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Cushing’s Syndrome and Lung Cancer: What’s the Connection?

Posted on August 17, 2022
Medically reviewed by
Todd Gersten, M.D.
Article written by
Jodie Rothschild

It is not uncommon to have more than one disease at the same time, especially when one of those diseases is cancer. One condition that might affect people with lung cancer — especially those with neuroendocrine tumors or small cell lung carcinoma (SCLC) — is paraneoplastic Cushing’s syndrome. “Paraneoplastic” means that it is not directly related to the tumor itself.

Cushing’s syndrome will affect just 1 percent to 5 percent of people with SCLC, and even fewer who have non-small cell lung cancer. But many people with lung cancer will develop at least one sign or symptom of Cushing’s syndrome.

What Is Cushing’s Syndrome?

Cushing’s syndrome, also called hypercortisolism, occurs when there are high levels of cortisol in the blood. Cortisol is a kind of glucocorticoid, a steroid hormone made naturally in the body. Cortisol production is controlled by three parts of the body:

  • The hypothalamus, a gland in the brain
  • The pituitary gland, which is attached to the hypothalamus
  • The two adrenal glands, located at the top of each kidney

Understanding Glands and Hormones

Glands are specialized organs that send messages throughout the body by releasing molecules called hormones.

Cortisol levels are regulated by a basic process that involves these steps:

  1. When cortisol levels are low, the hypothalamus releases corticotropin-releasing hormone (CRH).
  2. CRH tells the pituitary gland to release adrenocorticotropic hormone (ACTH), which signals the adrenal glands to release cortisol.
  3. When cortisol levels in the blood get high enough, CRH and ACTH production slow down.
  4. Cortisol levels start to drop, and when they get low enough, the hypothalamus releases more CRH.

Certain diseases and medications can disrupt this cycle. If cortisol levels remain too high for too long, a person will develop Cushing’s syndrome.

Causes of Cushing’s Syndrome

The most common cause of Cushing’s syndrome involves exogenous glucocorticoids — they come from outside the body. Steroid medications such as prednisone and dexamethasone are very similar to cortisol, and long-term use of high doses can result in Cushing’s syndrome.

Too much endogenous cortisol — from within the body — can also lead to Cushing’s syndrome. Tumors or abnormal growth of the pituitary gland (also called Cushing’s disease) or the adrenal gland can cause high cortisol levels. In ectopic Cushing’s syndrome, cancer cells in other parts of the body start releasing ACTH.

The Role of Cortisol in the Body

To understand Cushing’s syndrome, it is important to know about cortisol’s many roles in the body. Cortisol is often referred to as the “stress hormone” because it is released when a person feels tense or faces a fight-or-flight situation. Cortisol causes increases in:

  • Heart rate
  • Blood pressure
  • Blood sugar
  • Respiration (how the body uses sugar and oxygen to make energy)
  • Muscle tension

At the same time, body functions that are not helpful during a fight-or-flight situation, such as those involving the digestive and reproductive systems, are inhibited. Cortisol also:

  • Helps regulate thyroid function
  • Reduces insulin secretion, which helps regulate metabolism
  • Acts as an anti-inflammatory
  • Helps regulate the immune system
  • Affects learning and memory
  • Plays a part in maintaining salt and water balance
  • Supports developing fetuses

Symptoms of Cushing’s Syndrome

A host of possible symptoms go along with Cushing’s syndrome, including:

  • A fatty hump on the upper back, between the shoulder blades (often called a buffalo hump)
  • Weight gain, especially in the stomach area
  • A round face (called a moon face)
  • Red cheeks
  • Stretch marks, especially on the torso
  • Acne
  • Easily bruised, thinning skin
  • Longer healing time
  • Infections
  • Muscle weakness
  • Fatigue
  • Brittle bones (osteoporosis)
  • High blood pressure
  • High blood sugar and diabetes
  • Memory issues
  • Excessive growth of facial and body hair
  • Loss of menstrual periods (amenorrhea)
  • Difficulty getting erections (erectile dysfunction)

How Is Cushing’s Syndrome Diagnosed?

Blood and urine tests might be done to measure cortisol levels. If levels are high, a procedure called inferior petrosal sinus sampling may be performed next. Small tubes are placed in veins near the groin and then carefully moved up to the veins that drain from the pituitary gland (called the inferior petrosal sinuses), where blood samples are taken. Doctors can then measure how much ACTH the pituitary is producing, which helps show them if this is the reason for the extra cortisol. They may also do a CT scan or an MRI scan to look for a pituitary tumor.

The doctor might also suggest doing a dexamethasone suppression test. The person takes a dexamethasone pill at night, and cortisol levels are measured in the morning. Dexamethasone is a glucocorticoid that is similar to cortisol. This drug usually reduces ACTH secretion by the pituitary, which slows cortisol secretion by the adrenal glands. If someone has Cushing’s syndrome, dexamethasone will not lower cortisol levels.

