Diagnosis of adrenal disorders Flashcards
What is the function of the adrenal cortex?
- Steroid hormone synthesis and function
- Glucocorticoids (cortisol)
- Mineralocorticoids (aldosterone)
Which two disease states are associated with the adrenal cortex?
Cushing’s disease and Addison’s disease.
What is the funciton of the adrenal medulla?
- Catecholamine synthesis and functions
- Adrenaline and noradrenaline
What is a disease state associated with the adrenal medulla?
Pheochromocytomas
What is the chemical structure of aldosterone and cortisol common to?
4 ring structure common to all steroids
What is released from the glomerulosa of the adrenal cortex?
Mineralocorticoids (aldosterone)
What is released from the fasciculata of the adrenal cortex?
Glucocorticoids (cortisol) and some androgens
What is released from the reticularis of the adrenal cortex?
Sex steroids, androgens and some cortisol
What is hydrocortisone?
Cortisol
What is cortisone?
- Biologically almost inactive metabolite of cortisol, doesn’t actually have much activity.
- In liver, is metabolised back to cortisol, hence its use as a therapeutic.
What is the major glucocorticoid?
Cortisol
What is cortisone acetate?
- Very weak glucocorticoid
- Metabolite of cortisol
What do aldosterone, cortisol and tesosterone/oestrogen originate from?
Cholesterol
What are the 4 actions of glucocorticoids?
- Stimulation of gluconeogenesis (liver)
- Mobilisation of amino acids (muscle)
- Stimulation of lipolysis (adipose tissues)
- Immunosuppression
What does too much cortisol lead to?
- Weight gain
- Wasting of muscle, skin and bone
- Hyperglycaemia
- (muscle amino acid → glucose)
- Hypertension (salt retention)
- Inhibition of linear growth (if before puberty)
What are the 2 different types of hypercortisolism?
ACTH-dependent and ACTH-independent
What is ACTH-dependent hypercortisolism usually caused by?
- Pituitary adenoma (“Cushing’s disease”)
- Ectopic ACTH syndrome
What is ACTH-independent hypercortisolism usually caused by?
- Adrenal adenoma or carcinoma
- ACTH-independent nodular hyperplasia
- Administration of glucocorticoids (common side effect of treatment) – most common cause
What is the most common cause of ACTH-independent hypercortisolism?
Administration of glucocorticoids.
What are the signs and symptoms of Cushing’s disease hyperadrenocortisolism?
- Hypertension
- Apparent obesity
- Muscle wasting, think skin, metabolic derangements (e.g. diabetes)
- All direct actions of glucocorticoids
How is endocrine testing performed?
- Biochemical Testing first then radiology
- Repeat the test
- Do not measure random hormones, measure:
- Hormone and trophic hormone
- Stimulation if underactive
- Suppresion if overactive
- Regulated reagent and hormone (ca/PTH), glc/insulin
- 24hr urine assay
Instead of measuring random hormones, what is measured?
- Hormone and trophic hormone
- Stimulation if underactive
- Suppresion if overactive
- Regulated reagent and hormone (ca/PTH), glc/insulin
- 24hr urine assay
What are the different ways of diagnosis by hormone measurement?
- Assay of hormone and regulated metabolite Ca & PTH, glucose & insulin
- Assay of hormone and trophic factor
- T4 and TSH
- Cortisol and ACTH
- Oestrogen and FSH/LH
- Testosterone and LH
- Stimulation or suppression test
- 24 hour urine test
How is suspected Cushing’s syndrome investigated?
- 24h urine free cortisol measurement
- Check diurnal variation: serum cortisol & plasma ACTH at 0800 and midnight
- Check that negative feedback loop is working: dexamethasone supp’n test – most common test
- Cranial MRI/ adrenal CT as indicated
What is the most common investigation performs for suspected Cushing’s syndrome?
Dexamethasone suppression test - check that the negative feedback loop is working.
What does not enough cortisol cause?
- GI symptoms (anorexia, nausea, vomiting, diarrhea, weight loss)
- Low blood pressure (salt wasting)
- Darkening of the skin (if ACTH secretion is stimulated)
- Muscle weakness (both skeletal and cardiac muscle)
- Increased susceptibility to infection
- Death
What are the causes of adrenocortical insufficiency?
- Genetic: Enzyme defect in cortisol biosynthesis
- Genetic: metabolic defect: adrenoleukodystrophy
- Autoimmune adrenal destruction – most common
- Infectious disease: adrenal destruction by tuberculosis (other countries)
What happens to sodium and potassium levels in Addison’s disease?
Salt-wasting state results in low serum sodium and high serum potassium
What is Addison’s disease treated with?
Cortisol and fludrocortisone
What are the signs and symptoms of excess adrenal androgens?
- Premature pubic hair
- Hirsutism, acne
- Enlargement of penis or clitoris (child)
- Behavioural changes
- Linear growth spurt
- Rapid epiphyseal fusion (child)
- Muscular habitus
- Deepening of voice.
What is congenital adrenal hyperplasia (CAH)?
- Due to 21-hydroxylase def in 90% of cases
- Autosomal recessive
- Variable impairment of cortisol and aldosterone biosynthesis
- Prenatal ACTH stimulation → adrenal hyperplasia
What are the 3 different presentations of CAH in females?
- Infant with ambiguous genitalia OR
- Premature pubic hair & enlarged clitoris OR
- Adolescent hirsutism and acne
What are the 2 different presentations of CAH in males?
- Adrenal crisis in a baby aged 2-3 weeks OR
- Premature sexual development at age 2-3 years
How is CAH treated?
By replacing cortisol
What are the clinical uses of glucocorticoids?
- Replacement if inadequate production (pituitary disease, Addison’s disease)
- Anti-inflammatory and immunosuppressive properties.
- Used to treat inflammatory conditions e.g. arthritis, dermatitis, asthma, autoimmune diseases
Which glucocorticoids have no mineralocorticoid activity?
Synthetic glucocorticoids, e.g. Dexamethasone
What are the two regulators of aldosterone secretion?
- Increase [K+] in extracellular fluid
- Angiotensin II
What are the actions of mineralocorticoids?
- Aldosterone regulates [Na+], [K+] in extracellular fluids
- Increased resorption of Na+, water
- Increased excretion of K+ from the kidney distal tubule
What does excess aldosterone result in?
- → hypertension (salt retention)
- → weakness (hypokalaemia)
What does aldosterone deficiency result in?
- → Dehydration, salt depletion & postural hypotension.
- → Cardiac arrhythmias (hyperkalaemia)
What will happen if the adrenal glands are removed surgically?
Death within just a few days, due principally to a loss of mineralocorticoid activity.
What is Conn’s syndrome?
- Adrenocortical tumour secreting aldosterone (mineralocorticoid excess)
- Present with hypertension or with weakness due to low potassium
- High sodium, low potassium, low renin
- Cured by surgery
What happens to renin levels in hyperaldosteronism?
Decreases and therefore angiotensin II does, too.
