What is Cushing’s syndrome? 
Cushing’s syndrome is defined as a type of hypercorticolism: high levels of the hormone cortisol are detected in the blood. This hormone is often secreted during stress along with adrenaline (or epinephrine for you Americans): it increases blood sugar levels, encourages the recruitment of tissue repairing proteins and enhances your brain’s ability to burn up glucose in situations where high alertness is needed. This is good in short doses, such as if you need to run away from something potentially life-threatening because that can determine the difference between life and death.

Hang on then,  how can too much cortisol be a bad thing?

Despite its usefulness during acutely stressful situations, it can turn pathological (disease-causing) if the dose of cortisol is high for an extended period of time, i.e. during times of chronic stress, as the body simply isn’t equipped to efficiently deal with high levels of cortisol for more than a couple of hours at a time. This happens because of the other effects that cortisol has: it suppresses the immune, reproductive, growth and digestive systems because they are considered as low-priority during high stress situations, hence why people that are chronically stressed become sick more often.

What are the symptoms of Cushing’s syndrome? 

Pic: http://www.physio-pedia.com/images/0/06/Cushings-syndrome2.jpg

There are many symptoms to look out for: they include the following:

  • Moon face
  • Poor wound healing often associated with easy bruising and thin skin
  • Red cheeks
  • Delays in bodily growth
  • Central body obesity
  • Bone wastage (i.e. osteoporosis) and muscle wastage
  • High blood pressure (hypertension)
  • Androgen (male sex hormone) excess, particularly in females
  • Thick neck
  • Buffalo hump
  • Diabetes mellitus

What are the steps in diagnosis? 

There are four key steps in diagnosis of Cushing’s syndrome: they are highly dependent on the coordination behind the doctors and the lab staff to make the correct diagnosis.

  1. Cortisol hypersecretion: determine urine free cortisol (24hr urine collection)
  2. Loss of circadian rhythm/sleep-wake cycle: cortisol levels typically drops during sleep: they remain high in Cushing’s
  3. Loss of negative feedback (dexamethasome)
  4. Differential diagnosis of pituitary Cushing’s versus adrenal tumour

How is Cushing’s detected in the laboratory? 

Pic: http://www.southend.nhs.uk/media/36979/urinecontainers24h.jpg

The method of separating Cushing’s syndrome from other diseases which can trigger the production of excess ACTH is through the DXM, or dexamethasone suppression test. Dexamethasone is an example of a corticosteroid, which is produced by the adrenal gland, specifically within the adrenal cortex. A 24 hour urine specimen (within a large plastic container) is brought in first: it contains a low dose (approximately 1-2mg) of dexamethasone. If the low dose of DXM is suppressed at the 2mg level after a day, then Cushing’s is automatically eliminated as a cause of excess ACTH, because this is considered as normal.




What if DXM isn’t suppressed? 

The result is considered abnormal (i.e. category 3 which I mentioned above is satisfied), and the second stage, or high dose DXM test is carried out. A plasma specimen is sent in with 8mg of dexamethasone. The ACTH (adrenocorticotropic hormone) and the DXM suppression are tested at the same time and these results are put together in order to make a diagnosis. It can go one of three ways:

Pic: http://www.grhealth.org/media/image/Adrenal%20Surgery/adrenal_tumor.jpg

  1. Adrenal TumourIf the ACTH is unable to be detected but the DXM is not suppressed
  2. Ectopic ACTH Syndrome: If the ACTH is elevated but the DXM is not suppressed, the excess ACTH is being produced externally i.e. in the lungs
  3. Cushing’s Syndrome:  If the ACTH is normal to elevated and the DXM is suppressed to less than 50% of the baseline, then the problem lies in the pituitary gland.

What is Addison’s disease? 

Addison’s disease is defined as hypoadrenalism: a characteristic feature of Addison’s is the atrophy (shrinkage) of the adrenal gland and the impairment of the body’s ability to secrete both cortisol (which I discussed above) and aldosterone. Aldosterone is a steroid hormone which regulates the cycling of salt and water within the body.

Hang on, wait, you said adrenal gland? What does this have to do

with the brain? 
It’s true: the primary form of adrenal insufficiency is an autoimmune disease which attacks the adrenal gland, which as the picture alongside shows, are located on top of the kidneys.The secondary form, however, is a disorder at the hypothalamic-pituitary level. Lab tests are done and correlated with the doctor’s findings in order to differentiate between the primary and secondary types. The symptoms are the same for both types, however primary type tends to have obvious symptoms, whereas the secondary type has symptoms that are more subtle in nature.

What are the symptoms of Addison’s disease? 

Pic: http://www.passpaces.com/images/Addison%20pic.gif

The symptoms have some similarities to Cushing’s syndrome, but there are some major differences as well. The symptoms include the following:

  • Skin hyperpigmentation and accentuation at the nipples, friction areas, skin creases and scars
  • Hypotension (low blood pressure)
  • Diarrhoea
  • Loss of weight (emaciation)
  • Anorexia
  • Vomiting
  • Virilization
  • Hyperkalaemia (high potassium levels)
  • Hyponatraemia (low sodium levels)

The excess pigmentation is due to excess ACTH: they stimulate the melanocytes or melanin-producing skin cells. The change in mineral levels is due to the malfunctioning adrenal gland, so therefore they are absent in the secondary form of adrenal insufficiency.

How is Addison’s detected in the lab? 

Addison’s is detected in the lab by comparing the serum ACTH and the aldosterone levels. If the ACTH level is high above the baseline but the aldosterone is low, it is likely that the patient has primary adrenal insufficiency (i.e. Addison’s), but if the ACTH is low and the level of aldosterone end ups normal (>4mg/dL), then the cause of the abnormality needs to be further examined.

What are the other things that may lead to an excessive ACTH level? 

Doctors and lab staff must be careful when diagnosing adrenal insufficiency,  because there are multiple conditions which can lead to primary adrenal insufficiency, hence the clinical history needs to be cross-checked with the lab results. Such conditions include the following:

Pic: http://s1.hubimg.com/u/6511332_f260.jpg

  • High pressure
  • Autoimmune disease (where the body’s own immune system attacks itself)
  • Granulomatus disease such as tuberculosis (TB)
  • Fungal infections
  • Cytomegalovirus (CMV)
  • Neoplastic infiltration such as amyloid, haemachromatosis, adrenoleucodystrophies
  • Anticoagulants
  • Infections in the adrenal gland such as Pseudomonas
  • Bilateral adrenalectomy
  • Human immunodeficiency virus (HIV)
  • ACTH resistance syndrome
  • Congenital adrenal hypoplasia