Hypoadrenal disorders Flashcards
How are adrenocortical steroids synthesised?
Cholesterol —-(lots of steps)—> progesterone
Progesterone –> 11-deoxycorticosterone (21-hydroxylase)
11-deoxycoritcosterone –> corticosterone (11-B hydroxylase)
Corticosterone –> aldosterone (18 hydroxylase)
Progesterone –> 17-OH progesterone (17 hydroxylase)
17-OH prog –> sex steroids
17-OH prog –> 11-deoxycortisol (21)
11-deoxycortisol –> cortisol (11)
What are the clinical features of Addison’s disease?
Symptoms develop gradually + are non-specific:
- Fatigue
- Lightheadedness upon standing or difficulty standing
- Muscle weakness, joint and muscle pains
- Fever, sweating, headache
- Weight loss
- Anxiety
- Nausea, vomiting, diarrhoea
- Changes in mood or personality
- Cravings for salt or salty foods due to loss of sodium through urine
- Mouth pigmentation, darker hair, more pigmented skin (MSH and ACTH both from POMC)
- Patches of vitiligo
Signs:
- Very low BP w or w/o orthostatic hypotension
- Hyperpigmentation of skin not exposed to sun
- Low 9am cortisol, high ACTH
- Negative synacthen test
Define Addisonian crisis
A constellation of symptoms that indicates severe adrenal insufficiency as a result of either previously undiagnosed Addison’s disease, a disease process suddenly affecting adrenal function (e.g. adrenal haemorrhage), or an intercurrent problem (e.g., infection, trauma) in someone known to have Addison’s disease
- Medical emergency
- Potentially life-threatening situation
What are the features of an Addisonian crisis?
- Sudden penetrating pain in legs, lower back, or abdomen
- Severe vomiting and diarrhoea, resulting in dehydration
- Hypotension (no aldosterone)
- Syncope
- Confusion, psychosis, slurred speech
- Severe lethargy
- Hypoglycaemia (glucocorticoid deficiency)
- Hyponatremia, hyperkalemia, hypercalcemia
- Convulsions
- Fever
What are the clinical features and hormonal consequences of complete 21-hydroxylase deficiency?
- No aldosterone
- No cortisol
- Overflow of 17-hydroxyprogesterone tf lots of sex steroids (high testosterone)
- Genital abnormality in girls - labial fusion, clitoral hypermegaly
- Virilisation
- Hypotension
- Baby loses consciousness after 1 day due to salt-losing Addisonian crisis
What are the clinical features and hormonal consequences of partial 21-hydroxylase deficiency?
- Low aldosterone, low cortisol
- Long period of slightly raised testosterone: hirsutism, precocious puberty
- High other sex steroids
- Little bit hypotensive, but not life-threatening
What are the clinical features and hormonal consequences of 17-hydroxylase deficiency?
- High aldosterone (hypertensive, hypokalaemic)
- No cortisol
- No sex steroids
- Never go through puberty
- Borderline hypoglycaemia
- Infections common (no cortisol)
- No Addisonian crisis bc normal aldosterone
What are the clinical features of hormonal consequences of 11-B hydroxylase deficiency?
- Build-up of 11-deoxycorticosterone (active aldosterone receptor agonist)
- Hypertensive, hypokalaemic, virilised child
- Boys tend to be missed bc look normal
- No Addisonian crisis bc normal aldosterone
