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Adrenal Disorders
(Addison’s Disease & Cushing’s Syndrome)

Diagnosis and Biomarkers of Adrenal Gland Dysfunction

Addison’s disease

Addison’s disease is typically diagnosed based on assessment of the clinical signs and symptoms described earlier. Laboratory tests are performed to assess electrolyte levels in the blood as well as serum levels of cortisol and ACTH; computed tomography (CT) scans of the adrenal or pituitary glands are sometimes performed as well (Betterle 2002). Low serum cortisol with increased serum ACTH levels is indicative of Addison’s disease (Al-Aridi 2011). Cortisol levels vary according to the time of the day (diurnal variation), with levels normally peaking no later than 8 AM (Lipworth 1999). Therefore, an 8 AM cortisol test is performed to check for cortisol levels in the blood, which are decreased (<3 µg/dL) in Addison’s disease (PubMed 2011b; Lipworth 1999; Betterle 2002). Further, individuals with Addison’s disease do not show an increase in serum cortisol level when given an injection of cosyntropin (a synthetic form of ACTH); this procedure is referred to as an ACTH stimulation test (Betterle 2002; Neary 2010).

On the other hand, people with Addison’s disease specifically due to hypothalamic or pituitary disorders will show low levels of both ACTH and cortisol (Neary 2010). Upon fasting, these individuals often develop very low glucose levels in the blood (hypoglycemia), as their body is unable to produce glucose from stored fat and proteins (Betterle 2002).Abnormally low blood levels of levels of DHEA-sulfate (DHEA-S) along with decreased cortisol and aldosterone levels are indicative of adrenal insufficiency, warranting further testing of HPA axis function (Al-Aridi 2011).

Cushing’s syndrome

The typical physical characteristics of Cushing’s syndrome are diagnostic and are further confirmed by laboratory test results. People with Cushing’s syndrome generally have grossly increased levels of free cortisol in their urine and, although cortisol levels normally show diurnal variation, this variation is not observed in Cushing’s syndrome (Papanicolaou 1998). Measurement of ACTH levels can also help to distinguish between the 2 variants of Cushing’s syndrome (ACTH-dependent and ACTH-independent) (Tritos 2012; Newell-Price 2007). Magnetic resonance imaging (MRI) and CT scans are useful for the diagnosis of pituitary and adrenal tumors (Arnaldi 2003; Tritos 2012).