Lecture 20: Adrenal steroids Flashcards
What are the two adrenal corticosteroids and the main example of each, and what is the stimulation pathway of their release
Mineralocorticoids: Aldosterone
Glucocorticoids: Cortisol
- Hypothalamus releases CRF
- Which acts on the pituitary corticotrophs to release ACTH
- Stimulates Adrenal cells to make aldosterone and cortisol
( aldosterone release also triggered by angiotensin 2 and high blood K+) - Cortisol feeds back negatively on the pituitary and hypothalamus
What is the 3 main effects of mineralocorticoid (eg. aldosterone)
Effects
1. Reabsorption of Na+ (and Water) from kidney tubule, increasing intravascular volume -> BP increase
- Excretion of K+ in urine (lower K+ in blood)
- Increase excretion of H+ in urine (alkalosis)
What is the 3 main effects of glucocorticoid (eg. cortisol)
- Increases gluconeogenesis in the liver.
- Promotes overall increase of blood Na+
- Na+ absorption in small intestine
- decreases GFR to allow more Na+ and water reabsorption
but inhibits ADH for water reabsorption - Promotes increased vascular tone
What signs does primary adrenal insufficiency/ Addisons disease cause
Damage to adrenal glands causing deficiency in cortisol and aldosterone
- Increased pigmentation in skin flexures, nails, buccal mucosa, freckles due to increased ACTH (lack of feedback inhibition of cortisol)
Increasing ACTH also increases 3 Melanocyte stimulating hormone MSH as they are cleavage product of POMC.
(ACTH also contains a-melanocyte stimulating hormone)
- Hyponatremia
- Hypoglycaemia -> brain damage
- Hypotension -> cardiovascular collapse
What are signs of excess glucocorticoid (cortisol) - Cushings Syndrome
- Generalised obesity in children and truncal obesity in adults
- Earlier puberty and profound growth failure = short and fat kid
- Moon face
- Thinning skin- violaceous striae, facial plethora, easy bruising
- Androgen (precursor to cortisol) excess: hirsuitism, amenorrhoea
- Myopathy: proximal weakness
- Glucose intolerance: diabetes mellitus
- Hypertension
- Osteoporosis: stops deposition of bone
What are the possible causes of excess glucocorticoid (cortisol) - Cushings Syndrome
- Primary functional adrenal tumour
- Multinodular adrenal hyperplasia
- ACTH secreting tumour: pituitary (cushings disease)
or ectopic (lung, gut etc) - Ovarian tumour
- Exogenous glucocorticoid intake: steroid creams absorbed systemically
How is acute adrenal insufficiency treated- Addisons crisis:
cardiovascular collapse, hypoglycaemia, hypotension, low na and cl, high K+, acidaemia
- Fluid and electrolyte resuscitation for volume depletion
- Hydrocortisone replacement for lost cortisol
- Ionotropic support for the heart
- Treatment of precipitating illness
What does 21 hydroxylase catalyse in the steroid synthesis pathway and what are the effects of defective enzyme
21 hydroxylase catalyses conversion of
a) progesterone to deoxycortisterone in Aldosterone synthesis pathway
b) 17-OH-progesterone to 11 deoxycortisol in Cortisol synthesis pathway
- Defect in this enzyme leads to no cortisol or aldosterone being made= salt wasting
- Loss in negative feedback on ACTH so increased ACTH
- ACTH causes increased production of precursors of Progesterone and 17-OH-Progesterone which diverts it down the pathway to produce Androstenedione -> Testosterone leading to androgen excess
- Adrenal hyperplasia
What does 11B hydroxylase catalyse in the steroid synthesis pathway and what are the effects of defective enzyme
11B hydroxylase catalyses conversion of
a) deoxycortisterone to corticosterone in Aldosterone synthesis pathway
b) 11-deoxycortisol to Cortisol in the cortisol synthesis pathway
- Defect in this enzyme leads to loss of Cortisol and Aldosterone
- Increased ACTH secretion due to reduced negative feedback
- Build up in deoxycorticosterone which has mild mineralocorticoid effects- so no apparent mineralocorticoid deficiency and 11-deoxycortisol.
- Congenital adrenal hyperplasia
