Pathophysiology
Summary
Primary hyperaldosteronism and secondary hyperaldosteronism involve excessive secretion of aldosterone from the zona glomerulosa in the adrenal glands. Primary hyperaldosteronism is due to intrinsic dysfunction of the adrenal gland. The main causes are bilateral idiopathic hyperaldosteronism, featuring hyperplasia in both adrenal glands and aldosterone-secreting adenomas, which are unilateral well-circumscribed tumors with eosinophilic ‘spironolactone bodies.’ These adenomas don't induce contralateral adrenal atrophy as ACTH levels remain normal. Rarer causes include adrenal gland carcinoma and ectopic aldosterone-secreting tumors in organs like the kidneys and ovaries.
Hyperaldosteronism results in a variety of metabolic effects, include hypokalemia and subsequent metabolic alkalosis. It initially presents with secondary hypertension from the overactivation of RAAS and volume overload. However, chronic RAAS activation results in increased RBF and pressure natriuresis, which activates atrial stretch receptors to release ANP. ANP then acts to increase sodium and water excretion. Elevated aldosterone triggers an aldosterone escape mechanism, which partially offsets volume overload and hypernatremia but still results in mild hypernatremia and hypervolemia.
Diagnosis often shows low renin levels due to blood pressure-mediated negative feedback. A salt suppression test can confirm the condition if urine aldosterone remains high. Treatment includes surgical removal of aldosterone-secreting adenomas, low-sodium diets, and spironolactone, an aldosterone antagonist applicable to both primary and secondary forms.
In secondary hyperaldosteronism, the elevated aldosterone levels are a consequence of increased renin activity, which activates RAAS. Secondary hyperaldosteronism can be triggered by various conditions causing excessive peripheral edema, such as CHF, cirrhosis, and nephrotic syndrome. These conditions lead to decreased intravascular volume, impaired renal perfusion, and consequently, increased renin secretion. Additionally, secondary hyperaldosteronism can be induced by a renin-secreting tumor within the juxtaglomerular apparatus of the kidney or renovascular hypertension due to narrowing of renal arteries from atherosclerosis or fibromuscular dysplasia.
Glucocorticoids are produced in the middle layer of the adrenal cortex, the zona fasciculata. When this zone produces excess cortisol, it results in a condition known as Cushing's syndrome, or hypercortisolism. The most common adrenal cause is a cortisol-secreting adrenal adenoma, which leads to decreased ACTH levels due to negative feedback. As ACTH stimulates the adrenal gland, this decline causes atrophy of the adrenal tissue, specifically affecting the zona fasciculata on the contralateral side as well as non-tumorous tissue on the ipsilateral side. Another cause is nodular hyperplasia of the zona fasciculata, which mimics the signs and symptoms of a cortisol-secreting adrenal adenoma.
Cushing syndrome manifests clinically as central obesity, extremity wasting, skin atrophy, striae, and glucose intolerance. Treatment for hyperaldosteronism and Cushing's syndrome includes of the aldosterone antagonist spironolactone.
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FAQs
Primary hyperaldosteronism is a disorder characterized by the hypersecretion of aldosterone due to adrenal gland dysfunction, specifically in the zona glomerulosa. The most common cause is bilateral idiopathic hyperaldosteronism in which both adrenal glands are hyperplastic. The second most common cause is aldosterone-secreting adenoma, a well-circumscribed, single, yellow tumor that produces aldosterone. Adrenal gland carcinoma and ectopic aldosterone-secreting tumors in the kidneys or ovaries can also cause primary hyperaldosteronism.
Hyperaldosteronism results in upregulation of renal sodium-potassium pumps, leading to sodium retention and subsequent volume retention, causing severe secondary hypertension. Concurrently, this disorder also causes hypokalemia due to the excessive excretion of potassium in the urine. Over time, Primary Hyperaldosteronism initially results in severe volume overload and hypertension due to sodium and water retention and eventually leads to "pressure natriuresis," which is an increased excretion of sodium and water due to an increased glomerular filtration rate.
The salt suppression test, which involves administration of salt supplements and monitoring for persistently elevated urine aldosterone, can be used to diagnose primary hyperaldosteronism. In terms of treatment, aldosterone-secreting adenomas can be surgically removed while idiopathic hyperaldosteronism is usually managed non-surgically. Both dietary changes, like adopting a low-sodium diet, and pharmacological interventions, like spironolactone (an aldosterone antagonist), can be effective treatments.
Secondary hyperaldosteronism occurs as a result of increased renin, which activates the renin-angiotensin-aldosterone system (RAAS). Conditions causing excessive peripheral edema such as congestive heart failure, cirrhosis, nephrotic syndrome, and renovascular hypertension can cause secondary hyperaldosteronism. These conditions lead to decreased intravascular volume and reduced renal perfusion, stimulating increased renin secretion by the kidney and subsequent RAAS activation and elevated serum aldosterone. A renin-secreting tumor within the kidney's juxtaglomerular apparatus can also cause secondary hyperaldosteronism.
Cushing’s syndrome is a disorder that results from excessive exposure to glucocorticoids, such as cortisol. Hypercortisolism, which is characterized by central obesity, extremity wasting, as well as skin atrophy and striae. The most common cause of adrenal hypercortisolism is a cortisol-secreting adrenal adenoma, which leads to a decrease in ACTH due to negative feedback on the pituitary gland and hypothalamus. The resulting lack of ACTH stimulation causes adrenal atrophy, affecting particularly the zona fasciculata on the contralateral side and non-tumor tissue on the ipsilateral side.
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