Adrenal Insufficiency

Question 1

What is adrenal insufficiency?

Answer 1

Adrenal insufficiency is where the adrenal glands do not produce enough steroid hormones, particularly cortisol and aldosterone.

Steroids are essential for life and therefore the condition is life-threatening unless the hormones are replaced.

Question 2

Differentiate between primary, secondary and tertiary causes of adrenal insufficiency

Answer 2

Primary: destruction or dysfunction of the adrenal gland

Secondary: inadequate pituitary adrenocorticotrophic hormone (ACTH) release and subsequent cortisol production

Tertiary: inadequate hypothalamic corticotropin-releasing hormone and subsequent ACTH release

Question 3

What is Addison’s disease?

Answer 3

Addison’s disease, or primary adrenal insufficiency, is a disorder that affects the adrenal glands, causing decreased production of adrenocortical hormones (cortisol, aldosterone, and dehydroepiandrosterone).

This may be caused by a destructive process directly affecting the adrenal glands or by a condition that interferes with hormone synthesis.

Question 4

Briefly describe the pathophysiology of Addison’s disease

Answer 4

Addison’s Disease causes reduced production of glucocorticoids (such as cortisol), mineralocorticoids (such as aldosterone) and adrenal androgens (such as dehydroepiandrosterone).

The absence of cortisol leads to increased production of adrenocorticotrophic hormone (ACTH) because negative feedback to the pituitary gland is reduced.

The most common cause is autoimmune.

Question 5

What are the causes of Addison’s disease?

Answer 5

• Autoimmunity
• TB
• Adrenal metastases
• Lymphoma
• Opportunistic infection e.g. in HIV
• Adrenal haemorrhage

Question 6

Is Addison’s disease primary, secondary or tertiary adrenal insuffiency?

Answer 6

Primary

Question 7

What is secondary adrenal insufficiency?

Answer 7

Secondary adrenal insufficiency is a result of inadequate ACTH stimulating the adrenal glands, resulting in low cortisol release.

This is the result of loss or damage to the pituitary gland. This can be due to surgery to remove a pituitary tumour, infection, loss of blood flow or radiotherapy.

Question 8

Briefly describe the pathophysiology of secondary adrenal insufficiency

Answer 8

Secondary adrenal insufficiency occurs in patients with pituitary or hypothalamic involvement. This results in decreased ACTH secretion, which ultimately results in adrenal failure.

Question 9

What are the causes of secondary adrenal insufficiency?

Answer 9

• Iatrogenic (due to long-term administration of corticosteroid)
• Intracranial disorders (e.g. pituitary tumours)
• Subarachnoid haemorrhage
• Traumatic brain injury

Question 10

What is Sheehan’s syndrome?

Answer 10

Sheehan’s syndrome is due to massive blood loss during childbirth which leads to pituitary gland necrosis.

Question 11

What risk factors are associated with Addison’s Disease?

Answer 11

• Female sex
• Presence of adrenocortical autoantibodies
• Adrenal haemorrhage
• Use of anticoagulants

Question 12

What is tertiary adrenal insufficiency?

Answer 12

Tertiary adrenal insufficiency is the result of inadequate CRH release by the hypothalamus.

This is usually the result of patients being on long term oral steroids (for more than 3 weeks) causing suppression of the hypothalamus.

Question 13

Why should long-term steroid use be tapered down slowly?

Answer 13

When the exogenous steroids are suddenly withdrawn the hypothalamus does not “wake up” fast enough and endogenous steroids are not adequately produced. Therefore long term steroids should be tapered slowly to allow time for the adrenal axis to regain normal function.

Question 14

What are the signs of adrenal insuffiency?

Answer 14

• Significant weight loss secondary to anorexia
• Mucosal and cutaneous hyperpigmentation
• Postural hypotension
• Vitiligo

Question 15

What are the symptoms of adrenal insufficiency?

Answer 15

• Fatigue and weakness
• Anorexia
• GI symptoms including nausea, vomiting, constipation and abdominal pain
• Flu-like symptoms e.g. headache and low-grade fever
• Increased thirst or urination
• Loss of axillary or pubic hair in women
• Anxiety or depression

Question 16

Where does bronze hyperpigmentation occur in adrenal insufficiency?

Answer 16

Generalised and more pronounced in areas of increased friction, such as palms, knuckles, and scars.

Question 17

Why does bronze hyperpigmentation occur in adrenal insufficiency?

Answer 17

Due to increased pituitary ACTH hormone there is increased stimulation of melanocyte activity.

Question 18

Why is there a decrease in libidio and pubic/ axillary hair in biologically female patients?

Answer 18

Decreased adrenal androgen production.

Question 19

What investigations should be ordered in adrenal insufficiency?

Answer 19

• Serum electrolytes
• Blood urea
• FBC
• Morning serum cortisol
• Synacthen® test
  
  • Note: short
• Serum ACTH
• Adrenal autoantibodies
• CT or MRI of adrenal glands
• MRI pituitary

Question 20

Why investigate serum electrolytes?

Answer 20

Hyponatraemia (low sodium) is a key biochemical clue. Sometimes the only presenting feature of adrenal insufficiency is hyponatraemia.

