Hyper/Hypoadrenocorticism Flashcards
Where are the adrenals located?
The adrenal glands are Located at the cranial pole of the kidneys within the retroperitoneal space
Elongated and are often asymmetrical, being moulded around the neighbouring vessels
Will adults or juveniles have larger adrenals?
Size varies greatly and generally those of juveniles are larger than adults
How big are a medium sized dogs adrenals?
A medium-sized dog’s adrenals will on average measure 2.5 x 1 x 0.5cm
What do the zones of the adrenals produce?
Medulla: Catecholamies
Cortex:
Zona glomerulosa- Mineralocorticoids
Zona fasciculata- Glucocorticoids (some adrogens)
Zona reticularis- Androgens (some glucocorticoids)
The medulla is made up of what kind of tissue?
What does it contain?
It consists of Neuroendocrine tissue and contains Sympathetic ganglion cells
What are catecholamines?
Epinephrine (adrenaline)
Norepinephrine (noradrenaline)
What is the blood supply to the adrenals?
Adrenals supplied by superior, middle, and inferior suprarenal arteries which branch before entering adrenal capsule.
Within the capsule, arteries branch to give three patterns of blood distribution:
Capsular capillaries
Cortical fenestrated capillaries
Medullary arterioles
The cortex of the adrenals is supplied by what type of capillaries?
Cortical fenestrated capillaries supply cortex and drain into medullary fenestrated capillaries
The medulla of the adrenals is supplied directly by what?
Medullary arterioles go directly to medulla
Define glucocorticoids
A class of steroids hormones that bind to the glucocorticoid receptor. The name glucocorticoid (glucose + cortex + steroid) derives from its role in the regulation of the metabolism of glucose, its synthesis in the adrenal cortex and its steroidal structure
Define mineralocorticoids
Mineralocorticoids (e.g. aldosterone): A class of steroid hormone characterised by their effects on salt and water balance. The name mineralocorticoid derives from early observations that these hormones were involved in the retention of sodium (a mineral)
What controls glucocorticoid release?
Within the hypothalamus there are neurones called the “paraventricular nuclei”
These synthesise and release corticotrophin releasing hormone, or CRH
This control is partly diurnal but also highly influenced by a negative feedback pathway, based on circulating cortisol levels.
When required, CRH is transported down axons to the median eminence. Here the neurones terminate in the “portal capillary bed”
The CRH is then released and travels via the pituitary portal blood system to the pars distalis in the anterior pituitary
Once CRH is in the anterior pituitary, it causes cells called corticotrophin cells to make and release ACTH
ACTH is synthesized from pre-pro-opiomelanocortin (pre-POMC).
ACTH then travels through the systemic circulation to the adrenal glands where is stimulates the adrenal cortex to make glucocorticoid steroid hormones, predominantly cortisol
What controls mineralocorticoid release?
Main stimulus for aldosterone release is low blood pressure-RAAS
High serum potassium also stimulates release
Role of ACTH only minor
What does over secretion of glucocorticoids cause?
hyperadrenocorticism (HAC)
Under secretion of glucocorticoids and mineralocorticoids is called…
primary hypoadrenocorticism (Addison’s)
Once released what happens to glucocorticoids?
Once released, glucocorticoids are transported in the blood 90% bound to plasma proteins
They bind to specific cell membrane or cytosolic receptors at their target
These receptor-steroid complex is then transported to the nucleus
Here the complex binds to glucocorticoid response elements (GRE)
Resulting in altered gene expression
What are the effects of glucocorticoids on metabolism?
Stimulates gluconeogensis
Stimulates glycogenolysis
Causes proteolysis
Promotes lipolysis
What are the effects of glucocorticoids on fat?
Mobilisation from peripheral stores
What are the effects of glucocorticoids on muscle?
catabolism of muscle
What are the effects of glucocorticoids on the liver?
Gluconeogenesis
Antagonise insulin
What are the effects of glucocorticoids on the kidney?
Increased GFR
Block ADH action
What are the effects of glucocorticoids on the skin?
Follicular atrophy
Sebaceous gland atrophy
What are the effects of glucocorticoids on bone?
Reduce calcium levels
Osteopaenia (loss of protein and mineral)
What are the effects of glucocorticoids on the brain?
Causes hunger and thirst
What are the effects of glucocorticoids on the immune system?
Release neutrophils from marginated pool
Down regulates immune response
What are the effects of aldosterone?
Plays a central role in the regulation of BP
Acts on cells of distal tubule and collecting duct to increase reabsorption of Na, Cl and hence water
Stimulates secretion of H+ in exchange for K+ in the collecting tubules, so regulating acid/base
What are androgens?
