Addison’s disease + Cushing’s syndrome Flashcards
What are the three parts of the adrenal cortex and what do they produce?
- Zona glomerulosa: Mineralocortiocoids (eg aldosterone)
- Zona fasiculata: Glucocorticoids (eg cortisol)
- Zona reticularis: Androgens
Define Addison’s disease
Addison’s disease refers to chronic primary adrenal insufficiency resulting in reduced adrenocortical hormones (particularly cortisol and aldosterone).
In developed countries most cases are caused by autoimmune destruction of the adrenal glands.
Adrenal insufficiency results in which electrolyte abnormalities?
- Metabolic acidosis
- Hyperkalaemia
- Hyponatraemia
- Hypoglycaemia
Risk factors for Addison’s disease
- Female gender
- Other autoimmune conditions: T1DM, Hashimoto’s thyroiditis, rheumatoid arthritis
Symptoms of Addison’s disease
- Lethargy and generalised weakness
- Nausea and vomiting
- Weight loss
- Salt cravings
- Collapse and shock: Addisonian crisis
Signs of Addison’s disease
- Hyperpigmentation: particularly of the palmar creases; seen in 92%
- Vitiligo
- Loss of pubic hair in women
- Hypotension and postural drop
- Associated autoimmune conditions
Primary investigations in Addison’s disease
-
Early morning cortisol (8-9am)
- <100nmol/L: highly suggestive of Addison’s, admit to hospital
- 100-500nmol/L: refer the patient for an ACTH stimulation test
- >500nmol/L: Addison’s is unlikely
- ACTH stimulation test (short Synacthen test): gold standard
- 8am ACTH: increased in Addison’s due to loss of negative feedback from cortisol
- Adrenal antibodies: anti-21-hydroxylase suggests autoimmune aetiology
- U&Es: mineralocorticoid deficiency causes hyponatraemia and hyperkalaemia
Describe the short synacthen test
It is usually performed in the morning when the adrenal glands are more “fresh”.
The test involves giving synacthen which is synthetic ACTH.
The blood cortisol is measured at baseline, 30 minutes and 60 minutes after administration. The synthetic ACTH will stimulate healthy adrenal glands to produce cortisol and the cortisol level should at least double.
A failure of cortisol to rise to at least double the baseline indicated primary adrenal insufficiency.
Addison’s disease management
- Hydrocortisone in 2-3 doses divided through the day with a total of 20-30mg
- Fludrocortisone once daily for mineralocorticoid replacement (50-300 micrograms)
Patient education:
- Advise patients to wear a MedicAlert bracelet or carry steroid cards in case of an Addisonian crisis
- Advise patients to double hydrocortisone dose if they develop an intercurrent illness
What is an Addisonian crisis?
An acute presentation of severe Addisons where the absence of steroid hormone leads to a life threatening presentation.
It can be the first presentation of Addisons disease or triggered by infection, trauma or other acute illness in some one with established Addisons.
It can occur with previously normal adrenal function when patients suddenly stop long term steroid therapy.
Clinical features of Addisonian crisis
Symptoms
- Nausea and vomiting
- Abdominal pain
- Trigger eg infection or MI
Signs
- Hypotension
- Hypovolaemic shock
- Reduced GCS
Investigations in Addisonian crisis
- 12 lead ECG: hyperkalaemic changes include flat P waves, short QT interval, broad QRS, ST depression, and tented T waves
- VBG: can be conducted quickly and will reveal metabolic acidosis with hyponatraemia and hyperkalaemia. Patients may also be hypoglycaemic.
- U&Es: hyponatraemia and hyperkalaemia
- FBC and CRP: leukocytosis and raised inflammatory markers may suggest underlying infection as precipitant
- TFTs: hypothyroid states may mimic an Addisonian picture
Management of Addisonian crisis
- IV fluids: for resuscitation; consider dextrose if hypoglycaemic
- Corticosteroid: hydrocortisone 100mg IV and a further dose 6 hours later
- Fludrocortisone is not required in the acute stage (as hydrocortisone exerts an effect at the mineralocorticoid receptor)
Classes of causes of Cushing’s syndrome
- ACTH-independent causes (ACTH not raised):
- ACTH-dependent causes (ACTH raised)
Describe the HPA pathway
- The hypothalamus releases CRH (corticotropin releasing hormone)
- The anterior pituitary releases ACTH (adrenocorticotropic hormone)
- The adrenal cortex releases cortisol
- Cortisol exerts negative feedback on ACTH and CRH
