Adrenal Cortical Nodular Disease: Understanding Your Pathology Report

Section Editor: Jason Wasserman MD PhD FRCPC
November 4, 2026

Adrenal cortical nodular disease is a noncancerous condition in which one or more small, round growths called nodules form in the adrenal cortex. The adrenal cortex is the outer layer of the adrenal gland, and each kidney has one adrenal gland on top. The cortex makes cortisol, a hormone that helps the body handle stress and control blood sugar, along with several other hormones. Adrenal cortical nodular disease is benign, which means it does not spread to other parts of the body.

Older pathology reports called this condition hyperplasia, using names such as nodular adrenal cortical hyperplasia or macronodular adrenal hyperplasia. The World Health Organization (WHO) classification of endocrine tumors, published in 2022, replaced these names. Studies showed that each nodule grows from a single abnormal cell, so the nodules behave like very small benign tumors rather than a simple increase in normal cells.

Some people have a single small nodule found by chance on a scan. Others, including some children and young adults with an inherited syndrome, have many nodules in both glands that make too much cortisol. This article explains the three types of adrenal cortical nodular disease, the syndromes linked to them, and what the findings in your adrenal pathology report mean.

Who gets adrenal cortical nodular disease?

Adrenal cortical nodular disease can occur at any age, but each of its three types tends to affect a different group of people. The single small nodules of the sporadic type are common in adults and become more common with age. The micronodular type affects both adrenal glands and usually appears in children, teenagers, and young adults, most often girls and young women. The macronodular type also affects both glands and is usually diagnosed in adults, often in their forties to sixties.

What causes adrenal cortical nodular disease?

Adrenal cortical nodular disease develops when cells in the adrenal cortex acquire gene changes that make them grow and produce hormones without the usual controls. Normally, the adrenal cortex makes cortisol only when the pituitary gland in the brain sends a signal called ACTH. Many of the gene changes in this condition switch on the same pathway that ACTH uses. As a result, the cells behave as if they are constantly stimulated.

For the sporadic type, the exact cause is usually unknown. These nodules are thought to be very small adenomas that develop as people age.

The two types that affect both adrenal glands are different. Almost all cases of the micronodular type, and a substantial share of the macronodular type, are caused by an inherited gene change or are part of a syndrome. A person born with one non-working copy of the gene in every cell needs only a second change in a single adrenal cell for a nodule to form. This explains why the nodules are multiple and appear in both glands. The conditions linked to adrenal cortical nodular disease include:

Carney complex. An inherited condition usually caused by a change in the PRKAR1A gene. It causes spotty skin pigmentation, noncancerous growths called myxomas in the heart and skin, and overactive hormone glands. A form of micronodular disease called primary pigmented nodular adrenocortical disease develops in about a quarter to more than half of people with Carney complex.
Isolated micronodular disease. Some children and young adults have micronodular disease without other features of Carney complex. Changes in the PRKAR1A, PDE11A, PDE8B, or PRKACA genes are found in some of these families.
ARMC5 gene changes. These are the most common known cause of the macronodular type. They are found in about 1 in 5 to 1 in 4 people with the macronodular type who have no family history. They are also found in most families where several relatives are affected. Some reports also link ARMC5 to meningioma, a usually noncancerous tumor of the lining around the brain.
KDM1A gene changes. These are found in a small number of people with the macronodular type, fewer than 5 in 100. They cause a pattern called food-dependent Cushing syndrome, in which cortisol rises after each meal.
Multiple endocrine neoplasia type 1 (MEN1). An inherited condition that causes tumors in several hormone-producing glands. The adrenal glands can develop adenomas or macronodular disease. Our article on multiple endocrine neoplasia type 1 (MEN1) describes this condition in detail.
Familial adenomatous polyposis (FAP). An inherited condition caused by changes in the APC gene, best known for causing many polyps in the colon. Adrenal nodules, including the macronodular type, are more common in people with FAP. Our article on familial adenomatous polyposis explains this condition.
Hereditary leiomyomatosis and renal cell cancer. An inherited condition caused by changes in the FH gene. It has rarely been linked to the macronodular type.
McCune-Albright syndrome. A condition caused by a change in the GNAS gene that occurs early in development, before birth, and is present in only some of the body’s cells. It is not inherited from a parent. It can cause bone changes, skin patches, early puberty, and, less often, nodules in both adrenal glands with high cortisol, sometimes in the first months of life.

What are the symptoms of adrenal cortical nodular disease?

The symptoms of adrenal cortical nodular disease depend on whether the nodules make too much cortisol. Most people with the sporadic type have no symptoms. Their nodules do not make extra hormones, and doctors usually find them by chance on a CT or MRI scan done for another reason.

The micronodular and macronodular types often make too much cortisol. Long-term excess cortisol is called Cushing syndrome. Symptoms can include:

Weight gain around the abdomen and face, with a rounded face.
Thin skin, easy bruising, and purple stretch marks.
Muscle weakness, especially in the thighs and upper arms.
High blood pressure and high blood sugar.
Thinning bones that break more easily.
Mood changes, poor sleep, and tiredness.

