Hyperadrenocorticism Flashcards
Diagnosis & treatment
1
Q
HAC causes
A
- Pituitary dependent (80-90%)
– Micro and macro adenomas, adenocarcinomas
– [Subgroup pars intermedia] - Adrenal dependent (10-20%)
– Functional adrenal adenomas and carcinomas (50:50) - Iatrogenic
– Exogenous steroids - [Ectopic ACTH]
2
Q
How does pituitary dependent HAC work?
A
- making too much ACTH and not listening to negative feedback of cortisol being made in response
- Much in the anterior lobe but there’s a proportion (particularly in dogs) where do have pars intermedia disease.
3
Q
PDH vs ADH (re what hormones they increase)
A
- PDH increases ACTH which increases cortisol
- ADH just increases cortisol
3
Q
Why is diagnosis difficult?
A
- PDH + ADH + psychological stress + chronic illness all cause an increase in cortisol
4
Q
Canine hyperadrenocorticism - signalment, CS
A
- Middle aged to old dogs
- More females than males
- Polydipsia, Polyuria
– Secondary diabetes insipidus - Polyphagia
- Muscle wasting and weakness (pot-belly, panting)
- Skin thinning, calcinosis cutis, pigmentation, bruising
- Symmetrical hair loss
- Reproductive dysfunction
5
Q
Abdominal radiograph findings
A
- Good contrast
- Hepatomegaly
- Pot-bellied appearance
- Calcinosis cutis
- Distended bladder
6
Q
Thoracic radiograph findings
A
- Tracheal and bronchial wall mineralisation
- Pulmonary metastasis
- Osteoporosis
7
Q
Haematology - what you would expect
A
Stress leukogram
* Neutrophilia (mature)
* Lymphopaenia
* Monocytosis
* Absolute eosinopaenia
8
Q
A
8
Q
A
9
Q
Haematology - what would make you question HAC diagnosis, or consider it more complicated
A
- Neutropaenia
- Lymphocytosis
- Band neutrophils
- Eosinophils present
- Anaemia
10
Q
Clinical chemistry - what you would expect
A
- Increased alkaline phosphatase activity
– There is a steroid induced isoform in the dog - Increased ALT activity
– “steroid hepatopathy” - Hyperglycaemia
– Hepatic gluconeogenesis
– Insulin insensitivity - Elevated phosphorus
– Steroid effect on bone turnover - Increased cholesterol and triglyceride
– Steroid effect of lipid metabolism - Mildly abnormal bile acids
11
Q
Clinical chemistry - what would make you question HAC diagnosis, or consider it more complicated?
A
- Normal alkaline phosphatase
- Normal ALT
- Significant elevation in creatinine
- Hypercalcaemia
- Markedly abnormal bile acids
12
Q
Urinalysis - what you would expect
A
- USG <1.030 despite often mild dehydration
- Mild glucosuria in some cases
- Proteinuria in some cases
- Positive urine culture
– Reduced immune function
– glucosuria
13
Q
Urinalysis - what would make you question HAC diagnosis, or consider it more complicated?
A
- USG >1.030
14
Q
Diagnosis of hyperadrenocorticism - what 2 questions to ask
A
1 Is hyperadrenocorticism present?
2 If so, what is the source; pituitary or adrenal?
15
Q
Endocrine diagnostic tests for diagnosis
A
- Low-dose dexamethasone
- ACTH response
- Urinary cortisol:creatinine ratio
- Steroid induced alkaline phosphatase
16
Q
Endocrine diagnostic tests - for differentiation between source
A
- Dexamethasone suppression (low, high and mega)
- Endogenous ACTH
17
Q
Low-dose dexamethasone test
A
- Resistance of abnormal pituitary-adrenal axis to suppression by dexamethasone
- 0.01 to 0.015 mg/kg dexamethasone (Azium) IV
- Dexamethasone sodium phosphate acceptable but adjust for active ingredient
*3samples@ at 0, 3 to 6 and 8 hours - 8 hour cortisol result > 30 - 40 nmol/L is a positive test result
18
Q
ACTH response
A
- Measure of adrenocortical reserve
- 0.25 mg Synacthen IV/IM
- Or 5µg/kg IV/IM
– Lower doses reported - Samples at 0 and 1 hour
*1hourcortisol >500-600nmol/Lispositive
*Subnormal responses suggest exogenous steroid - Consider functional adrenal neoplasia in some flat mid-range and subnormal responses
19
Q
Urinary cortisol: creatinine
A
- One or more morning urine samples at home in non-stressed environment
- Definition of positive depends on laboratory
- Can combine with repeat after several doses of oral dexamethasone for differentiation
– Day 1
– Day 2
– Day 3 following 3x 0.1mg/kg oral dexamethasone
19
Q
Pros & cons of LDDxST
A
Advantages
* Highly sensitive
* Extreme confidence in a negative test result
* May differentiate as well as diagnose
Disadvantages
* Long test (8 hours)
* Poor specificity (up to 56% false positives in NAI)
* Not appropriate if history of exogenous steroids
20
Q
Pros & cons of ACTH stim
A
Advantages
* Short test (1 hour)
* More specific than LDDST
* More confidence in a positive test result
* Test of choice in suspect iatrogenic and in monitoring trilostane (Vetoryl)
Disadvantages
* Less sensitive than LDDST (especially in adrenal)
* Cannot provide differentiation
21
Q
Pros & cons of UCCR
A
Advantages
* Inexpensive
* Convenient for owner
* Highly sensitive
* Extreme confidence in negative results (SnOut)
Disadvantages
* Very poor specificity (some as low as 24%)
22
When should I test?
