Dexamethasone suppression test — MRCPsych Paper A MCQ

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EasyNeuroimaging, neuroendocrinology and psychoneuroimmunologyDexamethasone suppression testMRCPsych Paper A

A 44-year-old woman with a severe major depressive episode undergoes a correctly performed dexamethasone suppression test as part of a research protocol. Her cortisol concentration fails to suppress. Which neuroendocrine abnormality best explains this result?

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Correct answer: B — Impaired negative feedback in the HPA axis

Dexamethasone is a synthetic glucocorticoid that normally suppresses hypothalamic CRH and pituitary ACTH secretion through negative feedback, thereby reducing cortisol production. Cortisol non-suppression in some people with severe major depression reflects reduced glucocorticoid-receptor sensitivity and impaired negative feedback within the hypothalamic–pituitary–adrenal (HPA) axis. The test is a research marker rather than a diagnostic test for depression. Pituitary dopamine blockade primarily increases prolactin. Primary adrenal failure causes deficient cortisol production rather than persistent cortisol secretion after dexamethasone. Peripheral thyroid hormone resistance affects the hypothalamic–pituitary–thyroid axis, while melatonin excess concerns pineal and circadian physiology rather than glucocorticoid feedback.

Reference: Pace TWW, Miller AH. Cytokines and glucocorticoid receptor signaling: relevance to major depression. Annals of the New York Academy of Sciences. 2009;1179:86–105. https://pubmed.ncbi.nlm.nih.gov/19906234/