Androgens are also steroid hormones
Androgens are precursors for all oestrogens
Stimulate or control the development and maintenance of male characteristics by binding to androgen receptors
What are the most important androgens?
Testosterone
Dihydrotestosterone (DHT)
Dehydroepiandrosterone (DHEA)
Androstenedione
Androgens can be given as anabolic steroids to increase appetite and body weight as they cause…
Protein synthesis from amino acids
Increase muscle fiber size
Increase bone growth and remodeling
Hyperadrenocorticism is aka…
Cushing’s disease
In dogs Hyperadrenocorticism (HAC) has two forms…
Pituitary-dependent (PDH) 80-90% cases
Adrenal-dependent (ADH) 10-20% cases
What does Pituitary-dependent HAC cause?
Excess ACTH secretion and bilateral adrenal hyperplasia
In adrenal dependant HAC, ACTH levels are ………………., why?
ACTH concentration low or undetectable as these are Independent of pituitary control so cortisol production is independent of ACTH
What is the signalment for adrenal dependent HAC?
Generally seen in older dogs (median 11-12 years)
Larger breed dogs appear more at risk
Females slightly more at risk
What is the signalment for pituitary dependent HAC?
PDH seen in middle-aged dogs (median 7-9 years)
Poodles, Dachshunds and small Terriers predisposed to PDH
No sex predisposition for PDH
What are the clinical signs of HAC?
PU/PD (most cases) Abdominal enlargement (pot belly) Polyphagic Hepatomegaly Muscle wasting/weakness Lethargy/exercise intolerance / panting Skin changes (alopecia) Reproductive changes Calcinosis cutis
What causes the pot belly in HAC
Re-distribution of fat into the abdomen
Hepatic enlargement
Wasting and weakness of abdominal muscles
What causes the muscle wasting in HAC?
Caused by protein catabolism
Decreased muscle mass apparent over limbs, spine and temporal region
What causes changes to the skin in HAC?
Thinning and reduced elasticity causes prominent abdominal veins
Due to protein catabolism (atrophic collagen) and loss of subcutaneous fat
The animal also has Excessive scale and comedones and is Easily bruised
What is calcinosis cutis?
Firm, slightly elevated plaques surrounded by erythema
Secondary infection common
Neck, axilla, ventral abdomen and inguinal areas
What is the signalment for feline HAC?
Rare
middle aged to older cats
Approx 75-80% due to PDH and 20-25% due to ADH
Pituitary Hyperadrenocorticism (HAC) in horses is also known as…
Pituitary Pars Intermedia Dysfunction (PPID)
What hormones have a positive and negative effect on POMC breakdown?
CRH and ADH have a positive effect on this, a dopamine has a negative effect
So in horses how does PPID cause Hyperadrenocorticism?
In PPID there is a pars intermedia adenoma which causes excessive production of POMC’s derived peptides eg. ACTH and from that arises Hyperadrenocorticism
How does dopamine control POMC?
D2 dopamine receptors cause Inhibition of expression of POMC mRNA expression and POMC hormone release from the pars intermedia
What are the symptoms of PPID?
Hirsutism Weight Loss/wastage PU/PD Laminitis Recuuring infections Pot belly Lethargy Neorlogical signs eg narcolepsy and blindness Infertility
What causes Hirsutism in PPID?
Chronic elevation of MSH
What causes PU/PD in PPID?
Pituitary compression induces decreased secretion of ADH
ACTH/cortisol inhibit ADH action
Hyperglycaemia/glucosuria osmotic diuresis
What causes laminitis in PPID?
High glucocorticoid concentration Persistent hyperinsulinaemia (high levels of insulin) and persistent hyperglycaemia
What causes the recurring infections in horses with PPID?
Increased concentration of immunosuppressive hormones: Cortisol / α-MSH / β-endorphins
What causes the lack of muscle and pot belly in horses with PPID?
Glucocorticoids have catabolic effect of skeletal muscle
What causes the lethargy in horses with PPID?
Increased β-endorphin
What causes the narcolepsy and blindness in horses with PPID?
Blindness: ± compression of optic chiasm
Narcolepsy: unknown but could be Lack of dopaminergic control
In horses the pars intermedia is more active in …………………. so we should avoid using the resting ACTH test then
Aug-oct
When testing for PPID and using the resting ACTH what can give us false negatives and positives?
False negatives: Sample not stored properly (chilled and separated ASAP), not accounting for season, early PPID
False positives: Stress and pain
Why do we not use base cortisol levels in diagnosing PPID?
Often normal with PPID, large variation throughout the day
How to we do a TRH mediated ACTH response when testing for PPID?
Baseline blood sample, Administer 1mg TRH, o Blood sample 10/30 minutes later, Measure ACTH concentration.
