Pituitary adenoma

By Jason Wasserman MD PhD FRCPC
April 23, 2025

A pituitary adenoma is a benign (noncancerous) tumor that develops from specialized cells in the pituitary gland. The pituitary gland is a small, pea-sized structure located at the base of the brain behind the nose and is sometimes called the “master gland” because it controls several hormone-producing glands in the body. Pituitary adenomas can affect hormone production and cause symptoms related to hormonal imbalance or pressure effects on surrounding structures. Another name for this type of tumor is pituitary neuroendocrine tumor (PitNET).

Types of pituitary adenomas

There are many different subtypes of pituitary adenomas. Each type is classified based on the type of pituitary cells from which it originates and the specific hormones the tumor cells produce. Pathologists use special tests to determine the particular type, as this information guides treatment and prognosis. The main groups include PIT1 lineage adenomas, TPIT lineage adenomas, SF1 lineage adenomas, and adenomas that do not show distinct lineage differentiation.

PIT1 lineage adenomas

Somatotroph adenomas

Somatotroph adenomas, also known as growth hormone-secreting adenomas, represent approximately 10 to 15 percent of all pituitary adenomas. These adenomas often cause increased growth hormone, leading to conditions such as gigantism or acromegaly. They may occur as part of genetic syndromes, such as familial isolated pituitary adenoma (FIPA), McCune-Albright syndrome, Carney complex, multiple endocrine neoplasia type 1 (MEN1), and X-linked acrogigantism. Somatotroph adenomas generally have a good prognosis, particularly the densely granulated subtype, which tends to be smaller and less invasive compared to sparsely granulated tumors.

Mammosomatotroph adenomas

Mammosomatotroph adenomas, which are rare (around 1 to 2 percent of pituitary adenomas), produce both growth hormone and prolactin. These tumors have been associated with genetic conditions such as Carney complex, MEN1, McCune-Albright syndrome, and familial isolated pituitary adenoma syndrome. They generally have a good prognosis after surgical removal, particularly when the condition is detected early.

Lactotroph adenomas

Lactotroph adenomas, commonly referred to as prolactinomas, are the most common type of pituitary adenoma, accounting for approximately 30% to 50% of all cases. They typically respond very well to treatment with medications called dopamine agonists. These adenomas are rarely associated with genetic syndromes, although occasional cases have been reported in association with MEN1 and familial isolated pituitary adenomas. The prognosis for lactotroph adenomas is excellent, as they are usually controlled effectively with medication.

Thyrotroph adenomas

Thyrotroph adenomas are rare, accounting for less than 1% of pituitary adenomas. These adenomas produce thyroid-stimulating hormone (TSH) and are sometimes referred to as TSH-producing adenomas. They can occasionally be associated with MEN1 syndrome and familial isolated pituitary adenoma syndrome. Thyrotroph adenomas tend to be invasive, making surgical treatment challenging and requiring careful medical management. Their prognosis varies depending on tumor size and invasiveness at diagnosis.

Mature plurihormonal PIT1-lineage adenomas

Mature plurihormonal PIT1-lineage adenomas are very rare tumors characterized by their ability to produce multiple hormones, including growth hormone, prolactin, and TSH. Their exact incidence is unknown, but they are considered extremely uncommon. They occasionally appear in syndromic settings and generally have a better prognosis compared to immature plurihormonal adenomas, often responding well to surgical removal.

Immature PIT1-lineage adenomas

Immature PIT1-lineage adenomas, previously called silent subtype 3 adenomas, are rare (representing only about 1 to 3 percent of pituitary adenomas) and typically show limited hormone production despite deriving from PIT1 lineage cells. These adenomas are sometimes associated with MEN1 syndrome and are usually aggressive, carrying a higher risk of invasion into surrounding tissues and recurrence after treatment.

Acidophil stem cell adenomas

Acidophil stem cell adenomas, a rare type of pituitary adenoma accounting for approximately 2 percent of these tumors, are characterized by rapid growth and aggressive behavior. They often exhibit resistance to typical treatments and may require a combination of therapies, along with careful long-term monitoring.

