorticism?
compatible history and clinical signs
compatible haematology and biochemistry results
basal cortisol to exclude the disease
ACTH to confirm
what haematology results suggest hypoadrenocorticism?
non-regenerative anaemia
absent stress leukogram (especially in a sick patient)
what biochemistry results indicate primary hypoadrenocorticism?
hyperkalaemia
hyponatraemia and hypocalcaemia
pre-renal azotemia 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 GC)
what basal cortisol result suggests hypoadrenocorticism is unlikely?
> 55nmol/l
what basal cortisol result suggests hypoadrenocorticism is likely?
<55nmol/L
which test can be used to confirm hypoadrenocorticism?
ACTH stimulation test - usually both pre- and post-ACTH cortisol concentrations below 20nmol/l with HOA
what is the protocol for an ACTH stimulation test?
collect serum for basal cortisol concentration
inject 5mcg/kg ACTH IV
collect second serum sample 60 min after
what happens to serum cortisol in a ACTH stimulation test if the dog has hypoadrenocorticism?
remains at same level (increases in normal dog)
how is an addisonian crisis treated?
IV fluids at shock doses (60-90ml/kg)
hydrocortisone or dexamethasone IV
treatment of hypoglycaemia and hyperkalaemia if necessary (glucose/insulin and calcium gluconate)
what are the considerations for using glucocorticoid therapy for primary hypoadrenocorticism?
most commonly prednisolone
trial and error dosage to limit polyphagia/PUPD/weight gain
increase dose if lethargy/V+/D+
double dose if stressful event
what is the long-term therapy for primary hypoadrenocorticism?
glucocorticoids PO
mineralocorticoids SC
what are the considerations for using mineralocorticoid therapy for primary hypoadrenocorticism?
desoxycortone pivalate (zycortal) - able to manage the need for GC separately from MC requirements starting dose 1.5mg/kg SC
how should we monitor patients with primary hypoadrenocorticism?
Ask for evidence of lethargy, V+, D+ - signs that would prompt increase in GC
blood test for mineralocorticoids - measure 10-14 days after DOCP admin for peak effect and 25-30 days after for duration of effect
what is the prognosis for hypoadrenocorticism?
good if well-managed - life-long medication
may need additional GC at times of stress
monitor dogs with atypical addisons for development of mineralocorticoid deficiency (may develop in future)
what are the possible causes of canine diabetes?
destruction of pancreatic beta cells
(genetics, immune-mediated pancreatic damage, pancreatitis, idiopathic)
insulin resistance leading to beta cell exhaustion
(obesity, concurrent disease, dioestrus, drugs)
which dogs are more prone to developing diabetes?
middle aged-older dogs
females more than males
breeds: australian/tibetan/cairn terrier, schnauzers, bichon, samoyed
what are the clinical findings with canine diabetes?
PUPD (secondary to glycosuria)
polyphagia and weight loss
cataracts
diabetic ketoacidosis (vomiting, collapse, dehydration)
concurrent disease (pyometra, cushings)
why do cataracts often form in dogs with diabetes?
due to altered osmotic relationship in the lens (due to sugar)
accumulation of sorbitol and galactitol causing swelling and rupture of the lens fibres
how is canine diabetes diagnosed?
concurrent glycosuria and persistent hyperglycaemia are necessary to confirm a diagnosis
what is fructosamine?
glycated proteins produced by irreversible non-enzymatic reactions between glucose and plasma proteins
why do we test for fructosamine in dogs with suspected diabetes?
shows an average of glycaemia of previous 2-3 weeks
how is canine diabetes treated?
insulin (essential)
diet
exercise
consistency and commitment from owners
what is the principle treatment of canine diabetes?
insulin supplementation
which insulin is most commonly used in treating canine diabetes?
Lente - intermediate acting
also need access to neutral insulin for DKA (short acting)
can oral hypoglycaemic drugs be used in treatment of canine diabetes?
Oral hypoglycaemic drugs are of no value in dogs! they always require insulin
which long-acting types of insulin are available?
PZI - recombinant human insulin
glargine - synthetic
what are the handling considerations for insulin?
store in fridge/avoid extremes of temperature
replace bottles after 4 weeks
invert to mix - let foam disperse then gently roll
use appropriate syringes
vary injection site (to avoid fibrosis)
why should intact canine females with diabetes be spayed?
progesterone is an antagonist of insulin - spaying will make them easier to stabilise
how can we alter the diet in patient with canine diabetes?
diabetic brands
should not contain simple sugars - calories provided by complex carbohydrates and proteins
increased fibre content in overweight dogs
what should the feeding schedule be for dogs with diabetes?
