Adrenal Flashcards
What type of molecules are mineralocorticoids, glucocorticoids and androgens?
Steroids.
What is the precursor for steroids?
Cholesterol.
How is adrenal steroidogenesis analogous to the story of Adam and Eve?
Female sex hormones are made from adrenal hormones, which are male sex hormones.
What is congenital adrenal hyperplasia (CAH)?
A group of autosomal recessive disorders characterized by a deficiency of mineralocorticoids and glucocorticoids.
Which molecule is most commonly deficient in congenital adrenal hyperplasia?
21-hydroxylase.
Which gene produces 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.
List 3 consequences of congenital adrenal hyperplasia (other than changes in hormone levels).
1 - The adrenal glands become hyperplastic.
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 molecules build up as a result of 21-hydroxylase deficiency?
What is the function of these molecules?
What happens to these molecules?
- Progesterone and 17-hydroxyprogesterone.
- These are precursors to mineralocorticoids and glucocorticoids respectively
- Progesterone is converted into 17-hydroxyprogesterone, which is then converted into androstenedione, a sex hormone precursor.
Which molecule, when in excess, is used as an indicator of 21-hydroxylase deficiency?
17-hydroxyprogesterone.
What is the prader scale?
- A rating system of 0-5 for the measurement of the degree of virilisation of the genitalia.
- More female characteristics lean towards 0, whereas more male characteristics lean towards 5.
What anatomical abnormality occurs at Prader stage 5?
The vagina and urethra form a common duct.
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.
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.
What causes these symptoms?
1 - Anovulation.
2 - Oligomenorrhea.
- This is due to exaggerated production of LH and FSH due to decreased negative feedback.
Define oligomenorrhoea.
Infrequent menstruation.
Define chronic anovulation.
- Infrequent bleeding intervals of >35d.
or
- Frequent bleeding intervals of <21d.
List 5 clinical signs of androgen excess.
1 - Hirsutism.
2 - Acne.
3 - Androgenic alopecia.
4 - Virilisation in women.
5 - Hypertension.
Which molecule, when in excess, is used as an indicator of androgen excess?
Testosterone.
What is polycystic ovarian syndrome (PCOS) according to the Rotterdam consensus criteria for diagnosis?
- A syndrome characterised by 2 out of the following 3 criteria:
1 - The presence of 26 or more ovarian follicles of 2-9mm in diameter and / or an increased ovarian volume.
2 - Androgen excess.
3 - Oligo- and/or anovulation.
What is the incidence of PCOS in women?
How does this compare to congenital adrenal hyperplasia in all births?
- PCOS has an incidence of 10% in women.
- Congenital adrenal hyperplasia has an incidence of 1/15,000 of all births.
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.
List 3 causes of androgen excess other than PCOS and congenital adrenal hyperplasia.
1 - Tumours.
2 - Cushing’s disease.
3 - Ovarian hyperthecosis.
What is ovarian hyperthecosis?
A benign hyperplasia of the theca cells of the ovaries.
Define adrenal incidentaloma.
An adrenal mass that has been incidentally discovered by imaging.
What is the incidence of adrenal tumours?
3-5% in the general population.
List 2 investigations that must be done when an adrenal incidentaloma is discovered.
1 - Whether the adrenal incidentaloma is related to excess adrenal hormone production.
2 - Whether the adrenal incidentaloma is malignant.
Give an example of a problem with adrenal imaging.
Adrenal imaging is sensitive but not very specific, so multiple imaging modalities are often needed, which is costly and causes worry.
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 (PCOS or CAH).
4 - Exclude phaeochromocytoma.
How is primary aldosteronism diagnosed?
By pairing plasma renin and plasma aldosterone.
How is Cushing’s syndrome diagnosed?
1 - Dexamethasone, a synthetic long-lasting glucocorticoid, is administered overnight.
2 - It occupies the glucocorticoid receptors in the hypothalamus and pituitary for much longer than the normal physiological glucocorticoids.
3 - The next morning, a blood sample is taken and endogenous glucocorticoid production is measured.
