Adrenal Gland Flashcards
Describe zona glomerulosa
lack 17alphahydroxlase. Produces aldosterone
Describe zona fasiculata
lacks aldosterone synthase. Produces cortisol
Describe zona reticularis
lacks aldosterone synthase. Produces androstenedione and DHEA -> converted to oestrogen and testosterone in the periphery
What is ACTH derived from
POMC (also produces beta endorphin and MSH)
What is cortisol stimulated by
Stress and has circadian rhythm
Describe cortisol relese pathway
CRH from hypothalamus -> ACTH from anterior pituitary -> stimulates adrenal cortex to synthesise and release cortisol -> negative feedback on corticotrophs
How do steroid hormone bind to receptors
Steroid hormone enters cells by diffusion and binds to cytoplasmic receptors -> dissociation of hsp90 from receptor
Hormone-receptor complex dimerises and is translocated to nucleus. Complex binds to hormone responsive element on DNA which leads to an increase in mRNA production
What are the effects of glucocorticoids
Decrease glucose uptake, glucose use, protein synthesis, Ca2+ absorption in gut, activity of osteoblasts Increase gluconeogenesis (hyperglycaemia), protein breakdown, Ca2+ excretion in kidney, activity of osteoclasts
What the anti-inflam effects of cortisol
Early - reduce redness, heat, pain, swelling
Late - reduce wound healing, repair and proliferation
What does cortisol decrease
Expression of COX2 Cytokine production Complement in plasma NO production Histamine release IgG production
What does cortisol increase
annexin-1, which inhibits PLA2 (produces arachidonic acid, which is a precursor to leukotrienes)
What does cortisol do on the mineralocorticoid receptor
increase Na retention, K excretion, water retention
What is the prevention mechanism for cortisol activation of mineralocorticoid
Cortisol has higher affinity for mineralocorticoid receptor than glucocorticoid receptor
Inactivate cortisol by conversion to cortisone (11bHSD enzyme)
11bHSD2 isoform expressed in aldosterone sensitive tissues: converts cortisol to cortisone
11bHSD1 expressed in liver, adipose, muscle: cortisone -> cortisol
What are the adverse effects of glucocorticoids
Suppression of response to infection Suppression of endogenous glucocorticoid production Metabolic effects Osteoporosis Iatrogenic Cushing's syndrome
What is the treatment for Cushing’s
Metyrapone - 11beta hydroxylase inhibitor
Ketoclonazone - inhibits steroid biosynthesis
Pasireotide - SSTR5 agonist
Cabergolien - dopamine D2 agonist
Mifeprestone - glucocorticoid receptor antagonist
What are the effects of aldosterone
Effects in distal tubule and collecting duct
Increased number of sodium channels in apical membrane (ENaC)
Increase in Na+/K+ ATPase in basolateral membrane
Increased Na/K exchange
What is spironolactone
Aldosterone antagonist
Used as K+ sparring diuretic
What is Addison’s
chronic adrenal insufficiency
What are the signs of Addison’s
Weakness, fatigue, anorexia, weight loss
Hyperpigmentation (increase of ACTH from POMC, POMC also activates MSH), hypotension, GI disturbances, salt craving, postural symptoms
What is Cushing’s
Prolonged exposure to elevated levels of cortisol or exogenous glucocorticoids
What are the signs of Cushing’s
obesity, hypertension, hirsutism (stimulation of androgen), striae, acne, bruising
What are the effects of Cushing’s
Osteoporosis
Negative nitrogen balance
Increased appetite obesity
Increased susceptibility to infection
What are the causes of primary hypoadrenalism
Destruction of adrenal cortex
Abrupt discontinuation of steroids
Autoimmune - Addison’s
TB
Surgery
Haemorrhage/infarction - meningococcal septicaemia (Waterhouse Friderichsen Syndrome)
Infiltration - Malignancy, amyloid (classic with lung cancer)
How to investigate primary hypoadrenalism
Random cortisol Short synacthen test Plasma ACTH (over 1000) Urea and electrolytes Adrenal antibodies
What is the treatment for hypoadrenalism
glucocorticoid (hydrocortisone, prednisolone), mineralocorticoid (fludrocortisone)
What is the NR of cortisol
171-526
What is the NR of K
3.5-5
What is the treatment for Cushing’s
Laparoscopic adrenalectomy (other adrenal gland can also atrophy) Replacement GC (hydrocortisone, periodic withdrawal) Psychological disturbance may continue
What is pheochromocytoma
Tumour of adrenal medulla - excess of adrenaline
Major impact on CV system
Urine or plasma collection
What are the genetic factors for pheochromocytoma
MEN2, von Hippel Lindau, NF-1, SDH
What are the clinical presentations of phaeo
Headaches, palpitations, sense of doom, chest pain, sweating, weight loss
How is phaeo diagnosed
24 urine metanephrine (metabolites of adrenaline)
Or plasma
What is the treatment for phaeo
Surgical removal after alpha and beta blockade treatment (phenoxybenzamine, doxazosin)
What is Conn’s syndrome
primary hyperaldosteronism - Low renin but high aldosterone (autonomous hypersecretion)
What are clinical presentations of Conn’s
Hypertension, hypokalaemia, alkalosis
What is the diagnosis of Conn’s
Measurement of PRA (suppressed) and aldosterone in salt-replete individuals
Selective venous sampling (IVC and sample from both adrenal glands, see where aldosterone is coming form)
What is the treatment of Conn’s
Remove the adenoma (laparoscopic)
Drug treatment:
Spironolactone, eplerenone
