While a short-term stress response can be beneficial, a prolonged response can have negative impacts on the body. Too much cortisol over an extended period of time can lead to fatigue, obesity, and other medical conditions like cushions disease. Below is a summary of medical conditions that can result from dysregulation of cortisol. Cushing’s Syndrome Cushing’s syndrome, or hypercortisolism, is a rare condition in which the patient experiences an excess of glucocorticoids, primarily cortisol. It is usually caused by prescription steroids (glucocorticoids) that are used as anti-inflammatories. However, it can also be caused by tumors on the adrenal or pituitary gland. Common symptoms include weight gain, insulin resistance, muscle weakness, high blood concentration of lipids, such as cholesterol (hyperlipidemia), high blood pressure (hypertension), high blood sugar (hyperglycemia), osteoporosis and thin skin. If left untreated, Cushing disease can be life threatening. Prognosis for patients with untreated Cushing’s syndrome is approximately 50% for 5-year survival. Fortunately, the Cushings is treatable. When caused by medications it can be remedied by reducing the dosage or stopping the medication. When caused by tumors, treatment typically revolves around removal of the tumors through surgery or radiation. Metabolism Disorders Recent studies have suggested that morbidity associated with obesity and other metabolic syndromes may be due to the dysregulation of cortisol.

There are several tretments in development to rectify dysregulation of cortisol. One is tissue-specific inhibitors of 11β-HSD1. Clinical trials have revealed that treatment with these inhibitors can reduce body weight, and blood pressure. However, these results have been inconsistent (Shah, et al., 2011; Feig, et al., 2011; Rosenstock, et al., 2010). Another option is inhibition of cortisol production in the adrenal gland. This method is typically used to treat Cushing syndrome. Inhibitors of aldosterone synthase may also reduce cortisol since aldosterone synthase is similar to the enzymes that produce cortisol. These inhibitors would be particularly useful in conditions in which both aldosterone and cortisol are dysregulated. The final option utilizes antagonists for the GRs and MRs. MR inhibitors are easily accessible, have low side effects and are currently used to improve survival following heart failure. Blocking this receptor has the additional benefit of blocking activation due to both cortisol and aldosterone. It has already been shown to stave off hypertension and abnormalities in the muscles of the heart in patients with metabolic syndrome.

Cortisol may contribute to obesity by interacting with regulators of weight and food intake. Leptin, the satiety hormone is secreted by fat cells in order to inform the brain of fat levels in the body and to control eating. High levels of leptin result in an inhibition of hunger.  A study that removed the adrenal gland in mice with low levels of leptin found that these mice lost weight, suggesting that glucocorticoids may contribute to leptin metabolism (Dubuc & Wilden, 1986). Another study found that administration of a steroid medication, dexamethasone, increased leptin levels when administered after eating in both average and obese patients (Laferrère, et al., 2002; Laferrère, Fried, Osborne, & Pi-Sunyer, 2000; Dagogo-Jack, Selke, Melson, & Newcomer, 1997). Ghrelin, the hunger hormone, induces feelings of hunger and promotes food intake. This hormone has been found to have an inverse relationship with cortisol during fasting, suggesting that cortisol may be used to mediate the effects of ghrelin. However, more research is needed before any solid conclusions can be drawn. Based on the previous evidence, it’s not a surprise that researchers have been investigating the link between stress and hunger. This association is also likely due to the fact that dysregulation of the HPA has been associated with multiple eating disorders such as binge eating disorder, bulimia and anorexia.

While cortisol dysregulation gets the most attention for its link to weight and stress, it is also connected to medical conditions like hypertension, reproduction issues, PTSD, addiction, depression, and autism. Hypertension A primary function of cortisol is regulation of blood pressure. Thus, when cortisol is dysregulated, blood pressure is often affected. In cases of Cushing’s syndrome, when there is an excess of glucocorticoids, a common response (nearly 80% of cases) is the development of hypertension (high blood pressure) . Nearly 30% of hypertension cases are thought to occur in response to cortisol dysregulation, specifically, This increase in cortisol related to hypertension is due to stimulation by ACTH. Reproduction Cortisol is not only involved in fat tissues, but it can also play a role in the function of reproductive organs.  The ovaries have GRs and they are influenced directly by the HPA through glucocorticoids, primarily cortisol (Andersen C. , 2002). In addition to the cortisol-binding protein (CBP), sex-hormone-binding globulin (SHBG) may also bind to cortisol. However, this interaction is not nearly as strong as the bond between CBP and cortisol. Like in other tissues, cortisol expression is regulated by 11β-HSD enzymes, which fluctuate over the course of the menstrual cycle. Post-traumatic Stress Disorder Being the stress hormone , it may come as no surprise that cortisol levels are altered in individuals with post-traumatic stress disorder (PTSD).

Testing for Cortisol Testing the level of cortisol in the body is used to assess the actibity of the HPA axis and as a test for many medication conditions. The most common way to test for cortisol is by collecting urine over a 24h period (known as urinary-free cortisol (UFC) and then testing the amount of cortisol in the urine. Another method is by examining the amount of cortisol in saliva. However, these methods have their drawbacks. Since cortisol levels fluctuate without the day, it can be difficult to get an idea of the overall levels of cortisol since these methods only capture one moment in time. Thus researchers and clinicians have moved toward using cortisol measurements in hair since hair can provide evidence of long term exposure to specific hormones. Cortisol as a Therapeutic Treatment As previously mentioned, glucocorticoids are often prescribed as anti-inflammatories for a variety of ailments, such as autoimmune diseases (multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, ulcerative colitis, psoriasis, and eczema). In these diseases, inflammation can become so severe that immune cells begin to attack other host cells. This can cause pain, swelling, cramping and itching. Glucocorticoids work by reducing the inflammation, which alleviates these symptoms. Glucocorticoids may also be used to treat allergies or asthma which are brought on by a strong immune response to allergens.