Adrenal insufficiency

Question 1

1) What is the main cause of primary adrenal insufficiency?

2) What is the most common infective cause of primary adrenal insufficiency?

Answer 1

1) Addison’s disease (80%)

2) TB.

Question 2

Aside from Addison’s disease and TB, name other causes of primary adrenal insufficiency.

Answer 2

1) Metastases from breast, lung and renal cancers (or adrenal malignancy)
2) Autoimmune infiltration diseases (haemochromatosis/ amyloidosis) or adrenal haemorrhage
3) Infections (HIV can cause this as well as TB)
4) Lymphomas

• *Can be remembered using the mnemonic ‘MAIL’
• **Congenital adrenal hyperplasia, adrenalectomy and medications can also be causes.

Question 3

1) What is meant by primary adrenal insufficiency?

2) What is meant by secondary adrenal insufficiency?

Answer 3

1) Primary adrenal insufficiency is when your adrenal glands are damaged and can’t make the cortisol you need.
2) Secondary adrenal insufficiency occurs when the pituitary gland doesn’t make enough of the hormone ACTH.

Question 4

Give 4 causes of secondary adrenal insufficiency.

Answer 4

1) Prolonged prednisolone (or corticosteroid) use
2) Pituitary adenoma
3) Sheehan’s syndrome
4) Hypothalamic/ pituitary dysfunction

Question 5

1) What is the most common cause of secondary adrenal insufficiency?
2) Describe two main differences between primary and secondary adrenal insufficiency.

Answer 5

1) Iatrogenic through long term steroid use suppressing the HPA axis (this is only apparent on steroid withdrawal).
2) Mineralocorticoid production remains intact in 2o. There is no hyperpigmentation in 2o, compared with when the cause is Addison’s disease as in 2o there is decreased ACTH.

Question 6

1) Which antibodies are specific to Addison’s disease?

2) What happens in Addison’s disease?

Answer 6

1) Antibodies against the adrenal cortex (adrenal autoantibodies) and/ or 21-hydroxylase antibodies.
2) There is destruction of the adrenal cortex which leads to glucocorticoid (cortisol) and mineralocorticoid (aldosterone) deficiency.

Question 7

1) What is Addison’s disease characterised by?
2) What is the main cause of Addison’s disease?
3) Addison’s disease can present with signs of critical deterioration which include what 3 conditions?

Answer 7

1) A deficiency in all hormones produced by the adrenal cortex.
2) Production of autoantibodies to the adrenal cortex ± 21-hydroxylase enzymes.
3) Shock, increased temperature and coma.

Question 8

Describe the effects of Addison’s disease on the negative feedback mechanism in the HPA axis.

Answer 8

Reduced levels of adrenal hormones prevents negative feedback to hypothalamus.
Hypothalamus continues to release CRH.
CRH causes anterior pituitary to continue to release ACTH so increasing amounts of ACTH are present.

**An increase in CRH will also stimulate the release of other hormones produced by the pituitary gland such as Prolactin.

Question 9

Describe the effects of a patient lacking in the following hormones:

a) decreased mineralocorticoids
b) decreased androgens
c) decreased glucocorticoids

Answer 9

a) decreased sodium and water retention = decreased BP and tachycardia.
b) decreased androgen levels have more of an effect on females, causing a decrease in libido.
c) weight loss, skin pigmentation and general fatigue.

Question 10

Patients with Addison’s disease are often diagnosed late with what characteristic appearance?

Answer 10

Lean, tired, tanned and tearful ± weakness, anorexia, dizziness, faints, flu-like myalgia/ arthralgia.

Question 11

State 10 signs or symptoms associated with patients presenting with Addison’s disease.

Answer 11

Tiredness
Dizziness
Weight loss
Nausea, vomiting, diarrhoea
Abdominal pain
Hyperpigmentation of skin  (increased ACTH cross reacts with melanin receptors)
Decreased libido (mainly female)
Arthralgia/ Myalgia
Low grade fever
Signs of dehydration
Hair loss
Cachexia
Postural hypotension
Tachycardia
Depression/ psychosis
Vitiligo
Pigmented palmar creases/ buccal mucosa (increased ACTH cross reacts with melanin receptors)

Question 12

Give 5 potential risk factors for the development of Addison’s disease.

Answer 12

Female gender
Autoimmune disease (e.g. Crohn.s disease)
Adrenal cortex autoantibody production
Adrenal haemorrhage
TB infection
Meningiococcal infection (with adrenal haemorrhage)
Use of medications that can induce AD.
HIV (opportunistic infection development)
Sarcoidosis
Metastatic malignancy

Question 13

Describe which blood tests you might carry out in a patient with suspected Addison’s disease.

