Mineralocorticoid Excess Insights

Physiology Of Aldosterone

Produced in the adrenal cortex's zona glomerulosa. Aldosterone synthesis is controlled by RAAS. Encouragement of Aldosterone: reduction in glomerular filtrate and hypotension. Aldosterone affects the DCT's principal cells. DCT channels: sodium channels in epithelium.

Physiological Action of Aldosterone 

Water and sodium retention has increased. Elevated excretion of H+ and potassium.

Function: Maintain the BP, Electrolyte balance

Raas Mechanism

Reduced glomerular filtrate or hypotension. Reduced renal blood flow. JG apparatus activation. Renin is released by JG cells. Renin converts angiotensinogen to angiotensin 1. Angiotensin converting enzyme converts angiotensin 1 to angiotensin 2. Angiotensin 2 causes vasoconstriction and releases the aldosterone, which results in sodium and water retention. Raised blood pressure.

Epidemiology Of Hyperaldosteronism

Primary hypertension is essential hypertension with an unknown etiology. Secondary hypertension is hypertension with an identified etiology. The prevalence of secondary hypertension ranges from 5 to 21%. Hypertension brought on by hypokalemia is more common when hyperaldosteronism is present.

Etiology

Compared to secondary hyperaldosteronism, primary hyperaldosteronism is more prevalent. Adrenal adenoma; the cause of primary hyperaldosteronism. Micronodular hyperplasia (more prevalent), Bilateral adrenal hyperplasia, Hyperplasia of macronodular buds. Conn's syndrome is more frequently caused by bilateral adrenal hyperplasia than by unilateral adrenal adenoma.

Rare Causes

• Because it is linked to early onset hypertension and the development of stroke, recognition is crucial.
• Family history will aid in determining the main transmission of hypertension.

Causes Of Mineralocorticoid Excess

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Rare Causes For Mineralocorticoid Excess

Syndrome Of Mineralocorticoid Excess (SAME)

11 beta HSD2 transforms cortisol into cortisone, which lowers cortisol levels. 11 beta HSD2 inactivation. Steroids' excessive stimulation of the mineralocorticoid receptor. Symptom: Childhood-onset hypokalemic hypertension

Type II same

• Milder mutation
• Potassium levels are normal.
• Hypertension is present. 
• It occurs in adults. 

Cushing's Syndrome

A surplus of cortisol will outweigh 11 beta HSD2's ability to inactivate into cortisone, activating the mineralocorticoid receptor. Overdosing on steroids.

Glucocorticoid Resistance 

Mutation of the glucocorticoid receptor  Increased cortisol production  Mineralocorticoid receptor activation. Overdosing on steroids.

Adrenocortical Carcinoma

Rare Cause

Congenital Adrenal Hyperplasia

Rare Cause

Deoxycorticosterone builds up when CYP11B1 or CYP17A1 mutations occur. This activates the mineralocorticoid receptor. Overdosing on steroids.

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Progesterone Induced Hypertension

Function as an aberrant ligand. Because of changes in the gene encoding the mineralocorticoid receptor. Overdosing on steroids

Liddle's Syndrome

Inheritance: Autosomal dominant 

Increased epithelial sodium channel activity  Similar physiological actions to hyperaldosteronism. The person will experience metabolic alkalosis, hypokalemia, and hypertension.

Clinical Features Of Hyperaldosteronism

Excess amount of sodium and water retention

Increase in fluid volume- Results in diastolic hypertension. No edema

Increased stroke volume, increased venous return, increased cardiac output, increased sodium and water retention from DCT, increased renal perfusion and polyuria, and increased fluid volume
Hypertension is the outcome.

 Under high pressure, more water and salt are expelled. It causes pressure diuresis and pressure natriuresis.  Known as the phenomena of aldosterone escape.

Potassium excretion causes hypokalemia.

• Potassium helps to maintain the action potential.
• The patient will develop.
• Proximal myopathy
• Flaccid paralysis
• Constipation
• Tachyarrhythmias
• Polyuria
• Polydipsia

H+ ion excretion 

Alkalosis in metabolism is the outcome. Symptoms include: Tetany (severe cases) ,  Muscle cramping

Aldosterone

The vascular system is directly impacted by aldosterone. It also increases cardiac remodeling. Reduced adherence. Hypertensive nephropathy, also known as renal nephropathy, causes hypertension due to hyperaldosteronism, which in turn damages the kidney and myocardium directly.