With PPID ACTH concentration is >100pg/mL after TRH
NOT SUITABLE JULY TO NOVEMBER
What tests do we do for PPID?
Resting ACTH
TRH mediated ACTH response
Combined DST-TRH test
Resting insulin
How do we do a combined DST-TRH test when diagnosing PPID?
Take a baseline blood sample, IV dexamethasone, sample 3 hours later and give IV TRH, blood sample 30 mins later and then 24h after dex
To use resting insulin for PPID testing what must we rule out?
Need to rule-out Equine Metabolic Syndrome
In a biochemistry profile for a HAC dog, what will be elevated and what will be reduced?
ALP- alkaline phosphatase (usually marked) in > 90% cases as its induced by steroids. ALT (mild-moderate) Cholesterol Bile acids (mild-moderate) Fasting glucose Parameters reduced Urea (BUN)
In urinalysis of a dog with HAC what is the protein: creatine ratio?
> 1 in half of dogs
What tests can we use to screen (does this animal have HAC?) small animals?
- Urinary cortisol:creatinine ratio
- ACTH stimulation test
- Low dose dexamethasone suppression (LDDS) test
- 17 alpha-OH progesterone
Is urine cortisol:creatinine good for snout or spin?
Snout
A low ratio make HAC extremely unlikely
Is the ACTH stimulation test good for spin or snout?
Spin
So Don’t exclude HAC if negative
How do you carry out an ACTH stimulation test for small animals?
Starve overnight
Collect heparin sample time 0
Inject synthetic ACTH i.v
Collect second sample 30-60 minutes later into heparin tube again
A positive result is very high cortisol after 30-60 min
Is low dose dex good for snout or spin?
Snout, detects 90-95% of cases.
How do you carry out a low dose dex test?
Starve overnight
Collect baseline heparin sample
Inject 0.01mg/kg dexamethasone i.v
Collect heparin samples at 3 and 8 hours
‘Positive result’ = cortisol > 50 nmol/l at 8 hours as negative feedback fails
How do we differentaite between adrenal dependant HAC and pituitary dependant HAC?
1. Endogenous ACTH PDHAC = increased ACTH ADHAC = decreased ACTH 2. Adrenal imaging 3. Pituitary imaging
Hypoadrenocorticism is aka…
Addison’s disease
Renin release is stimulated by..
Baroreceptors in the wall of the afferent arteriole
Cells of the macula densa in the early distal tubule which are stimulated by a reduction in Cl delivery
Cardiac and arterial baroreceptors
What does renin do?
Renin carries out the conversion of angiotensinogen to angiotensin 1
What enzyme converts angiotensin I to angiotensin II?
Angiotensin I is converted to angiotensin II by the enzyme ACE from pulmonary and renal endothelium
What are the effects of angiotensin II?
Increase sympathetic activity Increase tubular reabsorbtion of Na/Cl Increase tubular excretion of K Arteriolar vasoconstriction Aldosterone secretion ADH secretion
What causes Addison’s in dogs?
Idiopathic atrophy-
probably immune-mediated destruction
Iatrogenic caused by prolonged use of Exogenous steroids
What is the signalment for Canine hypoadrenocorticism?
Young-middle aged dogs. Median age 4-6 years
poodles, bearded collies, leonberger, great Dane, WHWT and Rottweiler
What does hypoadrenocorticism cause?
Aldosterone deficiency
Glucocorticoid deficiency
What are the clinical signs of chronic hypoadrenocorticism?
Anorexia, vomiting, diarrhoea, PU/PD, weakness, lethargy, depression and weakness
What are the clinical signs of acute hypoadrenocorticism?
Usually collapsed or extremely weak
May have recent history of V+/D+
Signs caused by hypovolaemic shock
MAY have paradox of relative bradycardia (due to hyperkalaemia)
What is the CBC of a dog with hypadrencorticism look like?
Lack of stress leucogram (so no neutrophilia or lymphopenia)
Anemia: decreased erythrocytosis due to lack of cortisol
What does the biochemistry profile of a dog with hypadrencorticism look like?
hyperkalaemia (increased K+)
hyponatraemia (Decreased Na+)
hypochloridaemia (Decreased Cl-)
Na:K ratio <23
Due to aldosterone deficiency:
Decreased renal tubular resorption of Na+ and Cl
Decreased excretion of K+ (and H+)
What does the urinalysis of a dog with hypadrencorticism look like?
Urinalysis will show a decreased urine specific gravity
What does the electrocardiogram of a dog with hypadrencorticism look like?
bradycardia, peaked T waves, widened QRS complexes, P wave amplitude or disappearance of P waves, ventricular asystole (failure to contract)
