Endocrine tumors develop when abnormal cells in an endocrine gland or organ grow and multiply uncontrollably. Over time, the new cells can develop into a solid mass of tissue known as a tumor.

In most cases, endocrine tumors are benign (noncancerous). In cases where they are malignant (cancerous), the cells that make up the tumor are capable of invading nearby tissues and spreading to other parts of the body, where they can form new tumors.

While many kinds of endocrine cancers are rare, some are common. For example, thyroid cancer, a type of endocrine cancer, is the seventh most commonly diagnosed cancer in women and the tenth most commonly diagnosed cancer in men in the United States. Other endocrine cancers include cancers of the adrenal glands, parathyroid glands, pituitary gland, hypothalamus, and pancreas.

Fortunately, effective treatments, including surgery, chemotherapy, radiation therapy, and medications, among other therapies, are available for endocrine cancers.

The endocrine system is a group of glands and organs that produces and secretes hormones. Hormones are chemicals that travel through the bloodstream to tissues around the body, where they regulate and coordinate many important processes in the body, including metabolism, growth, development, sexual function, reproduction, and mood.

An endocrine tumor can form when abnormal cells in an endocrine gland or organ arise and grow uncontrollably. There are two broad categories of endocrine tumors:

• Functioning tumors, which produce and secrete hormones. When a tumor arises from a hormone-producing cell, the cells that make up the tumor also produce and secrete excessive levels of the hormones made by the initial cell, which can cause a range of symptoms and problems in the body, depending on which hormone is involved.
• Nonfunctioning tumors, which do not produce or secrete hormones.

Both functioning and nonfunctioning tumors can develop into large masses that press against nearby tissues and organs, impairing their ability to work properly.

Cancer can develop in any endocrine gland or tissue in the body. Common types include the following:

• Thyroid cancer: The thyroid is a small, butterfly-shaped organ located at the base of the neck. It produces and secretes thyroid hormones that help regulate metabolism.
• Pituitary tumors: A pea-sized organ located just below the brain, the pituitary gland produces several different hormones that regulate the function of other endocrine glands, including the adrenal and thyroid glands, as well as the gonads (the ovaries and testicles). The pituitary helps control important functions of the body, including growth, blood pressure, metabolism, and sperm and egg production, among many others. Pituitary tumors are almost always benign. According to the National Cancer Institute, only around 0.1% to 0.2% of pituitary tumors are cancerous.
• Adrenal cancers: The two adrenal glands, located just above the kidneys, produce several different hormones that play an important role in regulating a number of essential bodily processes, including metabolism, the stress response, inflammation, blood pressure, and sexual development. Adrenal hormones include cortisol, aldosterone, and adrenaline (also known as epinephrine). A few types of cancer can occur in the adrenal gland, including adrenocortical carcinoma and pheochromocytoma, though the latter tumor is usually benign.
• Pancreatic cancers: Though the pancreas plays an active role in the digestive system, it’s also part of the endocrine system. Specialized neuroendocrine cells in the pancreas produce and secrete hormones, including insulin and glucagon, to help regulate blood sugar levels.
  
  Neuroendocrine cells have features of both nerve cells and hormone-producing endocrine cells. Cancerous tumors that develop from these neuroendocrine cells are called pancreatic neuroendocrine tumors (pancreatic NETs or pNETs) or islet cell tumors. Pancreatic NETs are rare and, according to the ACS, account for just under 2% of all pancreatic cancers. (Because neuroendocrine cells are found in various tissues throughout the body, including the gastrointestinal tract and lungs, NETs can also occur in those locations.)

• Parathyroid cancers: The four pea-sized parathyroid glands, located behind the thyroid gland in the neck, produce parathyroid hormone (PTH). PTH helps regulate blood calcium levels. When blood calcium levels are low, the parathyroid glands secrete PTH, which stimulates the release of calcium from bones into the blood, increases the absorption of calcium from food by the intestine, and prevents the kidney from excreting too much calcium in the urine. Together, these actions increase blood calcium levels. People with parathyroid cancer have severe hypercalcemia (high blood calcium levels). Parathyroid cancer is very rare.
• Hypothalamic endocrine tumors: The hypothalamus is a small part of the brain connected to the pituitary gland. It produces and secretes hormones that regulate the activity of the pituitary gland (which in turn secretes hormones that regulate the activity of several other endocrine glands). Cancer of hormone-secreting cells in the hypothalamus is rare.

The cause of most endocrine cancers is usually unclear.

Normally, the growth and production of new cells are tightly regulated to ensure that only healthy cells are produced and survive. In cancer, genetic changes—or mutations—in a single cell interfere with the careful regulation of cell growth and production. As a result, the affected cell grows and multiplies uncontrollably and can invade nearby tissues and spread to other parts of the body.

The genetic changes that trigger cancer may be inherited from one or both parents or may occur sporadically, meaning they are acquired during a person’s life. Sporadic mutations can occur randomly or due to environmental exposures, such as smoking tobacco products or radiation exposure.

Endocrine cancer symptoms vary greatly, depending on which part of the endocrine system is affected, whether the tumor has grown large enough to press against nearby tissues, and which hormones, if any, are produced and secreted in excessively high levels.

