w4 - adrenal physiology Flashcards
in males, most of the androgen is produced in the
testes
6 classes of steroid receptors
Glucocorticoid Mineralocorticoid Progestin Oestrogen Androgen Vitamin D
steroid hormones have an instantaneous effec
false
takes mins/hours/dyays
circulatory effects of glucocorticoids
incr CO
incr BP
incr renal flow and GFR
metabolic effects of glucocorticoids
incr blood sugar
inc lipolysis
incr proteolysis
cns effects of glucocorticoids
mood lability
reduced libido
euphoria
bone/connectiv tissue effects of glucocorticoids
accelerates osteoporosis
red calcium
red collagen formation
red wound healing
immune effects of glucocorticoids
red cap dilation
red leucocyte migration
red macrophage acitvity
red inflam cytokine
Clinical applications of corticosteroids
Suppress inflammation
Suppress immune system
Replacement treatment
purpose of mineralocorticoids
na/k pbalance
bp regulation
ECF volume
Mineralocorticoids receptors are found 4
kidneys
salivary glands
giut
sweat glands
until proven otherwise, Hyponatraemia + hyperkalaemia + hypotension =
Addisons disease
if suspected just treat it
addisons disease
primary adrenal insufficiency
causes of 2ndary insufficiency in adrenal glnad
lack of ACTH stimulation
iatrogenic (excess exogenous steroid)
pit/hypotha disorders
___ of adrenal cortex destroyed before symptomatic in addisons
90%
assoc autoimmune diseases of addisons
T1DM
autoimm thyroid
pernicious anaemia
features of addisons
Anorexia, weight loss Fatigue/lethargy Dizziness and low BP Abdominal pain, vomiting, diarrhoea Skin pigmentation
hyperpigmentation occurs in addison bcoz
ACTH reacts with a skin receptor causing pigmentation
how is adrenal insufficiency diagnosed
suspicious bio
- red Na, inc K
- hypoglycaemia
synACTHen test
-measure plasma cortisol before/after ACTH inj
normal :>250nmol/L, post ACTH >550nmol/L
ACTH shd be hiiighh
renin hiiii + aldosterone low
adrenal autoantibodies
imaging
maanagement of adrenal insuff
hydrocortisone as cortisol replacement
- if unwell = IV first
- 15-30mg daily
- try to mimic diurnal rhythm
fludrocortisone (aldosterone replacement)
education
- sick day = DBL up dosage
- vomiting = take it again or hospital for IV
- ID
t/f 2ndary adrenal insufficiency will require glucocorticoid
true
t/f 2ndary adrenal insufficiency will require mineralocorticoid
false
there is high levels of ACTH in 2ndary adrenal insufficiency t.fq
false
reduction in ACTH
clin features
- skin pale - no ACTH
- aldosterone lvls nomal
2ndary adrenal treated with fludrocortisone alone
false
hydrocortisone alone
17 year old female 3 year history of: Central weight gain Acne Amenorrhoea Hypertension Severe osteoporosis Proximal muscle weakness (myopathy) what is disease
Cushings
in males, what other clin feature in cushings
testicular atrophy
cushings syndrome is due to high levels of __
cortisol
cushings syndrome can be either ACTH dependent/independent, 3 causes for each
dependent
- pituitary adenoma (CUSHINGS DISEASE)
- ectopic ACTH (Carcinoid/carcinoma)
- Ectopic CRH
independent
- adrenlal adenoma
- adrenal carcinoma
- nodular hyperplasia
3 screening tests for cushings syndrome
overnight dexamethasone suppression test
24hr urinary free cortisol
late night salivary cortisol
test to diafgnose cushings syndrome
low dose dexamethasone suppression test
commonest cause of cortisol excess
iatrogenic
prolonged high dose steroid therapy (asthma/RA/IBS/transplants)
(usually oral, but can occur in injections and inhaled)
34 year old male 1 year history of hypertension No other past medical history No regular medications On examination: BP 168/98 mm Hg Renal function normal but plasma potassium low what is the likely disorder
too much mineralocorticoid (inap retention of Na)
conns syndrome
acromegaly
primary aldosteronism (PA) is defined as
Autonomous production of aldosterone independent of its regulators (angiotensin II/potassium)
spironolactone is a
mineralocorticoid receptor antagonist
cardio actions of aldosterone (mineralocoritcoid)
incr sympa flow
incr cardiac collagen incr pressure response
na retention
cytokine and ROS synthesis
clin featuress of PA
Significant hypertension
Hypokalaemia (in around 30%)
Alkalosis
another name for adrenal adenoma
conns syndrome
bilateral adrenal hypperplasia is the commonest cause of PA
diagnosis of PA
Step 1: confirm aldosterone excess
Measure plasma aldosterone and renin and express as ratio (ARR-aldosterone to renin ratio) (raised inveitgate further - saline suppression test -> confirmed if plasma aldo unable to suppress>50% with 2L of saline
step 2: confirm subtype
- Adrenal Ct - adeoma
- mibby adrenal vein sampling (done more in oldr) - confirm adenoma, is true source of aldo excess
management of PA
surgical
medical
-MR antagonists - spironolactone or eplerenone
Adrenal cortex is major source
glucocort
mineralocorti
androgens
Cortisol/androgen secretion regulated by __ ___ __ by a negative feedback mechanism
pit ACTh secretion
Aldosterone secretion controlled by renin-angiotensin system and
plasma K+
congenital adrenal hyperplasia is due to a deficiency of __ __, leading to a defiency in __and __V
21α hydroxylase
aldosterone
cortisol
Principles of Treatment of CAH for a) paeds b) adult physicians
a)) Timely recognition Glucorticoid replacement Mineralocorticoid replacement in some Surgical correction Achieve maximal growth potential
b) Control androgen excess
Restore fertility
Avoid steroid over-replacement
tests are looking for
17OH precursor
synACTHen test
histology of adrenal, where iis mineralo, gluco, androgens and catecholamines produced
mineralo = glomerulosa (Aldo)
gluco = fasciculata (cortisol))
androgen = reticularis
catecholamines = medulla
Clues to phaeochromocytoma
Labile hypertension
Postural hypotension
Paroxysmal sweating, headache, pallor,tachycardia
(can be none)
`phaeochromocytoma
neuroendocrine tumor of the medulla of the adrenal glands (originating in the chromaffin cells), or extra-adrenal chromaffin tissue (paraganglioma) that failed to involute after birth, that secretes high amounts of catecholamines, mostly norepinephrine
classic triad of phaechrocytoma
hyperT (50% paroxysmal)
headache
sweating
other symptoms of phaeoc
Palpitations Breathlessness Constipation Anxiety/Fear Weight loss Flushing – uncommon Incidental finding on imaging Family tracing
signs involved in phaeoc
Hypertension Postural hypotension in 50% cases Pallor Bradycardia and Tachycardia Pyrexia Signs of complications Left ventricular failure Myocardial necrosis Stroke Shock Paralytic ileus of bowel
why is phaeoc callled the 10% tumour
10% malignant 10% extra-adrenal [probably 20-30%] 10% bilateral 10% associated with hyperglycaemia 10% in children 10% familial (but probably 25%)
diagnosis of phaeoc
Identify the source of catecholamine excess
MRI Scan
Abdomen
Whole body
MIBG – meta-iodobenzylguanidine
PET Scan
Difficulties with borderline cases
therapy for phaeoc
Full α and β- blockade (A before B) Phenoxybenzamine (α-blocker) Propranolol, atenolol or metoprolol (β-blocker) Fluid and/or blood replacement Careful anaesthetic assessment
