An aldosterone-producing adenoma is a noncancerous (benign) tumor that develops in an adrenal gland, which is a small hormone-producing gland located on top of each kidney. In most cases, individuals develop a single tumor in one of the adrenal glands. The adrenal tumor produces too much of the hormone aldosterone, which is a condition known as primary hyperaldosteronism. Aldosterone helps regulate the body's fluid levels and blood pressure by controlling the amount of salt retained by the kidneys. Excess aldosterone causes the kidneys to retain more salt than normal, which increases the body's fluid levels and blood pressure. People with an aldosterone-producing adenoma may develop severe high blood pressure (hypertension), and they have an increased risk of heart attack, stroke, or an irregular heart beat (atrial fibrillation).

Aldosterone-producing adenomas are caused by mutations in one of several genes. The most commonly mutated gene is KCNJ5, accounting for an estimated 40 percent of the tumors, followed by the CACNA1D and ATP1A1 genes, which are mutated in about 9 percent and 6 percent of aldosterone-producing adenomas, respectively. Changes in other genes cause a small percentage of cases. Only about 60 percent of affected individuals have a mutation in one of the identified genes; additional unidentified genes are also thought to be involved in the condition.

The genes known to be involved in aldosterone-producing adenomas have roles in balancing the amounts of positively charged atoms (ions) of sodium (Na+), potassium (K+), and calcium (Ca2+) in cells. Each of the proteins produced from these genes transports certain ions across cell membranes. The flow of these ions creates an electrical charge across the cell membrane, which affects certain biochemical processes. In adrenal gland cells, this flow of ions helps control the production of aldosterone. Mutations in the KCNJ5, CACNA1D, or ATP1A1 gene lead to abnormal electrical charges across cell membranes. These abnormalities overactivate a biochemical process that increases adrenal cell growth and division (proliferation), which promotes adenoma formation. Overactivation of this biochemical process also increases aldosterone production, resulting in hyperaldosteronism and leading to hypertension.

Normal Function

The KCNJ5 gene provides instructions for making a protein that functions as a potassium channel, which means that it transports positively charged atoms (ions) of potassium (K+) into and out of cells. Potassium channels produced from the KCNJ5 gene are found in several tissues, including the adrenal glands, which are small hormone-producing glands located on top of each kidney. In these glands, the flow of ions creates an electrical charge across the cell membrane, which affects the triggering of certain biochemical processes that regulate aldosterone production. Aldosterone helps control blood pressure by maintaining proper salt and fluid levels in the body.

Health Conditions Related to Genetic Changes

Aldosterone-producing adenoma

Mutations in the KCNJ5 gene cause about 40 percent of aldosterone-producing adenomas, which are noncancerous (benign) tumors that form in the adrenal glands. The genetic changes involved in these tumors, called somatic mutations, are acquired during a person's lifetime and are present only in adrenal gland cells that give rise to the tumor.

KCNJ5 gene mutations associated with this condition change single protein building blocks (amino acids) in the potassium channel. The altered potassium channels are less selective, allowing other ions, particularly sodium, to pass through. The flow of sodium ions into adrenal gland cells affects the electrical charge across the cell membrane, activating another type of channel that allows calcium ions to enter. The influx of calcium ions overactivates a process called the calcium/calmodulin pathway that increases aldosterone production, resulting in excess aldosterone and leading to high blood pressure (hypertension) and an increased risk of heart attack and stroke. Overactivation of the calcium/calmodulin pathway in the adrenal glands also increases cell growth and division (proliferation), which promotes adenoma formation.

Familial hyperaldosteronism

Inherited KCNJ5 gene mutations have been identified in people with familial hyperaldosteronism type III. These mutations, known as germline mutations, are found in every cell of the body. Familial hyperaldosteronism causes hypertension, and some affected individuals have abnormally large adrenal glands (adrenal hyperplasia). As in aldosterone-producing adenomas (described above), KCNJ5 gene mutations result in production of less-selective potassium channels. The abnormal flow of ions through these channels leads to increased aldosterone production, causing hypertension.

Andersen-Tawil syndrome

MedlinePlus Genetics provides information about Andersen-Tawil syndrome

Romano-Ward syndrome

MedlinePlus Genetics provides information about Romano-Ward syndrome

Other Names for This Gene

• cardiac ATP-sensitive potassium channel
• CIR
• G protein-activated inward rectifier potassium channel 4
• GIRK4
• heart KATP channel
• inward rectifier K+ channel KIR3.4
• IRK-4
• KATP1
• KIR3.4
• LQT13
• potassium channel, inwardly rectifying subfamily J, member 5
• potassium inwardly-rectifying channel, subfamily J, member 5

Genomic Location

Aldosterone-producing adenomas are generally not inherited but arise from a mutation in the body's cells that occurs after conception. In particular, the alteration occurs in adrenal gland cells that give rise to the tumor. Such mutations are called somatic mutations.

Somatic cells are the cells in the body other than sperm and egg cells (which are called germ cells). In humans, somatic cells are diploid, meaning they contain two sets of chromosomes, one inherited from each parent. DNA mutations in somatic cells can affect an individual, but they cannot be passed on to their offspring.

Somatic cells. All organisms that are alive are made of one or more cells that are called somatic cells. In humans, somatic cells are diploid, meaning they contain two sets of chromosomes, one set inherited from each parent. Somatic mutations can impact the individual carrying the mutation, but cannot be passed on and have no effect on the offspring.

Belen Hurle, Ph.D., Former Associate Investigator, Division of Intramural Research

An alteration in DNA that occurs after conception. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. These alterations can (but do not always) cause cancer or other diseases. Also called somatic variant.

Aldosterone-producing adenomas cause up to 60 percent of cases of primary hyperaldosteronism. It is estimated that primary hyperaldosteronism accounts for 5 to 15 percent of cases of hypertension, which affects approximately 3 in 10 adults worldwide. However, the prevalence of aldosterone-producing adenomas is unknown.