Adrenals Flashcards
which parts of the adrenals make what?
zona glomerulosa (15%) = aldosterone
zona fasciculata (75% of width) = cortisol
zona reticularis (15%) = dehydroepiandrosterone (DHEA)
medulla = adrenaline/NA
brief summary of adrenal steroid synthesis
needs cholesterol
lipoproteins go into adrenocortical cells > mitochondria where it becomes pregnenolone
this leaves to the cortex and diff reactions in diff layers
zones of adrenal cortex - prodcution of their steroids are controlled by what?
G = ECG concentration of K and AngII
F and R = ACTH is trophic to these areas!
what is the HPA axis
corticotrophin releasing hormone from hypothal > anterior pit to release ACTH > adrenal cortex to release cortisol
action of aldosterone
increases ENaC in collecting duct > inc Na absorption, and K excretion > inc BC
**so can cause hypokalaemia!
actions of Ang II
renal: constrict arterioles, inc Na absorption
extra-renal
i. Vasoconstriction systemic - SNS activation
ii. Thirst
iii. ADH release – water retention
iv. Aldosterone release – sodium resorption + potassium secretion
v. Heart remodeling
what is the ACTH stimulation vs secretory ability test
ACTH stimulation: give ACTH i.e. synacthen > measure cortisol
tells you if the adrenals are responding to ACTH
secretory ability tests = central problem
e.g. insulin induced hypoglycaemia, glucagon stimulation, or metyrapone
1’ 2’ vs 3’ adrenal insufficiency
1’ = adrenal cortex problem = MR AND GC deficiency
2’ = pituitary, GC only
3’ = hypothal, GC only
1’ vs 2’ adrenal insufficiency cortisol, ACTH and synacthen results
1’: high ACTH, low cortisol. no cortisol with synacthen. Also will have hypoNa and hyperK, with high renin.
2’: low ACTH, low cortisol. will have cortisol with synacthen.
clinical manifestations of primary adrenal insufficiency
aldosterone deficiency > hypoNa (biggest Sx), hyperK, hypotension, crave salt
cortisol deficiency > hypoglycaemia + ketoacidosis, hypotension
no cortisol -ve FB on pituitary > produces POMC precursor for MSH > hyperpigmentation!
present either acute / chronic (anorexia, fatigue, wt loss etc)
long term Rx for 1’ adrenal insufficiency
- hydrocortisone 10-12mg/m2/day in 3 divided doses, ACTH to monitor
- fludrocortisone 50-150mcg/day - renin to monitor
aetiologies of 1’ adrenal insufficiency
inherited vs acquired:
- CAH (60%) infancy
- AI = addisons 15% child-adol
- TB!! globally
- APS types e.g. APECED
- X-ALD
- drugs / haemorrhage
- genetic causes e.g. abetalipoproteinaemia or Smith-Lemli-Opitx
adrenal crisis - key features
- hypotension, hypoNa, hyperK, hypogly, met acidosis, and non-specific sx
-treat above, and give them hydrocortisone 50-100mg/m2 IV - given fludrocort (florinef) once can tolerate oral fluids
- prevention with stress dose steroids: triple for 3 days, double for 2 days, then normal
key features of ALD
- X linked, ABCD1 gene!! Affects VLFCA transporter > build up in adrenals and brain
3 phenotypes:
- childhood cerebral form: initially like ADHD > actual problems
- adrenomyeloneuropathy - 20s
- addison disease only
inheritance of CAH
AR
key features of the classic CAH
= 21 hydroxylase deficiency (from zona G and F), so you get
1) aldosterone deficiency sx - SEVERE salt wasting
2) cortisol deficiency Sx
3) steroid precursors shafted to zonaR > masculinisation of females, early 2’ sex characteristics
4) the medulla usually develops from high cortisol, so you get weird HR responses
develops at D10-14 of life
key types of CAH
- 21 hydroxylase deficiency (most common)17-beta-hydroxyprog up
- 11 beta-hydroxylase deficiency: 11 deoxycortisol up
- 17-alpha hydroxylase deficiency
- congenital lipoid adrenal hyperplasia = StAR deficiency (worst)
key differentiation between the two most common types of CAH
11-beta hydroxylase will also cause low cortisol, high androgen Sx
BUT the 11 deoxycortisol buildup causes hypertension - high aldo
so present later - preamture adrenarche
key features of 17 alpha hydroxylase deficiency
- lack of this enzyme > no 17-hydroxyprogesterone, which is needed for androgens
- so low cortisol AND low androgens > poorly developed genitals
- aldo pathway doesn’t need it though - so this is active! you’ll get hyPERNa, hyPOK, and hypertension… which will feedback to low aldo
key features of congenital lipoid adrenal hyperplasia
- StAR deficiency - transporter, chol can’t enter
- all aren’t made
- most severe: neonatal insufficiency with all the symptoms
how do you treat classic CAH, and how do you know you’re over or under doing it?
