• Aldosterone is a steroid hormone in the mineralocorticoid family that plays a vital role in the maintenance of intravascular volume status sodium balance.
• Aldosterone is synthesized secreted by the zona glomerulosa of the adrenal cortex in response to low intravascular volume, decreased renal perfusion, hyperkalemia, acidosis.
• Disease states include Addison disease (hypoaldosteronism) Conn syndrome (hyperaldosteronism).

• Aldosterone is synthesized from cholesterol within the adrenal cortex by a series of steroidogenic reactions catalyzed by enzymes of the cytochrome p450 family. It is a steroid hormone that exerts its action by binding to an intracellular cytoplasmic receptor. This bound complex enters the cell nucleus stimulates DNA transcription, resulting in protein production that mediates the ultimate effects of aldosterone.
• Renin–angiotensin system (RAS) regulation: Aldosterone secretion is regulated primarily by RAS via the following mechanism:
  • Intravascular volume depletion triggers a decrease in renal perfusion pressure.
  • Renin is secreted by the juxtaglomerular cells of the afferent arteriole in response to this decrease in renal perfusion pressure.
  • Renin catalyzes the conversion of angiotensinogen to angiotensin I in plasma.
  • Angiotensin-converting enzyme (ACE) catalyzes the conversion of angiotensin I to angiotensin II, primarily in the lungs.
  • Angiotensin II stimulates the synthesis secretion of aldosterone.
• Adrenocorticotropic hormone (ACTH): Aldosterone is also under tonic control by ACTH (secreted by the anterior pituitary gl).
• Aldosterone hormone regulates volume blood pressure via:
  • Binding to mineralocorticoid receptors located in the principal cells of nephrons. This upregulates sodium/potassium pumps with resultant sodium water reabsorption potassium sercetion by the distal tubules collecting ducts. The net effect is the restoration of intravascular volume blood pressure.
  • Acting on alpha-intercalated cells of the late distal tubule collecting duct, resulting in increased renal hydrogen ion secretion.

• Aldosterone is produced by cells within the zona glomerulosa of the adrenal cortex.
• The adrenal gl is composed of the inner medulla which produces catecholamines the outer cortex which is divided into 3 histologic zones. Going from outside moving inwards:
  • The outermost zona glomerulosa is the source of aldosterone production.
  • Just beneath is the zona fasciculata, the source of glucocorticoid production.
  • The inner-most layer of the cortex is the zona reticularis, responsible for the production of rogens.

• Primary adrenocortical insufficiency (Addison disease)—a hypoaldosterone state:
  • Most common cause is autoimmune destruction of the adrenal cortex, resulting in acute adrenal crisis (1). Other causes of adrenocortical insufficiency include metastatic disease to the adrenal cortex, adrenal hemorrhage, infection of the adrenal gl (tuberculosis, opportunistic infections with HIV, fungemia), amyloid infiltration.
  • Characterized by elevated ACTH levels but decreased levels of glucocorticoids mineralocorticoids
  • Clinical features are related to the adrenocortical hormone deficiency. Hypoglycemia is caused by cortisol deficiency. Hypotension, hyperkalemia, metabolic acidosis, volume contraction are caused by aldosterone deficiency. Hyperpigmentation is caused by elevated ACTH secretion. Other signs symptoms include weakness, fatigue, lethargy, anorexia, nausea, abdominal pain, prerenal azotemia, hypercalcemia, convulsions, fever, syncope.
  • Treatment: Replacement of glucocorticoids (hydrocortisone, prednisone, methylprednisolone) mineralocorticoids (fludrocortisone)
• Secondary adrenocortical insufficiency is caused by decreased ACTH secretion, resulting primarily in a glucocorticoid deficiency. Mineralocorticoid deficiency is also seen but to a lesser degree.
  • Most common cause of secondary adrenocortical insufficiency is sudden withdrawal of long-term corticosteroid therapy (2). Other causes include pituitary tumor, pituitary surgery or radiation, postpartum hypopituitarism (Sheehan syndrome), sarcoid infiltration of the pituitary gl.
  • Chronic corticosteroid therapy suppresses the hypothalamus anterior pituitary, resulting in decreased production of corticotropin-releasing hormone (CRH) ACTH, respectively. Decreased levels of CRH ACTH cause atrophy of the zona fasciculata, resulting in glucocorticoid deficiency. During times of physiologic stress, the patient is unable to acutely increase cortisol production, resulting in acute secondary adrenocortical deficiency.
• Primary hyperaldosteronism is caused by aldosterone-secreting tumors.
  • Conn syndrome (aldosterone-secreting adrenocortical adenoma) is the most common cause. Bilateral adrenal hyperplasia occurs less commonly.
  • Characterized by hypertension, hypokalemia, metabolic alkalosis, a low renin state. Other signs symptoms include tetany, polyuria, an inability to concentrate urine.
  • Primary hyperaldosteronism may be present in 0.5–1% of patients with hypertension (3).
  • Treatment: Medically by spironolactone (aldosterone receptor antagonist), surgically with adrenalectomy

• Hypoaldosterone states:
  • Patients with adrenocortical insufficiency should continue their mineralocorticoid glucocorticoid replacement therapy up until their time of surgery. Clinical features of overt hypoaldosteronism include hyperkalemia, hyponatremia, acidosis, myocardial conduction defects. Administration of mineralocorticoids (fludrocortisone 0.05–0.1 mg/d) should occur preoperatively (1). Doses must be carefully titrated to avoid hypertension.
  • Additional perioperative stress dose of glucocorticoids may be necessary since these patients may not be able to mount an adequate stress response. The traditional recommendation is 200 mg hydrocortisone per 70 kg body weight per day. However, smaller doses of 100 mg per 70 kg body weight per day have been used with success (2).
  • The amount of perioperative hydrocortisone is based on the anticipated stress of the procedure. The relative degree of trauma depth of anesthesia should be considered.
• Hyperaldosterone states:
  • Patients presenting for elective surgery should be medically optimized in terms of their adrenocortical disorder. Preoperative EKG, glucose, serum electrolytes (particularly sodium potassium) should be checked. Volume status blood pressure should be optimized.
  • Primary aldosteronism (Conn syndrome) should be suspected in patients who present with concurrent hypertension hypokalemia, severe refractory hypertension, adrenal incidentaloma hypertension, or onset of hypertension at a young age.
  • Antihypertensive medications (e.g., spironolactone) should be maintained up to the time of surgery. Careful cardiac assessment is necessary because these patients have increased cardiac comorbidity. Serum sodium especially serum potassium should be checked prior to surgery. Hypokalemia is common. Severely hypokalemic patients should have their potassium replaced preoperatively.

• Cortisol
• Acute Adrenal Insufficiency

Joe C. Hong , MD