consistent quantity/timing/type of diet
if BID injections - feed half daily requirement at time of each injection
if SID - feed 1/3-1/2 at time of injection and remainder 8 hours later
ad libitum feeding for grazers
what is involved in the initial stabilisation of canine diabetes?
at home if possible - can take weeks-months
start with low dose
check blood glucose several times over first day in practice (q2-3hrs) - avoid hypoglycaemia
how should we monitor a dog with newly diagnosed diabetes?
any PUPD, polyphagia, weight loss
hypoglycaemia signs - lethargy, reluctance to exercise, collapse, seizure
how is a blood glucose curve performed?
either by serial blood glucose with glucometer or continuous glucose monitoring
what parameters are important to assess for the blood glucose curve?
nadir (lowest blood glucose reading)
duration of action
what is the renal threshold?
point at which glucose is excreted in the urine (patient presents as polyuric)
what might we find in urinalysis of a diabetic dog on treatment?
usually a mild amount of glucose in urine, especially before insulin administration
no glucose >24hours may indicate insulin overdose
ketones may indicate poor glycaemic control
what are the potential complications of insulin therapy?
hypoglycaemia - give small meal or glucose PO/IV
somoygi overswing - rebound hyperglycaemia caused by physiologic response to hypoglycaemia (rebound effect of overdosing insulin)
what should you do if the insulin has too short a duration of action?
(PUPD between injections)
switch to long acting insulin BID
what should you do if the insulin has too long a duration of action? (nadir >10hrs post-injection)
risk of hypoglycaemia and somoygi overswing
give SID or switch to short-acting formula
what are the long-term complications of diabetes in dogs?
cataract formation (common)
diabetic neuropathy (distal) (uncommon) diabetic nephropathy (uncommon)
hypertension - mechanism unclear
diabetic ketoacidosis
what is the prognosis for canine diabetes?
MST 3-5 years
good if well-managed with committed owners
what are the risk factors for feline diabetes?
old age obesity males indoor cats breeds: burmese, maine coon, russian blue and siamese
what is the pathophysiology of feline diabetes?
insulin resistance - genetics/obesity?
reduced insulin secretion - inflammation and beta cell damage/death
what are the possible causes of insulin resistance?
obesity
inflammatory/infectious disease - pancreatitis, UTI, CKD, dental disease, enteropathy
endocrinopathies - hyperthyroidism, acromegaly, hypercortisolism
what characterises the pre-diabetic stage in cats?
impaired fasting glucose - rarely documented
due to stress hyperglycaemia at vets
BG consistently >6.5 mmol/L
what characterises subclinical feline diabetes?
BG >10 and <60mmol/L persistently
would benefit from low carb diet, weight loss and possible insulin sensitisers (glipizide)
what characterises overt feline diabetes?
hyperglycaemia - BG >16mmol/L
increased fructosamine
glycosuria
what are the clinical signs of feline diabetes?
PUPD weight loss polyphagia DKA peripheral neuropathy cataracts (rare in cats)
how is feline diabetes diagnosed?
hyperglycaemia and glycosuria
(be aware of stress hyperglycaemia)
fructosamine test
how is feline diabetes treated?
insulin
diet
exercise
consistency and commitment
what insulin options are available for cats with diabetes?
prozinc (recombinant human insulin)
caninsulin (cats unpredictable in their response)
glargine insulin (can only be used under the cascade)
how do oral hypoglycaemic drugs work?
glipizide - increases insulin secretion, useful if owner decline insulin
used in conjunction with diabetic diet
what are the features of a diabetic diet for cats?
wet
high protein
low carbohydrate
high fibre less useful than in dogs
must be reliable intake
what are the effects of dietary management of diabetes in cats?
resolution in 30% of cats
reduction in insulin dose in 50%
what is diabetic ketoacidosis?
a serious complication of diabetes - concurrent with heart failure/pancreatitis/sepsis
what is the pathophysiology of DKA?
increased production of glucoregulatory hormones (glucagon/epinephrine/cortisol/GH)
lack of insulin allows the glucogenic effects of these stress hormones to be unopposed in liver/muscle/adipose tissue
leads to excessive free fatty acids breakdown and excessive ketone formation
what are the clinical signs of DKA?
PUPD, PP, weight loss
lethargy, anorexia and vomiting (with worsening ketosis and acidosis)
strong odour of acetone on breath (pear drops)
severe dehydration and hypovolaemia
what is the aim of DKA treatment/management?
restore water and electrolyte balance (Na, K, phosphorous)
provide adequate insulin to “switch off” ketone production
correct acidosis
identify any underlying disease
what supportive therapies can be given for DKA?
analgesia (if concurrent condition causing pain e.g. pancreatitis)
appetite stimulants/anti-nausea drug/NO or O tube
careful monitoring - ketosis can take 48-72hrs to improve
what is the prognosis for DKA?
