ChemPath - Adrenal Disease

Question 1

What are the layers of the adrenal glands and what do they produce

Answer 1

(From inside-out)
Medulla - catecholamines
Reticularis - androgens
Fasciculata - glucocorticoids
Glomerulosa - mineralocorticoids
Capsule
Fat

Question 2

What are the causes of wasted and hyperplastic adrenal galnds

Answer 2

Wasted - Addison’s disease, long-term steroids
Hyperplastic - Cushing’s, ectopic ACTH

Question 3

Describe the blood supply of the adrenal galnds

Answer 3

Many arteries around the edge (~57) but only 1 central vein
The left adrenal gland drains into the left renal vein
The right adrenal gland drains into the IVC

Question 4

What is polyglandular autoimmune syndrome type II (Schmidt’s syndrome), what causes it, and what are the clinical features

Answer 4

Addison’s disease + primary hypothyroidism

Autoimmune nature of both diseases - Abs against both the thyroid and adrenal glands

Primary hypothyroidism + hypoglycaemia (glucocorticoid deficiency) + hyperkalaemia/hyponatraemia (Addison’s)

Question 5

What is the diagnostic test for Addison’s disease

Answer 5

Short SynACTHen testing
1) Measure cortisol and ACTH at start
2) 250ug ACTH, IM
3) Check cortisol at 30 and 60 minutes

Cortisol will have no response in Addison’s

Question 6

How is Addison’s managed

Answer 6

0.9% saline IV
IV hydrocortisone

Question 7

What are the most common causes of Addison’s disease

Answer 7

UK - autoimmune
Worldwide - TB

Question 8

What are the differentials for an adrenal mass + high BP

Answer 8

Conn’s syndrome (aldosterone excess)
Cushing’s syndrome (cortisol excess)
Phaeochromocytoma (adrenaline excess)

Question 9

What is the diagnostic test for phaeochromocytomas

Answer 9

Urinary catecholamines (formerly VMA)= high

Question 10

What is the management of phaeochromocytoma

Answer 10

1) Immediate alpha blockade (phenoxybenzamine)  reflex tachycardia → move to step 2
2) Add beta blockade
3) Surgery

Question 11

What genetic conditions are associated with phaeochromocytomas

Answer 11

MEN2
von Hippel Lindau syndrome
Neurofibromatosis type 1

Question 12

What is Conn’s syndrome

Answer 12

Autonomic secretion of aldosterone from the zona glomerulosa

HTN + HYPOkalaemia

Question 13

What is the diagnostic test for Conn’s syndrome

Answer 13

Renin-aldosterone ratio = LOW

aldosterone release → HTN → suppression of renin production at the JGA

Question 14

What is the management of Conn’s syndrome

Answer 14

Spironolactone (Aldosterone blocker)
Surgery

Question 15

What is Cushing’s syndrome and what are the causes

Answer 15

Excessive production of cortisol
Pituitary-dependent Cushing’s DISEASE (ACTH production) (85%)
Ectopic ACTH e.g. SCLC (5%)
Adrenal adenoma (10%)
Oral steroid use

Question 16

What condition can mimic Cushing’s syndrome’s biochemistry i.e. high cortisol and how is it distinguished

Answer 16

Obesity (pseudo-Cushing’s)
Dexamethasone suppression test → ACTH falls → cortisol falls

Question 17

What is the diagnostic test for Cushing’s syndrome

Answer 17

Low-dose dexamethasone test

1) 12am salivary cortisol (must be asleep) → if low, the cause is not Cushing’s, will be high in those with Cushing’s

2) Low dose dexamethasone at 12pm → 1mg dexamethasone and measure cortisol before 9am next day
0.5mg dexamethasone every 6 hours for 48 hours

3) 9AM cortisol
If 9AM cortisol remains high → Cushing’s syndrome confirmed → do IPSS

Inferior Petrosal Sinus Sampling (IPSS)
- A catheter is fed into the jugular vein
- Distinguishes pituitary dependant from ectopic ACTH
- Elevated central/peripheral ACTH ratio: indicates pituitary source (Cushing’s disease)

Question 18

What is the high-dose dexamethasone suppression test and why is it no longer used

Answer 18

Was used to distinguish between causes of Cushing’s syndrome
Low cortisol and ACTH - pituitary cause
Low cortisol - adrenal adenoma
Neither suppressed - ectopic ACTH

Not done anymore as there is a false -ve rate of 20%, which means guessing it is pituitary dependent (85%) is more accurate

Question 19

Why does Cushing’s syndrome cause HTN

Answer 19

Cortisol can activate the mineralocorticoid receptor at high concentrations
An enzyme (11b-hydroxyteroid dehydrogenase) usually degrades cortisol before it can do so, but in Cushing’s the enzyme is overwhelmed

Question 20

What is the management of Cushing’s syndrome

Answer 20

Pituitary adenoma → surgery
Ectopic ACTH → ketoconazole, metyrapone, mifepristone
Adrenal mass → adrenalectomy ± steroid replacement

Question 21

What is Nelson’s syndrome

Answer 21

Removal of the adrenal glands → pituitary enlargement → compression of the pituitary stalk → hypopituitarism
Raised ACTH → pigmentation

Question 22

What are the features of 21-OH deficiency

Answer 22

Salt-losing crisis (low aldosterone)
Virilisation (high testosterone/androgens)