Endocrinology 7 - Hypoadrenal Disorders Flashcards
List the causes of adrenocortical failure
- Adrenal glands destroyed (tuberculosis Addisons or autoimmune Addisons)
- Enzymes in the steroid synthetic pathway not working - congenital adrenal hyperplasia
List the symptoms of hypoadrenalism
- Mucous membrane pigmentation
- Skin pigmentation darkening (tan, creases of palms, scars) and vitiligo
- Hair darkening
- Muscular weakness
- Loss of weight and nausea
- Feeling fatigue
- Postural hypotension
List the consequences of adrenocortical failure
- Fall in blood pressure
- Loss of salt in the urine
- Increased plasma potassium
- Fall in glucose (glutocorticoid deficiency)
- High ACTH resulting in increased pigmentation (as POMC makes both ACTH and MSH)
- Eventual death due to hypotension
How is addisons diseases tested for?
- 9am cortisol will be low, ACTH will be high
- Synacthen test - measure cortisol response following injection of synthetic ACTH
- Low sodium and high potassium
- Antibodies
- Measure urea
What is the commonest cause or congenital adrenal hyperplasia?
- 21-hydroxylase deficiency
- Can be complete or partial
Which hormones are absent in both complete and partial 21-hydroxylase deficiency? Why are they absent?
- Aldosterone and cortisol
- 21-hydroxylase converts progesterone to 11-deoxycosticosterone (interferes with aldosterone) and 17- OH prog to 11-deoxycortisol (interferes with cortisol)
How long can you survive with complete 21 hydroxylase deficiency?
Less than a few weeks
Which hormones are in excess in both complete and partial 21-hydroxylase deficiency?
- Sex steroids (particularly testosterone)
- This is because the sex steroid is the only pathway that can be undertaken (in complete this is more drastic than in partial)
How does 21-hydroxylase deficiency usually present?
- As a neonate with a salt losing addisonian crisis, as before birth the foetus gets steroids across the placenta
- Girls may have ambiguus genitalia
What is are the main reasons people with partial 21 hydroxylase deficiency present?
- Hirsutism and virilisation (too many androgens in utero, so therefore born with ambiguous genitalia) in girls
- Precocius puberty in boys
List the symptoms of partial 21-hydroxylase deficiency.
- Acne
- Recieding hair-line and baldness
- Facial hirsutism
- Androgenic flush
- Variable pigmentation
- Small breasts
- Heavy arms and legs
- Clitoral enlargement
What does excess 11 deoxycorticosterone cause?
Hypertension and hypokalaemia
Which hormones are deficient in 11-hydroxylase deficiency?
Cortisol and aldosterone, as these pathways are blocked (11-doxycorticosterone to corticosterone and 11-deoxycortisol to cortisol blocked)
Which hormones are in excess in 11-hydroxylase deficiency?
Sex steroids and testosterone, as well as 11-deoxycorticosterone
What are the problems with 11-hydroxylase deficiency?
Virilisation, hypertension (due to 11-deoxycorticosterone acting like aldosterone), low potassium
List the three pathways that happen in the adrenal cortex.
- Cortisol first to pregnenolone
- Mineralocorticoids (aldoserone)
- Glucocorticoids (cortisol)
- Sex steroids (testosterone)
- Similar structures - due to dehydrogenase
List the enzymes where things can go wrong in the adrenal cortex
- 21-hydroxylase
- 11-hydroxylase
- 18-hydroxylase
- 17-hydroxylase
How do adrenal glands look in autoimmune distruction?
They are atrophied, very small and not very useful
Which hormones are deficient in 17-hydroxylase deficiency?
- Cortisol and sex steroids
- Progesterone to 17-OH progesterone is blocked
Which hormones are in excess in 17-hydroxylase deficiency?
11-deoxycorticosterone and aldosterone
List the problems seen in patients with 17-hydroxylase deficiency
- Hypertension
- Low potassium
- Sex steroid deficiency
- Glucocorticoid deficiency
Describe the synthesis of adrenocortical steroids
- Cholesterol to progesterone
- Progesterone to 11-deoxycorticosterone (via 21-hydroxylase), to corticostrone via 11-hydroxylase to aldosterone via 18-hydroxylase
- Progesterone to 17 OH progesterone via 17 hydroxylase, to 11-deoxycortisol via 21 hydroxylase, to cortisol via 11 hydroxylase
- 17-OH progesterone to sex steroids
Define the term addisonian crisis
- A potentially fatal condition where the adrenal glands stop working and there is not enough cortisol
List the signs of addisonian crisis
- Extreme tiredness and weakness
- Confusion/psychosis
- Nausea, vomiting
- Fever
- Extremely low blood pressure
- Loss of consciousness
- Fast heart rate
