Endocrinology - Adrenal insufficiency

Question 1

what are the 2 types of adrenal insufficiency? what is the most common cause of each?

Answer 1

1. Primary insufficiency: inability of adrenal glands to produce enough steroid hormones. Most commonly caused by autoimmune destruction of adrenal glands (Addison’s disease - antibodies against steroid 21-hydroxylase). Clinical and biochemical insufficiency only seen when >90% of gland destroyed.
2. Secondary insufficiency: inadequate pituitary or hypothalamic stimulation of adrenal glands. Most commonly caused by suppression of hypothalamic-pituitary axis from exogenous steroid use.

Question 2

other than Addison’s disease, name possible causes of primary adrenal insufficiency.

Answer 2

Destruction of adrenal glands:

1. trauma or surgical removal
2. infection, e.g. TB, HIV, cryptococcosis
3. haemorrhage, e.g. anticoagulants, Waterhouse-Friderichsen syndrome (post-N. meningitidis infection)
4. infiltration, e.g. neoplastic, sarcoidosis, amyloidosis, haemochromatosis
5. congenital adrenal hyperplasia, e.g. 21-hydroxylase deficiency (most common cause in children)

Question 3

describe the symptoms of adrenal insufficiency

Answer 3

Can be acute (adrenal crisis) or insidious/chronic:

• extreme fatigue and weakness
• abdo. pain
• anorexia, nausea and vomiting
• diarrhoea/constipation
• muscle cramps and joint pains
• syncope or dizziness (due to hypotension)
• confusion, irritability and personality change

Question 4

describe the signs you may see in adrenal insufficiency

Answer 4

• hyperpigmentation
• hypotension
• postural hypotension

Question 5

why is hyperpigmentation a feature of Addison’s disease?

Answer 5

Due to increase in ACTH levels:

• ACTH produced from cleavage of POMC precursor which also produces alpha-MSH. MSH stimulates melanin production by skin melanocytes.
• ACTH also has some direct melanocyte stimulating effects.

Question 6

why is hypotension a feature of Addison’s?

Answer 6

loss of Na+ and water retention by aldosterone at kidney

Question 7

which investigations would you perform to Dx adrenal insufficiency?

Answer 7

1. Bloods
   - UandEs: often low Na+ and high K+ (normal levels do not exclude Dx)
   - cortisol (ideally measured at highest between 8-9am):
   low if <500 nanomol/L
   - ACTH: increased in primary insufficiency, decreased or normal in secondary
   - +/- renin and aldosterone levels: indicators of mineralocorticoid activity - in primary insufficiency, often have increased renin and decreased aldosterone
2. Other tests
   - ACTH stimulation test (Synacthen): administer ACTH IV or IM and measure cortisol level - do not rise in primary insufficiency
   - +/- adrenal autoantibodies: +ve in Addison’s
   - imaging, e.g. MRI brain when central causes suspected

Question 8

how would you manage a pt with Addison’s disease?

Answer 8

Hormone replacement:

• HYDROCORTISONE (glucocorticoid replacement) - 15-30 mg in 3 divided doses with highest in morning (stimulating normal diurnal adrenal rhythm), or twice daily regimens or modified-release once daily now available.
• FLUDROCORTISONE (mineralocorticoid replacement) - 50-300 micrograms per day, depending on activity levels, weight and metabolism

Pt advice:

• medical emergency ID bracelet and steroid card
• importance of not missing steroid doses and not stopping them abruptly
• intercurrent illness: if tolerating oral medications, dose should be doubled or trippled until better. If can’t take medication orally, seek medical help as need IM hydrocortisone and to learn how to administer. For major surgery/illness, dose may need to be increased up to 10x.

Question 9

what is the major complication of adrenal insufficiency? suggest 3 situations in which this might occur

Answer 9

Adrenal crisis

1. Addison’s disease pts when subject to intercurrent illness or stress, e.g. infections, injuries, pregnancy, MI, acute hypoglycaemia if DM
2. abrupt long-term steroid withdrawal
3. bilateral adrenal gland hemorrhage, e.g. Friderichsen-Waterhouse syndrome, MI, complicated pregnancy

Question 10

which investigations would you perform in someone with suspected adrenal crisis?

Answer 10

Bloods

• cortisol: <600 nmol/L often sufficient for Dx in acute situation
• ACTH
• UandEs: often now Na+ and high K+
• glucose: hypoglycaemia, possibly severe, is characteristic in children

Question 11

how would you manage a pt with suspected adrenal crisis?

Answer 11

1. IM/IV hydrocortisone succinate 100mg (adults)
2. rapid rehydration with IV 0.9% saline (several L may be required in first 48hrs; caution in chronic hyponatraemia as risk of central pontine myelinosis)
3. maintain pt on hydrocortisone at 200mg/24hrs (pref. by continuous IV infusion in 5% glucose) until clinical recovery
4. continuous cardiac and electrolyte monitoring
5. once stabilised, gradual reduction of IV steroids and re-institution of oral therapy
6. ID/Tx of underlying precipitating factor