Research & Education

Psuedo Cushing's

Adrenal exhaustion has garnered a significant amount of attention in the functional medicine community during the last several years. Certainly there has been no shortage of patients whose adrenal glands are unable to keep up with the demands of their busy stressful lives and who eventually experience debilitating physical and emotional fatigue. Along with subjective signs and symptoms a patient may exhibit adrenal burnout can be confirmed by salivary cortisol measurements which may fall significantly below the normal range. But what about the other side of the cortisol coin?

Just as one need not have full-blown Addison’s disease to have suboptimal adrenal function one need not have overt Cushing’s syndrome to have adrenal glands that are working overtime to produce elevated levels of cortisol. This underappreciated condition—functional hypercortisolism or subclinical Cushing’s syndrome—may be responsible for many cases of stubborn weight loss intractable blood sugar control and other issues that fail to resolve but which should otherwise be correctable through the appropriate interventions. 

The symptoms of chronically elevated cortisol which does not rise to the level of Cushing’s syndrome overlap somewhat with those of the full-blown condition: central obesity easy bruising impaired glucose tolerance depression and stretch marks not necessarily associated with obesity. (Women may also experience menstrual irregularities and hirsutism on the face or chin coupled with loss of hair on the head.) Individuals with functional hypercortisolism don’t usually display the exaggerated facial roundness (“moon face”) or fat deposition in the upper back (“buffalo hump”) associated with Cushing’s. The two conditions can also be distinguished through lab testing. In addition to saliva or urinary cortisol measurements a common diagnostic test for Cushing’s is the dexamethasone suppression test wherein the patient is given dexamethasone by mouth every 6 hours for 2 days with urine collected over three days (including the day before the start of dexamethasone to establish a baseline). In endogenous Cushing’s syndrome cortisol levels will remain dramatically elevated rather than being suppressed by the dexamethasone. In contrast in subclinical Cushing’s cortisol output will be appropriately suppressed. In less formal terms the signs and symptoms of Cushing’s often occur with sudden onset (unexplained rapid weight gain for example) while subclinical or pseudo-Cushing’s may be present for years.

Two conditions often associated with pseudo-Cushing’s are depression and alcoholism. Hypercortisolism brought on by excessive alcohol consumption typically recedes upon abstention from alcohol and the visible manifestations of high cortisol disappear in time. As for depression the dexamethasone suppression test has been employed to gauge the efficacy of antidepressant medication. Patients with depression frequently exhibit signs of HPA axis dysregulation but correcting the dysregulation doesn’t always result in improved treatment outcomes. It may be that at least in some patients depression and HPA axis abnormalities are a chicken/egg situation where it’s not straightforward which comes first. (It seems though that the endocrine imbalance is often directly involved in the pathogenesis of depression and may also play a role in alcoholism and suicidal behavior.) 

There are many purported causes of subclinical Cushing’s. Among these are “adrenal incidentalomas”—adrenal masses that are detected incidentally (often during abdominal surgery). Between 5-20% of these benign adrenal masses influence cortisol hypersecretion. The degree of cortisol elevation due to these masses may be different from that spurred by unremitting everyday stressors but even the latter if long-term and unresolved may eventually lead to signs and symptoms of subclinical Cushing’s. And the visible signs while unsightly are mild compared to more serious potential compromises in health that may develop. Due to the influence of cortisol on blood glucose regulation—and therefore ultimately insulin secretion—elevated cortisol can be a roadblock to weight loss and healthy blood sugar levels even when someone is following a healthy diet and engaging in appropriate amounts of physical activity. Moreover longer-term complications from pseudo-Cushing’s may include hypertension osteoporosis and type-2 diabetes.

For patients with overweight/obesity or hyperglycemia that fail to resolve even after adoption of a proper diet exercise regimen and targeted nutritional supplementation it may be useful to assess for subclinical Cushing’s. Many patients dedicate a great deal of time and money to engaging in healthy lifestyle habits and it can be downright demoralizing when they don’t see the results they expect. An endocrine issue they don’t even know they have could be all that’s standing in their way.