Mixed somatotroph-lactotroph adenomas

Mixed somatotroph-lactotroph adenomas are uncommon, making up about 1 to 4 percent of pituitary adenomas. They produce both growth hormone and prolactin from distinct cell populations within the tumor. These adenomas can appear in familial isolated pituitary adenoma syndrome and X-linked acrogigantism. Compared to pure somatotroph or lactotroph adenomas, mixed adenomas have a lower remission rate after treatment and require close follow-up.

TPIT lineage adenomas

Corticotroph adenomas

Corticotroph adenomas, part of the TPIT lineage, represent about 15 to 17 percent of pituitary adenomas. These adenomas produce ACTH and often lead to Cushing’s disease, characterized by excessive cortisol production. They rarely appear as part of genetic syndromes such as MEN1 or MEN4. Corticotroph adenomas generally have a favorable prognosis when diagnosed and surgically removed early, though large or invasive tumors present greater treatment challenges.

SF1 lineage adenomas

Gonadotroph adenomas

Gonadotroph adenomas arise from SF1 lineage cells and are common, accounting for approximately 30-50% of pituitary adenomas in adults. Although they can produce hormones such as follicle-stimulating hormone (FSH) or luteinizing hormone (LH), they typically do not cause symptoms of hormone excess. They are often discovered incidentally or due to pressure effects, such as headaches or changes in vision. Gonadotroph adenomas can occasionally appear as part of MEN1 syndrome or familial isolated pituitary adenomas and generally have a favorable prognosis if surgically removed. However, large or invasive tumors have a higher likelihood of recurrence.

Adenomas without distinct lineage differentiation

Null cell adenomas

Null cell adenomas represent fewer than 5 percent of pituitary adenomas and do not produce recognizable hormones. These tumors can behave aggressively, often invading surrounding structures, and therefore require careful management and close follow-up.

Plurihormonal adenomas

Plurihormonal adenomas are very rare (<1 percent) and characterized by unusual combinations of hormones from multiple cell lineages. Their prognosis is variable and depends on the hormones produced and the degree of invasiveness.

What causes a pituitary adenoma?

In most cases, the exact cause of a pituitary adenoma is unknown. These tumors generally occur spontaneously, meaning they develop without any identifiable cause. Researchers believe pituitary adenomas result from genetic or molecular changes that occur randomly in pituitary gland cells. These changes can cause cells to grow uncontrollably, leading to the formation of a tumor. However, these genetic changes are typically not inherited from parents and usually occur only in the cells that give rise to the tumor, rather than throughout the body.

While most pituitary adenomas are not linked to hereditary or genetic syndromes, a small proportion of these tumors develop in association with inherited genetic conditions. These conditions include multiple endocrine neoplasia type 1 (MEN1), characterized by tumors occurring in multiple endocrine glands, such as the pituitary, parathyroid, and pancreas. Carney complex, another rare genetic syndrome, is also linked with an increased risk of pituitary adenomas, along with skin pigmentation abnormalities and heart tumors. McCune-Albright syndrome, a genetic condition caused by mutations that occur early in embryonic development, can result in pituitary adenomas alongside other endocrine and skeletal abnormalities. Familial isolated pituitary adenoma (FIPA) syndrome affects families in which multiple members develop pituitary adenomas, often due to mutations in specific genes, such as the AIP gene.

Additionally, certain genetic alterations are frequently found within specific adenoma subtypes. For example, somatotroph adenomas often harbor mutations in the GNAS gene, whereas corticotroph adenomas can exhibit mutations in the USP8 gene. These genetic mutations usually occur spontaneously in pituitary cells rather than being inherited. Understanding these molecular and genetic alterations enables doctors to determine the most effective treatment approach and predict how the adenoma may behave.

Despite these known genetic associations, most people who develop a pituitary adenoma do not have any identifiable genetic risk factors or family history of the disease. Additionally, there is no strong evidence to suggest that lifestyle factors, environmental exposures, diet, or stress directly cause pituitary adenomas.

Is a pituitary adenoma a type of cancer?

No, pituitary adenomas are benign (noncancerous) tumors. They do not usually spread to other parts of the body, but can cause health problems by compressing or growing into nearby structures or by altering hormone levels.

How is this diagnosis made?

The diagnosis of a pituitary adenoma is usually made based on a combination of clinical symptoms, imaging studies, blood tests, and microscopic examination of tissue obtained during surgery or biopsy. Imaging studies such as magnetic resonance imaging (MRI) are typically the first tests performed. They can identify a tumor in the pituitary gland, revealing its size, shape, and relationship to surrounding structures.

