Small Cell Lung Cancer and Ectopic Cushing Syndrome

Small Cell Lung Cancer and Ectopic Cushing Syndrome

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Can Small Cell Lung Cancer Cause Cushing Syndrome

Medically reviewed by Julie Scott, DNP, ANP-BC, AOCNP — By Daniel Yetman on October 20, 2022The American Cancer Society (ACS) estimates that about 236,740 people will get a diagnosis of lung cancer in the United States in 2022. It also estimates that about 13% of them will get a diagnosis of small cell lung cancer (SCLC). SCLC develops in the neuroendocrine cells in your lung. These cells make up about 0.4% of the cells that line your airways. Their function is to produce hormones and other biologically active substances in response to electrical signals from your nervous system. When these cells become cancerous, they can produce excess hormones. Some people with SCLC develop a condition called ectopic Cushing syndrome. This syndrome is characterized by the excess production of hormones that increase levels of cortisol in your blood. Ectopic means the syndrome develops from tissues that don’t normally produce this hormone. Keep reading to learn more about the connection between SCLC and Cushing syndrome.

What s the connection between small cell lung cancer and ectopic Cushing syndrome

Up to 8% of people with cancer are thought to develop paraneoplastic syndromes. Paraneoplastic syndromes are groups of certain signs and symptoms that develop in some people with cancer. They’re caused by factors other than the direct invasion of cancer cells in a tissue. Some paraneoplastic syndromes develop due to an overreaction of your immune system to the cancer that damages healthy cells. Other syndromes, like ectopic Cushing syndrome, develop due to the excess production of hormones by cancer cells. SCLC is the type of cancer most associated with paraneoplastic syndromes. They’re thought to develop in about 10% of people with SCLC. Ectopic Cushing syndrome is one of the most common paraneoplastic syndromes in people with SCLC and is estimated to affect 1% to 5% of people. It’s more common in men and people over 40 years. Neuroendocrine tumors, such as SCLC and carcinoid tumors, are the types of lung cancers most associated with Cushing syndrome. It can also be caused by adenocarcinoma of the lung but is rare.

What is ectopic Cushing syndrome

Cushing syndrome, also called Cushing’s syndrome or hypercortisolism, is the excess production of the hormone cortisol. The most common cause of Cushing syndrome is a tumor of the pituitary gland. Ectopic Cushing syndrome makes up about 5% to 20% of cases of Cushing syndrome. It’s caused by the production of hormones by cancer cells that increase your cortisol levels. Cortisol has many functions in your body, such as:mediating your body’s stress responsecontrolling blood pressureincreasing the breakdown of glucose Usually, cortisol is produced in the following pathway:A part of your brain called the hypothalamus produces corticotropin-releasing hormone (CRH).CRH stimulates the release of adrenocorticotropic hormone (ACTH) from your anterior pituitary gland.ACTH stimulates the release of cortisol from your adrenal glands. In people with ectopic Cushing syndrome, cancer cells produce ACTH. Elevated levels of ACTH in your blood lead to excessive production of cortisol by your adrenal glands.

What are the symptoms of ectopic Cushing syndrome

Most people develop weight gain as an initial symptom, but about 10% of people have weight loss. Other symptoms can include:muscle weaknessperipheral edema, swelling in your lower legs or handshigh blood pressureweight gainmoon face, a full and puffy faceacnepurple stretch marks Symptoms can develop before or after lung cancer is diagnosed.

How do ectopic Cushing syndrome and Cushing syndrome compare

People with ectopic Cushing syndrome tend to have electrolyte disturbances and muscle weakness rather than typical features of Cushing syndrome, such as “moon face” (a buildup of extra fat on the sides of your face) or “buffalo hump,” which is a hump in your upper back. These symptoms are caused by chronically elevated levels of cortisol, but ectopic Cushing syndrome generally causes a sudden increase.

How is ectopic Cushing syndrome diagnosed

Doctors run a variety of tests to examine your hormone levels and differentiate ectopic Cushing syndrome from Cushing syndrome. Diagnostic tests may include:24-hour urine sample to measure your cortisol and creatinine levelsblood tests such as:ACTH testcortisol testfasting glucose testelectrolyte tests, specifically looking at potassium levelsimaging, such as computed tomography (CT) scans or magnetic resonance imaging (MRI) to look for the tumorlow dose and high dose dexamethasone tests, where you’re given the steroid dexamethasone to see how your cortisol levels change

How is ectopic Cushing syndrome treated

Treatment for ectopic Cushing syndrome should start as soon as possible to minimize complications. Treatment consists of targeting the underlying cancer, lowering cortisol levels, and treating specific symptoms that develop. Standard treatment for SCLC consists of some combination of:chemotherapyradiation therapysurgical removalimmunotherapylaser therapyendoscopic stent placement to open your airways Steroids may help reduce circulating levels of cortisol. Steroids that may be used include:ketoconazolemetyraponeetomidatemitotanemifepristone Examples of treatments for specific complications include:ComplicationTreatmentblood clotsanticoagulation medicationshyperglycemiaantidiabetic drugs
insulin infusioninfectionantivirals or antibioticslow blood potassiumIV potassium mineralocorticoid
receptor antagonistspsychosissedatives

What s the outlook for people with ECS

The outlook for people with ectopic Cushing syndrome largely depends on the outlook of the underlying cancer. Complications are very common when cortisol levels in your urine rise above 5 times of the upper limit of normal. It can cause fatal complications even if cancer is well controlled. Ectopic Cushing syndrome is associated with a poorer outlook for people with SCLC largely due to:advanced cancer stagepoor response to therapygreater susceptibility to infectionincreased risk of blood clots SCLC in general has a poor outlook. The ACS reports the 5-year relative survival rate as:StageSurvival ratelocal29%regional18%distant3%all stages7% Research also suggests people with SCLC that has spread to the adrenal glands may be prone to developing ectopic Cushing syndrome. Cancer that has spread to distant organs is associated with the poorest outlook.

Takeaway

Ectopic Cushing syndrome is a potential complication of cancer, and in particular, of SCLC. Ectopic Cushing syndrome occurs when cancer cells produce too much of the hormone ACTH, which raises levels of cortisol in your blood. Treatment of ectopic Cushing syndrome primarily involves treating the underlying cancer and taking medications to bring cortisol levels back into a normal range. SCLC with ectopic Cushing syndrome is generally associated with a poorer outlook than SCLC alone, but your doctor can give you the best idea of what to expect. Last medically reviewed on October 20, 2022

How we vetted this article

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ncbi.nlm.nih.gov/pmc/articles/PMC5334324/Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available. Current Version Oct 20, 2022 By Daniel Yetman Edited By Willow Banks Medically Reviewed By Julie Scott, DNP, ANP-BC, AOCNP Copy Edited By Suan Pineda Share this articleMedically reviewed by Julie Scott, DNP, ANP-BC, AOCNP — By Daniel Yetman on October 20, 2022

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