65. Secondary hyperaldosteronism

Page created on May 18, 2019. Last updated on December 18, 2024 at 16:57

Secondary hyperaldosteronism

Secondary hyperaldosteronism refers to increased production of aldosterone in response to increased renin levels, as part of the renin-angiotensin-aldosterone-system (RAAS).

Etiology:

• Renal artery stenosis (often due to atherosclerosis)
  • Atherosclerosis (90% of cases)
  • Fibromuscular dysplasia of the renal artery (10% of cases)
• Renin-secreting tumors
• Chronic renal failure
• Cirrhosis
• Hypovolaemia
• Congestive heart failure
• Hypoproteinaemia
• Diuretics

Renin-secreting tumors are rare.

Pathophys department makes it seem like secondary hyperaldosteronism is a very important condition which occurs in virtually all conditions, but in reality it’s only clinically important in certain conditions, like renal artery stenosis, renin-secreting tumours and severe oedema or ascites.

Pathomechanism:

The RAAS is activated when the RBF decreases, as the juxtaglomerular apparatus in the macula densa can sense changes in its perfusion. When perfusion decreases more renin is produced. Renin production is also stimulated when less Na⁺ reaches the macula densa in the distal tubule.

Any condition that causes fluid to move out from the intravascular space and into the interstitial space (oedema) will activate RAAS. This explains how RAAS is activated in heart failure, hypoproteinaemia, chronic renal failure and ascites.

In chronic renal failure the GFR is decreased, which causes less Na⁺ to reach the distal tubule, which stimulates renin production.

In cirrhosis plasma fluid is lost to the abdominal cavity as part of ascites formation. This reduces plasma volume, reducing the RBF and causing RAAS activation.

The fluid loss that occurs during diuretic therapy activates RAAS, if hypovolaemia is achieved.

Secondary hyperaldosteronism is most commonly seen as a compensatory mechanism of low blood pressure or hypovolaemia, which is what the RAAS system is designed to do. When it occurs as a compensatory mechanism, normal or low blood pressure rather than hypertension is seen.

Clinical features:

Secondary hyperaldosteronism can be divided into two categories, those associated with hypertension and those that are associated with normotension or hypotension.

Forms associated with hypertension:

• Renin-secreting tumors
• Renal artery stenosis
• Chronic renal failure

Forms associated with normal or low blood pressure:

• Hypovolaemia
• Diuretics
• Congestive heart failure
• Cirrhosis
• Hypoproteinaemia

Hypokalaemia and metabolic alkalosis can occur in all types.

Pseudohyperaldosteronism

Pseudohyperaldosteronism refers to the condition where there is stimulation of mineralocorticoid receptor, but the aldosterone level is low. Something other than aldosterone stimulates the receptor in these cases.

Etiology:

• Congenital adrenal hyperplasia
• Exogenous mineralocorticoid therapy
• Cushing syndrome
• Peripheral glucocorticoid resistance
• DOC-secreting tumors
• Syndrome of apparent mineralocorticoid excess (SAME)
• Liddle syndrome
• Excessive liquorice ingestion

Pathomechanism:

In congenital adrenal hyperplasia and DOC-secreting tumors the weak mineralocorticoid deoxycorticosterone (DOC) stimulates the mineralocorticoid receptors rather than aldosterone.

In Cushing syndrome and peripheral glucocorticoid resistance, the level of cortisol is high. Thanks to the spill-over mechanism cortisol can act on and activate mineralocorticoid receptors.

Syndrome of apparent mineralocorticoid excess (SAME) is a genetic condition where the enzyme that breaks down cortisol in the periphery is deficient. This increases the amount of cortisol that can activate mineralocorticoid receptors. The same enzyme is inhibited by liquorice, so excessive consumption of this candy gives the same effect.

Liddle syndrome is a genetic disorder where the aldosterone-dependant sodium channel in the distal tubules is mutated and chronically active, even in absence of aldosterone. This causes aldosterone-like effects without aldosterone.

Clinical features:

The clinical features are similar as in any hyperaldosteronism.