**_🧪Endocrinology🧪 - Adrenal Disorders Flashcards
What is a steroid (hormone)?
A hormone synthesised from cholesterol
How can a steroid be identified from its molecular structure?
If it contains the 4 benzene rings in the arrangement as seen in cholesterol
What is made in the adrenal cortex?
Corticosteroids:
Mineralocorticoids (aldosterone)
Glucocorticoids (Cortisol)
Sex steroids (Androgens, oestrogens)
What stimulates the production of angiotensin II?
Decrease in blood pressure
How does a decrease in blood pressure lead to increased levels of angiotensin II (A2)?
Decrease in blood pressure detected by juxtaglomerular cells, which secrete renin
Renin converts angiotensinogen in the liver to angiotensin I
ACE converts angiotensin I to angiotensin II (A2)
A2 promotes 21,11,18 hydroxylases, therefore promoting aldosterone synthesis
Aldosterone promotes sodium retention in the kidneys (by increasing reabsorption), therefore raising blood volume and pressure
What effect does ACTH have on the adrenals?
Promotes 17,21,11 hydroxylases, therefore increasing cortisol production
Compare the effect of A2 to cortisol on the adrenal cortex
ACTH increases activity of 17-hydroxylase, meaning cholesterol goes down the pathway of reactions to cortisol instead
What pattern of secretion does cortisol show?
Diurnal rhythm
What is Addison’s disease?
Primary adrenal failure
Main causes are either immune damage (atrophy) of the adrenals, or tuberculosis
Autoimmune destruction most common in UK
Tuberculosis most common worldwide
What are the biochemical markers for Addison’s?
Low steroid hormones (low cortisol, low aldosterone so low blood pressure)
High ACTH and MSH (no negative feedback from cortisol)
What are the symptoms of Addison’s?
Hyperpigmentation
Low blood pressure
Weakness
Weight loss
Gastrointestinal disturbances
What are the signs and symptoms of an adrenal crisis?
Fever
Syncope
Convulsions
Hypoglycaemia
Hyponatraemia
Sever vomiting/diarrhoea
What causes the increased pigmentation in Addison’s?
Increased MSH production
Why does MSH production increase in Addison’s?
Low cortisol means increased ACTH production
ACTH comes from precursor protein pro-opiomelanocortin (POMC)
POMC broken down to make ACTH, this process also creates MSH
MSH stimulates melanin production in melanocytes, causing hyperpigmentation
What are the causes of adrenocortical failure?
Destruction of adrenal glands (autoimmune/TB)
Dysfunction of enzymes in steroid synthesis pathway
Dysfunction of enzymes leads to congenital adrenal hyperplasia (CAH)
What are the consequences of adrenocortical failure?
Fall in blood pressure (postural hypotension)
Loss of salt in the urine (low sodium in plasma = hyponatraemia)
Increased plasma potassium (less potassium excreted in urine = hyperkalaemia)
Low glucose due to glucocorticoid deficiency
High ACTH causing increased pigmentation
Eventual death due to severe hypotension
What would prompt a test for Addison’s?
Clinical suspicion due to fatigue, classic biochemistry (low Na, high K)
What is the initial test for suspected Addison’s?
9am Cortisol
ACTH
What results after a 9am cortisol test would you expect to see in a patient suffering from Addison’s?
9am cortisol = low
ACTH = high
What test is carried out to confirm the diagnosis of Addison’s?
Short synACTHen test
Give 250μg of synACTHen intramuscularly
Measure cortisol response
What response would a typical Addison’s patient have to the short synACTHen test?
No/very little response to the synACTHen
E.G.:
9am cortisol = 100 (nm: 270-900)
9:30am cortisol = 150 (nm: >600)
Very little response, whereas a healthy person’s cortisol would rise to 600 or higher
What is the treatment for primary adrenocortical failure?
Patient needs replacement of cortisol and aldosterone
How is aldosterone replaced?
Fludrocortisone is given
Aldosterone has too short a half life for once daily injections
Fludrocortisone has an extra fluorine atom, this makes it non-biodegradable therefore dramatically increasing its half life
How is cortisol replaced?
Hydrocortisone (same molecule as cortisol) 3x daily
Prednisolone 1x daily
Why is prednisolone preferred to cortisol?
Longer half life, so can be given once daily
This means the multiple peaks and troughs of 3x daily doses can be avoided, instead giving a single smooth curve
2-3x higher affinity than hydrocortisone/cortisol, so smaller does can be given
What is congenital adrenal hyperplasia?
Deficiency of an enzyme(s) in the steroid synthesis pathway of the adrenal cortex
Most common is 21-hydroxylase deficiency
Can be complete or partial