Cushing’s Syndrome and Lung Cancer

Cushing’s syndrome (especially Cushing’s disease) is a rare paraneoplastic syndrome of lung cancer — it is not directly caused by cancer. But because Cushing’s syndrome can lead to serious complications, it is important to understand its symptoms and how it relates to lung cancer.

How Are Cushing’s Syndrome and Lung Cancer Related?

Paraneoplastic syndromes are indirectly caused by tumors, resulting from the body’s response to hormones, proteins, or other molecules that cancer cells sometimes secrete. One of the most common paraneoplastic syndromes that can happen with lung cancer is a specific type of Cushing’s syndrome — ectopic Cushing’s syndrome.

Ectopic means that extra ACTH is being made by the cancer cells, not the pituitary gland. SCLC and neuroendocrine tumors grow from a kind of cell called neuroendocrine cells, which means they are similar to nerve cells and endocrine (hormone-releasing) cells. Neuroendocrine tumors can begin secreting hormones that normal cells would not. Neuroendocrine tumors in the lungs can release ACTH, which tells the adrenal glands to start releasing cortisol.

More rarely, Cushing’s syndrome can occur if lung cancer spreads to the pituitary gland. If this happens, the pituitary gland will start producing too much ACTH, just as it does with Cushing’s disease.

Unique Symptoms

Not all of the traditional symptoms of Cushing’s syndrome will appear in people with lung cancer. This is because the prognosis for people with lung cancer who also have Cushing’s syndrome is poor, and sometimes symptoms such as stretch marks or a buffalo hump don’t have time to develop. For people with lung cancer, Cushing’s syndrome symptoms usually include:

  • High blood pressure
  • Water retention
  • Low potassium levels
  • High blood sugar levels

How Is Cushing’s Syndrome Managed?

Cushing’s syndrome that has been caused by lung cancer is usually managed with treatments for the lung cancer. Shrinking or removing the tumors will decrease ACTH levels, which will then lower cortisol levels.

Another option is to try to reduce the amount of cortisol secreted by the adrenal glands. This is done with medication, especially some combination of ketoconazole, metyrapone, etomidate, mitotane, and mifepristone.

If you have lung cancer and develop Cushing’s syndrome, it is important to manage both conditions to stay your healthiest, feel your best, and improve your quality of life.

Talk With Others Who Understand

MyLungCancerTeam is the social network for people with lung cancer and their loved ones. On MyLungCancerTeam, more than 6,000 members come together to ask questions, give advice, and share their stories with others who understand life with lung cancer.

Are you or a loved one living with lung cancer? Have you noticed symptoms that could be related to Cushing’s syndrome? Share your experience in the comments below, or start a conversation by posting on your Activities page.

References
  1. Comorbidity — National Cancer Institute
  2. Ectopic Cushing Syndrome in Adenocarcinoma of the Lung: Case Report and Literature Review — Cureus
  3. Cushing’s Syndrome — National Institute of Diabetes and Digestive and Kidney Diseases
  4. What Is Cushing’s Disease (Pituitary Cushing’s Syndrome)? — UCLA Health
  5. Adrenal Hormones — Endocrine Society
  6. Stress-Induced Redistribution of Immune Cells — From Barracks to Boulevards to Battlefields: A Tale of Three Hormones — Psychoneuroendocrinology
  7. Modulatory Mechanisms of Cortisol Effects on Emotional Learning and Memory: Novel Perspectives — Psychoneuroendocrinology
  8. Cushing Syndrome — Mayo Clinic
  9. Inferior Petrosal Sinus Sampling — UCLA Health
  10. Cushing Disease/Cushing Syndrome — Oregon Health & Science University
  11. Overnight Dexamethasone Suppression Test — University of Michigan Health
  12. Paraneoplastic Syndromes in Lung Cancer and Their Management — Annals of Translational Medicine
  13. Ectopic Cushing Syndrome in Small Cell Lung Cancer: A Case Report and Literature Review — Thoracic Cancer
  14. Neuroendocrine Lung Cancer — Stanford Medicine
  15. Neuroendocrine tumors — Mayo Clinic
  16. Metastatic Spread to the Pituitary — Neuroendocrinology
  17. The Frequency and Clinical Biology of the Ectopic Hormone Syndromes of Small Cell Carcinoma — Cancer
  18. Uncommon Presentations of Some Common Malignancies — Case 1. Sequential Paraneoplastic Endocrine Syndromes in Small-Cell Lung Cancer — Journal of Clinical Oncology
  19. Case-Series of Paraneoplastic Cushing Syndrome in Small-Cell Lung Cancer — Endocrinology, Diabetes & Metabolism Case Reports
All updates must be accompanied by text or a picture.
Todd Gersten, M.D. is a hematologist-oncologist at the Florida Cancer Specialists & Research Institute in Wellington, Florida. Review provided by VeriMed Healthcare Network. Learn more about him here.
Jodie Rothschild is principal of Rothschild Biomedical Communications and a proud member of both the American Medical Writers Association and Plain Language Association International. Learn more about her here.

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