January is Adrenal Cancer Awareness month. Many individuals and even healthcare providers and doctors know very little about adrenal cancer, and what the typical symptoms are.

Adrenocortical carcinoma (ACC), or adrenal cancer, is fortunately a rare cancer, but is notorious for being diagnosed at a late stage, quite aggressive, and deadly. The only opportunity for cure is through surgery to remove the affected adrenal gland and associated involved structures.

Adrenal cancer typically presents one of two ways:

1. through excess hormone production causing recognizable symptoms
2. via mass effect (large tumor size pushing on, or having spread into, surrounding or distant structures) causing other associated symptoms, primarily pain.

Both for doctors and patients it is very important to know the most common symptoms of adrenal cancer so patients can be diagnosed when adrenal surgery is still feasible.

Top Symptoms of Adrenal Cancer

The top 8 symptoms caused by excessive hormone production from adrenal cancer are:

• Weight gain (cortisol; Cushing’s syndrome)

• Muscle weakness (cortisol; Cushing’s syndrome)

• Pink or purple stretch marks on the skin (cortisol; Cushing’s syndrome)

• Easy bruising (cortisol; Cushing’s syndrome)

• High blood pressure, low blood potassium, and high blood sugar (cortisol; Cushing’s syndrome)

• Increased anxiety and fatigue

• Excessive facial or body hair (hirsutism) in a female, and other signs of male characteristics (virilization; testosterone)

• Enlarged breasts in a male, and other signs of female characteristics (feminization, estrogen)

The top symptoms which help in the diagnosis of adrenal cancer depend on location of where the adrenal cancer starts and size of the tumor at diagnosis. As the name signifies, adrenocortical cancer (ACC, or more simply, adrenal cancer) arises in the adrenal cortex. Each layer of the adrenal cortex is responsible for the adrenal production of a specific hormone: aldosterone (salt), cortisol (sugar), or androgens and estrogens (sex hormones). The overwhelming majority of the adrenal tumors discovered in the cortex are benign (non-cancerous). It is very important to have an experienced adrenal surgeon review your chart (labs and imaging) when a suspected over-producing adrenal tumor is identified, so that you can understand whether it is cancerous or potentially cancerous.

Roughly 50% of adrenal cancers overproduce cortisol contributing to symptoms of Cushing’s syndrome.

The most common symptoms of Cushing’s syndrome in adrenal cancer are:

• Central obesity
• Facial plethora (redness; flushing)
• Rounded face
• Skin atrophy
• Easy bruising
• Muscle weakness
• Supraclavicular fat pads (buffalo hump)
• Menstrual irregularity
• Hypertension
• Diabetes mellitus
• Osteoporosis with and without fractures

Adrenal cancer can also overproduce the sex steroid hormones (androgens and estrogens). In women, increased androgens (testosterone) can lead to the following symptoms:

• Hirsutism (initial development of, or increase in, facial hair)
• Acne
• Absence or changes in the menstrual cycle
• Increased libido (sex drive).

Figure 1. A woman with advanced adrenal cancer overproducing both cortisol and androgens (testosterone) causing a combination of Cushing’s syndrome as well a male characteristics (hirsutism and virilization).

In men, increased estrogen can cause:

• Gynecomastia (enlarged and tender breasts)
• Problems with libido (sex drive)
• Erectile dysfunction.

Aldosterone-producing adrenal cancer, although extremely rare, can lead to signs and symptoms of primary hyperaldosteronism, an underdiagnosed benign condition that can contribute to high blood pressure and low blood potassium levels.

Many patients will seek medical attention with symptoms causing these bodily changes, which typically come on quite slowly (usually over 1 to 3 years). When excess female hormones are produced in a female it can be hard to detect, 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. When the atypically produced sex steroid hormones are more prevalent in the opposite sex, it will often make the symptom presentation more obvious.  For example, seeing more facial hair in a female, or more pronounced breast tissue in a male, will typically sound the alarm and lead to further work-up. If you have an adrenal tumor with overproduction of sex steroid hormones, this almost always occurs in the setting of a cancerous tumor, so it is extremely important to undergo the appropriate work-up.

