Diagnostic accuracy of increased urinary cortisol/cortisone ratio to differentiate ACTH‐dependent Cushing's syndrome

Ceccato, Filippo; Trementino, Laura; Barbot, Mattia; Antonelli, Giorgia; Denaro, Luca; Regazzo, Daniela; Rea, Federico; Frigo, Anna Chiara; Concettoni, Carolina; Boscaro, Marco; Arnaldi, Giorgio; Scaroni, Carla

doi:10.1111/cen.13391

Cited by 23 publications

(14 citation statements)

References 23 publications

(62 reference statements)

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“…For patients with QoL assessment, UFC levels at baseline were not significantly higher in patients with ECS compared to CD patients. This is in contrast to earlier series, where UFC levels were higher in ECS (38). Our finding might be due to a selection bias as QoL assessment was only performed in long-term-surviving patients.…”

Section: Qol Assessment During Follow-upcontrasting

confidence: 96%

Surviving ectopic Cushing’s syndrome: quality of life, cardiovascular and metabolic outcomes in comparison to Cushing’s disease during long-term follow-up

Oßwald

Deutschbein

Berr

et al. 2018

European Journal of Endocrinology

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Section: Qol Assessment During Follow-upcontrasting

confidence: 96%

Surviving ectopic Cushing’s syndrome: quality of life, cardiovascular and metabolic outcomes in comparison to Cushing’s disease during long-term follow-up

Oßwald

Deutschbein

Berr

et al. 2018

European Journal of Endocrinology

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“…FEratio was higher in patients than in controls (irrespective of treatment with conv-HC or DR-HC): we could speculate that the reduction of E levels in AI patients could explain their increased salivary FEratio, because they used HC (which is F) or CA (activated to F in the liver). These ‘normal-increased’ F levels could be combined with a reduced activity of 11β-hydroxysteroid dehydrogenase type 2 in salivary glands in patients with AI, probably secondary to the enzyme saturation, as that observed in case of increased F levels in patients with CS ( 37 , 38 ). We correlated daily F and E exposure to GC replacement dose: we found no correlation among AUC Fa⟶Fb or AUC Ea⟶Eb with conv-HC, as previously reported considering CA ( 13 ) and recently remarked by Ross and colleagues ( 39 ) (using LC-MS/MS).…”

Section: Discussionmentioning

confidence: 77%

Improved salivary cortisol rhythm with dual-release hydrocortisone

Ceccato

Selmin

Sabbadin

et al. 2018

Endocrine Connections

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Introduction and AimThe purpose of replacement therapy in adrenal insufficiency (AI) is mimicking endogenous cortisol levels as closely as possible: dual release hydrocortisone (DR-HC) has been introduced to replicate the circadian cortisol rhythm. Multiple daily saliva collections could be used to assess the cortisol rhythm during real life: our aim was to study the salivary cortisol profile in AI.Materials and MethodsWe prospectively evaluated, in an observational study, 18 adult outpatients with AI (11 primary and 7 secondary AI), switched from conventional treatment (conv-HC, 25 mg/day) to the same dose of DR-HC. We collected six samples of saliva in a day, measuring cortisol (F) and cortisone (E) with LC-MS/MS. Forty-three matched healthy subjects served as controls.ResultsF levels were similar in the morning (and higher than controls) in patients treated with conv-HC or DR-HC; otherwise F levels and exposure were lower in the afternoon and evening in patients with DR-HC, achieving a cortisol profile closer to healthy controls. Daily cortisol exposure, measured with area under the curve, was lower with DR-HC. Morning F and E presented sensitivity and specificity >90% to diagnose AI (respectively threshold of 3 and 9.45 nmol/L). Total cholesterol and HbA1c levels reduced with DR-HC.ConclusionsSalivary cortisol daily curve could be used as a new tool to assess the cortisol profiles in patients treated with conv-HC and DR-HC. A lower daily cortisol exposure was achieved with DR-HC (despite the same HC dose), especially in the afternoon-evening.

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“…At this point, we faced a dilemma of diagnosis. To date, there were limited reports of false positives of BIPSS of EAS [19]. It reported cyclic or relatively normal cortisol levels without suppression of corticotrophin, or ectopic CRH tumors can lead to false positive conclusions [20].…”

Section: Discussionmentioning

confidence: 99%

Unusual ectopic ACTH syndrome in a patient with orbital neuroendocrine tumor, resulted false-positive outcome of BIPSS:a case report

Tan

Chen

et al. 2020

BMC Endocr Disord

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Background: Cushing's syndrome has been described as a complex endocrine disorder characterized with high cortisol concentration. Correct and early diagnosis of Cushing's syndrome is challenging. According to the latest guideline, bilateral inferior petrosal sinus sampling (BIPSS) is considered to be the gold standard for the differential diagnosis. However, in some unusual cases, this method may be false positive. Here, we presented a rare case of orbital neuroendocrine tumor secreting adrenocorticotrophic hormone with false positive inferior petrosal sinus sampling. Case presentation: A 48-year-old woman was admitted to West China Hospital of Sichuan University, presenting with fatigue, whole body edema for 1 year, alopecia and skin pigmentation for 5 months. Hormonal profiles including plasma cortisol and adrenocorticotrophic hormone (ACTH) measurements and low-dose dexamethasone inhibition test suggested that the patient had Cushing's syndrome. However, during tumor location phase, the results of high-dose dexamethasone inhibition test (HDDST) contradicted desmopressin (DDAVP) stimulation test. Thus, BIPSS was employed, and its results indicated a pituitary origin. Interestingly, MRI of sellar region showed an innocent pituitary but caught a serendipitous lesion in the lateral rectus muscle of left eye, which was later proved to be an orbital neuroendocrine tumor secreting ACTH by pathological and immunohistochemical results. ACTH level of the patients was < 0.1 ng/L and cortisol level was 51.61 nmol/L 1 week after surgery. At 24 months followup, the patient appeared stable with no complaints nor any symptoms of Cushing's syndrome, including moon face, purple striate and central obesity. The patient's life quality also improved significantly. Conclusion: We reported a rare case of endogenous Cushing's syndrome due to ectopic ACTH secreting from an orbital neuroendocrine tumor. This unique case of orbital EAS suggests that orbital venous blood backflow, owning to abnormal anatomic structures, may possibly lead to false positive BIPSS results.

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Diagnostic accuracy of increased urinary cortisol/cortisone ratio to differentiate ACTH‐dependent Cushing's syndrome

Abstract: Urinary FEr >1.15 was able to suggest EAS, with a diagnostic accuracy similar to that of other dynamic tests proposed to study ACTH-dependent CS.

Cited by 23 publications

References 23 publications

Surviving ectopic Cushing’s syndrome: quality of life, cardiovascular and metabolic outcomes in comparison to Cushing’s disease during long-term follow-up

Surviving ectopic Cushing’s syndrome: quality of life, cardiovascular and metabolic outcomes in comparison to Cushing’s disease during long-term follow-up

Improved salivary cortisol rhythm with dual-release hydrocortisone

Unusual ectopic ACTH syndrome in a patient with orbital neuroendocrine tumor, resulted false-positive outcome of BIPSS:a case report

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