- GC replacement
- overdoing: Cushing’s symptoms
- underdoing: adrenal crisis and androgen excess - fludrocort
- over: HTN, tachycardia, low renin
- under: salt wasting, high renin
comment on height in CAH
even with GC treatment, they get loss of final height of 8-10cm
what is non-classic CAH, and how does it differ from classic CAH?
also cased by 21-OH deficiency
but present AFTER neonatal period with hyperandrogenism e.g. acne, tall advanced bone age, WITHOUT adrenal insufficiency
Cushing’s syndrome vs disease
Cushing’s syndrome – prolonged glucocorticoid excess
Cushing’s disease – Cushing’s syndrome caused by a pituitary adenoma secreting ACTH
cushing’s syndrome - key features
- moon facies, fat
- CNS: depression, psychosis
- CVS: HTN
- bones: OP, poor growth
- gynae: amenorrhoea, delayed puberty
- hyperglycaemia
- skin: striae, acne, thin, bruising
- infection risk
steps to confirm cushing’s
- confirm high cortisol
- measure early morning
- measure after low dose dexa (suppression test)…should be low in the AM not high - determine cause with high dose dexa (which should act to neg FB on pituitary ACTH release)
- so for pituitary adenoma: ACTH suppressed, cortisol low
- for ACTH dependent: cortisol still high
large adrenals - what’s the cause?
unilat = adrenal tumour
bilat = pit tumour
key features of Conn’s syndrome
- primary aldosterone independent of RAAS from A) adenoma or B) bilat adrenal hyperplasia
- hyperNa, hypoK, HTN, low renin
- high aldo:renin ratio, giving fludrocort doesn’t suppress aldo
what is the main DDx of Conn syndrome, and how to differentiate?
Glucocorticoid suppressible hyperaldosteronism is diagnosed by dexamethasone suppression test
which neurocutaneous condition to think about in cunshing’s?
McCune-Albright syndrome = precocious puberty + fibrous dysplasia + café au lait
3 familial cancer syndromes for adrenocortical tumours
Li Fraumeni
MEN
APC for FAP
most common presenting symptom in children with adrenocortical tumours
virilisation - more androgens
how to treat Conn’s
adrenal adenoma = surgical resection
bilat adrenal hyperplasia = spiro
phaeochromocytoma - key features
- most adrenal medulla, but can be anywhere on the abdominal sympathetic chain
- catecholamines: headache, sweating, tachy, palps
- 80% familial: von Hippel Lindau, MEN (RET), NF1, TS, Stuge-Weber, ataxia telangectasia
how to differentiate between a neuroblastoma and a phaeochromocytoma
both secrete catecholamines
but neuroblastoma - higher DA and homovanillic acid
how to treat a phaeo before resection?
control HTN first to avoid crisis intra-op: alpha blocker FIRST 2/52, THEN beta-blocker for tachy.
