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Cushing's Syndrome


Read time: 15 mins
Family medicine or primary care practitioners can find Cushing's Syndrome to be particularly hard to detect, because it occurs so infrequently and displays non-specific symptoms. However, identification of symptoms is vital for diagnosis and treatment of Cushing's Syndrome to prevent irreversible organ damage and malignancies. Read our guide to the incidence of this condition, detailed pathophysiology, and a comprehensive description of the symptoms.


Cortisol, a hormone produced by the adrenal glands, has many roles including anti-inflammatory and anti-allergic actions in response to stressful situations such as illness or injury. 

Its production fluctuates over the course of the day with most typically produced in the early morning and very little at night. Levels tend to be minimal at around midnight and then start to rise at 2 am, peaking typically around waking.

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The HPA axis is a set of interactions between three glands; the hypothalamus, the pituitary gland and the adrenal gland. Together, these form a complex system that regulates endocrine release in the body. 

The hypophyseal portal system connects the hypothalamus and the pituitary gland and the fenestrated structure of the capillaries facilitates the rapid transport and exchange of hormones (Clarke, 2015). The HPA axis controls reactions to stress as well as processes such as digestion, mood, emotions, and energy storage and expenditure. When the HPA axis is activated by stress, it causes the release of cortisol from the adrenal glands. A negative feedback system ensures that cortisol levels remain within a healthy physiological range (Raff and Carroll, 2015).

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Excess secretion of cortisol can lead to chronic disorders, such as hypertension and glucose intolerance (Newell-Price et al., 2006). If left untreated, CS can become life-threatening as a result of systemic complications (Resmini, 2014). 

The symptoms of CS differ from patient to patient, may present in a cyclical fashion and frequently mimic those of other conditions, leading to difficulties in diagnosis. In addition, clinical presentation can vary by sex and by age (Newell-Price et al., 2006)

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Overview References

Clarke IJ. Hypothalamus as an endocrine organ. Compr Physiol 2015;5:217–53.

Fassnacht M, Terzolo M, Allolio B, Baudin E, Haak H, Berruti A, et al. Combination Chemotherapy in Advanced Adrenocortical Carcinoma. New Engl J Med 2012; 366:2189–97.

Ioachimescu AG, Remer EM, Hamrahian AH. Adrenal incidentalomas: a disease of modern technology offering opportunities for improved patient care. Endocrinol Metab Clin North Am 2015; 44:335–54.

Lindholm J, Juul S, Jørgensen JO, Astrup J, Bjerre P, Feldt-Rasmussen U, et al. Incidence and late prognosis of Cushing’s Syndrome: a population-based study. J Clin Endocrinol Metab 2001;86:117–23.

Newell-Price J, Bertagna X, Grossman AB, Nieman LK. Cushing’s Syndrome. Lancet 2006;367:1605–17.

Patel LM, Lambert PJ, Gagna CE, Maghari A, Lambert WC. Cutaneous signs of systemic disease. Clin Dermatol 2011; 29:511–22.

Newell-Price J. Etiologies of Cushing’s Syndrome. From: Contemporary Endocrinology: Cushing’s Syndrome: Pathophysiology, Diagnosis and Treatment. Bronstein MD (ed). 2011. Humana Press.

Patel LM, Lambert PJ, Gagna CE, Maghari A, Lambert WC. Cutaneous signs of systemic disease. Clin Dermatol 2011; 29:511–22.

Prague JK, May S, Whitelaw BC. Cushing’s Syndrome. BMJ 2013;346:f945.

Raff H, Carroll T. Cushing’s Syndrome: from physiological principles to diagnosis and clinical care. J Physiol 2015;593:493–506.

Resmini E. Persistent comorbidities in Cushing’s Syndrome after endocrine cure. Adv Endocrinol 2014;1–14.

Sharma ST, Nieman LK, Feelders RA. Cushing’s Syndrome: epidemiology and developments in disease management. Clin Epidemiol 2015;7:281–93.

Stratakis CA. Cushing Syndrome caused by adrenocortical tumours and hyperplasias (Corticotrophin-Independent Cushing Syndrome). In: Disorders of the Human Adrenal Cortes. Flück CE, Miller WL (eds). Endocr Dev. Basel, Karger 2008;13:117–32.

Valassi E, Santon A, Yaneva M et al, on behalf of The ERCUSYN Study Group. The European Registry on Cushing’s Syndrome: 2-year experience. Baseline demographic and clinical characteristics. Eur J Endocrinol 2011;165:383–92.

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