Small animal endocrinopathies Flashcards
Canine hypoadrenocorticism, diabetes (100 cards)
1
Q
What are the 3 zones of the adrenal cortex and what does each produce?
A
- Glomerulosa: mineralocorticoids (aldosterone)
- Fasciculata: glucocorticoids
- Reticularis: Androgens
2
Q
What is a potential, but less common, pathological process of adrenal insufficiency?
A
Mineralocorticoids abnormal first, and then progress to glucocorticoid deficient i.e. moving inwards starting at the glomerulosa
3
Q
What stimulates the release of aldosterone?
A
- RAAS
- Decreased BP detected by baroreceptors in macula densa in distal tubule, also cardiac and arterial baroreceptors
- Renin released from kidneys -> angiotensin release -> aldosterone release
- Also increased potassium concentratione
4
Q
What are the functions of aldosterone?
A
- Acts on distal tubule cells, and CD to increase reabsorption of Na and Cl and therefore water
- Stimulates K+ secretion into tubular lumen
- Stimulates secretion of H+ in exchange for k+ in collecting tubules and so regulates acid/base
5
Q
What are the different types of hypoadrenocorticism?
A
- Primary/Addison’s
- Secondary
- Iatrogenic
6
Q
What are the potential causes of primary hypoadrenocorticism?
A
- Idiopathic atrophy (immune mediated, associated with other endocrinopathies)
- Iatrogenic (e.g. drugs, mitotane, trilostane), or surgery )bilateral adrenalectomy)
7
Q
Describe the pathophysiology of primary hypoadrenocorticism
A
- Deficiency of glucocorticoids and mineralocorticoids
- Occurs with loss of 85-90% of adrenal cortex
- CRH and ACTH increase due to loss of negative feedback
8
Q
Describe the pathophysiology of secondary hypoadrenocorticism
A
- Deficiency of ACTH
- Only cortisol deficiency, electrolytes normal
- Rare
9
Q
Describe the pathophysiology of iatrogenic hypoadrenocorticism
A
- Exogenous steroids lead to adrenal atrophy
- Cortisol deficiency only
- Patient may have signs of Cushing’s syndrome
- Patient may develop signs of Addison’s if steroids abruptly discontinued
10
Q
Outline the signalment of canine hypoadrenocorticism
A
- Young-middle aged dogs (4-6yrs)
- 70% females
- Standard poodles, bearded collies, Great Dane, Rottweiler, WHWT, soft coated wheaten terrier (but any breed possible)
- Some inheritance
11
Q
In relation to hypoadrenocorticism, what should be considered inthe Nova Scotian Duck tolling retriever?
A
Juvenile Addison’s at 5mo-1yr old, immune mediated disease
12
Q
What are the pathophysiological effects of aldosterone deficiency?
A
- Loss of Na+, Cl- and H20
- Retention of K+ and H+
- Pre-renal azotaemia
13
Q
What are the pathophysiological effects of glucocorticoid deficiency
A
- Decreased stress tolerance
- GI signs, e.g. haemorrhagic gastroenteritis
- Weakness
- Appetite loss
- Anaemia
- Impaired gluconeogenesis
14
Q
Describe the common clinical history of a dog with hypoadrenocorticism
A
Waxing and waning with non-specific signs worsened by stress
- Anorexia, V/D, lethargy, depression, weakness
- Shivering, weight loss, PUPD, abdominal pain
- Should consider hypoA in any animal with waxing and waning signs esp GI
15
Q
What are the signs of acute hypoadrenocorticism?
A
- Marked hypovolaemia and azotaemia
- Paradoxical relative bradycardia (hyperkalaemia)
- Collapse, extreme weakness, hypothermia, recent history of V/D
- Abdo pain, melena (dark black tarry faeces) may feature,
16
Q
What oher condition might signs of an Addisonian crisis resemble?
A
Pancreatitis
17
Q
What are the common biochemical features of hypoadrenocorticism?
A
- Hyperkalaemia
- Hyponatraemia
- Hypocholridaemia
- Na:K ratio <23
- Hypercalcaemia
- Electrolyte changes may lag behind clinical signs and history - if normal but still suspicious repeat biochem in a few months
18
Q
What features of a complete blood count are common in hypoadrenocorticism?
