Pituitary tumors

ALSO KNOWN AS: Pituitary adenomas, pituitary carcinomas, teratomas, germinomas, choriocarcinomas, Rathke cleft cysts, gangliocytomas, prolactinomas

RELATED CONDITIONS: Multiple endocrine neoplasia type 1 (MEN 1), acromegaly, Cushing syndrome, panhypopituitarism, hypogonadism, diabetes insipidus, hyperthyroidism

DEFINITION: Pituitary tumors occur in the pituitary gland—a small organ in the sella turcica (a small bony space) in the brain's center just above the nose. Almost all pituitary tumors are adenomas, which are benign (not cancerous) glandular tumors. Malignant tumors (pituitary carcinomas) are rare. Among those, teratomas, germinomas, and choriocarcinomas usually occur in children or young adults. Rathke cleft cysts and gangliocytomas of the pituitary typically occur in adults. Cancers that metastasize to the pituitary from other sites are classified by their primary site and not as pituitary tumors.

Risk factors: People with multiple endocrine neoplasia type 1 (MEN 1) syndrome, a hereditary condition, have a very high risk of developing tumors of the pituitary along with tumors of two other glands, the parathyroid and pancreas. About 50 percent of the children of an affected parent will inherit the defective gene that causes MEN 1. Multiple endocrine neoplasia type 4 (MEN 4) syndrome, Carney complex, X-LAG syndrome, Von Hippel–Lindau syndrome, and isolated family acromegaly also increase an individual's risk of pituitary tumors.

Etiology and the disease process: The pituitary gland produces hormones that regulate the functions of other glands in the body. Most pituitary tumors start in the anterior pituitary gland. Pituitary adenomas remain confined to the skull but may grow into the walls of the sella turcica and surrounding nerves, vessels, and brain coverings. An enlarged pituitary can damage nearby parts of the brain. For example, damage to the optic nerve can lead to vision problems or even vision loss. About 75 percent of pituitary adenomas produce hormones and are, therefore, termed functional, while the rest do not and are termed nonfunctional. Pituitary tumors can cause overproduction of hormones. However, damage to pituitary tissue can also lead to hormone deficiency.

Adenomas are categorized as microadenomas, tumors smaller than one centimeter (cm), or macroadenomas, tumors larger than one cm. Microadenomas generate symptoms because of hormone overproduction and rarely because of damage to surrounding tissue, whereas macroadenomas cause symptoms by both hormone overproduction and tissue damage. Adenomas are further classified by the specific hormones produced—prolactin (prolactinomas, about 43 percent of all pituitary adenomas), growth hormone (GH, about 17 percent), adrenocorticotropin (ACTH, about 7 percent), thyroid-stimulating hormone (TSH, about 3 percent), and gonadotropin (which with null-cell, or nonfunctional, adenomas make up about 30 percent).

About 3 percent of all pituitary tumors are caused by inherited mutations in deoxyribonucleic acid (DNA) in people with MEN 1. Some 40 percent of GH-secreting adenomas have an acquired mutation in a specific protein called Gs alpha. It is unclear whether abnormal genes are essential for pituitary tumor formation. However, gene alterations probably result in the loss of regulatory mechanisms for hormone production and the growth of glandular cells, thereby promoting tumor growth.

Incidence: In the United States, pituitary tumors represent between 10 and 15 percent of all intracranial tumors, though scientists posit up to 20 percent of people may experience a pituitary tumor at some point. The incidence of acromegaly, a condition produced when the body creates too much growth hormone, is approximately three per one million people in men and women.

Symptoms: All adenomas can cause headaches and visual problems when they grow large enough to affect nearby tissues. Between 40 and 60 percent of individuals experience vision impairment. Macroadenomas can lead to neurologic symptoms such as double or blurred vision due to paralysis of eye movement, loss of peripheral vision, sudden blindness, facial numbness or pain, headaches, dizziness, and even loss of consciousness. The destruction of normal pituitary tissue by macroadenomas and pituitary carcinomas leads to a lack of normal body hormones such as cortisone, thyroid hormone, and sex hormones. This can result in nausea, weakness, weight loss or gain, irregular menses, erectile dysfunction, and decreased libido (mainly in men). Macroadenomas and pituitary carcinoma can also cause diabetes insipidus as a result of a lack of production of vasopressin (also called the antidiuretic hormone, ADH). If severe and untreated, this condition can lead to coma and death.

GH-secreting adenomas in children can stimulate excessive bone growth, leading to gigantism. Symptoms include being very tall and experiencing rapid growth, joint pains, and increased sweating. Adults with GH-secreting adenomas may develop acromegaly, characterized by the growth of the skull, hands, feet, and facial bones, leading to changes in the appearance of the face, joint pain, deepening of the voice, increased sweating, diabetes mellitus, kidney stones, heart disease, headaches, unusual hair growth, and thickening of the tongue, palate, and skin.