Hyperkalaemia (high potassium) is also possible.

Question 21

Why investigate blood urea?

Answer 21

In addition to hyponatraemia, hypercalcaemia, hyperkalaemia, and eosinophilia, elevated blood urea may be an indicator of adrenal insufficiency.

Question 22

Why investigate FBC?

Answer 22

Anaemia is present in 40% of patients.

Question 23

Why investigate morning serum cortisol?

Answer 23

Early morning cortisol (8-9am) has a role but is often falsely normal.

Question 24

At what time in the day should serum cortisol be measured? And why?

Answer 24

Blood should be drawn between 8 a.m. and 9 a.m., when cortisol levels peak.

Question 25

Why investigate using Synacthen® test?

Answer 25

A short synacthen test is the test of choice to diagnose adrenal insufficiency.

Question 26

Briefly describe the Short Synacthen Test (ACTH stimulation test)

Answer 26

The short synacthen test is the test of choice for adrenal insufficiency.

It is ideally performed in the morning when the adrenal glands are most “fresh”. The test involves giving synacthen, which is synthetic ACTH. The blood cortisol is measured at baseline, 30 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 (less than double the baseline) indicates primary adrenal insufficiency (Addison’s disease).

Question 27

Why investigate serum ACTH?

Answer 27

May be used to differentiate primary (adrenal) from secondary (pituitary) and tertiary (hypothalamic) adrenal insufficiency.

Question 28

How do the levels of ACTH differ in primary and secondary adrenal insuffiency?

Answer 28

In primary adrenal failure the ACTH level is high as the pituitary is trying very hard to stimulate the adrenal glands without any negative feedback in the absence of cortisol.

In secondary adrenal failure the ACTH level is low as the reason the adrenal glands are not producing cortisol is that they are not being stimulated by ACTH.

Question 29

Why investigate adrenal autoantibodies?

Answer 29

Adrenal autoantibodies are present in 80% of autoimmune adrenal insufficiency: adrenal cortex antibodies and 21-hydroxylase antibodies.

Question 30

Why investigate using CT or MRI of adrenal glands?

Answer 30

CT / MRI adrenals if suspecting an adrenal tumour, haemorrhage or other structural pathology (not recommended by NICE for autoimmune adrenal insufficiency).

Question 31

Why investigate using MRI of pituitary?

Answer 31

MRI pituitary gives further information about pituitary pathology.

Question 32

Briefly describe the treatment of adrenal insufficiency

Answer 32

Treatment of adrenal insufficiency is with replacement steroids titrated to signs, symptoms and electrolytes.

Hydrocortisone is a glucocorticoid hormone and is used to replace cortisol.

Fludrocortisone is a mineralocorticoid hormone and is used to replace aldosterone if aldosterone is also insufficient.

Plus: androgen replacement in biologically female patients

Question 33

What drug is used for glucocorticoid replacement in adrenal insuffiency?

Answer 33

Hydrocortisone is a glucocorticoid hormone and is used to replace cortisol.

Question 34

What drug us used for the mineralocorticoid replacement in adrenal insufficiency?

Answer 34

Fludrocortisone is a mineralocorticoid hormone and is used to replace aldosterone if aldosterone is also insufficient.

Question 35

How is the dosing of glucocorticoid and mineralocorticoid replacement therapy managed?

Answer 35

The adequacy of glucocorticoid replacement is guided by clinical symptoms. Persistent fatigue is symptomatic of insufficient dosage. Excessive weight gain or facial plethora is symptomatic of over-replacement.

Mineralocorticoid dosage is impacted by the mineralocorticoid potency of the glucocorticoid administered and is adjusted based on postural hypotension and serum potassium.

Question 36

What advice is given to patient’s with adrenal insuffiency?

Answer 36

Advice given:

• The need for lifelong glucocorticoid replacement treatment and the potentially life-threatening complications that may arise with inadequate replacement.
• How to adjust their replacement steroid medication during periods of illness (including fever), injury, or strenuous exercise.
• How to recognise the symptoms of an adrenal crisis and how to give intramuscular hydrocortisone in an emergency.
• The importance of carrying emergency information on their person, for example:
  
  • MedicAltert Identification
  • NHS Steroid emergency card

Question 37

Why do patient’s taking steroids carry a NHS Steroid emergency card?

Answer 37

This alerts healthcare professionals that the person is on steroid treatment that should not be stopped suddenly and includes a summary for emergency treatment of adrenal crisis.

Question 38

What happens to the doses of steroids during an acute illness?

Answer 38

Doses are doubled during an acute illness until they have recovered to match the normal steroid response to illness.

Question 39

What are the complications of adrenal insuffiency?

Answer 39

• Secondary Cushing’s syndrome
• Osteopenia and osteoporosis
• Treatment-related hypertension

Question 40

What differentials should be considered for adrenal insufficiency?

Answer 40

1. Acute abdomen

Question 41

How does adrenal insuffiency and acute abdomen differ?

Answer 41

Differentiating signs and symptoms:

• Severe dehydration, circulatory shock, nausea, vomiting and abdominal pain associated with adrenal crisis can be mistaken for an acute abdominal emergency.

Differentiating investigations:

• Dependent on the underlying pathology.