Adrenal Gland Flashcards
In the adrenals what hormones are made and where
Capsule
Zona glomerulosa: mineralcorticoids -> aldosterone
Zona fasiculata: glucocortiscoids -> cortisol
Zona reticularis: androgens -> DHEA
If you have adrenal insuffienctly what conditons can you have
- glucocorticoid
- mineralocorticoid
- adrenal androgen insufficiency
If you excess GC, MC, and andorgens what conditions do you have
Too much
- glucocorticoid excess → Cushing syndrome
- mineralocorticoid excess → Conn’s syndrome
- androgen excess → congenital adrenal hyperplasia, PCOS
What is CAH
- rare disorder
- affects 1 in 10000
- genetic disorder
- there is a lack of enzymes needed to make GC, MC, A
- (there’s a mutation in the enzyme)
What is the most common form of CAH
most common form is 21 hydroxylase deficiency
What enzyme is implicated in 21 hydorxlyase defiency and what does it do
- CYP21A2
- is needed to to make aldosterone and cortisol
- stops making GCs, and MCs
- they have adrenal insufficiency
- but also excess androgens
Explain how cortisol does negative feedback
- cortisol exerts a negative feedback
- it stops the pituarity releasing ACTH
- and stops hypothalamus from producing CRH
- if there is not enough hormones, then it can amplify the signal even further
What happens to the pituriatry adrenal axis in CAH
- Since we lack cortisol we lack the negative feedback systems, overproduction of CRH, ACTH
- excess ACTH causes hyperplasia of the adrenal gland
- excess of adrenal androgens
- affect the genitalia
- adrenal insufficiency (lack of cortisol)
- wasted salt (lack of aldosterone)
In summary what happens to hormones if you have CAH
- lose GC, MCs
- lots of androgens
- lots of ACTH, CRH
How do we diagnose CAH
look at enzyme before 21 hydorxylase
- typically we look at 17 OH progesterone as a key marker
- would be high
- use as a baseline or measure it after giving ACTH as a stimulation
How do we measure if we are giving someone too much treatment
- We also use androstenedione
- measures if we are giving too much
What are the two types of CAH
classic
androgen excess + cortsiol and aldoestrone defiency
non classic (most common) -> androgen excess (but no cortsiol and aldoestrone defeincy)
Symptoms and signs
What are the symptoms that you can get with CAH
Androgen excess
-common ground for classical and non classical
-ambigous genitalia (female babies)
-excess body hair, early sexual development
-irregular periods
Cortisol defiency
-fatigue
-weight loss
-muscle weakness
-emergency -> adrenal crisis
Aldoestrone defienecy
-low bp
-salt cravings
-salt wasting at birth -> emergency
this all depends on the mutation, there can be minor or total impairment
if you have less sevre mutation you have non classic
Signs
What happens to gentalia in CAH
46, XX DSD
- external genitalia go through development in the womb
- female fetus with congenital adrenal hyperplasia
- appearance dictated by how much androgen exposure
- if less androgens more “female-looking genitalia”
- more androgens more “male-looking genitalia”
Treatment
How is CAH treated
1) Replacement of deficient corticosteroids
- Glucocorticoid replacement
- Hydrocortisone,
- Prednisolone,
- Dexamethasone
- Mineralocorticoid replacement (not always)
- Fludrocortisone
2) Suppression of ACTH-driven androgen excess
- Higher glucocorticoid doses
- cortisol exerts a negative feedback
- androgen excess is driven by excess ACTH
- so you can dampen the effect of ACTH,
- so you give higher than normal doses. of GCs
- Modified-release hydrocortisone
Why is treating CAH described as a balancing act
- need to balance, treatment without causing places
- if you give to little you don’t dampen ACTH, rise in adrenal androgen
- can cause things like hiritusim, acne, menstrual irregularietes, reduced fertlity
- if you give too much, you cause metabolic consequences (cortsiol over replacement)
- can cause weight gain, central obesity, metabolic syndrome, osteprosis)
fertility in CAH
what happens hormonally
Too much glucocorticoid
- Suppression of LH and FSH
- Oligo-/Amenorrhea
Not enough glucocorticoids
- Androgen and progesterone excess
- Anovulation, oligomenorrhoea, failure to implant
What is TART
how is it implicated in CAH
Testicular adrenal rest tissue (TART)
- Arises from urogenital ridge,
- both adrenal and gonadal features come from the urogential ridge go to the gonads and ten start to growth with their adrenal ability when there is increase ACTH
- TART cells are dormant under ACTH they grow and compress testes inhibiting spermatogensis
- if you have CAH, growth can occur and effect the other tissues this can impair fertility
What are the causes of androgen excess in women
- non classic CAH
- PCOS
PCOS
What are the signs and symptoms of PCOS
- Chronic (or intermittent) Anovulation
- defined as frequent bleeding at intervals <21 d or infrequent bleeding at intervals >35 d.
