Pseudo-Cushing's syndrome

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]

Pseudo-Cushing's syndrome
SpecialtyEndocrinology

Signs and symptoms

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.

References
  1. Parveen June Kumar; Michael L. Clark (2005). Kumar and Clark clinical medicine. Elsevier Saunders. pp. 974–975. ISBN 978-0-7020-2763-5.
  2. C. W. Burke (1969). "The effect of oral contraceptives on cortisol metabolism". Journal of Clinical Pathology. 3: 11–18. doi:10.1136/jcp.s1-3.1.11. PMC 1436049.
  3. Gatta B, Chabre O, Cortet C, et al. (November 2007). "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. doi:10.1210/jc.2006-2829. PMID 17635947.
  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. doi:10.1530/EC-19-0435. ISSN 2049-3614. PMC 6993268. PMID 31846432.
  5. Gross BA, Mindea SA, Pick AJ, Chandler JP, Batjer HH (2007). "Diagnostic approach to Cushing disease". Neurosurgical Focus. 23 (3): 1–7. doi:10.3171/foc.2007.23.3.2. PMID 17961030.
  6. Newell-Price J, Trainer P, Besser M, Grossman A (1998). "The diagnosis and differential diagnosis of Cushing's syndrome and pseudo-Cushing's states". Endocrine Reviews. 19 (5): 647–72. doi:10.1210/edrv.19.5.0346. PMID 9793762.
  7. Allolio B, Fassnacht M (2006). "Adrenocortical Carcinoma: Clinical Update". Journal of Clinical Endocrinology and Metabolism. 91 (6): 2027–2037. doi:10.1210/jc.2005-2639. PMID 16551738.
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