Adrenal Gland (hypo) Flashcards
What is the steroid precursor ?
Cholesterol
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 reticularis
What is the overall effect of aldosterone?
Reduces potassium (Potassium excretion) Regulates sodium (sodium reabsorption) Maintains blood pressure
What are the four main enzymes involved in aldosterone synthesis within the adrenal cortex?
3-hydroxysteroid dehydrogenase
21-hydroxylase
11-hydroxylase
18-hydroxylase
What type of rhythm is exhibited by cortisol secretion?
Diurnal rhythm
What is the main cause of Addison’s disease in the UK?
Primary adrenocortical failure
(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?
Increased pigmentation Autoimmune vitilgo Low blood pressure (syncope) Weight loss Fatigue Hyponatremia, hypoglycaemia, Hyperkalaemia
What is the large precursor protein of ACTH?
Pro-opio-melanocortin (POMC)
Which peptide is cleaved from POMC subsequently being responsible for hyperpigmentation within 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 are the peptides that are formed from the cleavage of POMC?
ACTH, MSH, endorphins and enkephalins
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.
At what time is cortisol level usually elevated?
9am
What type of injections are administered during an synACTHen test?
Intramuscular injections
What pharmacological treatment is available for primary adrenocortical failure?
Fludrocortisone 50-100mg daily
Which atom is added to fludrocortisone?
Fluorine
What pharmacodynamic effect does fluorine have in fludrocortisone?
Fluorine does not exist in natural steroids, so its presence slows metabolism substantially. Binds to both mineralocorticoid and glucocorticoid receptors.
Has a longer half life (3.5h and effects seen for 18h)
How long are the effects of fludrocortisone seen for?
18 hours
Which two receptors are interacted with by fludrocortisone?
MR and GR.
What is the half-life for oral hydrocortisone?
Short half-life therefore requires more than once daily administration
How often per day is oral hydrocortisone administede?
Thrice daily
What is the stereochemical difference between prednisolone and cortisol?
There is an additional double bond, subsequently giving a longer half life and potency in comparison to cortisol.
What are the pharmacological advantages of (prednisolone)?
Longer half life
More potent that cortisol
x2.3 binding affinity
Which drug replacement therapy in Addison’s disease closely mimics the circadian rhythm?
Prednisolone
What three doses are available for prednisolone?
1mg
2.5mg
5mg
What is the recommended dose for prednisolone replacement therapy?
2mg-4mg once daily
What are the three treatments available for adrenal failure?
Hydrocortisone
Prednisolone
Fludrocortisone
What is the most common enzyme deficiency in congenital adrenal hyperplasia?
21-hydroxylase deficiency
Which adrenal hormones are affected in a congenital adrenal hyperplasia?
Aldosterone and cortisol
What stage does 21-hydroxylase catalyse in aldosterone synthesis?
Hydroxylation of progesterone to 11-deoxy corticosterone
What stage does 21-hydroxylase catalyse in cortisol?
17-OH progesterone to 11-deoxycortisol
Which hormones are increased in congenital adrenal hyperplasia?
Sex steroids (androgen production)
What are the clinical features for females with congenital adrenal hyperplasia?
Labial fusion ambiguous genitalia ambiguous in physical characteristics weight loss vomiting hypotension hyperpigmentation
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?
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 is concerned with the salt-washing feature of an Addisonian crisis?
Aldosterone
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 (responsive to ACTH).
What are the main associated symptoms of partial 21-hydroxylase deficiency that present later in life in girls?
Hirsutism and virilisation in girls
Male pattern baldness
Facial hair
Clitomegaly
Hyperplastic muscles
What are the main associated symptoms of partial 21-hydroxylase deficiency that present later in life in boys?
Precocious puberty in boys due to adrenal testosterone
Hyperplastic muscles
What stages of aldosterone synthesis is catalysed by 11-hydroxylase?
11-deoxy-corticosterone hydroxylation into corticosterone
What stage of cortisol synthesis is catalysed by 11-hydroxylase?
11-deoxycortisol hydroxylation into cortisol.
Which aldosterone precursor behaves analogous to aldosterone?
11 deoxycorticosterone
In excess, what effects can be caused by 11 deoxycorticosterone?
hypertension and hypokalaemia
Which three hormones are in excess in a 11-hydroxylase deficiency?
Sex steroids
Testosterone
11-deoxycorticosterone
What are the problems associated with a 11-hydroxylase deficiency?
Virilisation
Hypertension
Hypokalaemia (due to elevations in 11-deoxycorticosterone)
What stage is catalysed by 17-hydroxylase?
Progesterone hydroxylation into 17-OH-progesterone.
Which hormones are deficient in a 17-hydroxylase deficiency?
Cortisol
Sex steroids
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)
What is the equivalent dose for an intermediate acting prednisolone?
3mg
What is the relative glucocoritcoid potency for prednisolone?
x7
