Differential diagnosis of Cushing’s syndrome

Factitious Cushing’s syndrome is extremely rare. The diagnosis is challenging as cross-reactivity of synthetic corticosteroids or their metabolites in immunoassay measurements of plasma or urinary cortisol can make distinguishing between true and factitious Cushing’s syndrome difficult.

Thynne et al. report on a case of a 54-year old woman who presented with clinical and biochemical features of Cushing’s syndrome and an unsuppressed ACTH concentration.  They show that the key to the diagnosis of factitious Cushing’s syndrome in their patient was the recognition of the discordance between the normal plasma cortisol, mildly elevated salivary cortisol, and marked elevation of urine cortisol concentrations. This discrepancy was present during the initial investigations, but the significance was not fully appreciated until treatment with ketoconazole amplified the discordance.

Factitious Cushing’s syndrome can mimic endogenous ACTH-dependent hypercortisolism during initial investigations and inferior petrosal sinus sampling (IPSS). This case highlights the importance of (i) recognizing the significance of discordant results; (ii) using an ACTH assay capable of reliably differentiating ACTH-dependent from ACTH-independent Cushing’s syndrome; and (iii) appreciating that IPSS is only useful to localize the source of ACTH in confirmed ACTH-dependent Cushing’s syndrome. In this case, measurement of corticosteroids by HPLC-MS/MS was essential in reaching the correct diagnosis.

In her commentary on this study, Niemen commended the authors for courageously sharing with the wider clinical community their experience with the treatment of a Cushingoid patient. She writes that this interesting case illustrates a number of clinical points – first, the importance of understanding the vagaries of the assays used. In this case the ACTH level was low for Cushing’s disease. Secondly, mistakes could be avoided if multiple simultaneous measures of hypercortisolism are compared. Finally, the scheduling and interpretation of the IPSS must include an assessment of the duration and amount of hypercortisolism. IPSS is useful only if normal corticotrophs are suppressed.

Read full details of the case at Thynne et al. (2014) Clinical Endocrinology 80; 328-332; DOI: 10.1111/cen.12343 and the commentary at DOI: 10.1111/cen.12362