Adrenal gland

Question 1

What are the three layers of adrenal cortex/medulla and what hormones are they associated with respectively?

Answer 1

Zona glomerulosa - mineralocorticoids (aldosterone)
Zona fasciculata - glucocorticoids (cortisol)
Zona reticularis - adrenal androgens

Medulla - adrenaline/noradrenaline

Question 2

What is the biosynthesis of steroids?

Answer 2

Cholesterol –> pregnenolone –> separate pathways

Question 3

How are adrenal productions regulated?

Answer 3

Cortisol: hypothalamic-pituitary-adrenal axis
Aldosterone: renin-angiotensin system and potassium level

Question 4

How is renin-angiotensin system activated?

Answer 4

when blood pressure drops

Question 5

What are the major cortisol actions? and how can it be used therapeutically?

Answer 5

Principles of use:
Suppress inflammation
Suppress immune system
Replacement treatment

Role in treatment of:
- allergic disease
Inflammatory disease like RA, Crohn’s disease

Question 6

Dark skin, dehydrated, hypotensive, hyponatremia, hyperkalaemia, young

Answer 6

Addison’s disease - primary adrenal insufficiency
You can see symptoms for both lack of mineralocorticoids and glucocorticoids

Other causes of primary adrenal insufficiency include: congenital adrenal hyperplasia, adrenal TB/malignancy

2nd/3rd adrenal insufficiency:
Due to lack of ACTH stimulation
Iatrogenic
Pituitary/hypothalamic problem

Question 7

Clinical Addison’s Disease features

Answer 7

Anorexia, weight loss
Fatigue/lethargy
Dizziness and low BP
Abdominal pain, vomiting, diarrhoea
Skin pigmentation (due to conversion of ACTH to melanocyte stimulating hormone)

Question 8

Addison’s

Answer 8

autoimmune destruction of adrenal cortex
- 90% can be destroyed before clinical symptoms

Question 9

Diagnosis of adrenal insufficiency

Answer 9

hyponatremia, hyperkalaemia
(hypoglycaemia in kids)

Short synacthen test, measuring cortisol levels

ACTH levels, Renin/aldosterone
Adrenal autoantibodies (21-OH antibodies)

Question 10

Mx adrenal insufficiency

Answer 10

Do not delay treatment to confirm diagnosis (unlikely to do harm)

Hydrocortisone as cortisol replacement
- give IV first if unwell, then shift to oral
- 15-30mg daily in divided doses
- try to mimic diurnal rhythm

Fludrocortisone as aldosterone replacment
- add only after patient can start drinking and eating well
- carefully monitor BP and K+

Need education for sick day rules (hydrocortisone), cannot stop suddenly (if continuously vomitting - take an IM hydrocortisone and arrange hospital admission), need to wear identification (emergency steroid card)

Question 11

Adrenal crisis emergency

Answer 11

Saline
IV hydrocortisone

Question 12

clinical features Secondary adrenal insufficiency (lack of CRH/ACTH)?

Answer 12

Similar to primary except:
Pale skin
Does not need aldosterone replacement

Question 13

Clinical features of Cushing’s (too much cortisol)

Answer 13

commoner in women and ages 20-40

thinning of skin
Easy bruising
facial plethora
Striae
proximal myopathy
central obesity

Question 14

Causes of endogenous Cushing’s syndrome

Answer 14

1st pituitary
2nd Adrenal
3rd ectopic ACTH

Question 15

Too much aldosterone

Answer 15

hyperaldosteronism (Conn’s adenoma)

Question 16

Endocrine causes of hypertension

Answer 16

High cortisol
high aldosterone
high GF (acromegaly)
high adrenaline

Question 17

Primary aldosteronism

Answer 17

Autonomous production of aldosterone independent of its regulators (angiotensin II/potassium) - will result in low renin

Significant hypertension
Hypokalaemia in around 30%
Alkalosis

Question 18

Diagnosis & Mx of PA

Answer 18

Step 1: confirm aldosterone excess
Establish plasma aldosterone to renin ratio
If such ratio is raised, perform saline suppression test
Failure of plasma aldosterone to suppress by 50% with 2 litres of normal saline confirms PA

Step 2: confrim subtype
- Adrenal CT to demonstrate adenoma
- Adrenal vein sampling to confirm adenoma is true source of aldosterone excess (as incidental adrenal lumps are rather common, and increase with age)

Only unilateral adenoma would consider surgery (cuz removal of both adrenal glands would cause permanent hypo-cortisol), and only surgical consideration would need imaging PET-CT

Bilateral adrenal hyperplasia - spironolactone as mineralocorticoid receptor antagonist

Question 19

Congenital Adrenal Hyperplasia

Answer 19

Inherited disorder, deficiency in one of the enzymes necessary for cortisol synthesis

Usually identified in neonatal period

Question 20

Diagnosis CAH

Answer 20

• Basal 17-OH Progesterone levels (lack of 21-hydroxylase would lead to everything converting into testosterone, 17-OH P is one of the precursors) –> this is the hormone most likely to be deficient in the pathway
• genetic test

Question 21

Phaeochromocytoma (tumour of adrenal medulla or sympathetic chain, where it would be called paraganglioma)

Answer 21

Feels like panic attack - headache, sweats, palpitations
High levels of adrenaline/noradrenaline

MIBG scan (nuclear medicine scan) - check for disease elsewhere before surgery

Question 22

Diagnosis for phaeochromocytoma/paraganglioma

Answer 22

• confirm excess of catecholamines, checking 24 urine or plasma metanephrine

Question 23

Approach to therapy (PCMC)

Answer 23

Full alpha and beta blockade, only when sufficient alpha blockade [with phenoxybenzamine/doxazosin] (ie adequate BP control and evidence of postural drop), consider addition of b-blocker

B-blocker (propranolol, atenolol or metoprolol)

*Treatment: Surgery, total excision wherever possible, tumour de-bulking

Long-term follow-up, genetic testing, family tracing and investigation