Treatment of Familial Forms

Familial (i.e., inherited) forms of primary aldosteronism are relatively rare, accounting for perhaps 3% of diagnosed cases. They are most often discovered when serious hypertension develops in a child or young adult, although some less severe cases may go undiagnosed for much longer. The familial forms of primary aldosteronism are caused by differing genetic mutations that disrupt how the endocrine system and adrenal gland regulate aldosterone. The mutations invariably affect both adrenal glands.

Treatment of FH-1

FH-1 is the most well-known form of familial primary aldosteronism. It is also called Glucocorticoid Remedial Aldosteronism (GRA), and accounts for about 1% of all cases. GRA is characterized by an overproduction of aldosterone driven by adrenocorticotropic hormone (ACTH), a hormone secreted by the pituitary gland.

Treatment goal is to suppress ACTH. To this effect, patients are prescribed a low-dose and long-acting glucocorticoid, typically dexamethasone or prednisone. Management of GRA can be quite complex. At higher doses, medications can cause Cushing’s syndrome. In children, they can inhibit growth. When blood pressure is not controlled with glucocorticoid medication alone, patients must add a mineralocorticoid receptor antagonist to their treatment regimen. Unlike Spironolactone, Eplerenone limits the risk of interference with puberty, and is therefore the preferred choice for children.

Treatment of FH-2

FH-2 is more common (i.e., it may account for as many as 7% of all cases). Associated with chloride channel mutations, FH-2 presents as sporadic primary aldosteronism with either hyperplasia or an aldosterone-producing adenoma. FH-2 is treated with surgery when unilateral adrenal disease is documented on adrenal venous sampling and with mineralocorticoid antagonists when both adrenal glands are hypersecreting aldosterone.

Treatment of FH-3

FH-3 is estimated to represent 0.3% of all cases, and includes two different subtypes:

  • Type A leads to severe drug-resistant hypertension and hypokalemia in early childhood. This sub-type does not respond to mineralocorticoid receptor antagonists, and must be treated with bilateral adrenalectomy. People who have had bilateral adrenalectomy must take replacement hormones for life.
  • In the majority of the known Type B cases, overproduction of aldosterone was not associated with resistant hypertension. This sub-type is treated with mineralocorticoid receptor antagonists.

Treatment of FH-4 and FH-5

FH-4 and FH-5 have only been confirmed in a very limited number of cases. Besides excess aldosterone, known cases of FH-4 exhibited social skill alterations and development disorders, while FH-5 was found to involve seizures and neurologic abnormalities syndrome. FH-4 is treated with mineralocorticoid receptor antagonists, and FH-5 is treated with calcium channel blockers.

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References

  • John W. Funder, Robert M. Carey, Franco Mantero, M. Hassan Murad, Martin Reincke, Hirotaka Shibata, Michael Stowasser, William F. Young, The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, Volume 101, Issue 5, 1 May 2016, Pages 1889–1916, DOI: 10.1210/jc.2015-4061
  • William F. Young, Jr. Diagnosis and treatment of primary aldosteronism: practical clinical perspectives. The Journal of Internal Medicine, Volume 285, Issue 2, February 2019, DOI: 10.1111/joim.12831
  • Livia Lenzini, Selene Prisco, Brasilina Caroccia, Gian Paolo Rossi, Saga of Familial Hyperaldosteronism: Yet a New Channel, Hypertension, Vol 71, Issue 6, June 2018, DOI: 10.1161/HYPERTENSIONAHA.118.11150

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The Primary Aldosteronism Foundation is a registered 501(c)(3) public charity. Donations are tax deductible in the US.

©2021 Primary Aldosteronism Foundation

The Primary Aldosteronism Foundation is a registered 501(c)(3) public charity. Donations are tax deductible in the US.