UTILITY OF A SINGLE LATE-NIGHT PLASMA CORTISOL AND ACTH FOR THE DIAGNOSIS OF CUSHING SYNDROME.

OBJECTIVE: To evaluate the diagnostic efficacy of various screening tests for the diagnosis of Cushing syndrome (CS). METHODS: Thirty-five patients with CS and 16 patients of pseudo-CS were enrolled. Assessment of 24-h urinary free cortisol (UFC), late-night salivary cortisol (LNSC), overnight dexamethasone suppression test (ONDST), late-night plasma cortisol (LNPC), and adrenocorticotropic hormone (ACTH) on outpatient basis, and during sleep as well as in awake state after 48 hours of hospital admission. RESULTS: We found that 24-h UFC performed the best among the screening tests with sensitivity, specificity and areas under the curve (AUCs) of 96.0%, 99%, and 0.988, respectively, at a cut-off of 144.6 µg/24 h. A cut-off of 10.5 nmol/L for LNSC had sensitivity 85.7%, specificity 88.2%, and an AUC of 0.897. A cut-off of 412.4 nmol/L for LNPC on outpatient basis had sensitivity 88.2%, specificity 91.2%, and an AUC of 0.957. Cut-offs of 215 and 243.3 nmol/L for LNPC during sleep and awake states after acclimatization had sensitivity, specificity, and an AUC of 94.1%, 88.2%, and 0.958, respectively. An ONDST cut-off of 94.6 nmol/L provided sensitivity, specificity, and an AUC of 96.0%, 99.03% and 0.995, respectively. A cut-off of 30.3 pg/mL for late-night ACTH on outpatient basis had sensitivity 67.6%, specificity 99.9%, and an AUC 0.796.A cut-off of 22.6 pg/mL for ACTH during sleep state after acclimatization had sensitivity, specificity, and an AUC of 73.5%, 99.2%, and 0.827, respectively. CONCLUSION: UFC is the best screening test for CS. Furthermore, single measurements of LNPC and ACTH help to establish the diagnosis and ACTH dependency of CS in the majority of patients with CS. ABBREVIATIONS: ACTH = adrenocorticotropic hormone AUC = area under the curve CRH = corticotropin-releasing hormone CS = Cushing syndrome ECLIA = electrochemiluminescence immuno-assay LDDST = low-dose dexamethasone suppression test LNPC = late-night plasma cortisol LNSC = late-night salivary cortisol ONDST = overnight dexamethasone suppression test RIA = radio-immuno assay UFC = urinary free cortisol.

Diagnostic accuracy and comparison of BIPSS in response to lysine vasopressin and hCRH.

CONTEXT: Bilateral inferior petrosal sinus sampling (BIPSS) using hCRH is currently considered the 'gold standard' test for the differential diagnosis of ACTH-dependent Cushing's syndrome (CS). Vasopressin is more potent than CRH to stimulate ACTH secretion as shown in animal studies; however, no comparative data of its use are available during BIPSS. OBJECTIVE: To study the diagnostic accuracy and comparison of hCRH and lysine vasopressin (LVP) stimulation during BIPSS. PATIENTS AND METHODS: 29 patients (27-Cushing's disease, 2-ectopic CS; confirmed on histopathology) underwent BIPSS and were included for the study. Patients were randomized to receive hCRH, 5 U LVP or 10 U LVP during BIPSS for ACTH stimulation. BIPSS and contrast-enhanced magnetic resonance imaging (CEMRI) were compared with intra-operative findings of trans-sphenoidal surgery (TSS) for localization and lateralization of the ACTH source. RESULTS: BIPSS correctly localized the source of ACTH excess in 29/29 of the patients with accuracy of 26/26 patients, using any of the agent, whereas sensitivity and PPV for lateralization with hCRH, 5 U LVP and 10 U LVP was seen in 10/10, 6/10; 10/10,8/10 and 7/7,6/7 patients respectively. Concordance of BIPSS with TSS was seen in 20/27, CEMRI with BIPSS in 16/24 and CEMRI with TSS in 18/24 of patients for lateralizing the adenoma. Most of the side effects were transient and were comparable in all the three groups. CONCLUSION: BIPSS using either hCRH or LVP (5 U or 10 U) confirmed the source of ACTH excess in all the patients, while 10 U LVP correctly lateralized the pituitary adenoma in three fourth of the patients.

Uncommon presentations of primary systemic necrotizing vasculitides: the Great Masquerades.

INTRODUCTION: Systemic vasculitides are great masqueraders and at times their presenting manifestations can be very different from the usual recognized patterns. Such uncommon presentations of granulomatosis with polyangiitis (Wegener's granulomatosis), classical polyarteritis nodosa and unclassifiable vasculitides are described here with the relevant review of literature. METHODS: All patients diagnosed as having systemic vasculitides and classified as having granulomatosis with polyangiitis (Wegener's granulomatosis), classic polyarteritis nodosa, microscopic polyangiitis and unclassifiable vasculitis according to EMEA consensus methodology and followed up prospectively from June 2007 to December, 2011 were included. Details of uncommon presentations of these disorders were identified. RESULTS: Seventy-nine patients with systemic vasculitides were seen under our rheumatology services during this period. These included 45 patients with granulomatosis with polyangiitis (Wegener's granulomatosis), 18 with classic polyarteritis nodosa, five with microscopic polyangiitis, four with Churg-Strauss syndrome and seven with unclassifiable vasculitis. The uncommon presentations of granulomatosis with polyangiitis were a tumefactive subcutaneous mass in the thigh; prostatomegaly with obstructive uropathy and advanced renal failure; and predominant gastrointestinal (GI) vasculitis with thrombocytopenia and coagulopathy at presentation. The uncommon manifestations of classic polyarteritis nodosa were secondary antiphospholipid antibody syndrome and Budd-Chiari syndrome. One patient with massive lower GI bleeding required surgical resection of the large bowel which showed isolated necrotizing granulomatous GI vasculitis. Single organ vasculitis of the GI tract was diagnosed. CONCLUSIONS: Systemic necrotizing vasculitides may present with uncommon manifestations and a high index of suspicion is required for early diagnosis and prompt treatment to prevent adverse outcomes.