The pituitary gland, a small organ located at the base of the brain, functions as the body’s primary endocrine control center, often called the “master gland.” It secretes hormones that regulate growth, metabolism, reproduction, and stress response. A Pituitary Neuroendocrine Tumor (PitNET) represents an abnormal growth of the neuroendocrine cells within this gland. Most PitNETs are slow-growing and non-cancerous, but they can still cause significant health issues due to their delicate location and hormonal effects.
Defining Pituitary Neuroendocrine Tumors
The classification of these growths has recently shifted, with the World Health Organization introducing the term Pituitary Neuroendocrine Tumor (PitNET) to replace pituitary adenoma. This change aligns the pathology of the pituitary with other neuroendocrine tumors found elsewhere in the body. The PitNET nomenclature acknowledges that while the majority are benign, some tumors can exhibit aggressive behavior, such as local invasion or resistance to treatment.
PitNETs are broadly categorized based on their size and whether they secrete hormones. A microadenoma measures less than 10 millimeters, while a macroadenoma is 10 millimeters or larger. This size distinction is important because larger tumors are more likely to compress surrounding structures, leading to specific symptoms.
The most significant distinction is between functional and non-functional PitNETs. Functional tumors actively secrete an excess of one or more pituitary hormones, causing widespread systemic effects. Non-functional tumors do not produce excess hormones but cause symptoms only if they grow large enough to press on adjacent tissues. Non-functional PitNETs account for approximately 30% of all pituitary tumors and are typically macroadenomas when diagnosed.
Symptoms and Hormonal Effects
Symptoms of a PitNET fall into two main categories: those resulting from the tumor’s physical size (mass effects) and those caused by the overproduction of hormones from functional tumors. Mass effect symptoms occur when the growing tumor presses on neighboring neurological structures. The most common mass effect is pressure on the optic chiasm, the point where the optic nerves cross, which can lead to a loss of peripheral vision.
The physical presence of a large PitNET can also cause chronic headaches, facial pain, or numbness. A large tumor can compress the normal pituitary tissue, impairing its ability to produce necessary hormones, a condition called hypopituitarism. Symptoms of hormone deficiency include fatigue, unexplained weight changes, feeling cold, and low blood pressure.
Functional PitNETs cause distinct hormonal syndromes, with symptoms tied directly to the hormone being overproduced. Prolactin-secreting tumors (prolactinomas) are the most common functional type. They cause milky nipple discharge (galactorrhea) and menstrual irregularities in women, and decreased libido and erectile dysfunction in men.
A PitNET that secretes Adrenocorticotropic Hormone (ACTH) leads to Cushing’s disease, causing the adrenal glands to overproduce cortisol. This results in symptoms such as weight gain concentrated in the face and trunk, easy bruising, and muscle weakness. Tumors that produce excess Growth Hormone (GH) cause acromegaly in adults, marked by the gradual enlargement of the hands, feet, and jaw. Excess GH can also lead to systemic issues like high blood pressure and diabetes.
Identifying and Confirming the Diagnosis
The diagnostic process begins when a patient presents with symptoms suggestive of mass effect or hormonal imbalance. Initial blood and urine tests measure baseline hormone levels. These biochemical tests confirm the presence of a functional PitNET and identify the specific hormone involved, such as measuring prolactin or checking Insulin-like Growth Factor-1 (IGF-1).
For some hormonal conditions, like ACTH-secreting tumors, dynamic testing is required to confirm the diagnosis. These tests involve administering a substance to stimulate or suppress hormone release, helping distinguish a PitNET from other causes of hormonal imbalance. Urine collection over a 24-hour period may also be used to measure cortisol levels, providing an accurate assessment of overall hormone production.
Imaging is the next step, with Magnetic Resonance Imaging (MRI) of the brain’s sellar region considered the reference standard. MRI provides detailed images of the pituitary gland, allowing physicians to determine the tumor’s size, location, and relationship to surrounding structures, such as the optic chiasm. Using an intravenous contrast agent, often gadolinium, helps better delineate the tumor from normal pituitary tissue.
An ophthalmologic evaluation, specifically visual field testing, is performed if a macroadenoma is present. This testing assesses any loss of peripheral vision, which is a direct sign of mass effect on the optic chiasm. A tissue biopsy is rarely needed before treatment, as the combination of hormonal blood tests and specialized MRI typically establishes a definitive diagnosis.
Current Treatment Modalities
The management of a PitNET is determined by its size, whether it is functional or non-functional, and the severity of symptoms. First-line treatment is often surgical intervention, particularly for macroadenomas causing mass effect symptoms like vision loss, or for functional tumors that resist medical control. The most common surgical technique is the transsphenoidal approach, a minimally invasive procedure.
During transsphenoidal surgery, the surgeon accesses the pituitary gland through the nasal cavity and the sphenoid sinus, avoiding the need to open the skull. This approach allows for the safe removal of the tumor while preserving surrounding healthy pituitary tissue and minimizing recovery time. While the goal is total tumor removal, invasion into adjacent areas may result in residual tumor tissue.
Medical management is the first and most effective treatment for certain functional PitNETs. Prolactinomas are typically treated with dopamine agonists, which shrink the tumor and normalize prolactin levels. Other functional tumors, such as those secreting growth hormone, may be treated with somatostatin analogs to control hormone hypersecretion and reduce tumor volume.
Radiation therapy is reserved for tumors that cannot be fully removed surgically, recur after surgery, or do not respond to medication. Stereotactic radiosurgery delivers a highly focused dose of radiation to the tumor over one or a few sessions. This targeted approach aims to stop tumor growth and control hormone overproduction, providing long-term tumor control.