Blood tests play a critical role in diagnosing pituitary adenomas by measuring hormone levels produced by the pituitary gland. Depending on the clinical presentation and suspected adenoma type, your doctor will assess various hormones to determine the appropriate treatment. Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels are measured if a somatotroph adenoma is suspected, particularly when symptoms of acromegaly or gigantism are present. Prolactin levels are measured to evaluate lactotroph adenomas, particularly in patients experiencing irregular menstrual cycles, infertility, or difficulties with breast milk production. For suspected corticotroph adenomas, which produce adrenocorticotropic hormone (ACTH), blood tests are used to measure both ACTH and cortisol levels. Additionally, specialized tests such as the dexamethasone suppression test and 24-hour urinary cortisol measurement are often used to confirm Cushing disease, a condition associated with excess ACTH production.

Thyroid-stimulating hormone (TSH) and thyroid hormone levels (T4 and T3) are evaluated if a thyrotroph adenoma is suspected, usually indicated by symptoms of hyperthyroidism. Gonadotropins, specifically luteinizing hormone (LH) and follicle-stimulating hormone (FSH), are measured to diagnose gonadotroph adenomas, although these adenomas typically do not cause hormone excess symptoms. Nevertheless, measuring LH, FSH, estrogen (in women), and testosterone (in men) can identify subtle hormonal imbalances resulting from these tumors.

In addition to evaluating hormones produced directly by the pituitary gland, blood tests also assess hormone production from glands controlled by pituitary hormones, such as the adrenal glands, the thyroid gland, the ovaries, and the testes. For instance, ACTH produced by the pituitary gland stimulates cortisol production from the adrenal glands; thus, both ACTH and cortisol levels are measured together. Similarly, measuring TSH along with thyroid hormones (T4, T3) helps evaluate whether a thyrotroph adenoma is causing hyperthyroidism.

If a tumor is confirmed by imaging and hormonal studies, surgical removal or biopsy will be performed. Tissue samples from the tumor are sent to a pathologist who examines the cells under the microscope. The pathologist then uses specialized tests, such as immunohistochemistry (IHC), to identify specific hormones and proteins, thereby confirming the exact type of pituitary adenoma. This final step is crucial because it ensures that the diagnosis is accurate, guiding appropriate treatment and predicting how the tumor might behave over time.

What other tests may be performed to confirm the diagnosis?

To confirm the diagnosis and determine the specific type of pituitary adenoma, your pathologist may perform additional tests, including immunohistochemistry (IHC). Immunohistochemistry is a specialized laboratory method used to identify particular proteins within tumor cells. In this test, antibodies (special proteins designed to detect other specific proteins) are applied to tissue samples taken from the tumor. If the tumor cells contain the protein being tested, they will change to a particular color, and the result is considered positive. If the cells do not contain the protein, they will remain unstained, and the result is referred to as negative. Positive and negative results help pathologists determine precisely which hormones and transcription factors the tumor cells are making, which in turn helps identify the exact subtype of the adenoma.

