Steroid Abnormalities Flashcards
She has low Na+, high K+ and Urea
Remember that a “low” number is either<strong> less of substrate</strong> or <strong>excess fluid (</strong>diluting substrate)
A high pH, low HCO3 and low CO2
Urea: indirect measure of how kidney is functioning (produced in liver and excreted)
High urea → kidneys aren’t functioning well
A high pH, low HCO3 and low CO2<span> → <strong>Compensated metabolic acidosis</strong></span>
So she has hyponatraemia, hyperkalaemia, hypoglycaemia, intravascular volume depletion and metabolic acidosis
she likely has a combined glucocorticoid and mineralcorticoid deficiency
What do you look at in Glucocorticoid deficiency (cortisol)
- Hyponatraemia
- Hypoglycaemia
- Hypotensin
What do you look for in mineralcorticoid deficiency (aldosterone)
Also
- Hyponatraemia
- Hypotension
As well as
- Metabolic Acidosis (inc. H+)
- hyperkalaemia
Defining feature of glucocorticoid vs mineralcorticoi deficiency?
Both have hypotension and hyponatraemia.
But Glucocorticoid deficiency also has Hypoglycaemia
And Mineralcorticoid deficiency has Hyperkalaemia (inc K+) and metabolic acidosis
These symptoms are caused by differen things/systems so combined has a larger negative effect
What’s the mechanism of sy mptoms fromGlucocorticoid deficiency (cortisol)
Remember Cortisol acts to increase body glucose levels?
Hyponatraemia (decr. Na+) due to dilutional effect not SALT LOSS
- Unable to excrete a water load (reduced GFR) cortisol is important for vascular, no cortisol → vessels collapse and tissues (eg kidneys) aren’t perfused.
Low Na+ can be due to not being able to remove the free water in their body, retain water - Loss of cortisol inhibition of ADH: ADH stops you peeing, GC usually a negative feedback to this, but if gone we retain all our fluid and don’t pee much
Hypoglycaemia (low Glucose)
- Reduced Hepatic gluconeogenesis
Hypotension
- Loss of cortisol effects on vascular tone
Whats the mechanism of symptoms from mineralcorticoid deficiency?
Remember Aldosterone acts on the DCT of the nephron; Reabsorbs Na+, excretes K+ and H+
Hyponatraemia
- Urine Na+ loss and water (intravascular fluid) loss, and secondary ADH/vasopression secretion once ECF drops by 10%
- Na+ main ion in ECF but H2O always follows so your ECF volume changes.
- Therefore aldosterone deficiency loses salt and water, when you turn on ADH/vasopressin to maintain BP by retaining water (better to have dilute volume then no volume at all)
- so its Na+ loss plus the ADH activation that causes the hyponatraemia
Hyperkalaemia
- Reduced renal K+ excretion
Metabolic Acidosis
- Reduced renal H+ excretion
Draw a diagram on what stimulates Aldosterone (mineralcorticoid) and what this leads to?
..
Causes of Adrenal Failure (no glucacorticoid or mineralcorticoid)
Divide into
- Primary (adrenal Gland)
- Secondary/Teritary (pituitary/hypothalamus)
You need to think about the feedback loops (draw this out)
These feedback loops failing can lead you to get a good tan!
What is the reasoning behind her tanned skin and white patches of depigmentation
White areas of skin are called vitiligo; autoimmune disease which destroys melanocytes in skin and you get ares of depigmentation.
The Tan is from Primary** Adrenal Failure
- ACTH is a product of POMC (proopiomelanocortin)
- POMC cleavage → 1 ACTH and 3 MSH (melanocyte stimulating hormone)
- ACTH also contains an extra aMSH
Therefore if cortisol is deficient → no negative feedback loops → increased CRF (hypothalamus) → increased ACTH and MSH → tan skin
Where do you see the pidmentation that occurs from primary adrenal failure
Occurs generally, but especially…
- skin flextures
- Buccal mucosa (mouth)
- old scars
- freckles
- nails
ACTH is therefore regulated by CORTISOL (independent of mineralcorticoid axis)
What do you need to think about with an obese child, and what key observations should be made?
Is this an input/output (exogenous) obesity, or something endocrine/pathological endogenous?
