L02 - The Adrenal Gland Flashcards
What is congenital adrenal hyperplasia (CAH)?
A group of autosomal recessive disorders characterised by a deficiency of mineralocorticoids and glucocorticoids
Which enzyme is most commonly deficient in congenital adrenal hyperplasia?
21-hydroxylase
Which gene codes for 21-hydroxylase?
CYP21A2
Why does congenital adrenal hyperplasia cause high sex steroid hormone levels?
- There is no negative feedback from mineralocorticoids or glucocorticoids as they are no longer produced
- This increases the level of ACTH in the blood
- The adrenals respond by increasing sex steroid hormone production
What are the consequences of congenital adrenal hyperplasia (other than changes in hormone levels)?
1 - Adrenal gland become hyperplasia
2 - Newborn girls with the condition are virilised (a condition known as 46,XX disorder of sex development) as they are producing male sex hormones (androgens).
Which molecule, when in excess, is used as an indicator of 21-hydroxylase deficiency?
17-hydroxyprogesterone (17OHP) - a precursor for cortisol
Why do more males die from congenital adrenal hyperplasia than females?
- Congenital adrenal hyperplasia causes excessively high androgen production
- Since these are male sex hormones, females with the condition are more easy to identify as the female genitalia is virilised, whereas the male genitalia is unchanged
- More males are therefore undiagnosed at birth and die from losing the functions of mineralocorticoids and glucocorticoids (‘salt-wasting’ crisis)
How is congenital adrenal hyperplasia treated?
By replacing lost glucocorticoids and mineralocorticoids
List 3 symptoms of glucocorticoid excess.
1 - Obesity
2 - Osteoporosis
3 - Suppression of LH and FSH due to increased negative feedback, causing amenorrhoea
List 2 symptoms of glucocorticoid insufficiency.
1 - Anovulation
2 - Oligomenorrhea
- Due to androgen excess
List 5 clinical signs of androgen excess.
1 - Hirsutism
2 - Acne
3 - Androgenic alopecia
4 - Virilisation in women
5 - Hypertension
What is polycystic ovarian syndrome (PCOS)?
- A syndrome characterised by at least 2 of the following 3 criteria:
1 - Chronic (or intermittent) anovulation
2 - Androgen excess
3 - Polycystic appearance of ovaries on ultrasound
List 5 conditions that people with PCOS are at higher risk of developing.
1 - Insulin resistance
2 - Hypertension
3 - Type 2 diabetes
4 - Liver disease
5 - Cardiovascular disease
What causes of androgen excess must be ruled out before a diagnosis of PCOS is made?
1 - Congenital adrenal hyperplasia
2 - Ovarian hyperthecosis
3 - Cushing’s syndrome
4 - Adrenocortical carcinoma
5 - Adrenocortical adenoma
Define adrenal incidentaloma.
An unsuspected tumour in the adrenal glands found by chance during a CT/ultrasound for another condition
List 2 investigations that must be done when an adrenal incidentaloma is discovered.
1 - Is the tumour malignant?
2 - Is the tumour functional (hormone excess)?
Give an example of a problem with adrenal imaging.
It cannot differentiate between an adrenocortical carcinoma or a phaeochromocytoma
What is the procedure for attributing a known adrenal tumour as the cause of excess adrenal hormone production?
1 - Exclude primary aldosteronism
2 - Exclude Cushing’s
3 - Exclude adrenal androgen excess
4 - Exclude phaeochromocytoma
How is primary aldosteronism diagnosed?
To exclude primary hyperaldosteronism, blood pressure should be measured (aldosterone increases BP), as well as the aldosterone/renin ratio (the ratio will be increased in hyperaldosteronism).
How is Cushing’s syndrome diagnosed?
- To exclude Cushing’s disease, perform a Dexamethasone 1mg overnight test
- Dexamethasone binds to glucocorticoid receptors in the anterior pituitary gland, suppressing the production of ACTH via negative feedback
- In normal patients, this will suppress levels of cortisol, but in patients with Cushing’s disease, cortisol levels will remain high
How is a phaeochromocytoma diagnosed?
To exclude phaeochromocytoma (tumour within the adrenal medulla), plasma metanephrines (i.e. adrenaline metabolites) are measured
What is a phaeochromocytoma?
Catecholamine over-secreting tumours located in the adrenal medulla
List 2 characteristics of adenomas that are used to differentiate them from carcinomas in imaging.
1 - If the size of the tumour is <4cm, it is unlikely to be malignant & therefore is an adrenocortical adenoma
2 - If there is a low HU (<10) on a non-contrast CT, there is a high likelihood of an adenoma
When is an adrenal biopsy recommended?
Adrenal biopsy is not recommended in diagnostic work up unless there is a history of extra-adrenal malignancy & all of the following criteria are fulfilled:
1 - Lesion hormonally inactive (phaeochromocytoma excluded)
2 - Lesion not conclusively characterised as benign by diagnostic imaging
3 - Management would be altered by knowledge of histology
