Factitious Cushing's syndrome masquerading as Cushing's disease

Abstract

SummaryContext 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. Adrenocorticotropin (ACTH) is usually suppressed in factitious Cushing's syndrome. Patient A 54-year-old woman presented with clinical and biochemical features of Cushing's syndrome and an unsuppressed ACTH concentration. She denied recent exogenous corticosteroid use. Investigations and results Initial investigations revealed a markedly elevated urinary free cortisol, mildly elevated midnight salivary cortisol and normal morning cortisol concentration. Plasma ACTH was not suppressed at 13 ng/l (RR 10-60 ng/l). A pituitary MRI was normal, but inferior petrosal sinus sampling (IPSS) revealed a post corticotrophin releasing hormone ACTH ratio >20:1 in the left petrosal sinus. Ketoconazole therapy amplified discordance between the urinary free and morning plasma cortisol concentrations. Further investigation of this discordance using high-pressure liquid chromatography tandem mass spectrometry (HPLC-MS/MS) revealed a urinary free cortisol excretion of only 20 nmol/24 h, but prednisolone excretion of 16 200 nmol/24 h. Conclusions Factitious Cushing's syndrome can mimic endogenous ACTH-dependent hypercortisolism during initial investigations and 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.

Fatal factitious Cushing syndrome (Münchhausen’s syndrome) in a patient with macroprolactinoma and silent corticotrophinoma: case report and literature review

“…A reliable ACTH assay is crucial for differentiating ACTH-dependent from ACTH-independent Cushing syndrome. However, the performance of ACTH immunoassays has been questioned recently after several case reports showed unsuppressed ACTH levels in factitious CS, as in our patient [2, 7]. In addition, the intermittent intake of glucocorticoids could lead to fluctuating levels of ACTH [7].…”

“…In addition, the intermittent intake of glucocorticoids could lead to fluctuating levels of ACTH [7]. In the few cases of factitious CS in the literature, synthetic glucocorticoids detected in blood and urine by HPLC/MS confirmed the diagnosis since this method can discriminate similar molecules with a different mass to charge ratio [2]. …”

“…One type of MS is factitious Cushing syndrome, an extremely rare clinical situation in which the diagnosis is challenging mainly due to interference of the exogenous medication in cortisol immunoassays [2]. …”

Current status on histological classification in Cushing’s disease

“…Cushing's disease may also be misdiagnosed in cases whereby the exogenous sources of ACTH or cortisol are not located. Factitious Cushing syndrome is extremely rare but may mimic endogenous ACTH-dependent hypercortisolism during initial evaluation [31]. At this point a complete re-evaluation of the patient must be accomplished and a retrospective investigation of the evidence that led to the diagnosis of Cushing's disease must be analyzed and if necessary, all diagnostic testing should be repeated.…”

Factitious ACTH‐dependent, apparent hypercortisolism: The problem with late‐night salivary cortisol measurements collected at home

“…11 The most recent syndromic CS with "normal" ACTH due to prednisolone intake was postulated as due to intermittent exogenous steroid use or poor performance of the ACTH immunoassay near the lower limit of detection. 12 LC-MS/MS is the most important tool for the investigation of factitious CS. This technology allows the specific and multiple de-…”