adrenals Flashcards
what is cholesterol made from if not eaten in the diet
Acetyl-CoA in the liver
what is the division of corticosteroids
glucocorticoids (cortisol) mineralocorticoids (aldosterone)
pathway for cholesterol metabolism
acetyl Coa –> acetoacetyl CoA –> HMG CoA –> mevalonic acid + CoA –> squalene –> cholesterol
what is the feedback system for cholesterol
too much cholesterol –> negatively feeds back on HMGCoA reductase (converts HMG CoA –> Mevalonic acid+CoA)
what is the role of aromatase
androgens –> oestrogens
how are steroids removed from the body
they are eliminated after oxidation by CYP3A4 in the ER of the liver –> bile acids
what is the direct and indirect pathways of the way steroids change gene expression
sex steroids –> goes straight into the nucleus where it binds a SRE glucocorticosteroids –> goes into the cytosol and binds its R (which removes the Rs inhibitor - heat shock protein) - then go enter the nucleus and bind to its HRE
which drug is an inhibitor of the androgen receptor
cyproterone acetate
what clinical conditions is cyproterone acetate used for
- hirsutism in females - male-to-female gender change - prostate cancer - benign prostatic hyperplasia - priapism - chemical castration
what are the anterior pituitary hormones that stimulate sex steroid and corticosteroid production
FSH and LH –> sex steroids ACTH –> glucocorticosteroids
general function of mineralocorticoids
promote retention of sodium and water by the kidneys –> increased BP and BV
3 ways aldosterone is regulated
- angiotensin II
- ACTH
- local potassium levels
functions of cortisol
- stimulates protein breakdown (gluconeogenesis) - inhibits protein synthesis - increases blood glucose levels - inhibits the utilization of glucose by adipose tissue - facilitates lipid breakdown, and also fat deposition in certain areas - promotes weight gain by stimulating appetite
which hormone opposes cortisol
DHEA
how is cortisol moved through the blood
bound to transcortin
how do glucocorticoids suppress immune function
by suppressing cytokine synthesis (by elevating IKBa - inhibitor to NFKB)
how is dexamethasone
potent synthetic glucocorticoid
what are some of the uses of dexamethasone
- anti-inflammatory - counteract range of side effects of oncology Tx - promote maturation of the foetal lungs - altitude sickness - adrenal insufficiency
why do you need to slowly reduce the use of corticosteroids
because taking the steroids the adrenals significantly reduce steroid production, and therefore when you remove them quickly it may take some weeks to recover from the induced adrenal insufficiency
what is the action of leuprorelin
analogue of GnRH = interrupts the normal pulsatile stimulation of the GnRH receptors to indirectly downregulate the secretion of LH and FSH
use of leuprorelin
- chemical castration via inhibition of FSH and LH release - breast, ovarian and prostate cancer
where is testosterone produced in males
in Leydig cells
function of sertoli cells
spermatogenesis
what hormone/s do sertoli cells need to function
FSH and testosterone
what hormone/s do Leydig cells need to function
LH
what part of the adrenal gland produces testosterone in both males and females
zona reticularis
hormonal therapy for prostate cancer
- androgen deprivation therapy - blocks the effect of testosterone - leuprorelin - agonist of Rs for release of LH and FSH
hormonal therapy for breast cancer
- tamoxifen - oestrogen R antagonist - letrozole - aromatase inhibitor
what is the discrimination of the “neuro” and “endocrine” parts of the adrenal gland
adrenal medulla (modified sympathetic ganglion) - secretes catecholamines adrenal cortex (true endocrine gland) - secretes steroids
4 regions of the adrenals
adrenal medulla zona reticularis zona fasciculata zona glomerulosa
what does the adrenal medulla secrete
catecholameines (neurohormone)
what does the zona reticularis secrete
sex hormones
what does the zona fasciculata secrete
glucocorticoids
what does the zona glomerulosa secrete
aldosterone
what is the order of the layers of the adrenal gland from outside to inside
capsule zona glomerulosa zona fasciculata zona reticularis adrenal medulla
what stimulates the release of cortisol
HPAA
what are some other functions of CRH other than stimulation of ACTH
- effects on inflammation and immune responses - inhibition of appetite - signals the onset of labour - links to mood disorders
what is POMC
pro-hormone for ACTH and beta-endorphin in the anterior pituitary
