L02: Adrenal Gland Flashcards
What are the 3 layers of the adrenal cortex
Zona glomerulosa
Zona fasiculata
Zona reticularis
What hormone does the zona glomerulosa produce
Aldosterone
What hormone does the zona fasciulata produce
Cortisol
What hormone does the zona reticularis produce
DHEA
What is the inner layer of the adrenal gland called
Adrenal medulla
What does the adrenal medulla produce
Catecholamine: noradrenaline and adrenaline
What role does aldosterone have
Salt
What role does cortisol have
Sugar
What role does DHEA have
Sex
What does CAH stand for
Congenital adrenal hyperplasia
What is the major cause of CAH
21 Hydroxylase defiency
What stimulates the adrenal gland to produce cortisol
Hypothalamus pituitary axis
What does the pituitary gland release to the adrenal gland
ACTH
When there is 21 hydoxylase enzyme deficiency what happens to cortisol production
Decreases
When there is low cortisol what happen to cortisol feedback back to the hypothalamus
Reduced
If there is low cortisol feedback back to the hypothalamus what does the hypothalamus and pituitary do
Increase the release of ACTH to try and stimulate the release of cortisol
Instead of producing cortisol due to ACTH binding what does the adrenal glands produce instead
DHEA sex steroid (androgen)
Why is DHEA produced
It is not affected by the 21 hydroxylase enzyme deficiency
What does excess DHEA cause in new born baby girls
Virilization
Hyper plastic adrenals
What is the cause of of 21 hyrodoxylase enzyme
Mutation
Which from of 21 hydroxylase enzyme is likely to be mutated
CYP21A2
Which 2 categories of hormone is affected by 21 hydoxylase enzyme
Glucocorticoids: cortisol
Mineralocorticoid: aldosterone
How do we diagnose CAH
Look at level of the steroid 17OHP
What is 17OHP
The steroid produced prior to the block of 21 hydroxylase enzyme
What is virilization of the external female genitalia called due to excess androgen
46, XX, Disorder sex development (DSD)
How to we stage/classify virilization
Using the prader stage
How many stages are there in the prader stage
5
What happens to androgen and virilization as you increase the prader stage from 1 to 5
Androgens and virilization increases
What are the 3 forms of CAH
Classic CAH ‘salt wasting’
Classic CAH ‘simple virlising’
Non-classic CAH
Which hormones are deficiency in classic CAH ‘salt wasting’. Hint is in the name
Glucocorticoid deficiency: cortisol
Mineralocorticoid deficiency: aldosterone
What hormone is deficient in classic CAH ‘simple virilizing’
Glucocorticoid: cortisol
What hormone is deficient in non-classical CAH
Glucocorticoid: cortisol
What other condition does non-classical CAH resemble
PCOS
Which form of CAH is the most severe type
Classic CAH ‘salt wasting’
Which from of CAH is the mildest one
Non-classical CAH
What does the severity of CAH depend on
The mutation of the 21 hydroxylase enzyme
What is the treatment for CAH
1) Replacement of glucocorticoid and mineralocorticoid
2) suppression of ACTH to suppress androgen excess
Why is it important to give the correct amount of glucocorticoid
- Too much glucocorticoid: suppresses LH and FSH = oligo/amennorhea
- Too little glucocorticoid= androgen and progesterone excess because you get more release of ACTH and FSH/LH from the anterior pituitary gland = an ovulation, oligomenorrhea, failure to implant
What is testicular adrenal rest tissue (TART) occur, describe the process
1) during development adrenal and gonads are close together in the urogenital ridge
2) when they separate the both take adrenal and gonadal features
3) so with ACTH stimulate the testicles expand and compress the normal sperm production
4) this impairs infertility if left untreated
What are the signs and symptoms of classical CAH
Weight loss
Vomiting
Poor feeding
Failure to thrive
What are the signs and symptoms in non-classical CAH
Oligomenorhhea
Hirtusim
Male pattern baldness
Subfertility
To confirm classical CAH what investigation is required
