Recently, I’ve become aware of some Social Media influencers saying that “stress and elevated cortisol can prevent GLP-1 medications from working.”  And I’ve had plenty of patients come to me having been told by a “holistic practitioner” that they are suffering from “Adrenal Fatigue.”  

“Sorry, Wilma!  A couple of your vital organs decided to take a Personal Day…they’re a little tired.  Try not to stress…we’ll see you next week…or not!”

So this seems like as good a time as any to discuss Adrenal Physiology and hopefully put to rest this myth of Adrenal Fatigue, which would be better described as “Hypothalamic-Pituitary-Adrenal Axis Dysfunction.”  Just saying that mouthful more than once is fatiguing. And then we’ll also discuss true adrenal pathology, including Cushing’s (hypercortisolism) and Addison’s Disease (adrenal insufficiency).

The adrenal glands are like a couple of jelly donuts that sit on top of the kidneys; the adrenal cortex is the outer layer and the jelly in the middle is the adrenal medulla.  Normally, your hypothalamus produces corticotropin-releasing hormone (CRH), which signals the anterior pituitary to produce adrenocorticotropic hormone (ACTH), which then signals the adrenal glands to produce cortisol from a layer of the cortex called the zona fasciculata.  (The adrenal cortex also produces aldosterone and DHEA from the zona glomerulosa and reticularis, respectively, and the medulla produces catecholamines like norepinephrine and epinephrine).  However, the primary player in regulating this feedback loop is cortisol.

Cortisol is similar to insulin in that a lack of cortisol is incompatible with life, but excess cortisol makes it impossible to have any semblance of metabolic health.  People with autoimmune destruction of the adrenal gland, or Addison’s Disease, need lifelong replacement of cortisol and aldosterone or else they die.  (Interestingly, President JFK had Addison’s Disease).  Conversely, people with a pathologic excess of cortisol, called Cushing’s, cannot “Control their insulin, control their life” even if they’re doing all the right things.  That’s because excess cortisol is catabolic to muscle, anabolic to fat, leaves them “tired but wired,” and progressively ruins their lives unless they are appropriately diagnosed and treated.  The classic Cushing’s phenotype is someone who resembles Dr. Eggman from the original Sonic the Hedgehog games…comically thin extremities with truncal obesity, purple stretch marks, perpetually flushed cheeks even in the absence of embarrassing life situations, and a fatty hump that would make all the buffaloes on the Wyoming plains jealous.  Additionally, these folks often have resistant hypertension and poorly controlled blood sugars until either the pituitary or adrenal tumor that is sabotaging their metabolism is addressed.

However, the diagnosis of Cushing’s is rarely this straightforward.  For instance, I had a patient who was a total rock star; she was literally doing ALL THE RIGHT THINGS that would normally lead to metabolic optimization.  However, her lipid profile was characterized by low HDL-C and elevated fasting triglycerides.  Despite working out like a fiend, she was prediabetic and hypertensive.  And despite eating a monastically clean diet, she continued to steadily gain fat mass around the abdomen.  And guess what?  She had an adrenal adenoma, and within 6 months of its removal, her physique and labs matched her lifestyle, which was amazing.

So do we need to screen every single American for Cushing’s?  Obviously not.  But there are several situations where I would encourage clinicians to be comfortable obtaining either a late-night salivary cortisol or low-dose dexamethasone (1 mg) suppression test as screening tests for cortisol excess:

• The person has “chicken legs” and abdominal obesity.
• The person has poorly controlled diabetes on multiple medications (about ¼ of these types of patients had hypercortisolism in THIS STUDY).
• The person has a dyslipidemic and insulin resistant blood profile (elevated triglycerides, low HDL-C, etc.) despite TRULY pulling all the right levers when it comes to lifestyle.

And do we need to screen every single American for “Adrenal Fatigue?”  Well, if it existed, then maybe.  And does non-pathologic “Adrenal Dysfunction” contribute to feelings of tiredness and suboptimal quality of life?  Absolutely.  And if you have been diagnosed with “Adrenal Fatigue,” the solution is to identify the stressors in your life and find a way to manage those factors.  Easier said than done, but all the ashwagandha, rhodiola, and Holy Basil in the world is unlikely to help your situation unless you can find ways to navigate the stressful tyranny of life triumphantly.