Primary Aldosteronism

Question 1

… is a condition caused by an excess of the adrenal hormone aldosterone independent of the renin-angiotensin-aldosterone axis.

Answer 1

Primary aldosteronism is a condition caused by an excess of the adrenal hormone aldosterone independent of the renin-angiotensin-aldosterone axis.

Question 2

The hallmarks of disease Primary aldosteronism ) are….

Answer 2

The hallmarks of disease are hypertension and hypokalaemia - though hypokalaemia is often absent. Primary aldosteronism is increasingly being recognised as a common and under-diagnosed cause of secondary hypertension. Today prevalence is thought to be between 5-15% of patients with hypertension.

Question 3

Primary aldosteronism - Disease is caused by one of a number of subtypes:

Answer 3

Bilateral idiopathic hyperaldosternism (60-70%)
Aldosterone-producing adenoma (30-40%)
Unilateral hyperplasia (approx 3%)
Other (familial hyperaldosteronism, adrenal carcinoma)

Question 4

The adrenal gland is divided into two functionally distinct components, what are they?

Answer 4

The adrenal gland is divided into two functionally distinct components, an outer cortex and an inner medulla.

Question 5

The adrenal cortex is the outermost aspect of the adrenal gland. It is composed of three layers:

Answer 5

Zona Glomerulosa: mineralocorticoids - aldosterone is the key mineralocorticoid, release primarily controlled by the renin-angiotensin system (described below).
Zona Fasciculata: glucocorticoids - release controlled by hypothalamic-pituitary-adrenal axis (described below).
Zona Reticularis: androgens - produces dehydroepiandrosterone (DHEA).

Question 6

Adrenal medulla

The innermost aspect of the adrenal gland, composed of a single layer. Responsible for the production of three hormones:

Answer 6

Adrenaline
Noradrenaline
Dopamine

Question 7

Under normal conditions aldosterone release is primarily controlled by the…. System

Answer 7

Under normal conditions aldosterone release is primarily controlled by the renin-angiotensin system.

Question 8

Renin, a proteolytic enzyme, is released by granular cells of the juxtaglomerular apparatus in response to:

Answer 8

Renal artery hypotension
Sympathetic stimulation
Reduced sodium levels in the distal tubal

Question 9

In the blood renin cleaves … into …

Answer 9

In the blood renin cleaves angiotensinogen into angiotensin I.

Question 10

Angiotensin-converting enzyme (ACE), found primarily in the vascular endothelium of the lungs, cleaves angiotensin I to give angiotensin II.

Angiotensin II has multiple functions:

Answer 10

Stimulates adrenal cortex to release aldosterone
Causes vasoconstriction
Increases sodium reabsorption
Stimulates the release of anti-diuretic hormone (ADH)
Increases sympathetic permissiveness

Question 11

Aldosterone is a mineralocorticoid released from the zona glomerulosa of the adrenal cortex. It is released in response to:

Answer 11

Angiotensin II (primary stimulus)
ACTH
Potassium levels

Question 12

… of aldosterone leads to sodium and water retention and potassium wasting.

Answer 12

Hypersecretion of aldosterone leads to sodium and water retention and potassium wasting.

Question 13

In the presence of … excess the human body begins to retain sodium and water. The increase in volume and changes to systemic vascular resistance lead to hypertension. Hypokalaemia may result in 15-30% of cases from the increase in potassium excretion.

Answer 13

In the presence of aldosterone excess the human body begins to retain sodium and water. The increase in volume and changes to systemic vascular resistance lead to hypertension. Hypokalaemia may result in 15-30% of cases from the increase in potassium excretion.

Question 14

The volume expansion prompted by increased water reabsorption results in an ‘escape’ phenomenon. This is a diuresis that occurs in response to the water and sodium retention caused by raised aldosterone. The exact mechanisms are unclear but appear to involve:

Answer 14

Pressure natriuresis
Atrial natriuretic peptide release
Changes to reabsorption in the distal tubule

Question 15

In the vast majority of cases primary aldosteronism is caused by adrenal … adrenal …

Answer 15

In the vast majority of cases primary aldosteronism is caused by adrenal adenomas or adrenal hyperplasia.

Question 16

Bilateral idiopathic hyperplasia

Answer 16

Also called idiopathic adrenal hyperplasia, this the most common cause of primary aldosteronism, implicated in 60-70% of cases. It tends to cause a primary aldosteronism that is less severe than that caused by aldosterone-producing adenomas.

Question 17

Aldosterone-producing adenoma

Answer 17

Primary aldosteronism was first described by Conn in the 1950’s in patients with adrenal adenomas (hence the alternate name Conn’s syndrome). The autonomous adenoma produces aldosterone independent of normal mechanisms.

Once thought to be the most common cause of primary aldosteronism, it is implicated in around 30-40% of cases.

Question 18

Unilateral hyperplasia

Answer 18

This is caused by hyperplasia only affecting one gland. Far less common than the bilateral form and may be treated more like an aldosterone-producing adenoma.

Question 19

Familial hyperaldosteronism:

Answer 19

Type 1: Glucocorticoid-remediable aldosteronism
Type 2: Poorly understood, likely most common familial cause, appears to be due to an inherited adrenal adenoma or idiopathic adrenal hyperplasia.
Type 3: Mutations in KCNJ5 gene

Adrenal carcinoma is a rare cause.