Only test if you could believe a positive result
*Presenting signs
*Age
*ALKP
* Eosinophils
23
What conditions could potentially be misdiagnosed as hyperadrenocorticism?
*Young Min Schnauzers hypertriglyceridaemia
*Scottish terriers progressive vacuolar hepatopathy
24
How to make a diagnosis of HAC in diabetics
Can’t rely on usual evidence
* ALKP, ALT, Chol, PU/PD
Need to look for things we would not expect in a regular diabetic
* Hair loss, thin skin, bruising at venipuncture, persistent high insulin requirement
Treat DM first
* Provides data on insulin requirement
* Improves confidence in positive endocrine diagnostic tests
25
Differentiating origin
* Low dose dexamethasone
-- sufficient suppression for differentiation in 60% of positive LDDST
* High dose dexamethasone
-- 0.1 to 1.0 mg/kg IV - sample at 0, 3-6 and 8 hours
-- >50% suppression rules out adrenal source
* Endogenous ACTH
*Imaging (ultrasound/CAT/MRI)
26
Adrenal imaging - PDH vs ADH
* PDH: Symmetrically enlarged and normal conformation
* ADH: One enlarged gland and one atrophied gland
* May see invasion if a malignant tumour
* Complicated by “incidentalomas”
27
Pituitary imaging
* CT or MRI
* Size of a ‘normal vs ‘enlarged’ pituitary not clearly defined
* Useful if neurological signs to detect the presence of a large pituitary tumour
28
Treatment options - medical
* Trilostane (Licenced)
* Mitotane (opDDD; Lysodren) – not licenced for animals (special import scheme)
* Selegiline (not effective in majority, poss in combination with trilostane)
29
Treatment options - surgical
* Adrenalectomy for ADH
-- RVC done some adrenalectomy for PDH
* Hypophysectomy for PDH
-- Few centres worldwide
-- 3D surgical guides by Highcroft/Vet3D may improve accessibility
30
What is hyperadrenocorticism?
- chronic glucocorticoid excess
31
What is trilostane?
- Modified steroid
--intereferes with the conversion of the 3 beta end of the molecule that gets converted in the pathways
-- can reversibly bind in the enzyme process.
-- i.e. reversible competitive inhibitor
-- not particularly long lasting
32
What can happen to the adrenal glands are trilostane tx? What is the relevance of this?
- the adrenal glands can initially get bigger
--- reduced neg feedback so increased ACTH release
- so need to find balance of reduced signs from cortisol but enough to have a bit of neg feedback on the pituitary.
33
Rationale for SID therapy
* Not aiming for ablation of glucocorticoid production
* Aiming to preserve mineralocorticoid function
* Plan to allow some negative feedback to mitigate increases in pituitary ACTH output and/or mass enlargement in PDH
* Avoid Aggressive therapy
→ more complete inhibition of cortisol
→ loss of negative feedback on pituitary mass
→ increased ACTH output/pituitary mass enlargement
→ adrenal stimulation/enlargement
→ higher dose requirement
→ spiralling dose requirements
34
Other adrenal diseases - of the cortex
* Functional adrenal neoplasia (non- cortisol)
* Aberrant adrenal receptor activity
-- Food (GIP) associated
* “Atypical” hyperadrenocorticism
* Ectopic ACTH
* Congenital adrenal hyperplasia
* “Alopecia X”
-- ?non-adrenal
-- ?Trilostane responsive
35
Other adrenal diseases - of the medulla
* Phaeochromocytoma
36
Functional adrenocortical tumours
Classic:
* Cortisol secreting
-- Adrenal dependent hyperAC
* Aldosterone secreting
-- “aldosteronoma”
-- Conn’s syndrome
Non-classic:
* HyperAC associated with excessive sex hormone production by an adrenocortical tumor
* Hyperaldosteronism and hyperprogesteronism in a cat with an
adrenal cortical carcinoma
* Corticosterone- and aldosterone-secreting adrenocortical tumor
in a dog
* Deoxycorticosterone-secreting adrenocortical carcinoma in
a dog
37
Functional adrenocortical tumours (non-cortisol)
Glucocorticoid like:
* Presentation
-- Similar to HAC incl stress leukogram, ACTH suppression etc
* Diagnosis
-- ACTH stim
-> 17OP, androstenedione
-> Mid range or low cortisol with minimal change
* Treatment
-> Surgical (preferred)
-> Medical
Mineralocorticoid like:
* Presentation
-- Related to hypokalaemia
-- Muscle weakness
-- Cats ventroflexion of neck
* Diagnosis
-- ACTH stim
-> aldosterone
* Treatment
-- Surgical (preferred)
-- Medical
-> Spironolactone
38
Phaechromocytoma - CS
- Weakness/Collapse
- Weight loss
- Poor appetite
- Tachypnoea
- Polyuria/Polydipsia
- Tachycardia
- Hypertension
- Panting
- Restlessness
- High blood glucose: insulin resistance
39
Why might pheochromocytoma be confused with hyperAC?
* PU/PD/Panting
* Adrenal mass on imaging
* Hyperglycaemia
40
Phaechromocytoma - diagnosis
* May be diagnosed post-surgically
-- Histology – Tx for ADHAC
* Pre-surgical diagnosis
-- Urinary catecholamine metabolites
41
Phaechromocytoma - tx
Treatment – Surgical
* Local vessel invasion
Medical – symptomatic and pre-surgical * Adrenoceptor antagonists (Sympatholytics)
* Phenoxylbenzamine (alpha)
* Propanolol (Beta)