25% die or are euthanised, usually due to cost of treatment
with careful treatment, some patients can become healthy happy diabetics
cats can even enter DM remission after DKA
why does hyperadrenocorticism occur?
due to excessive production of cortisol as a consequence of pituitary or adrenal tumours
what effect does cortisol have on the pituitary gland/hypothalamus?
negative feedback on ACTH and CRH secretion
what are the 3 different types of cushing’s syndrome?
pituitary-dependent (PDH)
adrenal-dependent (ADH)
iatrogenic (administration of glucocorticoids)
what is the most common type of hyperadrenocorticism in dogs?
pituitary-dependent hyperadrenocorticism
what is the pathogenesis of PDH?
adenoma of pars distalis leading to overproduction of ACTH
bilateral adrenal hyperplasia
both leading to a loss of negative feedback on the pituitary gland
what dogs are more prone to developing PDH?
dachsunds, poodles, small terriers
no sex predisposition
middle aged-old dogs
what is macroadenoma?
a type of large pituitary tumour which can cause CNS signs (obtundation, seizure)
what is the pathogenesis of ADH?
adenomas/carcinomas of the adrenal glands, leading to excess cortisol and suppression of ACTH secretion
what happens to the contralateral gland with ADH?
atrophy of unaffected gland
which dogs are more likely to develop ADH?
females
>20kg
what is iatrogenic hyperadrenocorticism?
iatrogenic disease due to chronic administration of glucocorticoids - causes suppression of CRH and ACTH production
what can happen to the structure of the adrenal glands with iatrogenic hyperadrenocorticism?
bilateral adrenal atrophy
what are the major clinical signs of hyperadrenocorticism?
polyphagia
abdominal distension
lethargy/exercise intolerance
panting
hepatomegaly
PUPD causing nocturia/incontinence
skin changes/alopecia
what are the possible complications of hyperadrenocorticism?
progression of major signs
hypertension
DM from insulin resistance
pulmonary thromboembolism
neurological signs (obtundation/blindness/seizure)
pancreatitis
secondary infections (pyoderma/UTI)
glomerulopathy and proteinuria (cortisol-induced)
how is hyperadrenocorticism diagnosed?
screening tests - haematology, biochemistry, urinalysis
screening tests of HPA axis -
ACTH stimulation test
low-dose dexamethasone suppression test
urine cortisol:creatinine ratio
what does sensitivity mean?
probability of a positive result if the patient is affected
what does specificity mean?
probability of a negative result if the patient is not affected
what haematology results would you expect to see with hyperadrenocorticism?
mild erythrocytosis
mild thrombocytosis
stress/steroid leukogram (increased neutrophils and/or monocytes, decreased eosinophils and/or lymphocytes)
what biochemistry results would you expect to see with hyperadrenocorticism?
increased ALP and ALT
hypercholesterolaemia and hypertriglycerolaemia due to lipolysis
hyperglycaemia due to insulin antagonism
increased bile acids (cholestasis)
what urinalysis results would you expect to see with hyperadrenocorticism?
variable specific gravity
dilute urine +/- proteinuria/glycosuria
+/- UTI
urolithiasis (calcium oxalate)
what is important to consider when pursuing a diagnosis of HAC via tests of the HPA axis?
essential that some historical/clinical signs are apparent first
no recent steroid administration
what does the ACTH stimulation test involve?
measuring serum cortisol before and 1h post ACTH administration
administration of what type of drug will affect the ACTH stimulation test?
recent administration of glucocorticoids will affect result
what would be expected to happen to cortisol levels in the normal dog in the ACTH stimulation test?
small but significant rise
what would be expected to happen to cortisol levels in a dog with PDH/ADH in the ACTH stimulation test?
dramatic rise >600nmol/L
what would be expected to happen to cortisol levels with iatrogenic hyperadrenocorticism in the ACTH stimulation test?
levels stay the same - chronic steroid admin means unresponsive to ACTH
what are the advantages of performing the ACTH stimulation test?
less affected by non-adrenal illness than LDDST
good first-line test
useful for ruling out iatrogenic disease
can be used for monitoring response to treatment
what are the drawbacks of the ACTH stimulation test?
less sensitive than LDDST - beware of false negatives
doesn’t distinguish PDH from ADH
what is involved in the low dose dexamethasone suppression test? (LDDST)
comparison of serum cortisol concentration before and 4/8 hours after dexamethasone injection
what would be expected to happen to cortisol levels in the normal dog in the LDDST test?
cortisol drops significantly after 4 hours and is almost 0 after 8 hours
what would be expected to happen to cortisol levels in the ADH dog in the LDDST test?
flat line - no change in cortisol levels
what would be expected to happen to cortisol levels in the PDH dog in the LDDST test?
