Pseudo-Cushing's syndrome explained

Pseudo-Cushing's syndrome
Field:	Endocrinology

Pseudo-Cushing's syndrome or non-neoplastic hypercortisolism is a medical condition in which patients display the signs, symptoms, and abnormal cortisol levels seen in Cushing's syndrome. However, pseudo-Cushing's syndrome is not caused by a problem with the hypothalamic-pituitary-adrenal axis as Cushing's is; it is mainly an idiopathic condition, however a cushingoid appearance is sometimes linked to excessive alcohol consumption.^[1] Elevated levels of total cortisol can also be due to estrogen found in oral contraceptive pills that contain a mixture of estrogen and progesterone. Estrogen can cause an increase of cortisol-binding globulin and thereby cause the total cortisol level to be elevated.^[2]

Diagnosis

• Levels of cortisol and ACTH both elevated
• 24-hour urinary cortisol levels elevated
• Dexamethasone suppression test^[3]
• Late night salivary cortisol (LNSC)^[4]
• Loss of diurnal variation in cortisol levels (seen only in true Cushing's Syndrome)
• High mean corpuscular volume and gamma-glutamyl transferase may be clues to alcoholism
• Polycystic Ovarian Syndrome should be ruled out; PCOS may have similar symptoms

Differential diagnosis

• Differentiation from Cushing's is difficult, but several tools exist to aid in the diagnosis^[5]
• Alternative causes of Cushing's should be excluded with imaging of lungs, adrenal glands, and pituitary gland; these often appear normal in Cushing's
• In the alcoholic patient with pseudo-Cushing's, admission to hospital (and avoidance of alcohol) will result in normal midnight cortisol levels within five days, excluding Cushing's^[6]
• Another cause for Cushing's syndrome is adrenocortical carcinoma. This is a rare form of cancer with an incidence of 1-2 per million people annually. About 60% of these cancers produce hormones, with cortisol being the most frequent. Most patients present in an advanced disease state and the outcome is dismal.^[7]

Prognosis

• Blood results and symptoms normalise rapidly on cessation of drinking or remission of depression.

Notes and References

1. Book: Parveen June Kumar. Michael L. Clark. Kumar and Clark clinical medicine. 2005. Elsevier Saunders. 978-0-7020-2763-5. 974–975.
2. 10.1136/jcp.s1-3.1.11 . Journal of Clinical Pathology . 1969 . 3 . 11–18 . The effect of oral contraceptives on cortisol metabolism . C. W. Burke . 1436049 .
3. Gatta B, Chabre O, Cortet C, etal . Reevaluation of the combined dexamethasone suppression-corticotropin-releasing hormone test for differentiation of mild cushing's disease from pseudo-Cushing's syndrome . Journal of Clinical Endocrinology and Metabolism . 92 . 11 . 4290–3 . November 2007 . 17635947 . 10.1210/jc.2006-2829 . free .
4. Scaroni. Carla. Albiger. Nora M. Palmieri. Serena. Iacuaniello. Davide. Graziadio. Chiara. Damiani. Luca. Zilio. Marialuisa. Stigliano. Antonio. Colao. Annamaria. Pivonello. Rosario. January 2020. Approach to patients with pseudo-Cushing's states. Endocrine Connections. 9. 1. R1–R13. 10.1530/EC-19-0435. 2049-3614. 6993268. 31846432.
5. Gross BA, Mindea SA, Pick AJ, Chandler JP, Batjer HH . Diagnostic approach to Cushing disease . Neurosurgical Focus . 23 . 3 . 1–7 . 2007 . 17961030 . 10.3171/foc.2007.23.3.2 . free .
6. Newell-Price J, Trainer P, Besser M, Grossman A . The diagnosis and differential diagnosis of Cushing's syndrome and pseudo-Cushing's states. . Endocrine Reviews . 19 . 5 . 647–72 . 1998 . 10.1210/edrv.19.5.0346 . 9793762 . free .
7. Allolio B, Fassnacht M . Adrenocortical Carcinoma: Clinical Update. Journal of Clinical Endocrinology and Metabolism . 91 . 6 . 2027–2037 . 2006 . 16551738. 10.1210/jc.2005-2639 . free .