66 - Diagnosis of Adrenal Disorders Flashcards
Structure of all steroids (including aldosterone and cortisol)
Four ring structure
Alternative name for cortisol
Hydrocortisone
Cortisone
Biologically-inactive metabolite of cortisol.
Metabolised in the liver back into cortisol.
Three main synthetic pathways of steroids
1) Sex hormones
2) Mineralocorticoids (EG aldosterone)
3) Glucocorticoids (EG cortisol)
Actions of glucocotricoids 1 2 3 4
- Stimulation of gluconeogenesis (liver)
- Mobilisation of amino acids (muscle)
- Stimulation of lipolysis (adipose tissues)
- Immunosuppression
Effects of too much cortisol 1 2 3 4 5
· Weight gain · Wasting of muscle, skin and bone · Hyperglycaemia (muscle amino acid → glucose) · Hypertension (salt retention) · Inhibition of linear growth
Two forms of hypercortisolism
1) ACTH dependent
2) ACTH independent
ACTH dependent hypercortisolism common causes
1
2
– Pituitary adenoma (“Cushing’s disease”)
– Ectopic ACTH syndrome
ACTH-independent hypercortisolism common causes
1
2
3
– Adrenal adenoma or carcinoma
– ACTH-independent nodular hyperplasia
– Administration of glucocorticoids (common side effect of treatment)
Most common cause of hypercortisolism
Taking exogenous glucocorticoids
Cushing’s disease
2
3
4
Hyperadrenocortisolism Leads to: – hypertension – apparent obesity – muscle wasting, thin skin, metabolic derangements (eg. diabetes)
Symptoms of Cushing's disease (in descending order of incidence) 1 2 3 4 5 6 7 8 9 10
Moon face (with red cheeks) Obesity Hypertension Menstrual disorders Hirsutism (in females) Weakness (leads to thin arms and legs) Easily bruised Osteoporosis Ankle oedema Buffalo hump Acne
Basic manner in which hormone tests are carried out
- Biochemical Testing first then radiology
- Repeat the test
- Do not measure random hormones
- hormone and trophic hormone
- stimulation if underactive
- suppresion if overactive
- regulated reagent and hormone (ca/PTH), glc/insulin
- 24hr urine assay
Investigation of suspected Cushing's 1 2 3 4
- 24h urine free cortisol
- Check diurnal variation: serum cortisol & plasma ACTH at 0800 and midnight
- Check that negative feedback loop is working: dexamethasone suppression test (cortisol, ACTH should drop with administration of dexamethasone)
- Cranial MRI/ adrenal CT as indicated
Disease of low cortisol
Addison’s disease
Symptoms of Addison's disease 1 2 3 4 5 6
· GI symptoms (anorexia, nausea, vomiting, diarrhea, weight loss)
· Low blood pressure (salt wasting)
· Darkening of the skin (if ACTH secretion is stimulated, as affects melanocytes)
· Muscle weakness (both skeletal and cardiac muscle)
· Increased susceptibility to infection
· Death
Causes of adrenal insufficiency
1-4
- Genetic: Enzyme defect in cortisol biosynthesis
- Genetic: metabolic defect: adrenoleukodystrophy
- Autoimmune adrenal destruction (most common cause)
- Infectious disease: adrenal destruction by tuberculosis (other countries)
Very dangerous effect of Addison’s disease
Salt-wasting state results in low serum sodium and high serum potassium. Can lead to arrhythmias
Location of Addison’s pigmentation
1-4
- Knuckles of hands
- Knees
- Gums & oral mucosa
- General pigmentation
Cause and effects of congenital adrenal hyperplasia 1 2 3 4 5
- Due to 21-hydroxylase deficiency in 90% of cases
- Autosomal recessive
- Variable impairment of cortisol and aldosterone biosynthesis
- Prenatal ACTH stimulation → adrenal hyperplasia
- ↑androgen → virilisation
CAH effects in males
1
2
• Adrenal crisis in a baby aged 2-3 weeks
OR
• Premature sexual development at age 2-3 years
Treatment for CAH
Give cortisol early (get negative feedback)
Glucocorticoids (clinical), in order of least to most potent
1
2
3
1) Cortisol/cortisone
2) Prednisolone
3) Dexamethasone
Activity of cortisol and cortisone
Have equal mineralocorticoid and glucocorticoid activity
Effects of aldosterone
Causes K+ loss (excretion into the kidney distal tubule), Na+ and water retention.
Main stimulus for aldosterone release
Salt and water deficit
Effect of excessive aldosterone
1
2
1) Hypertension (Na+ retention)
2) Weakness (hypokalaemia)
Effect of deficient aldosterone
1
2
1) Dehydration, salt depletion & postural hypotension.
2) Cardiac arrhythmias (hyperkalaemia)
What would someone die of if the adrenals were removed?
No aldosterone
Syndrome of excessive aldosterone 1 2 3 4
Conn’s syndrome
• Adrenocortical tumour secreting aldosterone
• Present with hypertension or with weakness due to low potassium
• High sodium, low potassium, low renin
• Cured by surgery
Name for primary tumours of the adrenal medulla
Pheochromocytoma