A
- Lack of stress leukogram (no neutrophilia, eosinopaenia and lymphopaenia)
- Anaemia
- Lymphocytosis
- Eosinophilia
19
Q
What features of biochemistry and urinalysis are common in hypoadrenocorticism?
A
- Azotaemia
- Decreased USG
- Hypercalcaemia
- Hypoglycaemia
20
Q
What features may be seen on thoracic radiographs in hypoadrenocorticism?
A
Megoesophagus (but <1%)
21
Q
Explain megaoesophagus in hypoadrenocorticism
A
- May be muscle weakness, decreased Na and K = decreased membrane potential, decreased cortisol also associated with muscle weakness, reversible with treatment
22
Q
What features may be seen on an electrocardiogram in hypoadrenocorticism?
A
- Bradycardia
- Peaked T waves
- Widened QRS complexes
- Decreased P wave amplitude/complete disappearance
- Ventricular asystole
23
Q
What are the definitive diagnostic tests for hypoadrenocorticism?
A
- ACTH stim test
- Basal cortisol
24
Q
What results would be expected in an Addisonian dog on an ACTH stim?
A
Flatline cortisol following ACTH administration i.e. no increase in cortisol production
25
How is basal cortisol used in the diagnosis of Addison's?
- Depends on levels of cortisol
- >55nmol/L - rule out Addison's, bit below 55nmol/L may have false negatives
- Resting cortisol <28nmol/L higher specificity vs 55nmol/L basal, can rule IN Addison's if below 28nmol/L
26
What are the main treatment aims in hypoadrenocorticism?
- Restore intravascular volume (treat shock)
- Reverse hyperK
- Replace lost mineralocorticoids and glucocorticoids
- Correct life threatening arrhythmias
27
Describe the restoration of intravascular volume in an Addisonian crisis
- 0.9% saline or Hartmann's at 20-90ml/kg/hr
- Assess every 10-15mins until improvement
- Once restored reduce to maintenance (2ml/kg/hr), compensate for ongoing losses
- Continue unil hydration status, urine output, serum electrolytes and azotaemia are corrected
28
What is the importance of correcting electrolytes in an Addisonian crisis?
If sodium abnormal will continue to lose fluids
29
How is hyperkalaemia treated in an Addisonian crisis?
- Fluid therapy (normalise kidney outflow)
- 10% calcium gluconate (0.5-1ml/kg IV slow over 20 mins)
- IV dextrose/glucose (1ml/kg 50% dilute with saline, ideally via central line)
- IV soluble insulin (0.25-0.5IU/kg IV) with glucose at 2-3g/unit insulin
- Sodium bicarbonate 1-2mmol/kg
30
How are the mineralocorticoids and glucocorticoids dealt with in an Addisonian crisis?
- Dexamethaseon single dose 0.1-0.2mg/kg IV (glucocorticoids only)
- Hydrocortisone (initial 5mg/kg bolus over 5 min, then 1mg/kg IV q6h, balanced mineralocorticoid and glucocorticoid, short acting - frequent dose or CRI)
- Methylprednisolone sodium (1-2mg/kg IV), rare in practce
- Prednisolone oral (some mineralocorticoid activity)
31
What drugs are using in the long term treatment of hypoadrenocorticism
- Desocycortone pivalate
| - Fludrocortisone
32
Which drug is licensed in the long term treatment of hypoadrenocorticism?
Desoxycortone pivalate
33
Outline the use of desoxycortone pivalate in the treatment of hypoadrenocorticism
- Mineralocorticoid replacement only, use with pred
- IM inj. q20-30days
- Reassess and adjust dose/frequency regularly
34
Outline the testing required when using desoxycortone pivalate
- 10 day electrolyte test to show peak effect and assessment of adequacy of dose, use after each dose adjustment
- 25 days = pre-injection sample, assess adequacy of dosing interval
35
Outline the use of fludrocortisone in the ongoing treatment of hypoadrenocorticism
- Unlicensed
- Mineralo and glucocorticoid replacement
- Oral
- Prohibitively expensive for most
36
How is therapy for hypoadrenocorticism monitored?