Risk factors for endocrine tumors may include:

Thyroid cancer:

• Being female
• Being between 25 and 80 years of age
• Radiation exposure, such as head or neck radiation treatments in childhood
• Personal history of goiter, thyroid nodules, or a previous thyroid cancer diagnosis
• Family history of thyroid cancer or thyroid disease
• Certain genetic conditions including multiple endocrine neoplasia type 2A (MEN2A) and type 2B (MEN2B)
• Certain inherited conditions, including familial medullary thyroid cancer (FMTC), Cowden disease, Carney complex type 1, and familial adenomatous polyposis (FAP)

Pituitary Tumors:

• Certain inherited conditions, including multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4), Carney complex, McCune-Albright syndrome, familial isolated pituitary adenoma (FIPA)

Adrenal cancer:

• Certain inherited and genetic conditions, including Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, Carney complex, MEN1, familial adenomatous polyposis (FAP), Lynch syndrome, MEN2A, MEN2B, von Hippel-Lindau (VHL) syndrome, neurofibromatosis type 1 (NF1), hereditary paraganglioma syndrome, Carney-Stratakis dyad, Carney triad

Pancreatic neuroendocrine tumors:

• Smoking
• Alcohol consumption
• Family history of pancreatic NETs
• Certain inherited genetic syndromes, including NF1, MEN1, VHL syndrome
• Diabetes
• Chronic Pancreatitis

Parathyroid Cancer:

• Radiation exposure, such as from previous treatment with radiation therapy to the head or neck
• Certain inherited conditions, including familial isolated hyperparathyroidism (FIHP), hyperparathyroidism-Jaw tumor syndrome (HPT-JT), MEN1, MEN2A

Hypothalamic endocrine tumors:

• Neurofibromatosis

Doctors can perform a series of steps to check for endocrine cancer, including:

• A medical history to determine whether the patient has any risk factors for endocrine cancer, such as a family history of certain conditions or a medical condition associated with endocrine cancer
• A physical exam to evaluate symptoms and signs that could be caused by an endocrine cancer
• Lab tests to check for abnormal levels of hormones and/or other markers in the blood or urine
• Imaging studies, such as a computed tomography (CT) scan, magnetic resonance imaging (MRI) scan, ultrasound, or other imaging tests to look for evidence of abnormal tissue
• A biopsy to obtain a tissue sample for analysis that can check for the presence of cancer cells
• Genetic testing to determine the genetic makeup of tumor cells. In many cases, knowing a tumor’s genetic makeup helps health care providers choose the best treatment options.

Various treatment options are available for endocrine cancers. The treatment varies based on the type of cancer involved, how far it has progressed, and the patient’s overall health, among many other factors.

Endocrine cancer treatment may involve:

• Surgery to remove the cancerous tissue. In some cases, the entire affected organ may be removed. For example, adrenalectomy—the surgical removal of an adrenal gland—is frequently used to treat adrenal cancer.
• Radiation therapy, also known as radiotherapy, kills cancer cells by exposing them to high doses of radiation. It is often used after surgery to kill any remaining cancer cells.
• Chemotherapy involves the use of drugs to kill cancer cells. It may be given before surgery to reduce tumor size or after surgery to eliminate any cancer cells that remain.
• Targeted drug therapy uses drugs that target specific genes or proteins found in cancer cells.
• Ablation may be used to destroy tumors. During an ablation procedure, a probe is used to deliver heat, cold, alcohol, or other forms of energy to the tumor, thereby destroying the cancerous tissue.
• Embolization is a technique to cut off blood flow to—and kill—cancer cells. In an embolization procedure, substances are injected into a blood vessel to block blood flow to a tumor. Sometimes, beads that contain chemotherapy drugs (known as chemoembolization) or a radioactive isotope (known as radioembolization) are also injected into the blood vessel to deliver chemotherapy or radiation, respectively, to the tumor.
• Immunotherapy involves the use of drugs to enhance the ability of the patient’s immune system to fight against cancer.
• Hormone therapy may be used to suppress the production of—or block the effects of—excess hormones made by endocrine tumors. In other cases, cancer or cancer treatments such as surgery, chemotherapy, or radiation therapy can impair the ability of an endocrine gland to produce hormones. In these cases, patients may need to take hormones to replace those that the affected gland can no longer produce.
• Observation may be appropriate for select small thyroid cancers that are well differentiated and considered low risk. In such circumstances, patients may choose observation rather than immediate surgery.

The outlook for people with endocrine cancers can vary greatly depending on a number of factors, including which part of the endocrine system is affected, whether the cancer has invaded nearby tissues or spread to other parts of the body, how well the cancer responds to treatment, and patient age and overall health.

“Some of the greatest strengths of Yale’s endocrine neoplasia program are its people and the multidisciplinary approach to patient care,” says Sachin Majumdar Jr., MD, director of the Yale Medicine Endocrine Neoplasia Clinic. “When people seek care they have differing situations, needs, and goals, and therefore we work as a team to come up with individualized treatment plans. There is a close collaboration between specialties such as Endocrinology, Endocrine Surgery, Head and Neck Surgery, Neurosurgery, Endocrine Oncology, Radiology, Nuclear Medicine, Radiation Medicine, Cytopathology, Pathology, Molecular Medicine, and occasionally other specialists, who work together and meet at weekly Tumor Boards to discuss cases. The sharing of ideas, research, and communication across specialties fosters a robust approach to patient care that is not available outside of a program such as ours.”