In children, the most important clue is often weight gain combined with slowing of growth in height. In people with Carney complex, cortisol levels can rise and fall over weeks or months, so symptoms may come and go. In the macronodular type, cortisol excess is often mild and develops slowly over many years. Some people have no obvious symptoms, but the extra cortisol may still affect their blood pressure, blood sugar, and bones over time.

How is the diagnosis made?

The diagnosis of adrenal cortical nodular disease usually begins with blood, urine, or saliva tests that show the body is making too much cortisol. When the adrenal glands are the source, blood ACTH levels are low because the pituitary gland stops sending its signal when cortisol is already high. Our article on adrenal hormone tests explains these results. Abdominal CT or MRI then shows whether one or both adrenal glands contain nodules. In the macronodular type, both glands are often greatly enlarged, while in the micronodular type the glands may look normal because the nodules are so small.

A needle biopsy is rarely used for adrenal nodules. Instead, the diagnosis is confirmed when one or both adrenal glands are removed surgically (an adrenalectomy) and examined by a pathologist. The pathologist first examines the gland with the naked eye, counting and measuring the nodules and noting their color. Thin slices of the gland are then examined under the microscope. The pathologist assesses the size and number of the nodules, the cell types they contain, and the appearance of the adrenal cortex between the nodules.

The pathologist also confirms that the nodules are benign and come from the adrenal cortex. They look for features of adrenal cortical carcinoma, such as rapid cell division or growth into blood vessels, and these features are not found in nodular disease. Some laboratories use immunohistochemistry, a test that uses antibodies to highlight specific proteins in the cells. A stain for SF-1 confirms that cells come from the adrenal cortex. Stains for enzymes that make hormones, such as CYP11B1, can show which nodules are making cortisol. Not every laboratory uses these stains, and many reports will not mention them.

What are the different types of adrenal cortical nodular disease?

The 2022 WHO classification divides adrenal cortical nodular disease into three types. The types are based on nodule size, whether one or both glands are involved, and whether the nodules produce hormones. Your pathology report should name one of these types. If your report uses an older name, the closest current name is given in each item below.

Sporadic nodular adrenocortical disease. This is the most common type. It describes one or a few small nodules, each less than 1 cm, that do not make extra hormones and are not caused by an inherited condition. It can affect one or both adrenal glands. Reports written before 2022 may call this nodular adrenal cortical hyperplasia.
Bilateral micronodular adrenal cortical disease. This type describes many small nodules, each less than 1 cm and often only 2 to 5 mm, in both adrenal glands. The nodules usually make cortisol. This type mainly affects children and young adults and has two forms, described in the next two items.
Primary pigmented nodular adrenocortical disease (PPNAD). This micronodular form has nodules filled with dark brown pigment, which can make them look like black beads. The adrenal cortex between the nodules is usually thin and shrunken. Most people with PPNAD have Carney complex, so a diagnosis of PPNAD usually leads to testing for that condition.
Isolated micronodular adrenocortical disease (i-MAD). This rare micronodular form has small nodules without dark pigment. The cortex between the nodules is usually not shrunken.
Bilateral macronodular adrenal cortical disease. This type describes many larger nodules, each more than 1 cm, in both adrenal glands. Both glands are often much larger than normal. Most people with this type have some degree of cortisol excess. Reports written before 2022 may call this primary bilateral macronodular adrenal cortical hyperplasia, or ACTH-independent macronodular adrenal hyperplasia.

Two related conditions keep the name hyperplasia in the 2022 WHO classification and are not types of adrenal cortical nodular disease. Diffuse adrenal cortical hyperplasia describes enlargement of both glands caused by too much ACTH, usually from a pituitary tumor. Congenital adrenal hyperplasia is an inherited condition, present from birth, in which an enzyme needed to make cortisol does not work. People with long-standing congenital adrenal hyperplasia can also develop adrenal nodules and a noncancerous fatty tumor called a myelolipoma.

Other findings in your pathology report

A pathology report for adrenal cortical nodular disease describes the nodules and the rest of the adrenal cortex. Not every report includes every finding below, and wording varies between laboratories.

Number and size of nodules. The report usually states whether there is one nodule or many, and the size of the largest. The 1 cm cutoff separates micronodules from macronodules. This measurement helps the pathologist decide which type of nodular disease is present.
One or both glands. If both adrenal glands were removed, the report describes each one separately. Disease in both glands points to the micronodular or macronodular type and raises the possibility of an inherited cause.
Pigment. A dark brown pigment called lipofuscin inside the nodules is typical of PPNAD. When the report mentions pigmented nodules in a child or young adult, doctors usually consider testing for Carney complex.
Cell type. The report may describe clear cells, which are pale because they contain fat, or compact cells, which are pinker. Macronodules are usually made mostly of clear cells. Micronodules are usually made mostly of compact cells.
Atrophy of the adrenal cortex. Atrophy means the normal cortex between the nodules has become thin. This happens when the nodules make so much cortisol that the pituitary stops sending ACTH to the rest of the gland. It supports the conclusion that the nodules were making cortisol.
Myelolipomatous change. Some nodules contain small areas of fat and bone marrow tissue. This benign change does not alter the diagnosis.

