Adrenal Causes of Hypertension

Question 1

What is endocrinology about?

• Too much hormone - single nodule, multiple nodules, generalised increase in tissue (…)
• Not enough hormone
• Gland too big - which … … …
• Exclusion of … in a single nodule

Answer 1

• Too much hormone - single nodule, multiple nodules, generalised increase in tissue (hyperplasia)
• Not enough hormone
• Gland too big - i.e. squashes surrounding tissue
• Exclusion of cancer in a single nodule

Question 2

What is shown in this image?

Answer 2

Adrenal gland section - note the shape

below is CT image of it

Question 3

Layers of adrenal gland (GFR) and medulla

Cortex is divided into:

• Zona Glomerulosa - makes …
• Zona Fasciculata - makes …
• Zona Reticularis - makes …

Medulla makes … (adrenaline, noradrenaline, dopamine)

Answer 3

• Zona Glomerulosa - makes aldosterone
• Zona Fasciculata - makes cortisol
• Zona Reticularis - makes adrenal androgens
• Medulla makes catecholamines (adrenaline, noradrenaline, dopamine)

Question 4

Causes of Hypertension?

• … hypertension
• renal hypertension - primary renal …, renal artery …
• … causes

Answer 4

• essential hypertension
• renal hypertension - primary renal disease, renal artery stenosis
• endocrine causes

Question 5

Adrenal causes of Hypertension

• Primary …
  
  • zona glomerulosa - produces too much … due to either an …, hyper… or rare … causes
• …chromocytoma
  
  • tumour of the adrenal …
• some forms of … adrenal hyperplasia - … defect - uncommon

Answer 5

• Primary Hyperaldosteronism
  
  • zona glomerulosa - produces too much aldosterone due to an adenoma, hyperplasia or rare genetic causes
• Phaeochromocytoma
  
  • tumour of the adrenal medulla
• some forms of congenital adrenal hyperplasia - enzyme defect - uncommon

Question 6

What pathway is this? (what does it secrete)

Answer 6

Pathway for aldosterone secretion

Question 7

Pharmacology - hypertension

• Renin …
• ACE …
• A2 receptor …
• Aldosterone …

Answer 7

• Renin inhibitors
• ACE inhibitors
• A2 receptor blockers
• Aldosterone antagonists

Question 8

Primary Hyperaldosteronism - why screen?

• Individuals with PA have more … and … pathology than people with essential hypertension and similar blood pressure

Answer 8

Individuals with PA have more vascular and renal pathology than people with essential hypertension and similar blood pressure

Question 9

Hypertension - is it Primary Hyperaldosteronism? Who do we screen?

• younger or older people?
• people with hypo….
• people with … hypertension - control on … drugs or more

Answer 9

• younger or older people?
• people with hypokalaemia
• people with resistant hypertension - control on 4 drugs or more (inadequate control on 3 drugs)

Question 10

• What is resistant hypertension?
• Inadequate control on … drugs, control on … drugs or more

Answer 10

• Resistant hypertension is high blood pressure that does not respond well to aggressive medical treatment.
• Inadequate control on 3 drugs, control on 4 drugs or more

Question 11

What is shown here? (hypertension)

Answer 11

High aldosterone exists across the spectrum of hypertension

Question 12

How to find out if someone has Primary Hyperaldosteronism

• Initial screening tests:

1. suppressed …
2. normal/high …

• Confirmatory tests
  1. Oral or IV … suppression test

Answer 12

• Initial screening tests:

1. Suppressed Renin
2. normal/high aldosterone

• Confirmatory tests
  1. Oral or IV Na+ suppression test - aldosterone should go down, but if it doesn’t, you have diagnosis

Question 13

Primary Hyperaldosteronism - Tests for specific Aetiology:

• Adrenal … scan
• Adrenal … sampling - is the aldo secretion uni….?
• Metomidate … CT

Answer 13

• Adrenal CT scan
• Adrenal venous sampling - is the aldo secretion unilateral?
• Metomidate PET CT

Question 14

• What is adrenal venous sampling?
• When may it be done?

