Adrenal gland Flashcards
What is the embryonic link between gonads and adrenal gland?
Originate within close proximity before travelling to final location
In which part of the adrenal gland does the production of androgens occur?
Within the zona reticularis of the cortex
What is Congenital Adrenal Hyperplasisa (CAH)?
An autosomal recessive condition causing a partial or complete block in steroidgenesis of the adrenal cortex affecting cortisol production.
What is the most common cause of CAH?
21-hydroxylase deficiency due to a defect in CYP21. Results in cortisol deficiency and androgen excess, with or without aldosterone deficiency.
How does 21-hydroxylase deficiency result in the characteristics of CAH?
As cortisol (and aldosterone) pathways are blocked, ACTH stimulates excess production of DHEA and results in ambiguous genitalia = 46 xx, DSD
How is CAH diagnosed?
Measuring serum 17OHP (hydroxyprogesterone) levels.
HIGH = 21 OH deficiency as levels build up from the lack of progression into glucocorticoids.
Why do boys present later with CAH?
Present with normal genitalia, unless the have an aldosterone deficiency in which case they will present with adrenal crisis
What staging system is used to characterise the severity of CAH in females?
Prader staging
What will result from a lack of aldosterone?
Adrenal crisis due to a loss of salt
Why does adrenal crisis not present straight away?
Infant is protected for 10-14 day by the mother’s steroids.
What are the three types of severities that can result from 21 OH deficiency?
Severe salt wasting CAH - Low cortisol and aldosterone = dehydration and low BP. Presents within first 2 weeks of life
Moderate simple virilizing CAH - Low cortisol = mascularisation
Mild non-classical CAH = No change in cortisol or aldosterone
What are the two other deficiencies that can result in CAH?
17 OH
11 beta OH
Who are raised as female pseudohermaphrodite?
CAH females who are raised as males due to their high levels of androgens that were not treated in time. = 46 xx males
If CAH is not detected at birth what else may lead to diagnosis at a late stage?
Inhibition of growth as excess androgens causes epiphyseal plates to fuse early.
What treatment is used in CAH?
Glucocorticoids are given to downregulate ACTH to increase cortisol levels and decrease androgen levels.
What happens if too much glucocorticoids are given?
Obesity, osteoporosis, LH and FSH suppression = amenorrhea
What happens if too little glucocorticoids are given?
Adrenal crisis and androgen excess = anovulation and oligomenorrhea
What is an adrenal incidentaloma?
An adrenal benign or malignant tumour detected on a CT scan that is being carried out for other reasons. Detects 3-5% of cases.
What does a tumour of the adrenal gland result in?
Excess production of hormones from the medulla or cortex. Usually detected at late stage
How can you determine between hormone excess and a malignancy?
Imaging has poor sensitivity and specificity.
Exclude Cushing’s - Dexamethasone 1mg suppression test or 24hr urinary free cortisol.
Exclude phaeochromocytoma - measure plasma metanephrines (catecholamine metabolites)
Exclude primary hyperaldosteronism in pts presenting with high BP and low K - measure renin and aldosterone (diagnostic pair)
Measure DHEA as excess = malignancy
Exclude CAH with 17 OHP levels
Why would the removal of the adrenal gland in a Cushing’s patient be fatal?
The excess cortisol production will have inhibited the HPA and wouldn’t restart to return levels to normal, resulting in death.
Why are metanephrines measured instead of catecholamines?
Catecholamines have a shorter half life
How can imaging be used to determine between benign and malignant tumours?
Carcinomas are irregular and present with bleeding. More likely to be malignant in younger pts.
Cannot determine if ACC or Phaeo
A non-uniform,irregular, >4cm mass with a high density = risk of malignancy and requires surgery
Why are benign tumours less dense?
Contain more fat and water
What is a phaeochromocytoma?
Tumours of chromaffin cells in the adrenal medulla, causing excess secretion of Ad and NAd.
What is a paraganglioma?
A tumour in the sympathetic ganglia outside of the adrenal gland.
Is there a genetic link to phaeochromomcytomas?
40% have a genetic cause.
What is the most common mutation in Phaeo?
Most common is RET oncogene mutation resulting in multiple endocrine neoplasia (Adrenal, thyroid, parathyroid)
Requires whole family testing
Name 4 other mutations that result in phaeo.
VHL
NF-1
SDHC/D
SDHB
How do pts with Phaeo present?
Hypertension, headaches, sweating, palpitations, pallor, nausea, postural hypotension, supraventricular tachycardia, fever, weight loss, HF, MI
How can Phaeo be diagnosed?
24hr urinary metanephrines and plasma metanephrines
What must be done before surgery to remove Phaeo and why?
Must administer:
alpha blockade - e.g. doxazosin. Prevent vasoconstriction and therefor stroke or MI
beta blockade - e.g. propanolol. Treat tachycardia
If the Ad producing tumour is manipulated it will cause a hypertensive crisis due to the Ad release from the tumour and the Ad given in surgery.
Why must a FNA not be carried out for ACC or Phaeo?
ACC causes metastasis from seeding
Phaeo causes adrenal hypertensive crisis from Ad excess.
How should an ACC be treated?
Complete tumour removal through open surgery. Use adjuvant therapy e.g. mitotane. Survival increased if capsule remains intact.
Use cytotoxic chemo and mitotane if advanced
