Clinical Aspects of the Adrenal Gland Clinical Case & Discussion

Question 1

What are the 3 categories of adrenal hypofunction disorders?

Answer 1

• Adrenal destruction
• Adrenal dysgenesis (congenital adrenal structural developmental defects)
• Impaired steroidogenesis

Question 2

What are the causes of primary adrenal insufficiency (Addison’s disease)?

Answer 2

• Autoimmune destruction
• Infection (i.e TB)
• Infarction
• Invasion
• Infiltration
• Iatrogenic (long term steroid therapy suppresses the pituitary-adrenal axis but this only becomes apparent on withdrawal of the steroids)

Question 3

What test is +ve in 70% of cases of autoimmune Addison’s disease?

Answer 3

• 21-Hydroxylase adrenal autoantibodies

Question 4

What autoimmune diseases are commonly associated with autoimmune Addison’s disease?

Answer 4

Associated autoimmune diseases:

• Type 1 diabetes mellitus
• Thyroid disease
• Premature ovarian failure

Question 5

In Addison’s disease, state some common symptoms of primary adrenal failure

Question 6

What are the possible clues to the diagnosis of adrenal failure?

Question 7

How do we diagnose adrenal insufficiency?

Answer 7

Diagnosis of adrenal insufficiency:

• Routine blood: FBC, U&E, ↓glucose (due to ↓cortisol and therefore ↓gluconeogenesis), ↓Na+ and ↑K+ (due to ↓aldosterone)

Early morning cortisol:

> 450 nmol/L = Not Addison’s

< 350 nmol/L = Adrenal status uncertain

• Synacthen test

(Take 7 ml of blood to measure cortisol and ACTH levels. Then give 250mg of tetracosactrin IM. At 30 mins, take 7 ml of blood to measure cortisol. At 60 mins, take 7 ml of blood to measure cortisol. If impaired cortisol response and ACTH > 200ng/L, then diagnosis is Addison’s disease. If ACTH is <10ng/L, then diagnosis is secondary adrenal failure)

Question 8

Look at this flow chart!

Question 9

How is Addison’s disease (adrenal insufficiency) treated?

Answer 9

Glucocorticoid replacement:

• Hydrocortisone 20-30mg in 2-3 doses per day to ‘mimic normal diurnal variation’ (this is the main steroid used for adrenal insufficiency)
• Prednisolone
• Dexamethasone

Mineralocorticoid replacement:

• Fludrocortisone 50-300mg per day (synthetic steroid which binds to aldosterone receptors)

Question 10

State some adrenal disorders that are to do with hypersecretion

Answer 10

Adrenal cortex:

• Cushing’s syndrome (↑cortisol)
• Conn’s syndrome (↑aldosterone)

Adrenal medula:

• Phaeochromocytoma (↑catecholamines)

Question 11

What are the side effect of glucocorticoid therapy?

Answer 11

Question 12

Look at this for Cushing’s Syndrome:

Question 13

What is the approach to hypercortisolism?

Question 14

How do screen for suspected Cushing’s syndrome?

Answer 14

• 24 hour urinary free cortisol (normal 14–135 nmol/24h
• 1 mg overnight Dexamethasone suppression test taken at midnight. Measure serum cortisol at 9am. Normal < 50 nmol/L

Question 15

After screening for Cushing’s syndrome and confirming the diagnosis, what other tests can we do?

Answer 15

• Pituitary MRI (shows pituitary tumour)
• CT scan (for patients with a suspected adrenal tumour)

Question 16

What is Conn’s syndrome?

Answer 16

• Excess aldosterone

Question 17

Describe the pathophysiology of primary hyperaldosteronism

Answer 17

Pathophysiology of primary hyperaldosteronism:

• An aldosterone-producing tumour produces ↑aldosterone
• This leads to ↑Na+absorption, ↑blood volume, ↑BP and ↑K+ excreted in the urine
• This then leads to ↓renin release (in attempt to ↓BP)
• Thus ↑aldosterone,↓renin and so the A/R ratio ↑

Question 18

How do we screen to differentiate between primary and secondary aldosteronism?

Answer 18

Differentiating between primary and secondary aldosteronism:

• Primary: PA/PRA ratio > 20
• Secondary: PA/PRA ratio < 20 (could also mean essential hypertension)

PA = Primary aldosteronism

PRA = Plasma renin activity

Question 19

How do we diagnose hyperaldosteronism?

Answer 19

Clinical suspicion of hyperaldosteronism

Screening tests:

• Primary: PA/PRA ratio > 20
• Secondary: PA/PRA ratio < 20 (could also mean essential hypertension)

Confirmatory tests:

• 24 hour urine aldosterone > 12 μg/day and urinary Na+ > 200 mEq/day during 4 days of salt loading

Establishing the aldosterone source:

• CT scan of the adrenal glands
• Upright posture test
• Plasma 18-hydroxycorticosterone
• Adrenal venous sampling if CT scan is inconclusive or discordant eith posture test

Question 20

In primary hyperaldosteronism, plasma aldosterone will be ____ and plasma renin will be ____

Answer 20

In primary hyperaldosteronism, plasma aldosterone will be HIGH and plasma renin will be LOW

Question 21

How is Conn’s syndrome treated?

Answer 21

Surgery:

• Laparoscopic adrenalectomy

Question 22

What is phaeochromocytoma?

Answer 22

Catecholamine producing tumour

(adrenal medulla)

Question 23

How does phaeochromocytoma present?

Answer 23

• Hypertension
• Tachycardia

Paroxysmal attacks of:

• Headaches
• Sweating
• Palpitation
• Tremor
• Anxiety/fear
• Pallor

Question 24

Why is phaeochromocytoma known as the 10% tumour?

Answer 24

Phaeochromocytoma roughly follows the 10% rule:

• 10% malignant
• 10% extra-adrenal
• 10% multiple
• 10% hyperglycaemia
• 30% inherited origin

Question 25

How do we investigate phaeochromocytoma?

Answer 25

• Clinical suspicion of phaeochromocytoma
• 24 hour urine for total metanephrines (these are made when the body breaks down catecholamines)
• Abdominal/ adrenal CT/MRI (localisation)
• If a typical adrenal or paraaortic mass is found, consider 123-I MIBG scan

Question 26

How is phaeochromocytoma treated?

Answer 26

If a mass/tumour is found then:

• Give α blockade pre-op (phenoxybenzamine)
• Surgical resection

Question 27

What are most cases of congenital adrenal hyperplasia due to?

Answer 27

> 90% cases due to 21-hydroxylase deficiency