how does POMC make alpha-MSH
outside the pituittry ACTH is converted to alpha-MSH
functions of alpha-MSH
melanin synthesis immune response decreased food intake
explain the diurnal rhythm of cortisol release
- peaks in the morning - low in the night
how does cortisol protect against hypoglycaemia
by stimulating catabolism of energy stores (permissive for glucagon and catecholamine actions)
what is the effect on cortisol on calcium balance
decreased absorption increased excretion (bone breakdwon)
what does hyperaldosteronism cause
hypernatremia hypokalaemia hypertension
What is Cushing’s syndrome
a pituitary tumour that autonomously secretes ACTH -> excess cortisol
what does excess cortisol cause
- glucose excess (hyperglycaemia) - protein shortage - abnormal fat distribution with weight gain - wasting of muscle, skin and bone - hypertension - inhibition of linear growth
symptoms of Cushing’s syndrome
- excess gluconeogensis –> hyperglycaemia - muscle protein breakdown - lipolysis –> wasting - fat deposits in trunk and face - increased appetite - mood face - striae on abdomen - osteoporosis
what is Addison’s disease
primary adrenal insufficiency = hyposecretion of cortisol
what causes Addison’s disease
autoimmune destruction of adrenal cortex
what are the symptoms of Addison’s disease
- cardiac arrhythmias (due to K+ retention) - hypotension (due to Na+ depletion) - hypoglycaemia and decreased stress response (due to decreased cortisol) - GI symptoms - darkening of the skin - muscle weakness - increased susceptibility to infection
what are the cells called that produce catecholamines
chromaffin cells (in the adrenal medulla)
what are the catecholamines in the body
adrenaline noradrenaline dopamine
actions of catecholamines
- fight or flight response (increased HR, contractility, TPR and BP) - metabolic effects (increased glucose and FFA, increased BMR) - central effects (increased arousal and alertness) - stress responses
what is the response of the body to acute and chronic stress
- increased ADH (retain water) - increased adrenaline –> vasoconstriction –> increased renin –> increased aldosterone - increased adrenaline –> increased glucagon and decreased insulin - increased CRH –> increased cortisol
explain cortisone acetate
very weak metabolite of glucocorticoid
explain the 3 “pathways” from cholesterol
- mineralocorticoid pathway to aldosterone - glucocorticoid pathway to cortisol - sex hormone pathway to oestrogen and testosterone
2 broad types of hypercortisolism
ACTH dependent (eg pituitary adenoma) ACTH independent (adrenal problem)
what is the difference between cushings disease and cushings syndrome
cushings disease - pituitary adenoma cushings syndrome - ACTH independent
other than addison’s disease, what other things can cause adrenocorticol insufficiency
- enzyme defect in cortisol biosynthesis - metabolic defect - infectious disease (adrenal destruction by TB)
what are the serum levels of Na and K in someone with Addison’s disease
low serum sodium and high serum potassium
where is Addisonian pigmentation generally seen on the body
knuckles of hands knees gums and oral mucosa
commonest cause of adrenal adrogen excess
21-hydroxylase deficiency (congeital adrenal hyperplasia)
what causes the hyperplasia of the adrenals in CAH
the prenatal ACTH stimulation
3 presentations of CAH in females
- infant with ambiguous genitalia - premature pubic hair and enlarged clitoris - adolescent hirsutism and acne
2 presentations of CAH in males
- adrenal crisis in a baby aged 2-3 weeks - premature sexual development at 2-3 years
clinical uses of cortisol
- replacement if inadequate production (eg. pituitary disease or Addison’s disease) - treat inflammatory conditions
clinical presentation of someone with excess aldosterone
hypertension (Na retention) weakness (hypokalaemia)
clinical presentation of someone with deficiency in aldosterone
dehydration postural hypotension cardiac arrhythmias (hyperkalaemia)
if you were to remove the adrenal glands… what kills you
the loss of mineralocorticoid activity
what is the syndrome called due to adrenocortical tumour causing mineralocorticoid excess
Conn’s syndrome
what is a pheochromocytoma
tumour of the adrenal medulla
clinical presentation of pheochromocytoma
episodic bursts of palpitations, enormous hypertension, pallor, and feeling of impending doom
hormones secreted by the adrenal medulla
adrenaline and noradrenaline
