Predictive power of ACTH and cortisol in the early post-operative period following pituitary surgery: relationship to long term glucocorticoid requirement

2019 ◽  
Author(s):  
Katherine English ◽  
Viral Chikani ◽  
Christina Jang ◽  
Goce Dimeski ◽  
Sarah Olson ◽  
...  
Author(s):  
E. Sala ◽  
G. Carosi ◽  
G. Del Sindaco ◽  
R. Mungari ◽  
A. Cremaschi ◽  
...  

Abstract Purpose A long-lasting remission of acromegaly after somatostatin analogues (SAs) withdrawal has been described in some series. Our aim was to update the disease evolution after SAs withdrawal in a cohort of acromegalic patients. Methods We retrospectively evaluated 21 acromegalic patients previously included in a multicentre study (Ronchi et al. 2008), updating data at the last follow-up. We added further 8 patients selected for SAs withdrawal between 2008–2018. Pituitary irradiation represented an exclusion criterion. The withdrawal was suggested after at least 9 months of clinical and hormonal disease control. Clinical and biochemical data prior and after SAs withdrawal were analysed. Results In the whole cohort (29 patients) mean age was 50 ± 14.9 years and 72.4% were females. In 69% pituitary surgery was previously performed. Overall, the median time of treatment before SAs withdrawal was 53 months (IQR = 24–84). At the last follow up in 2019, 23/29 patients (79.3%) had a disease relapse after a median time of 6 months (interquartile range or IQR = 3–12) from the drug suspension, while 6/29 (20.7%) were still on remission after 120 months (IQR = 66–150). IGF-1 levels were significantly lower before withdrawal in patients with persistent remission compared to relapsing ones (IGF-1 SDS: -1.5 ± 0.6 vs -0.11 ± 1, p = 0.01). We did not observe any other difference between patients with and without relapse, including SAs formulation, dosage and treatment duration. Conclusion A successful withdrawal of SAs is possible in a subset of well-controlled acromegalic patients and it challenges the concept that medical therapy is a lifelong requirement.


1967 ◽  
Vol 55 (3) ◽  
pp. 440-450 ◽  
Author(s):  
Shaul Feldman ◽  
Nisim Conforti ◽  
Julian M. Davidson

ABSTRACT Chronic implantation of cortisol acetate in the basal medial hypothalamus resulted in a steady decrease in weight of the adrenal glands which remained severely atrophic up to 70 days post-implantation. At this time, however, the adrenal ascorbic acid depletion response to unilateral adrenalectomy was normal. The compensatory adrenal hypertrophy (CAH) response, which was inhibited in the immediate post-operative period, reappeared later, and had returned to normal by 21 days postoperatively. Intramuscular administration of cortisol in unimplanted rats inhibited CAH at 14 or 21 days following onset of treatment, and prevented the recovery of CAH in animals implanted 21 days previously with cortisol in the median eminence. The possibility is discussed that the differential recovery of the responses to unilateral adrenalectomy in implanted animals with continuing atrophy of the adrenal cortex is due to some adaptation of central nervous mechanisms subserving the CAH response.


2011 ◽  
Vol 96 (12) ◽  
pp. 3768-3774 ◽  
Author(s):  
Ferdinand Roelfsema ◽  
Daniel M. Keenan ◽  
Johannes D. Veldhuis

Background: The relationship between circulating ACTH levels and cortisol secretion in Cushing's disease is not precisely known. Hypothesis: Chronic ACTH hyperstimulation leads to decreased adrenal potency and is restored after normalization of ACTH secretion. Subjects: Subjects included 20 patients with Cushing's disease, eight patients in long-term remission, and 36 healthy controls. Outcomes: ACTH and cortisol secretion rates and analytical dose-response estimates of endogenous ACTH efficacy (maximal cortisol secretion), dynamic ACTH potency, and adrenal sensitivity (slope term) from 24-h ACTH-cortisol profiles were evaluated. Results: Both basal and pulsatile secretion of ACTH and cortisol were increased in patients with active disease but normal in cured patients. ACTH, but not cortisol pulse frequency, was amplified in patients and restored after successful surgical treatment. ACTH EC50, an inverse measure of potency, was higher during pulse onset in Cushing's disease (59 ± 7.4 ng/liter) than in controls (20 ± 3.7 ng/liter) (P < 0.0001) and remitted patients after surgery [15 ± 3.2 ng/liter, P value not significant (NS) vs. controls] and during pulse recovery phases [128 ± 18 (P <0.0001), 70 ± 8.4, and 67 ± 17 ng/liter (NS vs. controls), respectively]. Efficacy was increased in active disease and normalized after surgical treatment [patients, 38 ± 8.3 nmol/liter · min, vs. controls, 21 ± 2.3 nmol/liter · min (P <0.0001), and cured patients, 15 ± 3.2 nmol/liter · min (NS vs. controls)]. Sensitivity to endogenous ACTH did not differ among the three groups. Conclusion: The adrenal gland in Cushing's disease exhibits decreased responsiveness to submaximal ACTH drive and amplified efficacy, with unchanged sensitivity. These target-gland abnormalities are reversible in long-term remission after pituitary surgery.


