Adrenal diseases can be some of the more difficult to diagnose in medicine because of their widely varying and sometimes non-specific symptoms, like fatigue and depression. Let’s take a quick look at some of the symptoms of the different diseases of the adrenal, and the laboratory tests used for diagnosis.

1. Adrenal hyperfunction

Cushing syndrome (­increased cortisol)

  • Typical presentation: obese, depressed patient with high blood pressure and hyperglycemia.
  • Testing: cortisol + ACTH + dexamethasone suppression test.
  • There are four causes of Cushing syndrome: iatrogenic (patient taking exogenous steroids), ACTH-producing pituitary adenoma, cortisol-producing adrenal adenoma, and ectopic ACTH production (usually from lung carcinoma).
  • In all cases, cortisol is increased. ACTH is increased in with a pituitary adenoma and patients with ectopic ACTH production; it is decreased in patients on exogenous steroids and patients with adrenal adenomas. The dexamethasone suppression test (where you give the patient some dexamethasone – a very potent steroid – and see if their cortisol level goes down) is negative in all cases except pituitary adenoma, strangely. If you give patients with pituitary adenoma enough dexamethasone, the adenoma will produce less ACTH and the cortisol will go down.

Hyperaldosteronism (­increased aldosterone, obviously)

  • Primary (e.g., Conn syndrome – aldosterone-producing adrenal adenoma). Typical presentation: Patient with high blood pressure (maybe resistant to treatment) and low serum potassium. Testing: increased­ aldosterone, decreased renin.
  • Secondary (e.g., related to low renal blood flow causing increased renin production): Presentation depends on what’s causing renin to go up. Testing: ­ increased aldosterone, increased renin.

2. Adrenal insufficiency

Primary (Addison disease)

  • Typical presentation: tired, thin, “bronze” patient with no appetite. The patient is bronze because he/she is making a ton of ACTH, which comes from a big precursor molecule that also makes melanocyte-stimulating hormone! So the more ACTH you make, the more MSH you make, and the bronzer you get.
  • Testing: decreased cortisol, decreased mineralocorticoids, ­ increased ACTH. Can also do a rapid ACTH stimulation test – give ACTH, measure cortisol 1 hour later; cortisol should go down.

Secondary (pituitary hypofunction)

  • Typical presentation: may be similar to Addison disease – but no bronzing!
  • Testing: decreased cortisol, decreased ACTH

3. Adrenal tumors


  • Typical presentation: Nervous, sweaty patient with high blood pressure and headaches.
  • Testing: urinary catecholamines – vanillylmandelic acid (VMA), free catecholamines and metanephrines.


  • Typical presentation: child with fever, sick feeling, maybe with puzzling paraneoplastic symptoms such as flushing, sweating, and tachycardia.
  • Testing: the usual biopsy/staging procedures for cancer; can also see epinephrine, catecholamines, homovanillic acid (HVA) and VMA in the blood/urine.

So, now you know what lab tests to order – but you can’t diagnose it if you don’t think of it! So have a high index of suspicion for adrenal diseases, and endocrine diseases in general, if you have a patient with a bunch of seemingly unrelated symptoms – especially if there have been a bunch of previous misdiagnoses. Once these disorders are properly identified, there are usually relatively easy and successful treatment plans, and usually a happy outcome for the patient.