Abstract
Background:Bilateral inferior petrosal sinus sampling (BIPSS) has been the gold standard in differentiating a pituitary vs. an ectopic source of ACTH in Cushing’s syndrome however, it has many limitations. The ON-HDDST being simple to perform and the tests of choice in resource poor setting. The primary aim of our study was to consolidate the present knowledge regarding the diagnostic utility of ON-HDDST in localizing the source of ACTH.Method:We retrospectively studied 88 patients with ACTH dependent Cushing syndrome who underwent ONHDDST. Patient were considered as Cushing disease (CD) if either of the 3 criteria were met a) histopathological confirmed b) a central to peripheral gradient >2 was seen in BIPSS or c) pituitary adenoma ≥ 6mm seen in MRI of pituitary. Patient were considered as ectopic ACTH syndrome if the tumor was localized at any peripheral location by imaging or histopathological confirmed after surgery or if BIPSS shown a central to peripheral gradient of <2. Result: Out of total 88 ACTH dependent Cushing syndrome patients, 68 (77.3%) were proven CD and 20 (22.7%) were ectopic. There was no difference in basal serum cortisol however, S. Cortisol after ONHDDST was significantly different between the two with a median of 547.7 nmol/l (341-770) in ectopic vs 273.5 nmol/l (142-689) in CD (p=0.02). A positive response to ONHDDST (≥50% suppression) was seen in about 44 (65%) patients with CD and 5 (25%) patients with ectopic disease (p = 0.002). Among CD patient, 35 (76.1%) of those with microadenoma, 7 (43.8%) amongst macroadenoma and 2 (33%) patient with no visible tumor on MRI shown positive response to ONHDDST. In ectopic group, cortisol suppressibility was seen in 3 (50%) patient with occult tumor but only in 2(14.3%) patient with. ROC curve plotted for percentage suppression of cortisol after ONHDDST shown as AUC equal to 0.68 (p = 0.01). The best test parameters with sensitivity (65%), specificity (85%) and Accuracy (69%) were seen at 50% cutoff level as were the likelihood ratio for positive test (4.3), AUC (0.75), PPV (93.6%), NPV (41.4%). Conclusion: Our study has shown that ONHDDST has poor diagnostic value in differentiating between CD and ectopic ACTH syndrome whatever be the cutoff level of the cortisol suppression. However, this can still be utilized in setups where no alternative is available. For etiologic confirmation, another test with better sensitivity and specificity is preferable.
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