Adrenal Gland (hypo) Flashcards
What is the steroid precursor ?
Cholesterol
Examples of corticosteroids
Mineralocorticoids (Aldosterone)
Glucocorticoids (Cortisol)
Sex steroids (Androgens, oestrogens)
Which part of the adrenal cortex secretes aldosterone?
Zona glomerulosa
Which part of the adrenal cortex secretes cortisol?
Zona fasiculata
Which part of the adrenal cortex secretes androgens and oestrogens?
Zona fasiculata and reticularis
What is the overall effect of aldosterone?
Reduces potassium (Potassium excretion)
Regulates sodium (sodium reabsorption)
Maintains blood pressure
Effects of angiotensin II on the adrenals
3-hydroxysteroid dehydrogenase
21-hydroxylase
11-hydroxylase
18-hydroxylase
Effects of ACTH on the adrenals
Side Chain Cleavage
3 Hydroxysteroid dehydrogenase
21 hydroxylase
11 hydroxylase
17 hydroxylase
Steroid biosynthetic pathway
What type of rhythm is exhibited by cortisol secretion?
Diurnal rhythm
What is Addison’s
Primary adrenocortical failure
What is the main cause of Addison’s disease in the UK?
(Autoimmune induced destruction of the adrenal cortex)
Atrophy of the adrenal glands.
What is the main cause of Addison’s disease worldwide?
Tuberculosis
What are the clinical features of Addison’s disease?
Why do we see hyperpigmentation in patients with Addison’s disaese?
alpha-MSH (Melanocortin-stimulating hormone)
Which congenital condition is associated with adrenocortical failure?
Congenital adrenal hyperplasia
What are the consequences of adrenocortical failure?
1) Fall in blood pressure (hypotension)
2) Loss of salt in the urine (hyponatremia)
3) Increased plasma potassium (hyperkalaemia)
4) Fall in glucose due to glucocorticoid deficiency (Hypoglycaemia)
5) High ACTH resulting in increased pigmentation
Which adrenal hormones are predominantly insufficient in primary adrenocortical failure?
Aldosterone and cortisol
Where is pro-opio melanocortin synthesised?
Synthesised within the pituitary gland.
What clinical investigations are conducted for a patient suspected with Addison’s?
9am cortisol = low
ACTH = High
Short synACTHen test to measure the cortisol response (low response)
What is a synACThen test?
ACTH is administered to patients through intramuscular injections (250ug), and the cortisol response is measured (should stay low)
What pharmacological treatment is available for primary adrenocortical failure?
Fludrocortisone 50-100mg daily
Hydrocortisone thrice daily (10, 5, 2.5mg)
Prednisolone once daily (3mg)
What pharmacodynamic effect does fluorine have in fludrocortisone?
what receptors does fludrocortisone act on?
Fluorine does not exist in natural steroids, so its presence slows metabolism substantially.
Has a longer half life (3.5h and effects seen for 18h)
Binds to both mineralocorticoid and glucocorticoid receptors.
Why does oral hydrocortisone require more than once daly administration?
Short half-life
What are the pharmacological advantages of prednisolone (1-2 dehydro-hydrocortisone) compared to cortisol?
Longer half life
More potent that cortisol
Higher binding affinity
What three doses are available for prednisolone?
Is it enteric coated?
1mg
2.5mg
5mg
NOT enteric coated which slows absorption
What is the recommended dose for prednisolone replacement therapy? What hydrocortisone dose is this equivalent to?
2mg-4mg once daily
This would be an equivalent dose of 15-25mg hydrocortisone daily
What is the most common enzyme deficiency in congenital adrenal hyperplasia?
21-hydroxylase deficiency
Which adrenal hormones are deficient in a congenital adrenal hyperplasia complete 21-hydroxylase deficiency?
Aldosterone and cortisol
Which hormones are increased in congenital adrenal hyperplasia with complete 21-hydroxylase deficiency?
Sex steroids (androgens such as testosterone, oestrogen)
How long can a patient survive with diagnosed complete 21-hydroxylase deficiency?
Less than 24 hours
What is the age of presentation of complete 21-hydroxylase deficiency?
How does foetus get steroids in utero?
Physical features of this deficiency?
As a neonate with a salt losing Addisonian crisis
Before before (while in utero) foetus gets steroids across placenta.
Girls will be born with ambiguous genitalia due to excess testosterone production.
Which hormone are deficient in a partial 21-hydroxylase deficiency?
cortisol and aldosterone
Which hormones are in excess in a partial 21-hydroxylase deficiency?
Testosterone
What is the main difference between a partial 21-hydroxylase deficiency and complete deficiency?
Aldosterone and cortisol is still produced in smaller quantities
Partial can present at any age
What are the main associated symptoms of partial 21-hydroxylase deficiency that present later in life in girls and in boys?
Main problem in later life is hirsutism and virilisation in girls and precocious puberty in boys due to adrenal testosterone
Which aldosterone precursor behaves analogous to aldosterone?
11 deoxycorticosterone
In excess, what effects can be caused by 11 deoxycorticosterone?
hypertension and hypokalaemia
Which hormones are in excess in a 11-hydroxylase deficiency and what problems does this cause?
Sex steroids
Testosterone
11-deoxycorticosterone
Virilisation, hypertension and low K
Which hormones are deficient in a 17-hydroxylase deficiency?
Sex steroids, Cortisol
Which hormones are in excess in a 17-hydroxylase deficiency?
Aldosterone
11-deoxycorticosterone
What are the associated problems with a 17-hydroxylase deficiency?
Hypertension
Hypokaleia
Sex steroid deficiency
glucocorticoid deficiency (hypoglycaemia)
