This endocrine disorder is a rare disease, affecting about two to three people per million per year, with an age of onset or diagnosis of 25 to 46 years. There is a 3:1 ratio between women and men. Some scientific studies suggest an increased prevalence in people with uncontrolled type 2 diabetes, hypertension or early osteoporosis.
It should be noted that there are two types of Cushing's syndrome: ACTH-dependent (80%) and ACTH-independent, which is also divided into two categories (20%).
Different causes of Cushing's Syndrome
In ACTH-dependent Cushing's syndrome, the adrenal cortex receives excessive stimulation of a type of ACTH-specific melanocortin (hormone) receptor (MC2R), resulting in inappropriate and pathological secretion of sub-adrenal cortisol. There are two origins for this:
- a pituitary adenoma which is a non-malignant tumour that has developed within the ACTH-secreting pituitary gland;
- and an ectopic, non-pituitary secretion of ACTH usually through a neuroendocrine tumour (tumours that develop from hormone-producing cells) within the digestive system and lungs.
In ACTH-independent Cushing's syndrome, there are two different types, where glucocorticoid activity is increased without ACTH stimulation.
Benign adrenal adenoma, adrenocortical carcinoma or other types of bilateral adrenal disease can cause endogenous ACTH-independent Cushing's syndrome (produced by the body). The adrenal glands will then produce cortisol autonomously without ACTH stimulation.
The second type of ACTH-independent Cushing's syndrome is exogenous (not produced by the body) and has excessive glucocorticoid activity produced by the administration of glucocorticoids. The most common cause is oral glucocorticoid therapy at doses above physiology for the treatment of inflammatory diseases. This oral glucocorticoid therapy is common and is a frequent cause of serious side effects. Other routes of glucocorticoid treatment can lead to exogenous Cushing's syndrome, including intra-articular, spinal, inhaled, intervertebral, and even cutaneous, membranous or ocular glucocorticoids.
References :
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- Juszczak A, Morris D, Grossman A. Cushing’s Syndrome. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dungan K, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000 [cited 2021 Mar 12]. Available from: hpp://www.ncbi.nlm.nih.gov/books/NBK279088/.
- Lacroix A, Feelders RA, Stratakis CA, Nieman LK. Cushing’s syndrome. Lancet. 2015 Aug 29;386(9996):913–27. DOI: 10.1016/S0140-6736(14)61375-1
- Isidori AM, Lenzi A. Ectopic ACTH syndrome. Arquivos Brasileiros de Endocrinologia & Metabologia. 2007 Nov;51(8):1217–25. DOI: 10.1590/ s0004-27302007000800007
- Raff H, Carroll T. Cushing’s syndrome: from physiological principles to diagnosis and clinical care. J Physiol. 2015 Feb 1;593(3):493–506. DOI: 10.1113/ jphysiol.2014.282871
- Carroll TB, Findling JW. Cushing’s syndrome of nonpituitary causes. Currtipin Endocrinol Diabetes Obes. 2009 Aug;16(4):308–15. DOI: 10.1097/ MED.0b013e32832d8950
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