Pituitary tumour localization in patients with Cushing's disease by magnetic resonance imaging. Is there a place for petrosal sinus sampling?
Authors: de Herder Wouter W. , Uitterlinden Piet , Pieterman Herman , Tanghe Herve L. J. , Kwekkeboom Dlk J. , Pols Hulbert A. P. , Singh Ram , van de Berge J. Herbert , Lamberts Steven W. J. 
Published: March 2008

OBJECTIVE We wished to analyse the relative value and diagnostic accuracy of bilateral simultaneous inferior petrosal sinus blood sampling for plasma ACTH measurements when compared with pituitary magnetic resonance imaging (MRI) for the preoperative localization of microadenoma (tumour diameter <10 mm) within the pituitary fossa in patients with Cushing's disease.

DESIGN Pituitary MRIs were assessed blind and independently. The sinus blood sampling was performed before and after administration of corticotrophin releasing hormone (CRH). The ratios of the ACTH concentrations in plasma samples from the inferior petrosal sinuses to the concentrations in peripheral blood plasma samples (the IPS:P ratio) and the ratios of the ACTH concentrations in samples from both inferior petrosal sinuses (the inter‐sinus gradient) were calculated.

PATIENTS Twenty consecutive patients with Cushing's disease were prospectively studied. All but two patients subsequently underwent transsphenoidal exploration of the pituitary fossa.

RESULTS In three of 20 patients (15%), positioning of catheter tips in both inferior petrosal sinuses was unsuccessful. The diagnosis of Cushing's disease was confirmed by the greater basal IPS: P ratio amounting to 3; 2 0 in 13 of 17 patients (76%), and amounting to > 3 0 in CRH‐stimulated peak samples in 15 of 17 patients (88%). Anatomical variations of the inferior petrosal sinus, precluding reliable conclusions about lateralization of pituitary venous ACTH drainage, were observed in five of 20 patients (25%). Adding the three patients with technical failure and one patient who presented with a macroadenoma (tumour diameter 11 mm), this left interpretable data with regard to lateralization of the microadenomas in only 11 of 20 patients (55%). In 15 of 20 patients (75%) a pituitary microadenoma was found at MRI. In 14 of these 15 patients (93%) a tumour was indeed found at that position at subsequent transsphenoidal operation. Concordance between the lateralization by the intersinus gradient and microadenoma localization by MRI was observed in six of 11 cases (55%) when using basal samples and in seven of 11 cases (64%) when using peak samples obtained after stimulation with CRH. Concordance between the lateralization by the intersinus gradient and subsequent microadenoma localization at surgery was observed in seven of 11 patients (64%) before and in eight of 11 cases (73%) after CRH stimulation. Reversal of the intersinus gradient after CRH stimulation, suggesting a shift in the lateralization to the contralateral side of the gland, was found in three of 12 cases (25%).

CONCLUSIONS Bilateral simultaneous inferior petrosal sinus blood sampling for plasma ACTH measurements before and after CRH stimulation successfully confirmed the diagnosis of pituitary dependent Cushing's disease in 15 of 17 patients (88%) in whom this diagnosis was suspected on the basis of conventional biochemical testing. Magnetic resonance imaging, however, is superior to bilateral simultaneous inferior petrosal sinus blood sampling for the localization/lateralization of pituitary microadenomas in patients with Cushing's disease. Therefore, bilateral simultaneous inferior petrosal sinus blood sampling should be reserved for the assessment of those patients with Cushing's syndrome in whom either the results of biochemical tests are equivocal and/or subsequent pituitary magnetic resonance imaging gives unconvincing results.