hyperaldosteronism

Introduction

hyperaldosteronism is due to excessive aldosterone secretion from the adrenals and causes hypertension with hypokalaemia and metabolic alkalosis
it is characterized by a high serum level of aldosterone and a low serum renin level if primary and a high serum renin level is secondary
the same clinical features but with normal or low levels of aldosterone may be caused by pseudoaldosteronism which may be due to:
- licorice ingestion
  - licorice inhibits the 11-beta hydroxysteroid dehydrogenase type II (Protein:HSD11B2) enzyme resulting in inappropriate stimulation of the mineralocorticoid receptor by cortisol
- high gluocorticosteroid levels
- Liddle's syndrome (an extremely rare genetic disorder)
- apparent mineralocorticoid excess syndrome a rare AR disorder

note: serum renin levels will be low
idiopathic bilateral adrenal cortical hyperplasia (70% of cases)
adrenal adenoma
- Conn's syndrome
- large aldosterone-secreting adrenal adenomas
  - tend to be picked up on CT scans given their larger size
  - tend to have pathogenic KCNJ5 variants (30-40% of large aldosterone-secreting adrenal adenomas)
  - cells paradoxically resemble the cortisol- rather than aldosterone-secreting zone of the normal adrenal gland
- ZG-like aldosterone-secreting adrenal adenomas
  - tend to have pathogenic CACNA1D, ATP1A1 and ATP2B3 variants
  - tend to be smaller and missed on CT scans
  - cells resemble the physiological aldosterone-secreting cells of the adrenal zona glomerulosa (ZG)
- daily transient adrenal adenoma hyper-aldosteronism
  - discovered in 2023 ¹⁾
    - requires 24hr urine aldosterone to detect as serum levels may miss the transient rises
    - caused by a somatic mutation in aldosterone-producing adenomas of the gene which produces a protein called cell adhesion molecule 1 (CADM1)
    - seems to the the cause of 5-10% of cases of hypertension
    - Rx is unilateral adrenalectomy
adrenal carcinoma is an extremely rare cause
glucocorticoid remediable aldosteronism (aldosterone synthase hyperactivity), is an autosomal dominant disorder in which the increase in aldosterone secretion produced by ACTH is no longer transient.

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