Hyperadrenocorticism Flashcards
What does the adrenal cortex synthesise and secrete?
Steroid hormones
What does the adrenal medulla synthesise and secrete?
Amines
Feedback system for glucocorticoids
Hypothalamus -> CRH
Pituitary -> ACTH
Adrenal cortex -> glucocorticoids
GLucocorticoids negatively feedback on CRH and ACTH production
WHat are steroid hormones made of?
Cholesterol
Actions of ACTH
Stimulation of cholesterol delivery to mitochondria, where P450scc enzyme is located.
Long term actions include stimulation of genes coding for steroidogenic enzymes.
Canine hyperadrenocorticism
‘Cushing’s’
Can either be spontaneous or iatrogenic (exogenous prednisolone treatment).
Two forms of spontaneous hyperadrenocorticism
Pituitary-dependent (PDH)
Adrenal-dependent (ADH)
Pituitary dependent hyperadrenocorticism
80-90%
Caused by excess ACTH secretion (can be episodic) and bilateral hyperplasia
Normal negative feedback systems fail
Most tumours are microadenomas (<10mm)
Macroadenomas as slow growing and don’t always produce neurological signs
Seen in middle aged, small dogs
Adrenal dependent hyperadrenocorticism
10-20%
50% caused by adrtenal adenomas, 50% caused by carcinomas. DIfficult to distinguish.
Independent of pituitary control and plasma ACTH conc is usually low- often leads to atrophy of contralateral gland.
Generally older, larger dogs
Clinical signs of hyperadrenocorticism
Abdominal enlargement
Polyphagia
PU/PD
Hepatomegaly
Muscle wasting
Lethargy/exercise intolerance
Skin changes
Reproductive changes
Definition of polydipsia
> 100ml/kg/day
Usually manifests as incontinence or nocturia
Skin changes found in hyperadrenocorticism
Thinning and reduced elasticity
Prominent abdominal veins
Excessive scale and comedomes
Change in coat colour
Calcinosis cutis
Biochemical abnormalities often found in hyperadrenocorticism
Elevated: ALP (in 90%) , ALT, cholesterol, bile acids, lipids, fasting glucose
Reduced: Urea (BUN)
Haematological changes in hyperadrenocorticism
Stress leucogram
What is a stress leucogram?
Lymphopenia
Eosinopenia
Neutrophilia
Monocytosis
Erythrocytosis
Changes on urinalysis in hyperadrenocorticism
Isosthenuria or hyposthenuria
USG is often less than 1.010
UTIs are common
Radiographic findings in hyperadrenocorticism
Hepatomegaly, pot bellied, calcinosis cutis, distended bladder, +/- calculi, adrenal enlargement/calcification, +/- osteoporosis.
Thoracic can show mets if a carcinoma, tracheal and bronchial wall mineralisation, osteoporosis
Ultrasonographic findings in hyperadrenocorticism
Hyperplastic adrenals are larger but normal echogenicity
Compare size of both glands
Thickness >7.5mm for left gland considered sensitive
Diagnostic tests for hyperadrenocorticism
ACTH stimulation test
Low dose dexamethasone suppression test
High dose dexamethasone suppression test
Endogenous ACTH assay
17-alpha-OH progesterone assay
Urinary cortisol:creatinine ratio
Urine cortisol:creatinine ratio
Very sensitive screening test for HAC
Not very specific
Negative result will rule out HAC
Collect urine samples in stress free environment
ACTH stimulation test
Easy and quick
Quite specific, poor sensitivity
Detects approx 85% of PDH and >50% of ADH cases
Cannot differentiate between PDH and ADH
Protocol for ACTH stimulation test
Starve overnight
Collect heparin sample time 0
Inject Synacthen IV
Collect second sample 30-60mins later (heparin tube)
Normal result: pre stim <200nmol/l, post stim <600nmol/l
Positive result: post stim >600nmol/l
Low dose dexamethasone suppression test
Induces negative feedback to the pituitary, causing cortisol levels to fall if normal.
More sensitive - detects nearly 95% of PDH and most ADH
Cannot detect iatrogenic disease, and cannot be used to monitor treatment as specificity is reduced
Protocol for LDDS test
Starve overnight
Collect baseline heparin sample
Inject 0.01mg/kg dexamethasone IV
Collect heparin samples at 3 and 8 hours
Normal animals will suppress to <50% basal cortisol by 3hrs and remain suppressed
Postive result: Resting cortisol >40nmol/l at 8hrs (not supressed)
17 alpha-OH progesterone test
Elevated above control levels post ACTH.
Suggests an abnormality in cortisol production pathway rather than simply overproduction.
Not that specific.
Suggested sequence of screening tests for HAC
Low suspicion: try to rule out using urine cortisol:creatinine ratio
If suspicious: ACTH stimulation test - if clearly positive and fits with other findings then treat.
If negative but still suspicious do LDDS test - if positive treat.
If negative consider other DDX.
If equivocal results re test later
Tests to differentiate the cause of hyperadrenocorticism
Plasma endogenous ACTH concentration
Diagnostic imaging
High dose dexamethasone suppression test (no longer recommended)
Plasma endogenous ACTH concentration test
Endogenous ACTH concentrations in normal dogs: 13-46pg/ml
Dogs with adrenal tumours: <5pg/ml
PDH: >28pg/ml
Diagnostic imaging for differentiating ADH and PDH
US: if adrenals are similar size and normal shape it suggests PDH. A mass in adrenal area suggests ADH
Can use radiogrpahy to look for adrenal masses or mets of adrenal carcinoma
CT or MRI can be used to look for pituitary tumour
Treatment of PDH
Trilostane should be first choice drug.
Synthetic steroid, competitive inhibitor of enzyme system that synthesizes glucocorticoids, mineralocorticoids, and sex hormones.
Starting dose in 2mg/kg, then use lowest dose necessary. Monitor with ACTH stimulation test or single cortisol value pre-pill.
Treatment of ADH
Best prognosis if tumour can be completely removed surgically.
Pre-operative staging.
Complicated surgery- high morbidity and mortality rate.
Mitotane therapy also recommended.
Trilostane has had some success in controlling clinical signs - but only symptomatic treatment not treating underlying neoplasia.