• Somatotroph adenomas: This subtype is positive for growth hormone (GH) and the pituitary transcription factor 1 (PIT1). These proteins confirm that the tumor cells originate from cells that produce growth hormone. A positive result for GH helps explain symptoms such as acromegaly or gigantism.
• Mammosomatotroph adenomas: This subtype is positive for both growth hormone (GH) and prolactin, as well as PIT1. Positive staining for both hormones confirms a dual hormonal nature, accounting for symptoms of excess GH and prolactin.
• Lactotroph adenomas (prolactinomas):  This subtype is positive for prolactin and PIT1. Positive prolactin staining is important for confirming the cause of high prolactin levels and related symptoms, such as menstrual disturbances or breast milk production.
• Thyrotroph adenomas: This subtype is positive for thyroid-stimulating hormone (TSH) and PIT1. Positive TSH staining confirms that the adenoma cells are responsible for the elevated thyroid hormone levels and hyperthyroid symptoms.
• Mature plurihormonal PIT1-lineage adenomas: This subtype is positive for PIT1 and multiple hormones, including GH, prolactin, and sometimes TSH. Positive staining for multiple hormones confirms that the tumor cells can produce various hormones, leading to a combination of symptoms.
• Immature PIT1-lineage adenomas: This subtype is typically positive for PIT1 but exhibits limited or partial staining for hormones such as GH, prolactin, or TSH. The limited hormone positivity suggests that these tumors originate from immature cells, which helps identify their aggressive behavior.
• Acidophil stem cell adenomas: This subtype is positive for PIT1, with some prolactin positivity, but typically limited or absent GH staining. The distinctive staining pattern helps identify these tumors as aggressive and rapidly growing.
• Mixed somatotroph-lactotroph adenomas: This subtype comprises two distinct cell populations, one staining positively for GH and the other for prolactin, both of which are also positive for PIT1. These results confirm the presence of two distinct types of hormone-producing cells within the same tumor, leading to mixed hormonal symptoms.
• Corticotroph adenomas: This subtype is positive for ACTH (adrenocorticotropic hormone) and TPIT. ACTH positivity helps confirm that the tumor is responsible for conditions like Cushing’s disease, characterized by excessive cortisol production.
• Gonadotroph adenomas: This subtypes is usually positive for gonadotropins such as follicle-stimulating hormone (FSH) or luteinizing hormone (LH), and the transcription factor SF1. Positive staining confirms that the tumor originates from gonadotroph cells, even if symptoms of hormone excess are typically absent.
• Null cell adenomas: This subtype is characterized by negative staining for all pituitary hormones and transcription factors like PIT1, TPIT, and SF1. Negative staining results in these cases confirm that the tumor does not produce hormones, which helps distinguish these adenomas from other hormone-producing pituitary tumors.
• Plurihormonal adenomas: The tumor cells in this subtype exhibit unusual combinations of positive staining for hormones and transcription factors from multiple different cell lineages, such as PIT1 and SF1. These results confirm that tumor cells are capable of differentiating into multiple cell types, which explains their unique hormonal profile and associated symptoms.

Overall, these immunohistochemical tests provide essential information to pathologists, enabling them to accurately diagnose the tumor type, inform treatment decisions, and predict the tumor’s behavior.

What is an ectopic pituitary adenoma?

An ectopic pituitary adenoma is a rare type of pituitary tumor that develops outside of the pituitary gland itself. The term “ectopic” means that the tumor arises in an abnormal or unexpected location. Although pituitary adenomas usually form within the pituitary gland located at the base of the brain, ectopic adenomas occur in areas such as the sphenoid sinus (a cavity behind the nose), the nasal cavity, or even within structures close to the pituitary gland, such as the cavernous sinus or clivus.

Ectopic pituitary adenomas are thought to originate from pituitary gland tissue that, during early embryonic development, becomes displaced or separated from its normal location. Over time, these displaced pituitary cells can undergo the same type of growth and hormonal changes as those found in typical pituitary adenomas, eventually forming a tumor in an unusual location.

Symptoms of an ectopic pituitary adenoma depend on the location of the tumor and the hormones it produces. Like typical pituitary adenomas, ectopic adenomas can produce excess hormones, such as growth hormone (GH), prolactin, adrenocorticotropic hormone (ACTH), or thyroid-stimulating hormone (TSH), resulting in symptoms similar to those associated with hormone-producing adenomas located within the pituitary gland. In other cases, ectopic adenomas might not produce hormones at all and instead cause symptoms related to pressure on nearby structures, such as headaches, nasal congestion, facial pain, vision changes, or nerve-related symptoms.

Diagnosing an ectopic pituitary adenoma typically involves imaging tests such as magnetic resonance imaging (MRI) or computed tomography (CT) scans, which identify the location and extent of the tumor. Blood tests to measure pituitary hormones are also important, especially if the tumor is suspected of producing hormones. Surgical removal and microscopic examination of the tissue are often necessary to confirm the diagnosis, and specialized tests, such as immunohistochemistry (IHC), help determine the exact type of pituitary adenoma.

Because ectopic pituitary adenomas occur in unusual and sometimes challenging locations, treatment typically involves careful surgical removal, often requiring specialized surgical techniques. In some cases, additional treatments such as radiation therapy or medications may be necessary, particularly if the adenoma is difficult to completely remove surgically.

Although ectopic pituitary adenomas are rare, accurate diagnosis and careful management by experienced specialists can lead to successful treatment outcomes and relief from symptoms.