- Mid-luteal D21 progesterone in women with 21-35 day intervals.
- Polycystic ovarian (PCO) appearance of the ovaries (ultrasound)
- defined by the presence of 12 or more follicles 2–9 mm in diameter and/or an increased ovarian volume >10 mL(without a cyst or dominant follicle) in either ovary
- Androgen excess
- Clinical signs of AE: hirsutism, acne, androgenic alopecia
- Biochemical evidence of AE: increased serum testosterone
Why is PCOS described as metabolic disorder
and why is this a problem long term
- androgen excess
- can cause irrefular periods, inferiltiy or miscarriages
- insulin resistance
- can cause future hypertension, type 2 diabetes, lover disease, cardiovasuclar disease
Lifelong problems
- with no specific treatment and no means of metabolic risk
- PCOS affects multiple body disorders
What do they want to rename PCOS
FAME
Female AndroMEtabolsic syndrome
What needs to excluded before a diagnosis of PCOS
- congenital adrenal hyperplasia
- adrenal cancer
- adrenal adenoma
- Cushings disease
- ovarian hyperthecosis
- ovarian tumours
IF you see an adrenal incidentalomas you need to two key questions
what are they?
- need to know if its malignant
- risk is about 5-8%
- and is this adrenal mass producing hormones in excess
Incidentalmoas
Why do we need to know if its malignant
- adrenal cancer very rare and aggressive
- less than 50% will survive pass 5 years
- do not want to miss this diagnosis
- most adrenal tumors will be bengin tumors
Incidentalmoas
What is the best way to answer these questions diagnostalicly
like what tool would you use
- imaging
- good at ruling out malignancy
- BUT… hard to differentiate from benign from malignant
If we have an adrenal tumor what else do we need to look for
apart from maligancny
- tumor size
- If it is less than 4cm → risk of malignancy is 6-9%
- If it is more than 4cm → risk of malignancy is 31-34%
- we use CT scans without contrast (unenchanced)
- we look at hounsfield units
- <10 conclusively exclude malignancy
<10 for phaeochromocytoma also
adrenal tumors
How do we exculse hormone excess
what tests would you do
Exclude cortisol excess
- Serum cortisol at 8-9 a.m. after 1mg dexamethasone at 11 pm =
- 1mg-overnight dexamethasone suppression test (1mg-DST)
- normal cortisol would be below 50
Exclude aldosterone excess (primary aldosteronism)
- BP increase or K decreased: Paired Plasma Renin and Plasma Aldosterone
Exclude adrenal androgen excess
- Serum DHEAS, androstenedione, 17OHP (in tumours >4cm)
Exclude Phaeochromocytoma
- Plasma metanephrines
What is MACS
abnormal cortsol secretion typically from an adrenal tumor
how do we differneiate whether someone has MACS or cushings
based on clinical symptoms
Phaeochromocytoma
How do people with Phaeochromocytoma present
hypertension + hyperadrenergic spells (headaches, palpitations, profuse sweating)
but 2/3 Phaeochromocytomas present as incidentalomas
Phaeochromocytoma
How do we test for Phaeochromocytoma
Sensitive test
- Plasma metanephrines
Slightly less sensitive test, but slightly more specific:
- 24-h urinary metanephrines
Phaeochromocytoma
If in surgery you were to remove a Phaeochromocytoma what would happen
- blood pressure may spike
- when adrenal mass was removed blood pressure went pack to normal
How do we treat Phaeochromocytoma
Treatment
α-blockade
- stops too many catcehlomises being made
- blocks alpha 1 receptors
- phenoxybenzamine,
- doxazosin
What do we need to do during surgery of Phaeochromocytoma
- Surgery needs special anaesthesia requirements
- remember your removing a source of catecholamines which were keeping blood pressures regulated
- Ensure fluid resuscitation before, during and after surgery
Basically theres bits about genes
RET protooncogene
Multiple Endocrine Neoplasia (MEN) type 2
1) Phaeochromocytoma
2) Medullary thyroid carcinoma
3) parathyroid hyperplasia/tumour (MEN2A) or mucocutaneous neuroma (MEN2B)
Phaeochromocytoma are ssociated with germline conditions
more genes
check hamzas notes on what they all mean
What is the difference between an adrenal adednomw and cortcial carcinoma
Carcinoma
Large and has haemorrhage
Adenoma
Has darker
What do we need to rule out before
Primary aldosterone plasma renin
Adrenal and DHEA, 17 oh progesterone
