Primary Aldosteronism Flashcards
… is a condition caused by an excess of the adrenal hormone aldosterone independent of the renin-angiotensin-aldosterone axis.
Primary aldosteronism is a condition caused by an excess of the adrenal hormone aldosterone independent of the renin-angiotensin-aldosterone axis.
The hallmarks of disease Primary aldosteronism ) are….
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.
Primary aldosteronism - Disease is caused by one of a number of subtypes:
Bilateral idiopathic hyperaldosternism (60-70%) Aldosterone-producing adenoma (30-40%) Unilateral hyperplasia (approx 3%) Other (familial hyperaldosteronism, adrenal carcinoma)
The adrenal gland is divided into two functionally distinct components, what are they?
The adrenal gland is divided into two functionally distinct components, an outer cortex and an inner medulla.
The adrenal cortex is the outermost aspect of the adrenal gland. It is composed of three layers:
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).
Adrenal medulla
The innermost aspect of the adrenal gland, composed of a single layer. Responsible for the production of three hormones:
Adrenaline
Noradrenaline
Dopamine
Under normal conditions aldosterone release is primarily controlled by the…. System
Under normal conditions aldosterone release is primarily controlled by the renin-angiotensin system.
Renin, a proteolytic enzyme, is released by granular cells of the juxtaglomerular apparatus in response to:
Renal artery hypotension
Sympathetic stimulation
Reduced sodium levels in the distal tubal
In the blood renin cleaves … into …
In the blood renin cleaves angiotensinogen into angiotensin I.
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:
Stimulates adrenal cortex to release aldosterone
Causes vasoconstriction
Increases sodium reabsorption
Stimulates the release of anti-diuretic hormone (ADH)
Increases sympathetic permissiveness
Aldosterone is a mineralocorticoid released from the zona glomerulosa of the adrenal cortex. It is released in response to:
Angiotensin II (primary stimulus)
ACTH
Potassium levels
… of aldosterone leads to sodium and water retention and potassium wasting.
Hypersecretion of aldosterone leads to sodium and water retention and potassium wasting.
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.
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.
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:
Pressure natriuresis
Atrial natriuretic peptide release
Changes to reabsorption in the distal tubule
In the vast majority of cases primary aldosteronism is caused by adrenal … adrenal …
In the vast majority of cases primary aldosteronism is caused by adrenal adenomas or adrenal hyperplasia.
Bilateral idiopathic hyperplasia
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.
Aldosterone-producing adenoma
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.
Unilateral hyperplasia
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.
Familial hyperaldosteronism:
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.
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)
Chronic kidney disease
Cerebrovascular disease
Heart failure
Retinopathy
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
Muscle weakness
Paraesthesia
Mood disturbance
Polyuria/nocturia
Hypertension is essentially universal in primary aldosteronism. All other features are variably present: (2)
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.
Primary aldosteronism has been described with hypokalaemia but an absence of hypertension - this is normally in … …
Primary aldosteronism has been described with hypokalaemia but an absence of hypertension - this is normally in young women
Patients should be tested where a secondary cause for hypertension is suspected. This includes:
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
Diagnosis of primary aldosteronism requires a multi-tier testing approach.
Screening for primary aldosteronism
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.
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:
Oral sodium loading test
Saline infusion test
Captopril challenge test
Identifying the cause of primary aldosteronism
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.
Unilateral disease - primary aldosteronism
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.
Bilateral disease - primary aldosteronism
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.
Features of …
Primary aldosteronism
Unexplained hypertension is a key sign of …
Primary aldosteronism
Suspecting primary aldosteronism -
U+E - raised sodium, low potassium
ECG - hypokalaemia (inverted T waves) widened PR
OBS - BP measurement
ABG/VBG - metabolic alkalosis possible
ARR - what is this?
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)
Imaging/venous sampling for primary aldosteronism
CT adrenals or adrenal venous sampling
ECG may show findings characteristic of … in primary aldosteronism
ECG may show findings characteristic of hypokalaemia in primary aldosteronism
Surgical and medical management of primary aldosteronism
Adrenal adenoma - resection/adrenalectomy
Idiopathic adrenal hyperplasia - aldosterone agnostic - e.g. spironolactone (may cause gynaecomastia, nausea, rashes)
Unexplained hypertension and non-specific symptoms of mild hypokalaemia are typical of …
Primary aldosteronism
Renin is released by the … cells of the juxtaglomerular apparatus.
Renin is released by the granular cells of the juxtaglomerular apparatus.
… is associated with ECG findings of ST-depression, flattened/inverted T-waves and U-waves (which are upward deflections occurring after T-waves).
Hypokalaemia is associated with ECG findings of ST-depression, flattened/inverted T-waves and U-waves (which are upward deflections occurring after T-waves).
… … is a classical finding of primary aldosteronism however in practice it is infrequently found.
Metabolic alkalosis is a classical finding of primary aldosteronism however in practice it is infrequently found.
