Hyperaldosteronism Or CONN's Syndrome Explained and Treatment

Aldosterone is a mineral corticoid produced and released from the most superficial layer or zona glomerulosa of adrenal cortex. Cortisol which is a glucocorticoid and de-hydro-epiandosterone which is a sex hormone is produced and released from the deeper layers: zona fasciculata and zona reticularis of the adrenal cortex.

• In the cells of zona glomerulosa aldosterone is synthesized and released: 
• Cholesterol is taken from low density lipoproteins by the mitrochondria. 
• Cholesterol is converted to pregnenolone in mitrochondria. Pregnenolone is then taken up by endoplasmic reticulum and converted to progesterone. 
• Progesterone is converted to deoxycorticosterone in endoplasmic reticulum.
• Deoxycorticosterone is again taken up by mitrochondria and converted first to corticosterone and then to aldosterone.

Aldosterone acts on the epithelial cells of distal convulated tubule, collecting tubule and collecting duct of nephrons. When aldosterone acts on an epithelial cell, it enables the excretion of potassium ions into the lumen and enables the reabsorption of sodium ions and water from the lumen into the interstitial fluid.

Aldosterone also stimulates cells of large intestine, mammary glands, sweat glands and salivary glands to do the same functions. Aldosterone function may also be performed by its pre-cursors de-oxy-corticosterone and corticosterone.

Prolonged aldosterone excess:

Hypernatremia (Increased concentration of sodium in blood) +water retention leading to hypertension, hypokalemia (decreased concentration of potassium in blood), alkalosis or formation of HCO3- due to excessive H+ excretion.

Prolonged aldosterone deficiency: 

Hyponatremia + water loss, hyperkalemia, acidosis or formation of H2CO3.

Coticotropin releasing hormone (CRH) released by the hypothalamus acts on corticotropes (CRH releasing cells) of anterior pituitary to release adrenocorticotropic hormone (ATCH). ACTH mainly acts on fasciculata and reticularis cells and causes release of cortisol and dehydro-epiandosterone. The secretion of aldosterone from glomerulosa cells is mainly stimulated by renin-angiotensin system, little by ACTH and hyperkalemia.

Renin-angiotensin system: 

It is performed by the juxta-glomerular apparatus. The juxta-glomerular apparatus consists of part of the distal convulated tubule that is surrounded by a V-shaped fork formed by the afferent and efferent arteriole moving to and from the glomerulus. The smooth muscles of the arterioles forming the V-shaped fork are called granular cells. During low blood pressure, the granuler cells produce a substance called renin. Renin converts angiotensin (a plasma protein found in blood secreted by the liver cells) to angiotensin1. When blood containing angiotensin1 passes through the pulmonary capillaries an enzyme there, angiotensin converting enzyme converts angiotensin1 to angiotensin2.

Angiotensin2 acts on smooth muscles of blood vessels causing their vasoconstriction. Angiotensin2 also acts on granular cells inhibiting renin release by negative feedback. It acts on liver cells and stimulates them to release more angiotensin by positive feedback. It also acts on glomerulosa cells and stimulates them to release aldosterone. Opposite to that, low angiotensin2 levels in the blood stimulate granular cells to secrete renin so that more angiotensin2 can be produced.

Low BP causes renin release so that there can be vasoconstriction. The opposite is also true i.e. inhibition of renin in response to high BP.

Causes of low BP: 

Dehydration, hemorrhage, shock, stenosis of renal artery or low BP caused by movement from supine to erect position.

Catecholamines can also act on beta adrenergic receptors on luminal surface of granular cells and stimulate them to release renin which causes production of angiotensin2. Angiotensin2 acts on smooth muscles of arteries and causes vasoconstriction.

Primary hyperaldosteronism or CONN’S syndrome: 

Characterized by increased Na+ retention, water retention, hypertension, increased ECF expansion volume, hypokalemia, and alkalosis. High blood pressure is detected by receptors on the luminal surface of granular cells, inhibiting renin production.

Diagnosis: plasma with increased aldosterone and decreased renin.

Causes of CONN’S syndrome:

• Adrenal adenoma. 
• Bilateral hyperplasia of adrenal glands which may be due to congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH): 

It is caused by genetic defect in one of the enzymes that converts 17-hydroxy-pregnenolone to cortisol. Decrease in cortisol stimulates the cells of hypothalamus to secrete corticotropin stimulating hormone (that in turn causes the release of ACTH) and the corticotropes to release ACTH. Excessive release of ACTH causes hyperplasia of adrenal cortex.

Secondary hyperaldostronism: 

Different from primary as plasma sample contains both high aldosterone and renin. It is due to hypersecretion of renin secondary to granular cell tumor or low renal perfusion pressure. Therefore it is characterized by hypovolemia while primary hyperaldosteronism is characterized by hyper-volemia. A third distinguishing factor is that alkalosis is seen in primary but not in secondary because due to hypervolemia HCO3- is excreted in urine.

Treatment of primary and secondary hyperaldosteronism: 

It is aimed at decreasing the levels of aldosterone to decrease the symptoms. Aldactone is a drug mainly given for primary hyperaldosteronism. It competitively binds with aldosterone sensitive receptors on epithelial cells of distal convulated tubule and acts as an antagonist causing excretion of Na+ and water while retaining K+ and H+. In CAH cortisol is injected which inhibits corticotropin releasing hormone by negative feedback. The glomerulosa cells can detect both high levels of aldosterone and cortisol and in response the cells inhibit aldosterone release. In normal physiology an enzyme secreted by the granular cells binds to cortisol and does not allow it to perform its inhibitory effect on zona glomerulosa cells so that cortisol levels have no regulatory action on aldosterone. Glycirrhizic acid injected into plasma can bind with the enzyme, letting cortisol free to act on zona glomerulosa cells and inhibit release of aldosterone. Following glycirrhizic acid injection, cortisol is given that freely performs inhibition of aldosterone.

In blood sample:
Primary hyperaldosteronism: decrease in renin due to negative feedback caused by high levels of aldosterone.
Secondary hyperaldosteronism: increase in renin due to low BP.
Pseudo-hyperaldosteronism: hypertension, hypokalemia and acidosis are the symptoms but plasma levels are not high in aldosterone. It is due to genetic defect in the Na+, K+ and H+ pumps in distal convulated tubular cells that are retaining Na+ and excreting K+ and H+.