Hyperadrenocorticism Flashcards
Diagnosis & treatment
HAC causes
- 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]
How does pituitary dependent HAC work?
- 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.
PDH vs ADH (re what hormones they increase)
- PDH increases ACTH which increases cortisol
- ADH just increases cortisol
Why is diagnosis difficult?
- PDH + ADH + psychological stress + chronic illness all cause an increase in cortisol
Canine hyperadrenocorticism - signalment, CS
- 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
Abdominal radiograph findings
- Good contrast
- Hepatomegaly
- Pot-bellied appearance
- Calcinosis cutis
- Distended bladder
Thoracic radiograph findings
- Tracheal and bronchial wall mineralisation
- Pulmonary metastasis
- Osteoporosis
Haematology - what you would expect
Stress leukogram
* Neutrophilia (mature)
* Lymphopaenia
* Monocytosis
* Absolute eosinopaenia
Haematology - what would make you question HAC diagnosis, or consider it more complicated
- Neutropaenia
- Lymphocytosis
- Band neutrophils
- Eosinophils present
- Anaemia
Clinical chemistry - what you would expect
- 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
Clinical chemistry - what would make you question HAC diagnosis, or consider it more complicated?
- Normal alkaline phosphatase
- Normal ALT
- Significant elevation in creatinine
- Hypercalcaemia
- Markedly abnormal bile acids
Urinalysis - what you would expect
- USG <1.030 despite often mild dehydration
- Mild glucosuria in some cases
- Proteinuria in some cases
- Positive urine culture
– Reduced immune function
– glucosuria
Urinalysis - what would make you question HAC diagnosis, or consider it more complicated?
- USG >1.030
Diagnosis of hyperadrenocorticism - what 2 questions to ask
1 Is hyperadrenocorticism present?
2 If so, what is the source; pituitary or adrenal?
Endocrine diagnostic tests for diagnosis
- Low-dose dexamethasone
- ACTH response
- Urinary cortisol:creatinine ratio
- Steroid induced alkaline phosphatase
Endocrine diagnostic tests - for differentiation between source
- Dexamethasone suppression (low, high and mega)
- Endogenous ACTH
Low-dose dexamethasone test
- 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
ACTH response
- 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
Urinary cortisol: creatinine
- 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
Pros & cons of LDDxST
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
Pros & cons of ACTH stim
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
Pros & cons of UCCR
Advantages
* Inexpensive
* Convenient for owner
* Highly sensitive
* Extreme confidence in negative results (SnOut)
Disadvantages
* Very poor specificity (some as low as 24%)
When should I test?
Only test if you could believe a positive result
*Presenting signs
*Age
*ALKP
* Eosinophils
What conditions could potentially be misdiagnosed as hyperadrenocorticism?
*Young Min Schnauzers hypertriglyceridaemia
*Scottish terriers progressive vacuolar hepatopathy
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
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)
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”
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
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)
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
What is hyperadrenocorticism?
- chronic glucocorticoid excess
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
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.
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
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
Other adrenal diseases - of the medulla
- Phaeochromocytoma
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
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
Phaechromocytoma - CS
- Weakness/Collapse
- Weight loss
- Poor appetite
- Tachypnoea
- Polyuria/Polydipsia
- Tachycardia
- Hypertension
- Panting
- Restlessness
- High blood glucose: insulin resistance
Why might pheochromocytoma be confused with hyperAC?
- PU/PD/Panting
- Adrenal mass on imaging
- Hyperglycaemia
Phaechromocytoma - diagnosis
- May be diagnosed post-surgically
– Histology – Tx for ADHAC - Pre-surgical diagnosis
– Urinary catecholamine metabolites
Phaechromocytoma - tx
Treatment – Surgical
* Local vessel invasion
Medical – symptomatic and pre-surgical * Adrenoceptor antagonists (Sympatholytics)
* Phenoxylbenzamine (alpha)
* Propanolol (Beta)