Because adrenal cortical nodular disease is not cancer, your report will not include a cancer grade, a stage, or a description of surgical margins. These items apply only to cancers such as adrenal cortical carcinoma.

Genetic testing

Genetic testing is an important part of care for people with micronodular or macronodular adrenal cortical nodular disease, because many cases are caused by an inherited gene change. Germline testing for an inherited change is done with a blood or saliva sample. It looks at the DNA a person was born with, which is present in every cell. It is usually arranged through a genetics clinic or an endocrinologist, a doctor who specializes in hormone conditions.

Genetic testing is most often offered when:

PPNAD or another form of the micronodular type is found, especially in a child or young adult.
The macronodular type is found, since ARMC5 and KDM1A changes can be inherited.
A person has other features of Carney complex, MEN1, or FAP.
Other relatives have adrenal disease or Cushing syndrome.

The results are reported in standard categories. A pathogenic or likely pathogenic variant is a change known, or strongly expected, to cause the condition. A variant of uncertain significance means a change was found but its effect is unknown, and it is not treated as a positive result. Our article on variants of uncertain significance explains this result. A negative result in a person with nodules in both glands does not rule out an inherited cause, because not every gene involved is known.

Testing for McCune-Albright syndrome works differently. The GNAS change is present in only some of the body’s cells, so a blood sample may miss it. It is sometimes easier to find in tissue from the affected adrenal gland.

No test result in adrenal cortical nodular disease predicts response to a particular drug. Genetic testing is used instead to find an inherited condition, guide screening for other tumors linked to that condition, and offer testing to relatives. Our article on hereditary cancer syndromes explains how inherited gene changes are passed through families.

What is the prognosis?

The outlook for people with adrenal cortical nodular disease is generally very good, because the nodules are benign and do not spread. The small nodules of the sporadic type rarely cause problems and often need no treatment. Adrenal cortical carcinoma very rarely develops in people with Carney complex, but nodular disease itself does not turn into cancer in the great majority of people.

For people with the micronodular and macronodular types, the outlook depends mostly on how well the cortisol excess is controlled. Many effects of high cortisol, such as weight gain, high blood pressure, and high blood sugar, improve after treatment. Some effects, such as bone thinning, may improve only partly. When only one adrenal gland is removed, nodules in the remaining gland can grow and the cortisol excess can return years later. In children, controlling cortisol early helps protect growth and bone health.

For people with an inherited syndrome, the long-term outlook also depends on the syndrome’s other features. In Carney complex, for example, heart myxomas need regular monitoring because they can cause serious problems if they are not found early.

What happens after the diagnosis?

After a diagnosis of adrenal cortical nodular disease, the next steps depend on the type of disease. They also depend on whether one or both glands were removed and whether an inherited cause is suspected. An endocrinologist usually leads care, often working with an endocrine surgeon and a genetics team. Possibilities include:

Monitoring for the sporadic type. Small nodules that do not make hormones often need no treatment. Your doctors may repeat hormone tests or imaging to make sure nothing has changed.
Hormone replacement after surgery. If both adrenal glands were removed, the body can no longer make cortisol or aldosterone, a hormone that controls salt and water balance. Lifelong replacement tablets are needed, along with a plan for extra doses during illness. If one gland was removed, temporary cortisol replacement may be needed while the other gland recovers.
Follow-up of the remaining gland. If only one gland was removed, doctors check cortisol levels over time because the other gland may later make too much cortisol. In some situations, doctors may also consider medications that lower cortisol production.
Genetic counseling and testing. This is usually offered for the micronodular and macronodular types. If an inherited gene change is found, relatives can be tested for the same change.
Screening for related conditions. A confirmed syndrome leads to screening for its other features, such as heart and thyroid checks in Carney complex or colon screening in FAP.
Managing the effects of cortisol excess. Blood pressure, blood sugar, bone health, and growth in children may need ongoing care even after cortisol levels return to normal.

Our article on genetic testing for conditions other than cancer explains how to read a genetic test report and what results mean for family members.

Questions to ask your doctor

Which type of adrenal cortical nodular disease does my report describe?
Were the nodules found in one adrenal gland or in both?
How many nodules were there, and how large was the largest one?
Did the report mention pigment in the nodules?
Was the adrenal cortex between the nodules thin or shrunken?
Were the nodules making too much cortisol, and how was this confirmed?
If my report uses an older name such as hyperplasia, what is the current name for my condition?
Should I, or my child, have genetic testing for an inherited cause?
If an inherited syndrome is found, what other screening will be needed?
Should my children, brothers, sisters, or parents be tested?
Will I need hormone replacement, and for how long?
What should I do if I become sick while taking hormone replacement?
If only one gland was removed, how will the other gland be monitored?
How will my child’s growth and bone health be followed?