Question 20

Hypertension is generally asymptomatic but present in the vast majority of patients with primary aldosteronism. Long-standing hypertension may result in end-organ damage:

(4)

Answer 20

Chronic kidney disease
Cerebrovascular disease
Heart failure
Retinopathy

Question 21

Hypokalaemia affects around 10-30% of patients with primary aldosteronism. It is normally asymptomatic but may present with non-specific signs and symptoms including: 4

Answer 21

Muscle weakness
Paraesthesia
Mood disturbance
Polyuria/nocturia

Question 22

Hypertension is essentially universal in primary aldosteronism. All other features are variably present: (2)

Answer 22

Metabolic alkalosis: caused by increased urinary hydrogen excretion, multifactorial, due to hypokalaemia and direct effects of aldosterone on intercalated cells.
Hypokalaemia: low serum levels are present in 15-30% of patients. Urinary potassium may demonstrate inappropriate potassium loss in the setting of hypokalaemia.

Question 23

Primary aldosteronism has been described with hypokalaemia but an absence of hypertension - this is normally in … …

Answer 23

Primary aldosteronism has been described with hypokalaemia but an absence of hypertension - this is normally in young women

Question 24

Patients should be tested where a secondary cause for hypertension is suspected. This includes:

Answer 24

Hypertension and hypokalaemia (spontaneous or diuretic-induced)
Severe hypertension (systolic > 150, diastolic > 100)
Hypertension resistant to treatment
Hypertension and:
Adrenal incidentaloma
Sleep apnea
Family history of early onset hypertension
Family history of early onset CVA
Primary aldosteronism affecting all 1st degree relatives with hypertension

Question 25

Diagnosis of primary aldosteronism requires a multi-tier testing approach.

Answer 25

Question 26

Screening for primary aldosteronism

Answer 26

The aldosterone:renin ratio (ARR) is used as a screen in those with suspected primary aldosteronism. It compares serum levels of aldosterone and renin. A raised ratio should prompt further investigation.

Question 27

Those with a raised ARR will normally require confirmatory testing. In patients with positive ARR screening and spontaneous hypokalaemia, undetectable renin and a plasma aldosterone concentration > 20ng/dL confirmatory tests may not be needed.

Where indicated a number of tests are available:

Answer 27

Oral sodium loading test
Saline infusion test
Captopril challenge test

Question 28

Identifying the cause of primary aldosteronism

Answer 28

A CT of the adrenal glands is the next line investigation in people with positive ARR/confirmatory testing. It may provide evidence of an adrenal adenoma or hyperplasia. CT can be misleading and it is at times difficult to distinguish adenomas from non-functioning incidentalomas or even hyperplasia based disease.

The gold-standard to confirm laterality is adrenal vein sampling - it has an excellent ability to differentiate between bilateral and unilateral disease. It is however an invasive and technically difficult procedure with risk of bleeding, thromboembolism and contrast reactions. It should not be performed in patients unwilling or not fit for surgery.

Investigations and management are guided by expert MDTs. They may consider avoiding AVS and proceeding to unilateral adrenalectomy in select patients - typically young patients with frank primary aldosteronism and findings consistent with an adenoma on CT.

Question 29

Unilateral disease - primary aldosteronism

Answer 29

This includes patients with aldosterone-producing adenomas and unilateral hyperplasia. In those whom are fit and willing, unilateral adrenalectomy offers cure. This may be either laparoscopic or open depending on patient factors and local expertise.

Medical management with mineralocorticoid receptor antagonists (e.g. spironolactone) can be used as a bridge to surgery or as definitive management in those not for surgical intervention.

Question 30

Bilateral disease - primary aldosteronism

Answer 30

Mineralocorticoid receptor antagonists: Spironolactone, Eplerenone (newer, unlike spironolactone does not cause gynaecomastia).
ENaC inhibitor: Amiloride, a potassium-sparing diuretic, may be used if aldosterone antagonists are not tolerated.

Question 31

Features of …

Answer 31

Primary aldosteronism

Question 32

Unexplained hypertension is a key sign of …

Answer 32

Primary aldosteronism

Question 33

Suspecting primary aldosteronism -

Answer 33

U+E - raised sodium, low potassium
ECG - hypokalaemia (inverted T waves) widened PR
OBS - BP measurement
ABG/VBG - metabolic alkalosis possible

Question 34

ARR - what is this?

Answer 34

Aldosterone renin ratio - high (due to suppression of renin)
Test is not diagnostic - if abnormal move on to more definitive testing (e.g. serum aldosterone levels, saline suppression test, salt loading test)

Question 35

Imaging/venous sampling for primary aldosteronism

Answer 35

CT adrenals or adrenal venous sampling

Question 36

ECG may show findings characteristic of … in primary aldosteronism

Answer 36

ECG may show findings characteristic of hypokalaemia in primary aldosteronism

Question 37

Surgical and medical management of primary aldosteronism

Answer 37

Adrenal adenoma - resection/adrenalectomy

Idiopathic adrenal hyperplasia - aldosterone agnostic - e.g. spironolactone (may cause gynaecomastia, nausea, rashes)

Question 38

Unexplained hypertension and non-specific symptoms of mild hypokalaemia are typical of …

Answer 38

Primary aldosteronism

Question 39

Renin is released by the … cells of the juxtaglomerular apparatus.

Answer 39

Renin is released by the granular cells of the juxtaglomerular apparatus.

Question 40

… is associated with ECG findings of ST-depression, flattened/inverted T-waves and U-waves (which are upward deflections occurring after T-waves).

Answer 40

Hypokalaemia is associated with ECG findings of ST-depression, flattened/inverted T-waves and U-waves (which are upward deflections occurring after T-waves).

Question 41

… … is a classical finding of primary aldosteronism however in practice it is infrequently found.

Answer 41

Metabolic alkalosis is a classical finding of primary aldosteronism however in practice it is infrequently found.