Cushing's Syndrome : hormonal secretion patterns, treatment and outcome.

LUMCDiabetes, endocriene pathofysiologie en endocriene tumore

Propagation pathways of classical Labrador Sea water from its source region to 26°N

More than two decades of hydrography on the Abaco line east of the Bahamas at 26 degrees N reveals decadal variability in the salinity of classical Labrador Sea Water (cLSW), despite the long distance from its source region in the North Atlantic Ocean. Hydrographic time series from the Labrador Sea and from the Abaco line show a pronounced step-like decrease in salinity between 1985 and 1995 in the Labrador Sea and between 1995 and 2010 at the Abaco line, suggesting a time lag between the two locations of approximately 9 years. The amplitude of the anomaly at the Abaco line is 50% of the amplitude in the Labrador Sea. A similar time lag and reduction of amplitude is found in the high-resolution OFES model, in which salinity anomalies can be observed propagating through the Deep Western Boundary Current as well as through a broad interior pathway. On its way south to the Abaco line, the cLSW becomes 8 standard deviations saltier due to isopycnal mixing with Mediterranean Outflow Water (MOW). Climatological data in the North Atlantic suggests that the mixing ratio of MOW to cLSW at the Abaco line is 1:4 and that no variability in MOW is required to explain the observed variability at the Abaco line. The data studied here suggest that decadal cLSW anomalies stay relatively coherent while getting advected, despite the important role of interior pathways

Hormonal crises following receptor radionuclide therapy with the radiolabeled somatostatin analogue [177Lu-DOTA0,Tyr 3]octreotate

Introduction: Receptor radionuclide therapy is a promising treatment modality for patients with neuroendocrine tumors for whom alternative treatments are limited. The aim of this study was to investigate the incidence of hormonal crises after therapy with the radiolabeled somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate). Materials and methods: All177Lu- octreotate treatments between January 2000 and January 2007 were investigated. Four hundred seventy-six patients with gastroenteropancreatic neuroendocrine tumors and three patients with metastatic pheochromocytoma were included fo

Biochemical predictors of outcome of pituitary surgery for cushing's disease

Objective: Transsphenoidal surgery (TS) is the primary therapy for Cushing's disease (CD). The aims of this retrospective study were twofold: (i) investigate early and late results of TS forCD, and (ii) evaluate various postoperative tests in order to predict the outcome of TS. Methods: We reviewed the long-term outcome in 79 patients with CD who underwent TS (median follow-up 84 months, range 6-197). Within 2 weeks after surgery, morning serum cortisol concentrations were obtained (n = 78) and corticotropin-releasing hormone (CRH) (n = 53) and metyrapone tests (n = 72) were performed. Three groups of outcome were identified: sustained remission, early failure (persistent CD), and late relapse. Results: Immediate postoperative remission was achieved in 51 patients (65%), whereas 28 patients (35%) had persistent CD after TS. Ten patients developed recurrent CD after initial remission (20%). Morning cortisol: all relapses but one recorded serum cortisol >50 nmol/l. A cortisol threshold value of 200 nmol/l has a positive predictive value of 79% for immediate surgical failure (negative predictive failure [NPV] 97%). CRH test: CRH-stimulated peak cortisol ≥600 nmol/l predicted early failure in 78% (NPV 100%). All relapses recorded CRH-stimulated peak cortisol ≥485 nmol/l. Metyrapone test: 11-deoxycortisol ≥345 nmol/l predicted an early failure in 86% of cases (NPV 94%). Conclusion: Predictive factors of surgical failure are morning cortisol ≥200 nmol/l, 11-deoxycortisol ≥345 nmol/l after metyrapone and CRH-stimulated cortisol ≥600 nmol/l. CRH and/or metyrapone testing are not superior to morning cortisol concentration in the prediction of outcome of TS. Careful long-term follow-up remains necessary independent of the outcome of biochemical testing. Copyrigh

Profound amplification of secretory-burst mass and anomalous regularity of ACTH secretory process in patients with Nelson's syndrome compared with Cushing's disease

As described originally, Nelson's syndrome is characterized by grossly elevated ACTH concentrations, a sellar mass and skin hyperpigmentation emerging in the course of Cushing's disease after bilateral adrenalectomy. No detailed studies have defined whether the mechanisms directing ACTH secretion differ in Nelson's syndrome and untreated Cushing's disease. To address this pathophysiological issue, we studied nine patients fulfilling the criteria of Nelson's syndrome receiving glucocorticoid and mineralocorticoid replacement; nine patients with untreated pituitary-dependent Cushing's disease and nine gender- and age-matched controls. ACTH release was appraised by monitoring plasma ACTH concentrations in blood samples collected every 10 min for 24 h. ACTH secretion rates and endogenous decay were quantified by multiparameter deconvolution analysis. The orderliness of the ACTH release process was delineated by the approximate entropy (ApEn) statistic. Diurnal variation in ACTH secretion was appraised by cosinor analysis. Basal ACTH secretion was increased sixfold and pulsatile secretion ninefold in patients with Nelson's syndrome compared with Cushing's disease (P </= 0.01 and P </= 0.001, respectively). The increase in pulsatile secretion was due to an eightfold augmentation of burst mass. Event frequency was comparable in both patient groups (32 +/- 1 vs. 28 +/- 2 pulses/24 h), and higher than in normal controls (22 +/- 1 pulses/24 h, P <0.0001). Paradoxically, the consistency of subordinate patterns of serial ACTH release, albeit disrupted in active Cushing's disease, was normal in Nelson's syndrome (P = 0.014). Normal ACTH secretory-process regularity in Nelson's syndrome was attributable to a more reproducible (lower ApEn) succession of ACTH secretory-burst mass denoting more uniform amplitude evolution over 24 h (P = 0.007, Nelson vs. Cushing). However, the quantifiable regularity of serial interburst intervals (waiting times) was unexpectedly elevated in Nelson's syndrome (P = 0.022). Nelson patients maintained a significant diurnal rhythm in ACTH release, which was marked by a 15-fold greater amplitude (P = 0.0018 vs. Cushing's) and a 4-h acrophase (maximum) delay (P = 0.037 vs. control). The present detailed analyses delineate marked ACTH secretory-burst mass amplification and (amplitude-independent) anomalous regularity of successive pulse size and timing in Nelson's syndrome compared with Cushing's disease or controls. We postulate that the foregoing novel distinctions are due to unique tumoural secretory properties, concurrently required glucocorticoid replacement and/or hypothalamic injury associated with prior radiotherapy in Nelson's syndrom