40% flat line - no change
30% exhibit an escape V pattern - drops at 4 hours but significantly risen again at 8 hours
what are the drawbacks of the LDDS test?
less specific than ACTH stimulation test - beware false positives
affected by non-adrenal illness
not useful for iatrogenic disease
what are the advantages of the LDDS test?
excellent sensitivity (positive test strongly indicates PDH/ADH)
can distinguish PDH from ADH
what is involved in the urine cortisol:creatinine ratio test?
urine sample collected at home - 2 pooled morning urine sample
several days following ‘stressful event’ (e.g. vet visit)
what is the urine cortisol:creatinine ratio useful for?
useful to exclude HAC
i.e. normal results = cushings very unlikely
what is hyperadrenocorticism also called?
cushing’s disease
what is the drawback of the urine cortisol:creatinine ratio test?
highly sensitive but not very specific - false positives common
what tests are useful in differentiating PDH from an adrenal tumour?
low and high-dose dexamethasone suppression tests
imaging
endogenous ACTH concentration
what result would be expected from an ADH dog during a HDDS test?
flat line - no cortisol change
what result would be expected from a PDH dog during a HDDS test?
15% show flat line but most exhibit an escape V pattern as for LDDS test
what dose rate is given in the HDDS test?
0.1mg/kg
what would be seen on an abdominal ultrasound of a PDH dog?
symmetrical adrenal glands, enlarged or normal
what would be seen on an abdominal ultrasound of an AT dog?
asymmetrical adrenal glands
why might you perform an MRI on a dog with hyperadenocorticism?
the evaluate the pituitary gland and adrenal glands - 90% of PDH have a brain mass (microadenoma or macroadenoma)
why might an endogenous ACTH test be performed for hyperadrenocorticism?
to differentiate between PDH and AT
PDH = ACTH >45pm/ml
AT = undetectable ACTH
when should you pursue treatment of HAC?
only if very high index of suspicion through history, clinical signs, haem/biochem and specific testing
what treatment options are available for for PDH?
medical - trilostane
surgical - hypophysectomy, bilateral adrenalectomy
radiation therapy
how should trilostane be given?
with food, once or twice a day
how does trilostane work?
blocks production of cortisol at the level of the adrenal glands
how should cushings patients be monitored while on trilostane?
monitor clinical signs and ACTH stimulation test or pre-pill cortisol
side effects: GI signs, hypoadrenocorticism, adrenal necrosis
what is hypophysectomy?
complete surgical removal of the pituitary gland accessed via the soft palate
for which type of HAC is hypophysectomy the only potential curative option?
PDH
what is the prognosis for hypophysectomy?
goof long-term outcomes have been reported (3 years)
increasing pituitary tumour size associated with higher mortality and incidence of residual disease and relapse
what supportive treatment will hypophysectomy patients require long-term?
hormonal supplementation with glucocorticoids and thyroxine
transient diabetes insipidus means that DDAVP administration can often be discontinued
what is radiation therapy useful for in PDH?
may be effective in reducing the size of macroadenomas or eliminating neurological signs
what concurrent treatment is used with radiation therapy for PDH?
trilostane - reduction in secretion of ACTH is variable
what is the prognosis for treating PDH with radiotherapy?
mean survival time of 25 months reported
delayed improvement in clinical signs can occur
what type of HAC is adrenalectomy used to treat?
ADH
what are the complications of adrenalectomy?
haemorrhage hypertension acute hypercortisolaemia hyperaldosteronism wound breakdown
what treatment options are available for ADH?
adrenalectomy medical therapy (trilostane)
what medical therapy is used for treating ADH?
trilostane
generally more resistant to therapy - usually used for management pre-surgery
what other general treatment considerations are there for hyperadrenocorticism?
treatment may unmask other underlying diseases
reduced cortisol can cause pituitary lesions to expand (CNS signs)
what is the prognosis for PDH?
depends on age, overall health and owner commitment
mean survival following diagnosis is approx 30 months
what is the prognosis for ADH?
mean survival following successful surgery is 36 months
dogs with metastatic disease usually die/euthanased within 12 months
what most commonly causes hyperadrenocorticism in cats?
secondary to insulin-resistant diabetes mellitus
what are the signs of hyperadrenocorticism in cats?
cachexia
fragile skin syndrome - care with handling
alopecia (symmetrical, non-pruritic)
how is hyperadrenocorticism diagnosed in cats?
no increase in ALP
HDDS test and ACTH stimulation test (60+90 mins after injection)
how is hyperadrenocorticism treated in cats?
adrenalectomy if adrenal mass
no reliable treatment for PDH
what is the prognosis for hyperadrenocorticism in cats?
guarded to poor - worse than in dogs