- NOT ACTH stim test
| - Clinical signs (shakey, weak, anorexia, V/D), electrolytes
37
What is a potential risk of correcting sodium in a hypoadrenocorticism too quickly?
- Brain hyperosmolar, draws in water
- Add too many salts, blood hyperosmolar relative to brain, water out of brain = brain shrinks
- Myelin and axons strip away = seizuring and death
- CNS needs time to equilibrate
38
What is atypical hypoadrenocorticism?
Primary hypoadrenocorticism where glucocorticoid disturbance precedes mineralocorticoid, so no electrolyte imbalance, may go on to develop mineralocorticoid imbalance
39
What metabolic products may also be raised in hyperadrenocorticism?
Progesterone, androstendione, 17-alpha hydroxy progesterone etc.
40
Outline the physiological activity of the HPA axis
- Released by paraventricular nuclei in hypothalamus
- Into pars distalis, leads to ACTH release
- ACTH activates CYP450 enzymes and cholesterol metabolism produces cortisol + other metabolites
41
What are the potential causes of pituitary dependent hyperadrenocorticism?
- Microadenomas (<10mm diameter, 80% of cases)
- Macroadenomas (>10mm diameter, slow growing, not always neuro signs)
- 70% pars distalis, 30% pars intermedia
42
What are the potential causes of adrenal dependent hyperadrenocorticism?
- 50% are carcinomas, 50% adenomas
| - Mostly unilateral, can be bilateral
43
Describe the signalment of adrenal dependent hyperadrenocorticism
- Older dogs (11-12yrs) ADH
- Larger breeds more at risk of ADH
- Females more at risk vs males
44
Describe the signalment of pituitary dependent hyperadrenocorticism
- Middle ages dogs (7-9yrs)
- Small breeds: poodles, dachsunds, small terriers
- No sex predisposition
45
Give the most common clinical signs of Cushings
- Insidious onset, may initially be intermittent
- PUPD
- Abdo enlargement, polyphagia
- Hepatomegaly, muscle wasting/weakness, lethargy/exercise intolerance/panting, skin changes (alopecia tenting, visible vessels, comedones)
- alopecia
- Repro changes
- Calcinosis cutis
46
What less common signs may also be associated with Cushing's?
- V/D
- Pruritus
- Improvement of chroic pruritus/atopy (endogenous steroid increase = anti itch)
47
What is required for the diagnosis of Cushing's?
- High index of suspicion, thorough history and clin exam,
- Blood biochem and CBC
- Urinalysis
- imaging
- Diagnostic tests
48
What would these biochemistry findings indicate?
- Elevated ALP, ALT, cholesterol, bile acids, fasting glucose
- Reduced BUN
Cushing's
49
What findings would be expected on CBC in a Cushingoid dog?
- Lymphopaenia
- Eosinopaenia
- Neutrophilia
- Monocytosis
- Erythrocytosis
(Stress leukogram)
50
What findings would be expected on urinalysis in a Cushingoid dog?
- USG <1.015, but be <1.008 (hyposthenuric)
- UP:UC >1.0 (50% of dogs)
- Evidence of UTI
51
What findings may be seen on an abdominal radiograph of a Cushingoid dog?
Good contrast, hepatomegaly, pot-bellied appearance, calcinosis cutis, distended bladder
52
What types of diagnostic test are required to make a definitive diagnosis of Cushing's?
A screening test and a differentiation test
53
What screening tests are used for Cushing's?