Key Observations:
- Change in appearance overtime
- Growth Pattern (in kids)
- Other features suggestive of pathalogical issue
What can change in appearence tell us for obese patient?
Look at old photos to see a pattern of change
Simple Obesity: becomes apparent by 3-4 yrs of age with progressive worsening
Sudden weight increase often pathalogical
Childhood Glucocorticoid Excess: generalised obesity
Adult Glucocorticoid excess: leads to truncal obesity
What can Growth Patterns tell us for obese patient?
- Simple obesity drives growth
- fat kids are taller than you would expect from their genetic potential (mum/dad heights)
- Enter puberty earlier but end up at a height similar to parents
- Glucocorticoid Excess causes profound growth failure and a crossing of percentiles downwards
A SHORT fat kid is more likely to have an underlying cause for their obesity until proven otherwise!
What are other features/symptoms of glucocorticoid exess?
- Moon face due to obesity
- Thinning skin
- violaceous striae RED strecth marks not white
- facial plethora face ‘glows’ red
- bruising
- Androgen excess as ACTH produces androgens as well as GCs
- hirsutism excess hair
- amenorrhea/irreg. period
- Myopathy
- proximal weakness
- Glucose intolerance
- diabetes mellitus
- Hypertension
- Osteoporossis
Pregnenolone → progesterone → aldosterone → cortisol → androgens
So if you make lots and lots of cortisol you also make lots of male hormones,
Why would the K+ and renin be low in an obese girl with GC excess (Cushings Syndrome).
- Too much aldosterone → retaining too much Na+ → turn off renin by the feedback loop*
- And excess aldosterone means you excrete heaps of K+.*
BUT she has a glucocorticoid excess not mineral corticoid?!?
- Cortisol binds to the MC receptor with equal affinity, but is usually metabolised too rapidly to cortisone to have an activating effect
- With excess cortisol states Mineralcorticoid effects are seen; overrides kidneys ability to degrade
Guthrie Card (day 7): came back positive for 17 OH progesterone; markedly elevated
If no testis at birth, be cautious, could be a girl in disguise!!
17 OH progesterone is a metabolite of the adrenal gland, suggesting a defect in the adrenal gland, so this kid can’t make aldosterone/cortisol properly.
Check the Karyotype: 46XX
USS shows a normal uterus (no Sertoli Cells) ; therefore baby didn’t have haematuria but normal uterine withdrawal bleed (baby period) tat came out urogenital sinus, as they come out of being in excess estrogen with mum
This is due to a defect in cortisol synthesis with a defective enzyme
~95% from 21 hydroxylase Deficiency
Low cortisol → high ACTh with secondary stimulation of the adrenal cortex, excess production of adrenal precursors and adrenal hyperplasia (grows) and hyperfuncitoning
affects both pathways so low cortisol and aldosterone
Dark indicate high ACTH (is that due to defective cortisol??)
Is this early Puberty? Look at Gonad size; this is the 1st thing to develop in puberty so if not affected (<3mls) we know the androgens making the big penis are from somewhere else.
Sex Steroid androgens only come from 2 places
- Adrenal Glands: so HAS to be this (tall, big phallus, hair)
- Gonads
Super high BP and Low K+
WHat could this be
- PRecocious Puberty (but testis are <4ml)
- Primary Adrenal Pathology
- COngenital adrenal hyperplasia** more likely bc dark so making too much ACTH
- Functional adrenal Neoplasm
Congenital Adrenal Hyperplasia: due to 11 hydroxylase (21 hydroxylase main cause)
Therefore leads to a massive increase in deoxycortico steroid, which acts on the MC → excess aldosterone → hypertension and low K+, leading to low renin
Also low cortisol → increase of ACTH as compensation → excess androgens → virilisation
Manage of this
- Glucocorticoid Therapy to suppress ACTH
- Inhibition of central precocious puberty (as already been turned off by 10-11yrs bone age)
- Treat hypertension
Glucocorticoid excess in infancy (CUshing Syndrome)
Endogenous:
adrenal adenoma/carcinoma,
multinodular adrenal hyperplasia
ACTH producing pituitary microadenoma (cushing disease)
Ectopic ACTH syndrome
Ovarian Tumour
Exogenous