The clinical indicator of excess mineralocorticoids is: Approximately 50% of patients with primary aldosteronism experience hypokalemic hypertension.   Potassium levels are less than 3.5.  Hypermagnesemia will also happen.

Hypokalemia causes the renal tubules to absorb less magnesium, which increases the amount of magnesium lost through urine. Insufficient magnesemia.

• Osteoporosis
• Type 2 DM
• Cognitive dysfunction

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Osteoporosis

Overdosing on aldosterone led to increased excretion of calcium, decreased levels of calcium, activation of parathyroid hormone secretion, and increased resorption of bone, thus cause Osteoprosis

Type 2 DM

Insulin resistance is linked to hypoaldosteronism.  Impaired glucose metabolism  Type 2 diabetes mellitus development

Cognitive Dysfunction

The development of cognitive dysfunctions and decreased blood flow to the brain are caused by the vasoconstrictive properties of cerebral blood vessels exhibited by testosterone in cases of vascular dementia.

Cushing Syndrome 

• Hyperaldosteronism with increased cortisol secretion 
• MACE: Mild autonomous cortisol excess

Diagnostic Screening

Not every patient should use it. It need to be limited to hypertension linked to medication resistance. Serum potassium levels should be normal.  Hypertension in people under 40.  Hypertension with hypokalemia.  Hypertension with adrenal mass.
  Abstain from HTN medications such as ACE inhibitors, ARBs, beta blockers, and others;  Give up for a minimum of four weeks prior to doing an Aldosterone-renin ratio. Aldosterone-renin ratio screening
Mineralocorticoid antagonists and alpha-blockers are the only CCBs that the patient may continue taking.

Saline infusion test

Confirmatory test

The patient receives 2 liters of normal saline over the course of 4 hours. This results in an increase in renal perfusion, a decrease in testosterone levels, a failure to suppress testosterone to <140 pmol/L, and an excess of autonomous mineralocorticoids. 

Other tests

Oral sodium loading test

• Up to three days, 300 mmol of sodium chloride every day
• A rise in the excess of fluids.
• Lower levels of aldosterone; a decrease in RAAS.
• Verify the excess of aldosterone if not.

Fludrocortisone Suppression Test

• Sixth hourly + Nacl = 0.1 mg
• There is a drop in testosterone levels.
• If not, identify hyperaldosteronism as the cause.
Hypokalemia will precipitate, and hypertension will rise as a result.

Differential Diagnosis

Use a fine-cut CT scan (IOC) for adrenal imaging to visualize the morphology of the adrenal glands.  Adenomas measure less than one centimeter.  They are able to see the larger tumors but not the ones that are smaller than 5 mm.  To distinguish between unilateral and bilateral micronuclear adenoma, adrenal venous sample is used.

Adrenal Venous Sampling

 Difficult steps. A highly qualified radiologist is necessary.   The right adrenal vein is extremely challenging to cannulate.  Done on a surgical candidate who had no CT scan lesions.  Proof of a unilateral lesion in a person older than 40 years. Adrenal adenoma that is coincidentally inactive; comparison of testosterone levels.

A sample of aldosterone is drawn from the left, right, and inferior vena cava, Cortisol levels are also measured.  Aldosterone levels are recorded. To determine whether the catheter was inserted into the adrenal vein correctly. Vena cava gradient and each adrenal vein gradient: >3.

An Aldosterone/Cortisol ratio confirms lateralization.
• Pathology on the right side: >2 folds
• Pathology on the right and left sides: >2 folds

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Treatment

Surgical Resection 

Individual under 40 years old;  One lesion on the CT scan;  Verified excess of mineralocorticoids.  Adrenal venous sampling confirms the layering.  Only when a tumor is unilateral.  Procedure: Laparoscopic Adrenal Excision

Medical Management

Not candidates for surgery; bilateral hyperplasia verified by CT or AVS; excision causes a cortisol deficit; additionally advised in unilateral diseases; Before surgery . In order to prevent hypoaldosteronism following surgery.

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