- Cortisol:creatinine ratio
- ACTH stim test
- Low dose dexamethasone suppression test
- 17-alpha-OH progesterone
54
Outline how screening tests are used in the diagnosis of Cushing's
- Low suspicion: rule out with urine cortisol:creatinine ratio
- If use ACTH stim and clear positive + clinical findings that fit = treat
- If ACTH negative but high index of suspicion, perfrom LDDS
- If positive = treat, if negative, consider other ddx
- With equivocal results consider re-testing later
55
Outline how the urinary cortisol:creatinine ratio is carried out
- Easy
- Owner collects urine sample in morning at home (remove influence of stress)
- Low ratio = extremely unlikely
- High ratio = possible, but high number of false positives (but >100 strongly suggetive)
- Good to rule OUT
56
Describe the sensitivity and specificity of urinary cortisol:creatinine ratio for the diagnosis of Cushing's
- High sensitivity (~100%)
| - Low specificity
57
Describe the sensitivity and specificity of the ACTH stim test for the diagnosis of Cushing's
- Fairly high sensitivty, ~85% of PDH, >50% of ADH
- Best specificity (few false positives)
- Rule IN
58
Describe how the ACTH stim test for Cushing's diagnosis is carried out
- Starve overnight, collect heparin sample at T0
- Inject ACTH analogue IV
- Collect second sample 30-60min later in heparin tube
59
Compare the normal and positive result for Cushing's on an ACTH stim test
- Normal: pre-stim <200nmol/L, post stim <600nmol/L
| - Positive: post-stim >600nmol/L
60
What may lead to a false positive on an ACTH stim test?
Animals with infections, fracture, sepsis, renal failure, acute kidney injury etc as will have been under significant stress
61
Describe the sensitivity and specificity of the low dose dexamethasone suppression test for the diagnosis of Cushing's
- High sensitivity (90-95% PDH, most ADH)
- Low specificity, more false positives
- Good for ruling OUT
62
Describe the protocol for the low dose dexamethasone suppression test for Cushing's
- Starve overnight, collect baseline heparin sample
- Inject 0.01mg/kg dex IV
- Collect heparine samples at 3hr and 8hr
63
Compare the normal result and positive results on a low dose dexamethasone test for Cushing's
- Normal: suppress to 50% basal by 3hrs and remain suppressed
- Positive: cortisol >50nmol/L at 8hrs
64
How might the low dose dexamethasone test be used as a differentiation test for Cushing's?
- Limited use
| - Adrenals autonomous, no suppression in ADH even when suppress ACTH release further BUT not always
65
Outline the use of 17-alpha-OH progesterone when screening for Cushing's
- Extended adrenal package gives 5 additional hormones
- Interpret with caution
- Most non-cortisol Cushing dogs have increase in progesterone and 17-a-OH- progesterone due to cross-reactivity at receptors
66
What tests may be used have been identified as differentiation tests in Cushing's?
- Endogenous ACTH concentration
- Abdominal ultrasound
- (High dose dexamethasone suppression test)
67
Compare the prognosis for ADH and PHD
PDH better, more susceptible to medical management (NB if PDH, macroadenoma may cause neuro signs at some point)
68
Briefly outline endogenous ACTH concentration in Cushing's differentiation
- Labile hormone, test difficult in general practice, false negatives common
- Higher in PDH
69
Briefly outline the use of abdominal ultrasound for differentiation of hyperadrenocorticism
- Measure dimensions of adrenal glands
- PDH both same size +/- hypertrophy
- ADH one enlarged, the other atrophied
70
Outline the use of high dose dexamethasone suppression test in the differentiation of hyperadrenocorticism
- In PDH, high dose dex should inhibit pit ACTH secretion through -ve feedback so suppress cortisol
- AD autonomous = no cortisol suppression
71
What is the main disadvantage of the HDDS test for the differentiation of Cushing's?
25-30% of PDH cases fail to suppress with HDDS, no longer a recommended test
72
What other conditions does Cushing's predispose to?
- UTI
- Glomerulonephropathies
- Hypertension
- Thromboembolic disease
- Diabetes mellitus
73
What is the prognosis for Cushing's?
Well treated and monitored dogs ~5yrs
74
What management options are available for Cushing's?
- Medical (trilostane, mitotane)
| - Surgical (adrenalectomy)
75
Compare the drugs that can be used to treat Cushing's
Trilostane licensed, mitotane unlicensed
76
Describe the mechanism of action of trilostane
- Competitively inhibits 3-betahydroxysteroid dehydrogenase
- Decreases steroid production
- Reversible
- Low risk of side effects as duration of activity not prolonged
77
Describe the mechanism of action and key side effect of mitotane
- Cytotoxic
| - Can lead to Addisons
78
Outline the use of surgery in the treatment of Cushing's
- Choice of treatment for ADH
- Advanced imaging used prior to identify local invasion/metastatic disease
- Complication rate can be high
- Consider referral
79
What is a significant risk during adrenalectomy for the treatment of ADH?