Karyotyping and sequencing analysis of CYP21A2 locus
Serum 17OHP
Renal function and blood glucose
What are the investigation required for non-classical CAH
Early morning serum 17OHP
If in the investigation of non-classical CAH the serum levels of 17OHP is increased or borderline what test is required
ACTH stimulation test with measurement of 17OHP and cortisol
Androgens
Sequencing and analysis of CYP21A2
In classical CAH salt wasting what do we give to replace the minerolocortiocid and glucocorticoid deficiency
Mineralocoticoid: flufocortisone
Glucocorticoid: hydrocortisone
In classic CAH simple virilizing how do we replace the glucocorticoid deficiency
Hydrocortisone
How do we manage oligomenorhea and hirtusim in non classic CAH
Glucocorticoid therapy
Contraceptive pills
What does PCOS stand for
Polycystic ovary syndrome
What are the 3 Rotterdam diagnostic criteria for PCOS
1) Polycystic ovary appearance on ultrasound
2) androgen excess: hair growth, acne, male pattern baldness
3) an ovulation: irregular or absence menstrual cycle
To diagnose PCOS how many criteria’s should be met out of the 3
2 out of 3
What other key features does PCOS present with
Insulin resistance
Is there a treatment available for PCOS
NO
How is PCOS managed
- lifestyle interventions: diet, exercise, smoking, mental wellbeing
How do we diagnose adroitness excess using a biochemical test
Look for:
Increased free testosterone
Increase free androgen index
What are the pharmacological treatments available for PCOS
Combined oral contraceptive pills Metformin Anti-androgens IVF Ovulation induction: clomiphene or letrozole
What needs to excluded prior to PCOS
CAH Adrenal cancer Adrenal adenoma Cushing syndrome Ovarian hyperthescosis Ovarian tumours
What are the 2 questions to discover if there is an adrenal tumour
1) if there is hormone excess
2) if there is malignancy
Which tumours present with hormonal excess
Primary aldosteronism
Cushing’s syndrome
Adrenal androgen excess
Phaechromcytoma
What a benign nodules on the adrenal glands that produce cortisol excess called
Mild autonomous cortisol excess (MACE)
How is MACE different to Cushing’s
Patients do no present with typical signs
How do we diagnose MACE
1mg dexamethasone supression test
If the cortisol level are between 51-138 mmol/L what is the MACE
MACE-1
If the cortisol is greater than 138nmol/L what is the MACE
MACE-2
What are the cardio-metabolic risks in MACE
Hypertension
Type 2 diabetes
Dyslipidaemia
How do we diagnose phaechromocytoma
Measure metanephrines (metabolites of catecholamines)
Which conditions present with a malignant tumour
Adrenal carcinoma
What are adrenal carcinomas
High malignant tumours
How do we differentiate between adrenocortical adenoma (benign) and adrenocortical carcinoma (malignant)
Imaging
Tumour radiodensity via HU
Tumour diameter
What does imaging show for an adenoma and carcinoma
Adenoma : fatty
Carcinoma: necrosis
What does the tumour radiodensity (HU) show for an adenoma and carcinoma
Higher the density i,e above 10 the more likely it is going to be carcinoma
What does the tumour diameter show for an adenoma and carcinoma
Adenoma: smalller
Carcinoma: larger
What is adrenal incidentaloma
A finding of a adrenal gland mass upon imaging by accident
At what mass is urgent assessment needed due to high chance of malignant cancer
Mass is greater than 4cm
If the tumour is greater than 4 and has an tumour atentuation greater than 20 what should be carried out
Urine steroid metabolomics
What is the treatment for phaechromocytoma
Alpha blockade
Beta blockade
Surgery
If there is an adrenal tumour with hormone excess what should we exclude
Primary aldosteronism
Cushing syndrome, MACE
Phaechromocytoma
How would we exclude Cushing syndrome
Perform a dexamethosine 1mg test
How do we exclude primary hyperaldosteronism
Measure blood pressure - should be high
Aldosterone/renin ratio- should be high
How do we exclude phaechromocytoma
Measure plasma metanephrines