What are the key differences between Gitelman syndrome and Conn's (Primary Aldosteronism) syndrome, both of which present with hyperaldosteronism?

From the Guidelines

Gitelman syndrome and Conn's syndrome can be differentiated despite both presenting with hyperaldosteronism, with the key distinction lying in their pathophysiology and laboratory findings. Gitelman syndrome is a genetic disorder characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria, resulting from mutations in the SLC12A3 gene encoding the thiazide-sensitive sodium-chloride cotransporter in the distal convoluted tubule 1. In contrast, Conn's syndrome (primary aldosteronism) is caused by autonomous aldosterone production, typically from an adrenal adenoma or bilateral adrenal hyperplasia. The key distinction lies in their pathophysiology: Gitelman syndrome has secondary hyperaldosteronism due to renal salt wasting, while Conn's syndrome features primary aldosterone excess.

Some key differences between the two conditions include:

• Blood pressure: typically normal or mildly elevated in Gitelman syndrome but moderately to severely elevated in Conn's syndrome
• Laboratory findings: both conditions have hypokalemia and metabolic alkalosis, but Gitelman syndrome uniquely presents with hypomagnesemia and hypocalciuria, whereas Conn's syndrome shows suppressed plasma renin activity with elevated aldosterone-to-renin ratio 1
• Treatment approaches: Gitelman syndrome requires potassium and magnesium supplementation with potassium-sparing diuretics, while Conn's syndrome treatment involves surgical removal of adrenal adenomas or medical management with mineralocorticoid receptor antagonists like spironolactone or eplerenone. The treatment of choice for Conn's syndrome is surgical removal of adrenal adenomas or medical management with mineralocorticoid receptor antagonists, as recommended by the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1.

In terms of diagnosis, the aldosterone:renin activity ratio is currently the most accurate and reliable means of screening for primary aldosteronism, with a cutoff value of 30 when plasma aldosterone concentration is reported in nanograms per deciliter (ng/dL) and plasma renin activity in nanograms per milliliter per hour (ng/mL/h) 1. The diagnosis of primary aldosteronism generally requires a confirmatory test, such as an intravenous saline suppression test or oral salt-loading test. The use of mineralocorticoid receptor antagonists, such as spironolactone or eplerenone, is recommended for the treatment of primary aldosteronism, as they have been shown to be effective in lowering blood pressure and reversing left ventricular hypertrophy 1.

From the Research

Differentiation between Gitelman Syndrome and Conn's Syndrome

Gitelman syndrome and Conn's syndrome are two distinct disorders that can present with hyperaldosteronism, making differential diagnosis crucial. The key differences between the two syndromes are:

• Blood Pressure: Conn's syndrome is characterized by hypertension due to excess aldosterone production, whereas Gitelman syndrome typically presents with normal or low blood pressure 2, 3.
• Electrolyte Imbalance: Both syndromes can cause hypokalemia, but Gitelman syndrome is also associated with hypomagnesemia, hypocalciuria, and metabolic alkalosis 2, 4, 5, 3.
• Renin-Angiotensin-Aldosterone System: Gitelman syndrome is characterized by secondary hyperreninemic hyperaldosteronism, whereas Conn's syndrome is primary hyperaldosteronism 3, 6.
• Clinical Manifestations: Gitelman syndrome often presents with mild and nonspecific symptoms, such as muscle weakness, salt craving, and tetany, whereas Conn's syndrome typically presents with moderate to severe hypertension and hypokalemia 2, 6.

Diagnostic Considerations

To differentiate between Gitelman syndrome and Conn's syndrome, the following diagnostic considerations should be taken into account:

• Genetic Testing: Genetic diagnosis of Gitelman syndrome is recommended, and the diagnosis is confirmed when biallelic inactivating SLC12A3 mutations are identified 2.
• Biochemical Abnormalities: The presence of hypomagnesemia, hypocalciuria, and metabolic alkalosis is more suggestive of Gitelman syndrome, whereas primary hyperaldosteronism is more characteristic of Conn's syndrome 4, 5, 3, 6.
• Imaging Studies: Imaging studies, such as adrenal gland imaging, may be necessary to diagnose Conn's syndrome 6.

Treatment and Management

Treatment and management of Gitelman syndrome and Conn's syndrome differ significantly:

• Gitelman Syndrome: Treatment typically involves potassium and magnesium supplementation, aldosterone receptor antagonists, and liberal salt intake 2, 4, 5, 3.
• Conn's Syndrome: Treatment usually involves surgical removal of the aldosterone-producing adenoma or medical management with mineralocorticoid receptor antagonists 6.