What is the difference between Conn's syndrome (Primary Aldosteronism) and AVP (Arginine Vasopressin) resistance, also known as Nephrogenic Diabetes Insipidus?

From the Guidelines

Conn syndrome and AVP resistance are distinct conditions with different pathophysiologies and management strategies, and the most recent evidence from 2025 supports this distinction 1. The key difference between Conn syndrome (primary aldosteronism) and AVP (arginine vasopressin) resistance, also known as nephrogenic diabetes insipidus, lies in their underlying mechanisms and clinical presentations. Conn syndrome is characterized by excessive aldosterone production, typically from an adrenal adenoma or bilateral adrenal hyperplasia, leading to hypertension, hypokalemia, metabolic alkalosis, and suppressed renin levels 1. In contrast, AVP resistance involves kidney unresponsiveness to AVP, resulting in polyuria, polydipsia, and dilute urine despite normal or elevated AVP levels 1.

Pathophysiology and Clinical Presentation

• Conn syndrome: excess aldosterone affects sodium reabsorption and potassium excretion, leading to hypertension, hypokalemia, and metabolic alkalosis 1
• AVP resistance: impaired water reabsorption in the collecting ducts due to defective AVP signaling, resulting in polyuria, polydipsia, and dilute urine 1

Management Strategies

• Conn syndrome: surgical removal of adenomas or medical management with mineralocorticoid receptor antagonists like spironolactone (50-100 mg daily) or eplerenone (25-50 mg daily) 1
• AVP resistance: treating underlying causes, maintaining adequate hydration, and using thiazide diuretics (hydrochlorothiazide 25 mg daily), amiloride, or NSAIDs to reduce urine volume 1

Laboratory Findings

• Conn syndrome: low renin, high aldosterone, and hypokalemia 1
• AVP resistance: inability to concentrate urine despite water restriction, with serum osmolality usually >300 mOsm/kg H2O and urine osmolality usually <200 mOsm/kg H2O 1

In summary, the distinction between Conn syndrome and AVP resistance is crucial for proper diagnosis and management, and the most recent evidence from 2025 supports the use of specific management strategies for each condition 1.

From the Research

Difference between Conn's Syndrome and AVP Resistance

• Conn's syndrome, also known as primary aldosteronism, is a condition characterized by the overproduction of aldosterone, a hormone that regulates blood pressure and electrolyte balance 2, 3, 4, 5.
• The main symptoms of Conn's syndrome include hypertension, hypokalaemia, muscle weakness, fatigue, and polyuria 2, 4.
• AVP resistance, also known as nephrogenic diabetes insipidus, is a condition characterized by the inability of the kidneys to respond to antidiuretic hormone (ADH), leading to an inability to concentrate urine and resulting in polyuria and polydipsia.
• The key difference between Conn's syndrome and AVP resistance is the underlying cause of the symptoms: Conn's syndrome is caused by excess aldosterone production, while AVP resistance is caused by a defect in the kidney's ability to respond to ADH.
• In terms of treatment, Conn's syndrome is typically treated with mineralocorticoid receptor antagonists or adrenalectomy, depending on the underlying cause 3, 5, while AVP resistance is typically treated with desmopressin or other medications that help to reduce polyuria.

Diagnostic Criteria

• The diagnosis of Conn's syndrome relies on examination of serum renin and aldosterone concentrations, plasma renin activity, exercise or furosemide stimulation tests, and imaging studies 2, 3.
• The aldosterone-renin ratio is used as a first screening test for primary aldosteronism 3, 5.
• In contrast, the diagnosis of AVP resistance typically involves tests to evaluate the kidney's ability to concentrate urine, such as a water deprivation test or a desmopressin stimulation test.

Clinical Implications

• Conn's syndrome is associated with an increased risk of cardiovascular disease and other comorbidities, making early diagnosis and treatment important 3.
• AVP resistance can also have significant clinical implications, including dehydration and electrolyte imbalances, if left untreated.
• A correct diagnosis of either condition requires a comprehensive evaluation of the patient's symptoms, medical history, and laboratory test results.