Answer 14

• In AVS, adrenal veins are cannulated and from each a blood sample is drawn
• Used to determine cortisol and aldosterone

Question 15

CT scan - what diagnosis? (A)

Answer 15

Conn’s syndrome (primary hyperaldosteronism)

Question 16

What is this showing? (adrenal ….)

Answer 16

Adrenal venous sampling

Question 17

What kind of scan is this? (for Primary Hyperaldosteronism)

Answer 17

11C Metomidate PET scan

Question 18

Primary Hyperaldosteronism - Treatment

• Unilateral Adenoma
  
  • Laparoscopic …
  • Medical Treatment (sometimes)
• Bilateral Hyperplasia
  
  • medical treatment - aldosterone … such as
    
    • …lactone
    • eplerinone

Answer 18

• Unilateral Adenoma
  
  • Laparoscopic Adrenalectomy
  • Medical Treatment (sometimes)
• Bilateral Hyperplasia
  
  • medical treatment - aldosterone antagonists (such as….)
    
    • spironolactone
    • eplerinone

Question 19

Primary hyperaldosteronism can be caused by either hyperactivity in one adrenal gland (… disease) or both (… disease).

Answer 19

Primary hyperaldosteronism can be caused by either hyperactivity in one adrenal gland (unilateral disease) or both (bilateral disease).

Question 20

What 2 aldosterone antagonists can be used to treat primary hyperaldosteronism? (usually bilateral?)

Answer 20

• spironolactone
  
  • cheap but may lead to gynecomastia - men may not take
• eplerinone

Question 21

Medical treatment for men with primary hyperaldosteronism - which drug is better?

1. Spironolactone
2. Eplerinone

Answer 21

• Spironolactone is known to cause more gynecomastia or breast pain (up to 10%) in male patients than eplerenone (up to 0.5%)
• Therefore, eplerenone is better suited

Question 22

What is Phaechromocytoma?

Answer 22

Tumour of the adrenal medulla

Question 23

The adrenal medulla is a modified group of … - …. nerve cells innervated by … nerves

Answer 23

The adrenal medulla is a modified group of post-ganglionic nerve cells innervated by preganglionic nerves

Question 24

Adrenal medulla - secreting catecholamines

• …. neurons in spinal cord
• Adrenal medulla -> Tyrosine
• Tyrosine converted to L-….
• This is converted to - Dopamine
• Dopamine - excreted or converted to …
• this is converted to -> ….

Answer 24

• Sympathetic neurons in spinal cord
• Adrenal medulla - Tyrosine
• Tyrosine - L-DOPA
• L-DOPA - Dopamine
• Dopamine - excreted or converted to noradrenalin
• noradrenalin -> adrenalin

Question 25

_Products of the Adrenal Medulla_ * .... such as 1) dopamine, 2) ... and 3) ... * How is 2 converted to 3? (high levels of ...)

Answer 25

* **Catecholamines** such as 1) **dopamine**, 2) **Norepinephrine (Noradrenalin)** and 3) **Epinephrine (Noradrenalin)** * How is 2 converted to 3? - Cortisol (requires high levels)

Question 26

Are catecholamines essential for life?

Answer 26

No - useful for stress/fight/flight

Question 27

_Catecholamines - biological effects_ * **Adrenalin stimulates what receptors?** * **Vasoconstriction or Vasodilation?** * **What does this lead to in terms of blood pressure and skin?** * **What happens to glucose levels?**

Answer 27

* Noradrenalin stimulates **alpha 1 and 2 receptors** * **vasoconstriction** * **increased BP and pallor** * **glucose increases due to glycogenolysis**

Question 28

_Catecholamines - biological effects_ * **Noradrenalin stimulates what receptors?** * **Vasoconstriction or Vasodilation? (BV and muscle)** * **What does this lead to in terms of HR and skin?**

Answer 28

* Adrenalin stimulates **alpha 1, beta 1 and beta 2 receptors** * **Vasoconstriction, vasodilation in muscle** * **Increased HR, sweating**

Question 29

_Pathology of Phaeochromocytoma_ * ...% of phaeos are diagnosed in the mortuary

Answer 29

**20**% of phaeos are diagnosed in the mortuary

Question 30

_Presentation of Phaeochromocytoma_ * "spells" such as ... (5) * Hypertension, which may be ... or .... * ... Hx present

