January is Adrenal Cancer Awareness month. Many individuals and even healthcare providers and doctors know very little about symptoms of metastatic adrenal cancer, and what the most common symptoms are. Unfortunately, adrenal cancer is often aggressive, and is often not diagnosed in time for effective treatment. If adrenal cancer already has spread outside the adrenal gland (most commonly liver and lung), the cancer is often lethal. This is what we call metastatic (or Stage 4) adrenal cancer. If you ever had an adrenal mass found on a scan, you need to have your adrenal hormones checked and make sure it is not an adrenal cancer. If you have any of the below symptoms, it can be a sign of metastatic adrenal cancer.

Top 6 Symptoms of Metastatic Adrenal Cancer

• Symptoms from too much cortisol (Cushing’s syndrome)
• Abdominal or flank pain/discomfort
• Virilization/Feminization
• Rapid weight gain or loss
• Nausea, vomiting and lack of appetite
• Blood clots (thrombosis)

#1 Symptom of Metastatic Adrenal Cancer: Metastatic adrenal cancer can cause symptoms from too much cortisol (Cushing’s syndrome)

The majority of metastatic adrenal cancers are found because the overproduction of hormones causes symptoms, which then prompts patients to seek medical attention. More on the top symptoms of adrenal cancer. The most frequently produces hormone by metastatic adrenal cancer (stage 4) is cortisol. About 60% of adrenal gland cancers overproduce the hormone cortisol, contributing to symptoms of Cushing’s syndrome.

Adrenal Cushing's syndrome is by far the most common hormonal syndrome associated with metastatic adrenal cancer. Read more about Cushing’s syndrome symptoms, diagnosis, and treatment here:

• https://www.adrenal.com/cushing-syndrome/overview
• https://www.adrenal.com/blog/top-5-myths-about-adrenal-cushing-s-syndrome

#2 Symptom of Metastatic Adrenal Cancer: Metastatic adrenal cancer can cause abdominal or flank pain/discomfort

The adrenal glands are located on top of the kidneys very far back in the abdomen (technically in the retroperitoneum). That means that they can grow quite large before they cause any symptoms. For patients that have no hormone production, it is not unusual for the adrenal cancer to grow to the size of a cantaloupe before it causes pain in the abdomen and the flank. Almost all patients with metastatic adrenal cancer seek medical attention because of pain unless they have obvious hormone overproduction. Also, if adrenal cancer spreads to the liver, the growth of these metastases can cause pain and discomfort especially in the upper right portion of the abdomen.

Figure 1. CT scan showing an adrenal cancer that has spread to the liver (metastasis). This can cause pain and discomfort especially in the right upper abdomen or the flank.

#3 Symptom of Metastatic Adrenal Cancer: Metastatic adrenal cancer can cause virilization/feminization

Metastatic adrenal cancer can lead to overproduction of sex-steroid hormones. When excess female hormones are produced in a female it can be hard to diagnose, except at extremes of age such as early puberty in a child, or the return of vaginal bleeding in a post-menopausal woman. The same is true for excess testosterone in a male. The opposite, however, will often make the diagnosis obvious, such as when a woman begins to develop male characteristics (deeper voice, excess body hair) or when a man begins to develop enlarged breasts (gynecomastia). Some of these hormone overproduction diseases have specific names:

• Virilization (acquisition of male traits in a female because of excess testosterone production)
• Feminization (acquisition of female traits in a male because of excess estrogen production)
• Precocious puberty (puberty occurring too early because of excess sex steroids produced)

Figure 2. Breast development in a man (gynecomastia) on the CT scan (yellow arrows) due to an adrenal cancer producing too much Estrogen in a man.

#4 Symptom of Metastatic Adrenal Cancer: Metastatic adrenal cancer can cause rapid weight gain or loss

Weight gain is one of the most common adrenal gland cancer symptoms. About 60% of adrenal gland cancers overproduce cortisol and lead to rapid weight gain. The mechanism is the same as for patients with non-cancerous adrenal tumors over-producing cortisol.

The difference is that often, the weight gain is very rapid and happens over a much shorter period of time. Patients with adrenal gland cancer can gain significant weight (10—30 lbs.) in just a few weeks. Weight gain as an adrenal gland cancer symptom can also frequently present as central obesity, which occurs around the center of the body and is also called visceral fat. Learn more about adrenal gland tumors and weight gain.

However, unintentional rapid weight loss is also a concerning feature and is associated with many cancers, especially advanced stage 4 metastatic adrenal cancer. This is particularly common when the tumor is not overproducing cortisol.

#5 Symptom of Metastatic Adrenal Cancer: Metastatic adrenal cancer can cause nausea, vomiting and lack of appetite

Similar to other types of metastatic, stage 4 cancers, adrenal cancers can cause many different gastrointestinal symptoms. Nausea and vomiting as well as loss of appetite is quite common in metastatic adrenal cancer

#6 Symptom of Metastatic Adrenal Cancer: Metastatic adrenal cancer can cause blood clots (thrombosis)

Blood clots are unfortunately very common in metastatic adrenal cancers and are due to two factors:

• Increased hypercoagulability from too much cortisol. Too much cortisol is notorious for making the blood too sticky leading to venous thrombosis. In the legs this is called deep venous thrombosis (DVT) and can cause leg swelling. If the blood clot travels through the veins, they end up in the lungs causing pulmonary embolus. Pulmonary embolus (clots to the lungs) is very common in sever Cushing’s syndrome and can be very dangerous, and in fact deadly, since the blood cannot be properly oxygenated before returning to the heart
• Direct tumor invasion into the major vein (Inferior vena cava; IVC) of the body. Adrenal cancer can infamously grow through the veins from the adrenal into the major veins of the body (IVC) all the way to the heart. This is very dangerous and problematic and very difficult to treat (Figure 3).

Figure 3. Graphic showing both pathways of tumor blood clots (thrombosis) from an adrenal cancer. Right-sided adrenocortical carcinoma (ACC) reaching the right atrium (RA) through thrombosis of the right adrenal vein (RAV; black arrow) to the inferior vena cava (IVC). B, Left-sided ACC reaching the RA through thrombosis of the left adrenal vein (LAV; white arrow), left renal vein, and IVC. RV indicates right ventricle, and SVC, superior vena cava.

Dr. Tobias Carling, of the Carling Adrenal Center, is one of the world's leading experts in adrenal gland surgery. Dr. Carling performs more adrenal operations than any other surgeon in America. Dr. Carling left Yale University in 2020 to open the Carling Adrenal Center in Tampa, Florida.

To discuss the details of your case with Dr. Carling and become his patient, fill out the new patient form and he will be in touch with you shortly.

Additional Resources: 

• Learn more about the Carling Adrenal Center
• Learn more about Dr. Tobias Carling
• Learn more about our sister surgeons at the Norman Parathyroid Center, Clayman Thyroid Center and Scarless Thyroid Surgery Center
• Learn more about the Hospital for Endocrine Surgery