Since roughly 60% of adrenal cancers make too much hormone (aldosterone, cortisol, testosterone, estrogen, and other androgens, such as DHEA-S), the initial evaluation should include blood and urine testing to measure for the above-mentioned adrenal hormones.  

Figure 2. CT scan showing liver metastasis (arrows) from a left adrenal cancer. This cancer overproduced estrogen in a man, and the first symptoms were enlargement of the breasts (gynecomastia).

Top symptoms of adrenal cancer caused by mass effect

In roughly 40% of adrenal cancer patients, the first symptoms will be related to the large tumor size. 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 adrenal cancer seek medical attention because of pain unless they have obvious hormone overproduction.

The top 5 symptoms of adrenal cancer caused by a mass effect of the tumor are:

• Belly or back/flank pain
• Increased belly girth (growing waistline)
• Fluctuations in weight (unexpected gains or losses)
• Decreased appetite, feeling “full” quicker than normal
• Leg swelling and other associated symptoms due to compression of the tumor on surrounding structures (organs or blood vessels).

Compression on blood vessels can cause leg swelling, related to decreased blood flow back to the heart. Since adrenal cancer is aggressive, initial symptoms can be related to already existing distant spread (metastasis), most commonly to the liver (presenting with pain), lungs (shortness of breath and decreased exercise capacity), or bone (pain and muscle weakness).

Patients with adrenocortical cancer can also be completely asymptomatic, but also have comorbidities like hypertension, osteoporosis, diabetes, or low potassium.  So again, it takes an evaluation with an expert adrenal surgeon to best interpret your work-up to-date, to guide you as to whether adrenal cancer should be a concern.  

Figure 3. MRI scan showing a right adrenal cancer (arrow). This cancer overproduced cortisol in a woman, causing very severe Cushing’s syndrome with Central obesity, facial flushing, rounded face, easy bruising, muscle weakness, hypertension, and diabetes.

To summarize, in about half of patients with adrenal cancer, symptoms are caused by the hormones made by the cancerous tumor; whereas, in the other half, symptoms occur because the tumor has grown so large that it presses on nearby organs and blood vessels. Adrenal cancer can be difficult to diagnosis based on symptoms alone.  Should you notice any of the above symptoms, they may be related to a benign or cancerous tumor of the adrenal gland or related to something else entirely. However, if the suspicion for adrenal cancer is even a faint consideration between you and your doctor, it is imperative that you act quickly to obtain the necessary blood and urine testing and scans (typically a CT scan) and have the results reviewed by an expert adrenal surgeon. Time is of the essence in adrenal cancer, since it can be aggressive and is often diagnosed late, particularly since the symptoms are not always unique and definitive. Surgery is the only opportunity for cure, so take your symptoms seriously, act swiftly, and hopefully outlive your diagnosis.    

Ideally, adrenal cancer is diagnosed at an early stage when surgery is likely to be curative. Thus, it is important to understand who is at a higher risk for getting this rare cancer. 

We do know that adrenal cancer can occur when there is a mutation in the adrenal cell’s genetic make-up. Individuals with certain inherited syndromes have a genetic make-up that can make them more susceptible to developing adrenal cancer. However, more often, the genetic mutation is sporadic, meaning there is no inherited pattern identified in most patients with adrenal cancer, making symptoms more common than genetic make-up in driving adrenal cancer diagnosis. 

The inherited syndromes that increase an individual’s risk of certain cancers, accounting for roughly 15-20% of all adrenal cancers, are:

• Li-Fraumeni syndrome
• Beckwith-Wiedemann syndrome
• Von Hippel-Lindau syndrome
• Multiple endocrine neoplasia (MEN) types 1 and 2
• Familial adenomatous polyposis (FAP)
• Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC)
• Neurofibromatosis type 1
• Carney complex

These individuals need to be followed by a genetic counselor and a medical endocrinology team to ensure they do not develop adrenal cancer.

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