Answer 30

* "spells" * **headache, sweat** * **pallor, palpitation** * **anxiety** * Hypertension * **permanent** * **intermittent** * **family Hx**

Question 31

_Several A-D Genetic conditions are associated with Phaechromocytoma_ * ... Type 1 (NF1) * Multiple Endocrine ... Type 2 (MEN 2) * Von hippel - ... Syndrome

Answer 31

* **Neurofibromatosis** Type 1 (NF1) * Multiple Endocrine **Neoplasia** Type 2 (MEN 2) * Von hippel - **Lindau** Syndrome

Question 32

* What genetic condition is this? (Associated with phaeochromocytoma)

Answer 32

* **Neurofibromatosis Type 1 (NF1)**

Question 33

The picture below shows Axillary freckling - what condition is this present in? (associated with phaeochromocytoma)

Answer 33

Neurofibromatosis Type 1 (NF1)

Question 34

What do people in a MEN2a family develop? (3 things)

Answer 34

* **Medullary carcinoma** of the thyr**o**id * Develop **bilateral pheochromocytoma** * Also may develop **primary hyperparathyrodism**

Question 35

To prevent children from developing a medullary carcinoma in a MEN2a family, what would you do?

Answer 35

* Total thyroidectomy at age 5/6/7 to prevent development * Screen for other complications

Question 36

* What is this image showing? (can get it in Von Hippel-Lindau syndrome) * What is it often associated with?

Answer 36

* Retinal Hemangioglioblastoma * often associated with a cerebellar haemangioglioblastoma (shown below)

Question 38

_Phaeochromocytoma - Biochemical Diagnosis_ * **24 hour ... test** * measure the ... and ... * measure ... to see if too much dopamine being made * **Plasma (if issue with other method)** * measure ... and ... * also measure the ... as above

Answer 38

* **24 hour urine test** * measure the **normetanephrines** and **metanephrines** * measure **3 methoxytyromine** to see if too much dopamine being made * **Plasma (if issue with other method)** * **noradrenalin** and **adrenalin** * **metanephrines** as above

Question 39

_What else elevates the measured catecholamines?_ * Obstructive .... .... * ... like drugs * L-... * Labetalol (hypertensive drug with some beta blocker activity)

Answer 39

* Obstructive **sleep apnoea** * **Amphetamine** like drugs * **L-DOPA** * Labetalol

Question 40

_Why do we not measure dopamine in 24 hour urine?_ * Urine dopamine does not come from the adrenal medulla, it comes from ... and .... so we measure what instead?

Answer 40

Urine dopamine does not come from the adrenal medulla, it comes from **kidney** and **nervous system** so we measure **methoxytyramine** instead

Question 41

Pathology of adrenal medulla - what is shown?

Answer 41

Phaeochromocytoma - larger than adenomas in Conn's syndrome (average 4cm)

Question 42

To be sure of a phaeochromocytoma. we do a ... scan

Answer 42

To be sure of a phaeochromocytoma. we do a **MIBG** scan

Question 43

_Other imaging for phaeochromocytoma_ * .... ... scan to show extra-adrenal "phaeos" or metastases

Answer 43

* PET CT scan

Question 44

_Management of phaeochromocytoma_ before surgical procedure (laparoscopic ... ) give... * ... blockers - prevent hypertension * **phenocybenzamine** * **doxazocin** * ... blockers afterwards * propranolol * then surgery once blockade is satisfactory

Answer 44

* **surgery = laparoscopic adrenalectomy** * **alpha blockers** * phenocybenzamine * doxazocin * **beta blockers** * propranolol * laparoscopic adrenalectomy

Question 45

_Post-adrenalectomy care_ * Consider ... testing as ...% are ... * annual ... tests (via 24 hour urine and plasma) * additional treatment if it is ... (10% are)

Answer 45

* Consider **genetic** testing as **30**% are **genetic (13 mutations so far)** * annual **metanephrines** (via 24 hour urine and plasma) * additional treatment if it is **malignant** (10% are)