2005 ◽  
Vol 63 (5) ◽  
pp. 549-559 ◽  
Author(s):  
A. Brew Atkinson ◽  
Adele Kennedy ◽  
M. Ivan Wiggam ◽  
David R. McCance ◽  
Brian Sheridan

Author(s):  
Marcelo Bérgolo ◽  
Guillermo Cruces ◽  
Andrés Ham

This article carries out a validation exercise of vulnerability measures as predictors of poverty at the aggregate and micro levels based on short and long term panel data for Argentina and Chile. It then compares their performance to that of deprivation indicators. The main findings indicate that while vulnerability measures are good predictors of poverty in the aggregate, the same does not occur at household level. These results imply that while useful, vulnerability estimates require incorporating shocks to attenuate biased estimates if they are to be used for targeting purposes.


2012 ◽  
Vol 9 (11) ◽  
pp. 4323-4335 ◽  
Author(s):  
B. J. Huser ◽  
J. Fölster ◽  
S. J. Köhler

Abstract. Long-term data series (1996–2009) for eleven acidic headwater streams (< 10 km2) in Sweden were analyzed to determine factors controlling concentrations of trace metals. In-stream chemical data as well climatic, flow, and deposition chemistry data were used to develop models predicting concentrations of chromium (Cr), lead (Pb), and zinc (Zn). Data were initially analyzed using partial least squares to determine a set of variables that could predict metal concentrations across all sites. Organic matter (as absorbance) and iron related positively to Pb and Cr, while pH related negatively to Pb and Zn. Other variables such as conductivity, manganese, and temperature were important as well. Multiple linear regression was then used to determine minimally adequate prediction models which explained an average of 35% (Cr), 52% (Zn), and 72% (Pb) of metal variation across all sites. While models explained at least 50% of variation in the majority of sites for Pb (10) and Zn (8), only three sites met this criterion for Cr. Investigation of variation between site models for each metal revealed geographical (altitude), chemical (sulfate), and land-use (silvaculture) influences on predictive power of the models. Residual analysis revealed seasonal differences in the ability of the models to predict metal concentrations as well. Expected future changes in model variables were applied and results showed the potential for long-term increases (Pb) or decreases (Zn) for trace metal concentrations at these sites.


2009 ◽  
Vol 160 (4) ◽  
pp. 529-533 ◽  
Author(s):  
SJCMM Neggers ◽  
WW de Herder ◽  
JAMJL Janssen ◽  
RA Feelders ◽  
AJ van der Lely

BackgroundWe previously reported on the efficacy, safety, and quality of life (QoL) of long-acting somatostatin analogs (SSA) and (twice) weekly pegvisomant (PEG-V) in acromegaly and improvement after the addition of PEG-V to long-acting SSA.ObjectiveTo assess the long-term safety in a larger group of acromegalic patients over a larger period of time: 29.2 (1.2–57.4) months (mean (range)).DesignPegvisomant was added to SSA monotherapy in 86 subjects (37 females), to normalize serum IGF1 concentrations (n=63) or to increase the QoL. The median dosage was 60.0 (20–200) mg weekly.ResultsAfter a mean treatment period of 29.2 months, 23 patients showed dose-independent PEG-V related transient liver enzyme elevations (TLEE). TLEE occurred only once during the continuation of combination therapy, but discontinuation and re-challenge induced a second episode of TLEE. Ten of these patients with TLEE also suffered from diabetes mellitus (DM). In our present series, DM had a 2.28 odds ratio (CI 1.16–9.22; p=0.03) higher risk for developing TLEE. During the combined therapy, a clinical significant decrease in tumor size by more than 20% was observed in 14 patients. Two of these patients were previously treated by pituitary surgery, 1 with additional radiotherapy and all other patients received primary medical treatment.ConclusionLong-term combined treatment with SSA and twice weekly PEG-V up to more than 4 years seems to be safe. Patients with both acromegaly and DM have a 2.28 higher risk of developing TLEE. Clinical significant tumor shrinkage was observed in 14 patients during combined treatment.


Author(s):  
Xi Fu ◽  
Xiaoxi Wu ◽  
Zhifang Zhang

Abstract This paper investigates whether and how the disclosure tone of earnings conference calls predicts future stock price crash risk. Using US public firms’ conference call transcripts from 2010 to 2015, we find that firms with less optimistic tone of year-end conference calls experience higher stock price crash risk in the following year. Additional analyses reveal that the predictive power of tone is more pronounced among firms with better information environment and lower managerial equity incentives, suggesting that extrinsic motivations for truthful disclosure partially explain the predictive power of conference call tone. Our results shed light on the long-term information role of conference call tone by exploring the setting of extreme future downside risk, when managers have conflicting incentives either to unethically manipulate disclosure tone to hide bad news or to engage in ethical and truthful communication.


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