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. Mounting evidence suggests that excess cortisol is linked to obesity, hypertension, dyslipidemia, diabetes, metabolic syndrome and fatty liver.

Cortisol tissue levels are regulated by 11β-HSD enzymes. These enzymes influences cortisol activity in tissues by inducing the conversion of inactive cortisone into active cortisol.  This process takes place in the muscle, liver, bone and fat (adipose) tissues. In reverse, enzyme 11β-HSD2 converts active cortisol back into inactive cortisone. Since these enzymes found in adipose tissue and adipose can significantly increase in obese people, the activity of these enzymes may play a significant role in dysregulation of cortisol in obesity and related conditions. The influence of 11β-HSD1 on metabolic conditions was demonstrated in a study by Masuzaki et al (2001) that found that mice that overexpress 11β-HSD1 in adipose tissue developed obesity, diabetes and dyslipidemia. A similar study using mice that did not express 11β-HSD1 had less fat and did not develop diabetes even on a high calorie diet (Morton, et al., 2004).