The significant decrease in cortisol levels in patients with Cushing's disease who received pasireotide supports its potential use as a targeted treatment for corticotropin-secreting pituitary adenomas. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00434148.).

Objective: Ectopic ACTH syndrome (EAS) occurs in about 5-10% of all patients with ACTH-dependent hypercortisolism with most of them caused by intrathoracic neoplasms. It may be associated with overt malignancies or with occult and indolent tumors. We assessed the accuracy of dynamic tests, inferior petrosal sinus sampling (IPSS) using desmopressin, and imaging in the work-up diagnosis of EAS. Design and subjects: Tumor markers, imaging, and outcome data from 25 patients (13F/12M) aged 18-72 years. High dexamethasone suppression test (HDDST), desmopressin test, GHRP-6 test, corticotropin-releasing hormone (CRH) test, IPSS, computed tomography (CT), magnetic resonance imaging (MRI), and 111 In-pentetreotide scintigraphy were revised. Results: In 5 out of 20 patients HDDST was positive. In 13 patients who underwent desmopressin test, ACTH-and cortisol-positive responses were seen in six and five patients respectively. GHRP-6 test was positive in two out of three cases. Two patients underwent CRH test with negative response. In the seven patients submitted to IPSS using desmopressin in six of them, none had ACTH gradients. CT was positive in 15 out of 21 patients and MRI in 8 out of 17 cases.111 In-pentetreotide scintigraphy was positive in three out of five patients. Fourteen patients had intrathoracic tumors, five had pheochromocytomas, three had pancreatic tumors, one had a glomic tumor, and had three occult tumors. Six out of 11 patients with metastasis died and 3 others without metastasis died. Conclusions: IPSS with desmopressin was helpful for differential diagnosis. Patients initially harboring occult carcinoids may also exhibit severe hypercortisolism and those harboring tymic carcinoids had poor prognoses when compared with bronchial carcinoids and pheocromocytomas.European Journal of Endocrinology 155 725-733

The prevalence of Nelson's syndrome was 47% in our series of 30 patients with Cushing's disease after bilateral adrenalectomy. No clinical or laboratory data before adrenalectomy predicted the development of the syndrome. The value of prophylactic pituitary irradiation could not be evaluated from our clinical material. However, after adrenalectomy, the presence of hyperpigmentation and ACTH levels above 154 pmol/l had positive predictive value for the development of Nelson's syndrome. In this situation magnetic resonance imaging (MRI) of the pituitary is mandatory and, if no tumour is detected, MRI should be repeated at intervals.

In the largest Phase III study of medical therapy in Cushing's disease, significant improvements in signs and symptoms were seen during 12 months of pasireotide treatment, as UFC levels decreased.

ObjectiveTwenty-four-hour urinary free cortisol (UFC) sampling is commonly used to evaluate Cushing’s syndrome. Because there are few data on UFC variability in patients with active Cushing’s disease, we analysed baseline UFC in a large patient cohort with moderate-to-severe Cushing’s disease and assessed whether variability correlates with hypercortisolism severity. These data will help clinicians establish the minimum number of UFC samples required to obtain reliable data.DesignObservational study (enrolment phase of Phase III study).MethodsPatients (n = 152) with persistent/recurrent or de novo Cushing’s disease and mean UFC (mUFC) ≥1·5×ULN (normal: 30–145 nmol/24 h) were included. Mean UFC level was calculated from four 24-h urine samples collected over 2 weeks.ResultsOver 600 24-h UFC samples were analysed. The mUFC levels of samples 1 and 2 and samples 3 and 4 were 1000 nmol/24 h (SD 1872) and 940 nmol/24 h (SD 2148), respectively; intrapatient coefficient of variation (CV) was 38% for mUFC. The intrapatient CV using all four samples was 52% (95% CI: 48–56). The intrapatient CV was 51% (95% CI: 44–58) for samples 1 and 2, 49% (95% CI: 43–56) for samples 3 and 4 and 54% (95% CI: 49–59) for samples 1, 2 and 3. Variability in mUFC increased as UFC levels increased. There were no correlations between UFC and clinical features of hypercortisolism.ConclusionsThere is intrapatient variability of approximately 50% in 24-h UFC measurements, which is relevant to targets set to estimate any treatment effect. Analysing more than two 24-h collection periods in individual patients does not result in a relevant decrease in variability. Interestingly, UFC levels did not correlate with hypercortisolism severity.