18 - Disorders of Adrenocortical Function Flashcards
What is Cushing’s syndrome caused by?
Excess cortisol secretion
What is the difference between Cushing’s syndrome and Cushing’s disease?
Cushing’s disease is due to a specific case of benign ACTH secreting pituitary adenoma, but syndrome is due to general symptoms from chronic cortisol exposure
What are some of the signs and symptoms of Cushing’s disease and the reasons behind these?
- Hyperglycaemia with polyuria and polydipsia due to increased muscle proteolysis and hepatic gluconeogenesis
- Thin arms and legs and muscle weaknesss due to proteolysis
- Fat in abdomen and weight gain due to increase lipogenesis
- Stria on lower abs, arms and thighs due to proteolysis and easy bruising
- Bacterial infections and acne due to immunosupression, antiinflammatory and anti-allergic effects of cortisol
- Back pain and collapse of ribs due to osteoporosis due to loss of bone matrix protein
- Hypertension from sodium retention
A patient is taking hydrocortisone and prednisone for rheumatoid arthiritis, they start to develop a buffalo hump and hyperglycaemia, what do they have and what should the treatment be?
- Cushing’s syndrome as these are steroid drugs and have the same effects as cortisol and mineralcorticoids
- Take them off of the drugs slowly
What can steroid drugs be used to treat and what are some examples?
What is a chronic cortisol insufficiency referred to as and what is this caused by?
Addison’s disease
- Disease of the adrenal cortex e.g autoimmune
- Disorders of the pituitary or hypothalamus decreasing ACTH or CRF
- Rare causes: fungal infection, adrenal cancer, adrenal haemorrhage after trauma
- Leads to insufficiency of cortisol and mineralcorticoids if autoimmune so can lead to crisis
What is the difference between Addison’s disease and an Addisonian crisis?
- Addison’s is a chronic dehabilitating disorder
- Addisonian is an acute life threatening emergency when you have addison’s disease
What are some symptoms of Addison’s disease?
- Initial non-specifific symptoms: tiredness, muscle weakness, anorexia, vague ab pain, weight loss, diziness
- Dehydration
- Increased skin pigmentation
- Postural hypotension due to fluid depletion
- Hypotension
- Hypoglycaemic episodes, especially on fasting
Why do you get hyperpigmentation in Addison’s disease?
- Occurs mainly on exposed areas of body, points of frction, scars, palmar creases and buccal muscosa
- Increase in ACTH as well as other products of POMC that stimulate melanocytes to make more melanin
What is an Addisonian crisis exacerbated by and what are the symptoms?
- Severe stress
- Salt deprivation
- Infection
- Trauma
- Cold exposure
- Steroid drug withdrawal
- Overexertion
How can you treat an Addisonian crisis?
- IV cortisol (hydrocortisone)6
- Fluid replacement (dextrose in saline)
TO AVOID COMA AND DEATH
How do you test adrenocortical function clinically?
- Measure plasma cortisol and ACTH
- 24h urinary excretion of cortisol and break down products (17-hydroxysteroids)
- ACTH stimulation test
- Dexamethasone supression test
How do you distinguish between Cushing’s disease and between adrenal tumours/ectopic ACTH production?
- Dexamethasone: steroid that when given orally would supress ACTH and therefore coritsol
- In Cushings, will suppress plasma cortisol by more than 50% as still sensitive to potent steroids.
- Supression won’t occur in the other two cases
How can you dynamically test for Addison’s disease?
- Administer Synacthen IM (analogue of ACTH)
- Will normally increase plasma cortisol by >200nmol/L
- With Addison’s, this does not happen
What is congenital adrenal hyperplasia?
- Genetic defect in one or more of the enzymes involved in synthesis of corticosteroid hormones from cholesterol
- Lack of cortisol, PG releases lots of ACTH causing adrenal hyperplasia
- Mainly 21-hydroxylase deficiency
What are the symptoms of congenital adrenal hyperplasia and why?
- Precursor of gluco and mineralcorticoids, 17a-hydroxypredenolone is diverted to more androgen synthesis (androstenedione and testosterone)
- Salt wasting crisis* due to loss of aldosterone
- Genital ambiguity* in female infants
What is Conn’s syndrome?
- Primary hyperaldosteronism due to hyperactive adrenal glands
- Unilateral form: adenoma
- Bilateral form: familial hyperaldosteronism type I and II
- Low renin compared to secondary hyperaldosteronism
What are some examples of nuclear receptors and what is their structure?
- Steroid
- Vitamin D
- Thyroid
- Hydrophobic hormon binding region, DNA binding region and variable region. Sequence homology in hormone binding regions of the receptors
When high levels or cortisol are present, what receptors does it start binding to and why?
- Sequence homology so binds to their hormone binding site with low affinity
- Will bind to mineralocorticoid and androgen receptors when at high levels!!
What do androgens stimulate?
Growth and development of male genital tract and sexual characteristics like height, body shape, facial and body hair, low voice pitch, anabolic muscle protein
What happens when there is an oversecretion of androgens in females?
- Acne
- Hirsutism
- Menstrual problems
- Virilisation
- Increased muscle bulk
- Deepening voice
What do oestrogens stimulate in females?
- Growth and development of female genital tract
- Breasts
- Broad hips
- Accumulation of fat in breast and buttocks
- Body hair distribution
- Weakly anabolic
- Decrease circulating cholesterol levels
How can you tell the cause of Cushing’s syndrome>
Explain why purple striae as depicted in the patient below are often seen in Cushing’s syndrome?
