Objective: A number of factors can influence the reported outcomes of transsphenoidal surgery (TSS) for Cushing's diseaseincluding different remission and recurrence criteria, for which there is no consensus. Therefore, a comparative analysis of the best treatment options and patient management strategies is difficult. In this review, we investigated the clinical outcomes of initial TSS in patients with Cushing's disease based on definitions of and assessments for remission and recurrence. Methods: We systematically searched PubMed and identified 44 studies with clear definitions of remission and recurrence. When data were available, additional analyses by time of remission, tumor size, duration of follow-up, surgical experience, year of study publication and adverse events related to surgery were performed. Results: Data from a total of 6400 patients who received microscopic TSS were extracted and analyzed. A variety of definitions of remission and recurrence of Cushing's disease after initial microscopic TSS was used, giving broad ranges of remission (42.0-96.6%; median, 77.9%) and recurrence (0-47.4%; median, 11.5%). Better remission and recurrence outcomes were achieved for microadenomas vs macroadenomas; however, no correlations were found with other parameters, other than improved safety with longer surgical experience.

Context:Although bilateral inferior petrosal sinus sampling (BI-PSS) with CRH stimulation is the most accurate procedure for the differential diagnosis of ACTH-dependent Cushing's syndrome (CS), 4 -15% of patients with Cushing's disease (CD) fail to demonstrate diagnostic gradients. Preliminary data suggest that a more potent stimulation by the combined administration of CRH plus desmopressin during BIPSS may provide some diagnostic advantage. A crucial issue, however, is whether such an amplified stimulation may affect the specificity of the procedure, and this was the main aim of the present study. Objective:We investigated the diagnostic accuracy of BIPSS performed by CRH plus desmopressin stimulation. Design and Setting:A retrospective analysis was conducted at a single tertiary care center. Participants:Fifty-four patients were admitted for the investigation of ACTH-dependent CS. CD was diagnosed in 47 patients; occult ectopic ACTH syndrome (oEAS) was histologically confirmed in seven patients. Intervention(s):All patients underwent BIPSS with CRH plus desmopressin administration. Additional noninvasive tests included CRH test, high-dose dexamethasone suppression test, desmopressin test, and pituitary magnetic resonance imaging. Main Outcome Measures:Gradients of inferior petrosal sinus (IPS) to peripheral (IPS/P) ACTH were calculated before and after stimulation with CRH plus desmopressin. Results:The sensitivity for a basal IPS/P gradient greater than 2 was 61.7%, with 100% specificity and a diagnostic accuracy of 66.7%. After stimulation with CRH plus desmopressin, receiver operating characteristic (ROC) curve analysis showed that a cutoff gradient of more than 2 offers the best test performance. In total, 46 of 47 patients with CD had an IPS/P gradient greater than 2, but none of the patients with oEAS, resulting in a sensitivity of 97.9%. The specificity was 100%, diagnostic accuracy was 98.2%, and the positive and negative predictive values were 100 and 87.5%, respectively. A subgroup of 18 patients (16 with CD and two with oEAS) had contradictory responses to routine tests with CRH and/or high-dose dexamethasone suppression test; sensitivity, specificity, and accuracy of BIPSS in this subgroup were 100%. Conclusions:The application of a combined stimulation with CRH plus desmopressin during BIPSS is associated with a high sensitivity but no loss of specificity. (J Clin Endocrinol Metab

A combined stimulus using CRH and desmopressin appears to induce a higher ACTH output from pituitary corticotroph adenomas during BIPSS, which may improve the diagnostic sensitivity of this procedure.

Loss of desmopressin response indicates favorable prognosis and, if used in addition to basal cortisol levels, improves the accuracy of the postoperative assessment of CD.

Non-invasive modalities (ultrasound, computerized tomography, MRI and somatostatin receptor scintigraphy) often fail to localize insulinomas smaller than 1.5 cm in diameter. Recently, regionalization of such occult insulinomas was facilitated by the arterial stimulation and venous sampling (ASVS) technique, using calcium as the insulin secretagogue. However, so far experience with this technique has been limited to a few tertiary referrals centres worldwide. In these case studies we report our experience in three consecutive patients with occult insulinomas. Three consecutive patients (all men 34, 51 and 56 years of age) with insulin-mediated hypoglycaemia were studied. Diagnosis of insulin hypersection was established by the finding of a high amended insulin: blood sugar ratio during fasting. Localization of a pancreatic mass lesion was unsuccessful by ultrasound, CT and/or MRI in all patients. Two patients had negative octreotide scans. In all patients after the infusion of calcium sequentially into the gastroduodenal, splenic and the superior mesenteric arteries, insulin levels rose significantly in right hepatic vein samples giving rise to diagnostic gradients from the splenic artery (in 2 patients) and gastroduodenal artery (in 1 patient), regionalizing insulinomas in the tail and head or neck of the pancreas respectively. The simultaneously obtained angiogram was positive in only 1 patient, in whom it corresponded to the insulin gradient. Regionalization of these occult tumours was subsequently confirmed at laparoscopy in the 2 patients operated. It is concluded, that the arterial stimulation venous sampling technique is an effective method in regionalizing occult insulinomas and should complement invasive angiography whenever the latter procedure is performed.