Clinical Aspects of the Adrenal Gland Clinical Case & Discussion

Question 1

What are the main hormones secreted by the adrenal gland?

Answer 1

• Aldosterone
• Cortisol
• DHEA and androgenic steroids
• Norepinephrine / epinephrine

Question 2

What are the two most common diseases of adrenal hyposecretion?

Answer 2

• Addison’s disease
• Congenital adrenal hyperplasia (deficiency in one of the enzymes necessary for aldosterone / cortisol production, most commonly 21-hydroxylase)

Question 3

Causes of Addison’s Disease? Pathophysiology?

Answer 3

• Autoimmune (90%)
• TB / metastasis
• Destruction of the adrenal cortices (via lymphocyte infiltration) results in steroid and mineralocorticoid deficiency

Question 4

Symptoms of Addison’s disease?

Answer 4

• Weight loss / anorexia
• Weakness
• Malaise
• nausea
• Vomiting
• Diarrhoea

Question 5

Clinical signs of Addison’s Disease?

Answer 5

• Skin pigmentation / vitiligo (loss of pigment in patches)
• Hypotension
• Hypoglycaemia
• Hyponatraemia

Question 6

Investigations for Addison’s disease?

Answer 6

• Early morning blood [cortisol]: >450nmol/L not Addison’s
• Short Synacthen: administer tetracosactrin (ACTH) via IM / IV injection, if cortisol doesn’t rise significantly over 30-180min then likely Addison’s

Question 7

How can you tell if low cortisol is due to primary adrenocortical insufficiency (Addison’s) or secondary insufficiency? (pituitary?)

Answer 7

• Check if plasma ACTH is suppressed or normal/elevated

Suppressed suggests secondary issue

Question 8

Management of Addison’s disease? (or of low cortisol / aldosterone in general)

Answer 8

• Hydrocortisone: glucocorticoid replacement (cortisol)

- Fludrocortisone: mineralocorticoid replacement (aldosterone)

Question 9

What should patients taking hydrocortisone do when they are ill? (infection / UTI)

Answer 9

• Double their hydrocortisone dose

Question 10

What are some endocrine causes of hypertension?

Answer 10

• Phaeochromocytoma
• Acromegaly
• Cushing’s Syndrome
• Hyperparathyroidism
• Hypothyroidism / Hyperthyroidism
• Congenital adrenal hyperplasia

Question 11

What are the adrenal disorders of hypersecretion?

Answer 11

• Cushing’s Syndrome (cortisol / sex steroids)
• Conn’s syndrome (aldosterone)
• Phaeochromocytoma (catecholamines)

Question 12

Approximately what percentage of Cushing’s syndrome cases are ACTH independent? What are they mostly due to?

Answer 12

• 20% ACTH-independent

- Mostly due to adrenal tumour

Question 13

Investigations for suspected Cushing’s syndrome?

Answer 13

• 24-h urine [free cortisol]
• Low dose dexamethasone test (measures responsiveness of adrenals to ACTH, cortisol should decrease after dexamethasone)

Question 14

How does the dexamethasone test work? How can it differentiate between pituitary and adrenal causes of Cushing’s?

Answer 14

• Dexamethasone suppresses ACTH, gets administered overnight. Normally cortisol is suppressed the next morning due to this, if not abnormal cortisol secretion
• High dose of the drug will cause ACTH-dependent Cushing’s patients to have lower cortisol the next morning, ACTH-independent cortisol will not be affected by drug

Question 15

What is the function of aldosterone and what does this mean for Conn’s syndrome patients?

Answer 15

• Aldosterone functions to increase water reabsorption at the kidney tubules

Conn’s patients:

• Increased blood volume
• Increased blood pressure
• Increased urine K (bc aldosterone causes Na reabsorption which water follows, but K moved into urine)

Question 16

How does primary hyperaldosteronism differ from secondary hyperaldosteronism?

Answer 16

Primary: low renin activity in plasma, but still high aldosterone concentration and activity

Secondary: high renin activity in plasma causing the high aldosterone concentration and activity

Question 17

Investigations for suspected Conn’s syndrome?

Answer 17

• Aldosterone : renin ratio (high in primary)
• Blood [Potassium] (low in Conn’s)
• 24 h urine aldosterone and Na (both high Conn’s)
• CT adrenal gland

Question 18

Management of Conn’s syndrome?

Answer 18

• Spironolactone (aldosterone antagonist)

- Resection of adenoma / hyperplasia

Question 19

What is phaeochromocytoma?

Answer 19

• Tumour of the adrenal medulla causing increased secretion of noradrenaline and adrenaline
• 90% benign unilateral
• 10% malignant / extra-adrenal / multiple
• 30% hereditary

Question 20

Symptoms of phaeochromocytoma?

Answer 20

Paroxysmal:

• Headache
• Sweating
• Palpitations
• Tremor
• Pallor
• Hypertension

Question 21

Investigations for phaeochromocytoma?

Answer 21

• 24h urinary catecholamines (from textbook)
• MRI adrenal
• PET adrenal

Question 22

Management of phaeochromocytoma?

Answer 22

• phenoxybenzamine (alpha receptor blocker)

- Surgery to remove mass

Question 23

Why does 21-Hydroxylase deficiency cause congenital adrenal hyperplasia?

Answer 23

• No 21-hydroxylase = no cortisol / aldosterone
• No negative feedback on ACTH production
• ACTH continuously stimulates adrenal gland, leads to hyperplasia

Question 24

What are some symptoms of Addisonian Crisis (acute adrenal failure)?

Answer 24

Weakness, fatigue, anorexia, weight loss 100%

Skin pigmentation or vitiligo 92%

Hypotension 88%

Unexplained vomiting or diarrhoea 56%

Question 25

Treatment of Addisonian Crisis?

Answer 25

• Hydrocortisone injection

- Fluids with electrolytes