Answer 13

Serum ACTH: increased
Presence of adrenal autoantibodies
Serum cortisol: decreased
FBC, U&Es, Creatinine: hyponatraemia, hyperkalaemia and uraemia. Eosinophilia may also be present.
Glucose: decreased (due to decreased cortisol)
Plasma renin & aldosterone: to assess mineralocorticoid function.

**TFTs may be carried out as a main differential diagnosis for Addison’s disease is Grave’s disease.

Question 14

State which radiological investigations you might carry out for a patient with suspected Addison’s disease.

Answer 14

CT scan: assess for adrenal haemorrhage or adrenal tumours.

CXR/AXR: assess for neoplasms or signs of TB infection.

Question 15

What are the main investigations to request in a patient with suspected Addison’s and what would the results be?

Answer 15

1) Serum cortisol level: low (<500)
2) U&Es: low sodium, high potassium, high urea (although absence of these does not exclude diagnosis)

**Depending on the severity of the low cortisol, either admit to hospital (if <100) or refer to endocrinologist (100-500).

Question 16

Describe how a diagnosis of Addison’s disease would be confirmed.

Answer 16

Usually confirmed in secondary care in specialist endocrinology unit.
A short synacthen test (ACTH stimulation test) should be done in secondary care to confirm the diagnosis, as it has a high sensitivity in Addison’s disease.

Question 17

Describe 2 tests which can help to differentiate primary from secondary adrenal insufficiency.

Answer 17

1) Adrenocorticotrophic hormone (ACTH) levels — serum ACTH levels are high in Addison’s disease (primary adrenal insufficiency) but are low in secondary adrenal insufficiency.
2) Plasma renin and aldosterone levels — renin levels are typically high and aldosterone levels low in Addison’s disease. In secondary adrenal insufficiency, the renin-angiotensin system can function normally.

Question 18

How is the short synacthen test performed?

Answer 18

Blood samples are obtained to check serum cortisol levels before and 30 minutes after administering 250 micrograms of tetracosactide (a synthetic analogue of ACTH) intravenously or intramuscularly.

Question 19

Describe the results of the short synacthen test in patients with Addison’s disease.

Answer 19

A normal response to the ACTH stimulation test is an increase in the serum cortisol level.
In people with adrenal insufficiency, serum cortisol levels do not increase adequately in response to tetracosactide because the adrenal cortex is already receiving maximum stimulation from endogenous ACTH.

Question 20

What does conservative management of Addison’s disease/ adrenal insufficiency consist of?

Answer 20

Patient education about never to miss a steroid dose. 
Sick day rules (double dose)
Steroid alert card/ bracelet. 
MediAlert bracelet. 
Family education.

Question 21

What does the medical management of Addison’s disease consist of?

Answer 21

1) Glucocorticoid replacement: hydrocortisone: 15-30mg daily in divided doses to resemble natural cycle of corticosteroid release (10mg morning, 5mg afternoon, 5mg evening).
2) Mineralocorticoid replacement: fludrocortisone: 50-300mcg daily.

**Androgen replacement is rarely given, but DHEA can be prescribed by some specialists if necessary (it is unlicensed for this indication).

Question 22

When might surgical management be required for patients with adrenal insufficiency?

Answer 22

In primary or secondary adrenal insufficiency where there is a causative tumour.

Question 23

What 3 complications of Addison’s disease might you need to monitor and treat?

Answer 23

1) secondary Cushing’s syndrome
2) secondary HTN
3) Osteopenia/ osteoporosis

Question 24

Describe the term ‘adrenal crisis’.

Answer 24

A sudden drop in glucocorticoid levels meaning that the body has a massively reduced level of adrenal hormones. Often happens because a patient has suddenly stopped taking glucocorticoid replacement or because they are not taking enough.

Question 25

Name 4 precipitating factors of an adrenal crisis.

Answer 25

Infection
Trauma
Surgery
Missed medication

Question 26

How does a patient suffering an adrenal crisis often present?

Answer 26

Often in shock (tachycardia, hypotension, oliguria) with other features including weakness, confusion and potentially coma.

An alternative presentation is with hypoglycaemia.

Question 27

How should patients suffering an adrenal crisis be managed?

Answer 27

If suspected, treatment should be given before biochemical results are obtained.
Bloods for Cortisol and ACTH straight to lab.
100mg hydrocortisone IV stat.
Check ECG to see if Calcium gluconate needed.
Monitor CBG (IV glucose may be needed)
IV fluid bolus (500mL 0.9% NaCl)
Fludrocortisone may be needed.

**Switch to oral steroids 72 hours after if patient stable.