If malignant tumour can end up with adrenal storms in surgery and lose patient under GA
80
How should a canine hyperadrenocorticism case be monitored?
- History, clinical exam and ACTH stim test
- Regular monitoring following administration of trilostane in order to titrate dose
- Recheck 10-14 days after initiating/changing treatment
- Perform ACTH stim 4-6 hours post medication
81
What are potential complications of trilostane treatment?
- Signs of hypoadrenocorticism with over doses
- Steroid withdrawal
- Necrosis of adrenal glands when start on trilostane, but minimal side effects
82
What is the prognosis for a case of hyperadrenocorticism?
- If well managed, several years
83
Outline the cost implication to the owner associated with canine HAC
- Drugs add up quickly
| - Surgery (is possible) is a one off cost (£3-5k) as animal will be cured after
84
Which cat breed is predisposed to diabetes mellitus?
Burmese cats
85
Compare the pathogenesis of diabetes mellitus in cats and dogs
- Cats due to insulin resistance
| - Dogs due to reduced insulin production
86
What does NIDDM mean?
Non insulin dependent diabetes mellitus, produce some insulin but no response peripherally leading to hyperglycaemia
87
How does failure of glycaemic control lead to further insulin resistance?
- Chronic hyperglycaemia impairs insulin secretion
- if over 2 weeks, leads to glycogen deposition and cell death as a result
- Termed glucose toxicity
88
What is the role of glucose and lipid in type II diabetes?
Glucose and lipid toxicity occur with chronic high circulating levels of lipid/glucose which impair insulin secretion
89
What are potential underlying causes of impaired insulin secretion in the cat leading to a diabetic state (type II) and how will these lead to diabetes?
- Pancreatitis
- Pancreatic neoplasia
- Acromegaly
- Hyperadrenocorticism
- Lead to reduced secretion of insulin, or reduced insulin sensitivity (acromegaly, HAC)
90
What are potential causes of peripheral insensitivity to insulin in cats?
- Obesity
| - Stress (multicat household, comorbidities, chronic disease)
91
Briefly describe type I diabetes in cats
- Rare in cats
| - Usually due to immune mediated destruction
92
What is the result of amyloid deposition in the pancreas of a cat?
Diabetes, end stage, no recovery
93
Describe the pathophysiology of diabetes mellitus in the cat
- Decreased tissue utilisation of glucose, amino acids, FFAs
- Increased gluconeogenesis, glycogenolysis, tissue catabolism
- Osmotic diuresis and secondary PD
- Polyphagia
- Cataracts due to osmotic effects
- Ketoanaemia, ketoacidosis
94
Why does polyphagia occur with diabetes mellitus?
Insulin required in satiety centre of brain
95
Outline a diagnostic plan for cats with suspected diabetes mellitus
- Clinical history
| - Confirmatory tests: urine glucose, fructosamine, rule out other possible causes
96
What condition would this clinical history be suggestive of in a cat?
- 13yo MN
- PUPD
- Weight loss, polyphagia
- Plantigrade stance, peripheral neuropathy
- Diabetes mellitus
- (Hyperthyroidism)
- Typically DM: middle aged-older cats, neutered males over represented
97
Why is a simple blood test not good for diagnosis of diabetes mellitus in the cat?
Stress hyperglycaemia can be significant
98
What are the advantages and disadvantages of a fructosamine test in a cat for diabetes mellitus?
- Shows long term picture of hyperglycaemia, better indicator of glucose metabolism over last 2-3 weeks
- Volatile parameter affected by concurrent disease (e.g. reduced albumin, common in older of hyperthyroid cats)
99
What value on a fructosamine result would indicate diabetes mellitus in a cat?
>400umol/l
100
What condition commonly occurs with diabetes mellitus in cats and dogs and what is the importance of this?
An active UTI, impacts on ability to stabilise patient