ACTH-secreting adenomas can stimulate the adrenal gland's production of steroid hormones and subsequently cause Cushing syndrome. The symptoms are weight gain, increased body hair, fat deposits in the neck, headache, mood swings, irregular menses, high blood pressure, high blood sugar, osteoporosis, easy bruising, and purple stretch marks on the abdomen.

Prolactin-producing adenomas (prolactinomas) are difficult to spot in children. They are most common in young women, in whom high prolactin levels can cause irregular menses and abnormal breast milk production (galactorrhea), and in older men, in whom they cause impotence or libido loss. They also cause vision loss, headache, infertility, low sex drive, and lactation in individuals not pregnant or breastfeeding.

TSH-secreting adenomas cause hyperthyroidism, with symptoms such as an enlarged thyroid, weight loss, increased appetite, rapid heartbeat, tremors, anxiousness, sleeping problems, frequent bowel movements, and feeling warm or hot.

Gonadotropin-secreting adenomas are not very common. They produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which may cause irregular menses.

Nonfunctional adenomas may be the most common pituitary tumors, but they are rarely detected, as they do not cause symptoms and are typically detected by (MRI) or computed (CT) scans taken for other reasons.

Screening and diagnosis: Knowing what hormone an adenoma produces is critical in choosing the treatment and determining the prognosis. Biochemical testing for GH-secreting adenomas includes checking for excessive production of GH and insulin-like growth factor 1 (IGF-1). If both levels are very high, the patient clearly has a pituitary tumor. If the levels are only slightly increased, a glucose suppression test is done.

Biochemical testing for ACTH-secreting adenomas includes measuring levels of ACTH and cortisol in blood samples and of cortisol and other steroid hormones in urine samples taken at different times during the day. These tests may be repeated after taking dexamethasone, a cortisone-like drug. These tests are also used to distinguish patients with ACTH-secreting adenomas from patients with other diseases, such as adrenal gland tumors, which cause similar symptoms.

Tests to measure blood levels of prolactin, TSH, LH, and FSH can identify patients with prolactinomas, TSH-secreting adenomas, or gonadotropin-secreting tumors. If tests for excessive hormone production are negative or the levels are lowered, a pituitary adenoma is considered nonfunctional.

Macroadenomas and pituitary carcinomas and particularly metastatic cancer can damage the part of the pituitary gland that produces vasopressin, leading to diabetes insipidus. This can also occur as a side effect of the surgical treatment of pituitary tumors. Diagnosis of diabetes insipidus is made by tests to measure sodium levels and total salt concentration (osmolality) of the blood and urine. In addition, a water deprivation test may be necessary.

Imaging tests (MRI and CT scans) visualize tumors. Venous blood sampling may be necessary to confirm the presence of ACTH-secreting adenomas if they are too small to be detected by MRI scans. Testing of vision and visual fields also helps to detect pituitary tumors. A biopsy can provide a closer analysis of the type of tumor.

No staging system exists for pituitary tumors, as they are nearly always benign. Pituitary carcinomas are too rare for a staging system to develop. The most useful information in treating an adenoma is whether it is a macroadenoma or a microadenoma, whether it produces hormones, and which hormones it produces.

Treatment and therapy: Pituitary tumors may be treated surgically, medically, radiotherapeutically, or with combinations of these therapies. Which therapy is used depends on the type of tumor.

Prognosis, prevention, and outcomes: Pituitary tumors are usually curable. The prognosis depends on the type of pituitary tumor and the patient’s general health and age.

Bibliography

Asa, Sylvia L., et al. "Overview of the 2022 WHO Classification of Pituitary Tumors." Endocrine Pathology, vol. 33, no. 1, 2022, pp. 6-26. doi.org/10.1007/s12022-022-09703-7.

Bioletto, Fabio, et al. "Radiomic Analysis in Pituitary Tumors: Current Knowledge and Future Perspectives." Journal of Clinical Medicine, vol. 13, no. 2, 2024, p. 336. doi.org/10.3390/jcm13020336.

Cecil, Russell L. Goldman-Cecil Medicine. 27th ed., Elsevier, 2024.

Dai, Congxin, et al. "How to Classify and Define Pituitary Tumors: Recent Advances and Current Controversies." Frontiers in Endocrinology, vol. 12, 2021, p. 604644. doi.org/10.3389/fendo.2021.604644.

Nachtigall, Lisa B. Pituitary Tumors: A Clinical Casebook. Springer, 2018.

"Pituitary Adenomas." Cleveland Clinic, 72 June 2022, my.clevelandclinic.org/health/diseases/15328-pituitary-adenomas. Accessed 20 July 2024.

"Pituitary Tumors Treatment (PDQ®)–Patient Version." National Cance Institute, 10 Mar. 2023, www.cancer.gov/types/pituitary/patient/pituitary-treatment-pdq. Accessed 20 July 2024.

Robert C., et al. Holland-Frei Cancer Medicine. Wiley-Blackwell, 2023.

"What Are Pituitary Tumors?" American Cancer Society, 10 Oct. 2022, www.cancer.org/cancer/types/pituitary-tumors/about/what-is-pituitary-tumor.html. Accessed 20 July 2024.