4 - Patients with Cushing’s syndrome will not have suppressed glucocorticoid production.
What is a phaeochromocytoma?
A tumour arising from the chromaffin tissue of the adrenal medulla that causes excess production of catecholamines.
List the 3 catecholamines.
1 - Adrenaline.
2 - Noradrenaline.
3 - Dopamine.
List the breakdown products of adrenaline and noradrenaline.
When are adrenaline and noradrenaline normally broken down?
1 - Metanephrine.
2 - Normetanephrine.
- Adrenaline and noradrenaline are constantly being broken down as part of normal biological processes.
Which substance is measured when diagnosing a phaeochromocytoma?
Why?
- Metanephrines.
- Metanephrines stay in the blood for longer than normetanephrines so are more suitable as a diagnostic test.
List 2 characteristics of adenomas that are used to differentiate them from carcinomas in imaging.
1 - Adenomas are more homogenous than carcinomas.
2 - Adenomas have a higher fat content than carcinomas due to the presence of cholesterol.
How is fat content measured in CT scans?
By measuring the tissue density (units of Hounsfields).
What tissue density of an adrenal tumour is indicative of an adenoma (as opposed to a carcinoma)?
Why?
- 10 Hounsfields or less.
- Such a low density is indicative of a high fat content, which is characteristic of adrenal adenomas.
List 3 treatments for adrenal tumours:
1 - Surgical removal of the tumour.
If the tumour is not amenable to surgery:
2 - Mitotane with chemotherapy.
What is mitotane?
An adrenal cytotoxic agent (the mechanism is unknown).
When is an adrenal biopsy recommended?
When there is a history of extra-adrenal malignancy and all of the following additional criteria are fulfilled:
1 - The lesion is hormonally inactive (phaeochromocytoma has been excluded).
2 - The lesion has not been conclusively characterised as benign by imaging.
3 - Management would be altered by the knowledge of this histology.
What is the name of tumours of sympathetic ganglia outside of the adrenal medulla?
Paragangliomas.
What is multiple endocrine neoplasia (MEN)?
A combination of:
1 - Phaeochromocytoma.
2 - Medullary thyroid carcinoma.
3 - Parathyroid hyperplasia (characteristic of MEN2A).
4 - Mucocutaneous neuroma (MEN2B).
What causes multiple endocrine neoplasia?
Mutation of the RET protooncogene.
Define protooncogene.
A normal gene which, when mutated, becomes an oncogene.
What is Von Hippel Lindau syndrome?
A combination of:
1 - Haemanigoblastoma.
2 - Phaeochromocytoma.
3 - Renal angioma.
4 - Renal cancer.
List the organs that are affected by haemangioblastomas.
1 - Cerebellum.
2 - Retina.
3 - Spinal cord.
What are angiomas?
Benign tumours derived from endothelial cells.
What causes Von Hippel Lindau syndrome?
Mutations to the VHL gene.
What is neurofibromatosis?
A group of genetic conditions which cause tumours to develop in nervous tissue.
List 2 characteristics of neurofibromatosis.
1 - Neurofibromas.
2 - Café au lait patches.
What is succinyl dehydrogenase?
What is significant about mutations to the B subunit of succinyl dehydrogenase?
- An enzyme involved in the Krebs cycle.
- Mutations to the B subunit of succinyl dehydrogenase usually result in malignant phaeochromocytomas.
List 4 common complications of phaeochromocytomas.
1 - Hypertension.
2 - Postural hypotension (due to low plasma volume).
3 - Tachycardia.
4 - Myocardial infarction.
List 4 treatments of phaeochromocytomas.
Alpha blockade:
1 - Phenoxybenzamine.
2 - Doxazosin.
Beta blockade:
3 - Propranolol.
Other:
4 - Surgery, but only if alpha blockers have been given first.
5 - Chemotherapy.
Why is alpha blockade necessary before surgery to remove a phaeochromocytoma?
If pressure is applied to a phaeochromocytoma without prior alpha blockade, a large amount of catecholamines are released.
