Chief Medical Officer, Strongbridge Biopharma
Approximately 25,000 Americans are living with Cushing’s syndrome but our understanding of the disease is still lacking. We talked to Frederic Cohen, chief medical officer at Strongbridge Biopharma, about what causes Cushing’s and why it can be so difficult to detect.
Can you give a brief overview on what Cushing’s syndrome is?
Cushing’s syndrome is a rare endocrine disorder that is usually not inherited and typically affects adults. It is characterized by a variety of symptoms and physical abnormalities that are caused by excessive amounts of the hormone cortisol.
Cortisol is a vital hormone made by the adrenal glands. The body uses cortisol to maintain normal bodily functions of everyday life, like regulating your blood sugar and metabolism. For people who do not have Cushing’s syndrome, the highest levels of cortisol are secreted into the blood in the first hour after waking in the morning, with additional cortisol secreted in bursts at any time of day or night in response to external stresses, like infections, surgery, and trauma, or internal stresses like fear and anxiety. This additional cortisol secretion is needed to maintain the body’s organs in a state that can respond to stress.
For those with endogenous Cushing’s syndrome, the adrenal glands secrete cortisol in a disordered way throughout the day and night, not in response to stress, but due to an internal cause, usually because a tumor is driving the excessive production of cortisol. Such tumors are often found at the base of the brain in the pituitary gland, where they secrete another hormone called ACTH.
Excess ACTH produced by the tumors in the pituitary then drives the production of excess cortisol in the adrenal glands. When a pituitary tumor causes the excess cortisol production, it’s called Cushing’s disease which accounts for more than 70% of Cushing’s syndrome in adults in the U.S. Other causes of Cushing’s syndrome are tumors in the adrenal glands themselves or in very rare cases, tumors that can secrete ACTH outside of the pituitary.
Endogenous Cushing’s syndrome is different from exogenous Cushing’s syndrome based on what causes the production of excess cortisol. In endogenous, it’s an internal cause, like a tumor, while in exogenous, it’s an external cause. Exogenous Cushing’s syndrome is caused by medicines that are intended to deliver cortisol-like hormones as therapy (drugs like prednisone, fluticasone, etc.). If given in sufficiently high doses for a period of time, these medicines can cause exogenous Cushing’s syndrome.
What are the signs and symptoms of Cushing’s syndrome?
Signs and symptoms of Cushing’s syndrome vary widely and can mimic much more common conditions, such as the common forms of obesity, Type-2 diabetes, high blood pressure, and polycystic ovary syndrome, which makes diagnosing it challenging.
Rapid weight gain and inability to lose weight are sometimes noticed first, but other early symptoms include a change in appearance, a change in sexual or reproductive function, trouble sleeping, or difficulty focusing attention. Signs and symptoms that are more specific to underlying excess cortisol as the cause include muscle weakness predominantly in the hips and shoulders (i.e., proximal), new-onset of facial redness, wasting of the arms and legs with increased fat in the abdomen and face, wide purplish stretch marks, bruising with no obvious trauma, and fat pads above the collarbone. Oftentimes, there are no specific symptoms present, just the signs that there has been a change in metabolism or blood pressure.
About how many people are affected by endogenous Cushing’s syndrome?
In the United States, approximately 25,000 adults are diagnosed with endogenous Cushing’s syndrome. In general, more women than men are affected, and the most common cause is a benign pituitary tumor.
What are some issues or problems brought on by this rare disease?
Over time, the excess cortisol secretion characteristic of Cushing’s syndrome can lead to problems with essentially every system in the body, from the blood to the brain, from the immune to digestive system. The list of potential problems is long, and signs and symptoms can vary widely between affected people, so much so that no two cases seem to be identical.
Commonly, though, people with Cushing’s syndrome tend to suffer from excessive weight gain or difficulty maintaining normal weight, high blood pressure, obstructive sleep apnea, diabetes or prediabetes, changes in mood (heightened emotions/irritability/depression), insomnia, anxiety, or mood changes.
Other symptoms and signs include bone fragility (osteopenia/osteoporosis); recurrent and chronic infections, especially fungal; digestive problems; altered appearance of skin (excess hair, new-onset acne, stretch marks, thinning); leg swelling and fluid retention; blood vessel thinning and blood clots; altered face and body appearance (such as facial rounding, facial redness, accumulation of fat above the collarbone, or on the back of the neck); trouble with sexual function or reproduction (such as menstruation; and vision and eye problems, especially cataracts and glaucoma.
Cushing’s syndrome is a serious condition that must be treated as soon as it is diagnosed. Stopping the excess cortisol in the body is the most important step when it comes to effective treatment, rather than only treating the complications of Cushing’s syndrome, like high blood pressure or obesity.
Fortunately, early and effective treatment to reduce cortisol production will greatly reduce the most serious complications and comorbidities of the syndrome that can lead to early death, such as heart attacks, strokes, serious infections, and blood clots, and can also positively impact many of the syndrome’s symptoms, quality of life, and functioning.
Why is it important to continue conducting research and clinical studies for Cushing’s syndrome?
Significant unmet medical needs remain in the diagnosis and treatment of endogenous Cushing’s syndrome that can be positively impacted by clinical research. Focusing on treatment, we estimate that 4,000 of the approximately 7,000 patients with active Cushing’s syndrome (i.e., experiencing signs and symptoms of Cushing’s syndrome) are either not being treated for excess cortisol or, if they are being treated, continue to be exposed to excess cortisol despite current treatment.
Healthcare providers depend on rigorous evidence to support their treatment recommendations, and that evidence is best obtained through established research methods, like clinical trials.