Ectopic ACTH secretion is a rare medical condition characterized by the abnormal production of adrenocorticotropic hormone (ACTH) from sources outside of the pituitary gland. This overproduction of ACTH then stimulates the adrenal glands to release excessive amounts of cortisol, a hormone that regulates various bodily functions. The resulting high cortisol levels can lead to a condition known as Cushing’s syndrome, which presents with a range of physical and metabolic changes.
Understanding ACTH and Its Normal Role
Adrenocorticotropic hormone, or ACTH, is a hormone normally produced by the pituitary gland. The primary function of ACTH is to stimulate the adrenal glands to produce and release cortisol. Cortisol plays many roles throughout the body.
Cortisol helps regulate the body’s response to stress, influences metabolism by controlling the use of fats, proteins, and carbohydrates, and suppresses inflammation. It also contributes to regulating blood pressure, blood sugar levels, and the sleep-wake cycle. The production and release of ACTH and cortisol are part of a feedback system, where rising cortisol levels signal the pituitary gland and hypothalamus to reduce ACTH production, maintaining balance.
Where Ectopic ACTH Secretion Comes From
This unusual production is most commonly caused by non-pituitary tumors that aberrantly secrete ACTH. These tumors can arise in various parts of the body, producing ACTH independently of the body’s normal regulatory mechanisms.
Small cell lung cancer (SCLC) is a frequent cause. Other common sources include carcinoid tumors, which can be found in the lungs, thymus, or gastrointestinal tract. Pheochromocytomas and paragangliomas, which are neuroendocrine tumors, can also secrete ACTH. In about 12% of cases, the specific tumor causing the ectopic ACTH secretion may not be immediately identified, even after extensive imaging.
How Ectopic ACTH Secretion Affects the Body
The continuous excess of cortisol due to ectopic ACTH secretion leads to a wide array of symptoms affecting multiple body systems. Individuals often experience rapid weight gain, particularly in the face, which can appear rounded (moon face), and around the torso, sometimes forming a fatty hump between the shoulders (buffalo hump). Muscle weakness and thinning of the arms and legs can also occur.
Skin changes are common, including thin, fragile skin that bruises easily, and the appearance of purple stretch marks (striae) on the abdomen, thighs, breasts, and underarms. High blood pressure (hypertension) and elevated blood sugar levels, sometimes leading to new-onset diabetes, are also frequent manifestations. Mood changes, such as depression and irritability, as well as an increased susceptibility to infections, can further impact an individual’s health.
Identifying and Managing Ectopic ACTH Secretion
Identifying ectopic ACTH secretion begins with confirming consistently high cortisol levels in the body. Initial diagnostic tests often include a 24-hour urine free cortisol test or late-night salivary cortisol measurements to assess overall cortisol production. Once hypercortisolism is confirmed, further tests are conducted to determine the source of the excess ACTH.
Measuring ACTH levels in the blood helps differentiate between pituitary and non-pituitary causes. Imaging scans, such as CT scans, MRI, and PET scans, are then used to locate the tumor responsible for the ectopic ACTH production. In some cases, a specialized procedure called bilateral inferior petrosal sinus sampling (IPSS) may be performed to confirm whether the ACTH source is from the pituitary gland or elsewhere in the body. Management strategies primarily focus on treating the underlying tumor, which may involve surgical removal, chemotherapy, or radiation therapy, depending on the tumor type and location. Additionally, medications can be prescribed to block cortisol production, or in severe cases where the tumor cannot be found or controlled, surgical removal of the adrenal glands (adrenalectomy) may be considered to manage the excessive cortisol levels.