Small cell lung cancer (SCLC) is an aggressive type of lung cancer known for its rapid growth and tendency to spread early. While it primarily affects the lungs, SCLC can sometimes produce hormones not normally associated with lung tissue. One such hormone is adrenocorticotropic hormone (ACTH), leading to a condition known as ectopic ACTH syndrome. This hormone production can significantly impact a person’s health by disrupting the body’s normal hormonal balance.
Understanding ACTH and Ectopic Production
Adrenocorticotropic hormone (ACTH) is produced by the pituitary gland, a small gland at the base of the brain. Its role is to stimulate the adrenal glands, atop the kidneys, to produce cortisol. Cortisol, often called the “stress hormone,” regulates metabolism, reduces inflammation, and manages the body’s response to stress. Pituitary ACTH production is controlled by the hypothalamus in the brain, forming a feedback loop.
However, in small cell lung cancer, some cancer cells produce ACTH independently of the pituitary gland. This is termed “ectopic production” because the hormone is made by tissues that do not normally produce it. These SCLC cells release large, unregulated amounts of ACTH into the bloodstream. The excess ACTH overstimulates the adrenal glands, leading to abnormally high cortisol production.
Recognizing the Symptoms
The continuous excess cortisol production due to ectopic ACTH from SCLC leads to symptoms resembling Cushing’s Syndrome. Individuals may experience weight gain, especially around the abdomen and face (“moon face”). Muscle weakness, particularly in the arms and legs, can develop, stemming from muscle protein breakdown due to high cortisol.
High blood pressure (hypertension) is a symptom, contributing to cardiovascular risks. Blood sugar levels can elevate, sometimes leading to new-onset or worsening diabetes. Common skin changes include thinning skin, easy bruising, and purple or reddish stretch marks (striae) on the abdomen, thighs, and breasts. Mood disturbances, such as irritability, anxiety, or depression, can also manifest due to hormonal imbalance.
Confirming the Diagnosis
Diagnosing ACTH production linked to SCLC involves tests to measure hormone levels and locate the tumor. Initial blood tests measure circulating ACTH and cortisol levels; elevated levels, especially very high ACTH, suggest ectopic production. A 24-hour urine collection measures total cortisol excreted, assessing daily production.
To confirm the ACTH source and differentiate from other Cushing’s Syndrome causes, suppression tests are conducted. A high-dose dexamethasone suppression test determines if cortisol production can be suppressed by a synthetic steroid. Unlike pituitary-driven Cushing’s, ectopic ACTH from SCLC does not suppress with high-dose dexamethasone. Imaging scans (CT or MRI of chest and abdomen) locate the SCLC tumor and identify adrenal gland enlargement from chronic overstimulation.
Managing the Condition
Managing SCLC with ACTH production requires a comprehensive approach, addressing both the cancer and excess ACTH effects. Cancer treatment often involves systemic therapies like chemotherapy (drugs to destroy cancer cells) and radiation therapy (high-energy rays). Immunotherapy, which helps the immune system fight cancer, may also be part of the SCLC treatment plan. The goal is to reduce tumor burden, decreasing ACTH production.
Simultaneously, medications manage high cortisol symptoms. Drugs like ketoconazole, metyrapone, or osilodrostat block enzymes in adrenal glands, reducing cortisol synthesis. Mifepristone blocks cortisol’s effects at the receptor level. In rare cases where medical management is challenging, surgical removal of one or both adrenal glands (adrenalectomy) may be considered to eliminate the cortisol source. This dual strategy, involving oncologists, endocrinologists, and other specialists, improves patient outcomes and quality of life.