scholarly journals Persisting Muscle Dysfunction in Cushing’s Syndrome Despite Biochemical Remission

2020 ◽  
Vol 105 (12) ◽  
pp. e4490-e4498 ◽  
Author(s):  
Frederick Vogel ◽  
Leah T Braun ◽  
German Rubinstein ◽  
Stephanie Zopp ◽  
Heike Künzel ◽  
...  
Keyword(s):  
Muscle Strength ◽  
Grip Strength ◽  
Cushing’S Syndrome ◽  
Muscle Function ◽  
Tertiary Care ◽  
Cushing's Syndrome ◽  
Muscle Dysfunction ◽  
Long Term Outcome

Abstract Context Glucocorticoid-induced myopathy is a characteristic symptom of endogenous Cushing’s syndrome (CS). Its long-term outcome is largely unknown. Objective To evaluate long-term muscle function following the remission of endogenous CS. Study Design Observational longitudinal cohort study. Setting Tertiary care hospitals and a specialized outpatient clinic. Patients As part of the prospective multicenter German Cushing’s Registry, we assessed muscle strength in patients with overt endogenous CS. We studied the patients at the time of diagnosis (n = 88), after 6 months (n = 69), and thereafter annually, following surgical remission over a period of up to 4 years (1 year: n = 55; 2 years: n = 34; 3 years: n = 29; 4 years: n = 22). Muscle function was evaluated by hand grip strength and by chair rising test. Results Grip strength was decreased to 83% of normal controls (100%) at the time of diagnosis. It further decreased to 71% after 6 months in remission (P ≤ 0.001) and showed no improvement during further follow-up compared with baseline. Chair rising test performance improved initially (8 seconds at baseline vs 7 seconds after 6 months, P = 0.004) but remained at this reduced level thereafter (7 seconds after 3 years vs 5 seconds in controls, P = 0.038). In multivariate analysis, we identified, as predictors for long-term muscle dysfunction, age, waist-to-hip ratio, and hemoglobin A1c at baseline. Furthermore, muscle strength during follow-up was strongly correlated with quality of life. Conclusion This study shows that CS-associated myopathy does not spontaneously resolve during remission. This calls for action to identify effective interventions to improve muscle dysfunction in this setting.

Long-term morphological, hormonal, and clinical follow-up in a single unit on 118 patients with adrenal incidentalomas

2010 ◽  
Vol 162 (4) ◽  
pp. 779-785 ◽  
Author(s):  
R Giordano ◽  
E Marinazzo ◽  
R Berardelli ◽  
A Picu ◽  
M Maccario ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Cumulative Risk ◽  
Cushing's Syndrome ◽  
Endocrine Function ◽  
Adrenal Incidentalomas ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Significant Clinical Improvement

ObjectiveTo evaluate long-term morphological, functional, and clinical outcome in adrenal incidentalomas.Design and methodsA total of 118 patients (77 F and 47 M; age 62.3±1.0 years) with adrenal incidentalomas were evaluated at baseline and followed-up for median 3 years (range 1–10 years) by clinical, biochemical, hormonal, and morphological evaluation. Among them, six patients with diagnosis of subclinical Cushing's syndrome (SCS) underwent surgery.ResultsAt entry, 86% (n=102) of tumors were nonfunctioning (NF) and 14% (n=16) showed SCS. Comparing NF with SCS patients, a significantly higher percentage of dyslipidemia was found in the group of SCS patients (50 vs 23%,P=0.033). During follow-up, adrenal function remained normal in all NF patients, none of them developed subclinical or overt endocrine disease. The cumulative risk of mass enlargement was globally low (25%), but progressive up to 8 years. SCS was confirmed in all patients, and none of them shifted to overt Cushing's syndrome. The cumulative risk of developing metabolic–cardiovascular abnormalities was globally low (22%), but progressive up to 8 years and new diseases were recorded in the group of NF patients only (three patients with dyslipidemia, four with impaired fasting glucose/impaired glucose tolerance, and three with diabetes mellitus). SCS patients who underwent surgery did not show any significant clinical improvement.ConclusionsThe risk of mass enlargement, hormonal, and metabolic impairment over time is globally low. Conservative management seems to be appropriate, but further prospective studies are needed to establish the long-term outcome of such patients, especially for metabolic status, cardiovascular risk profile and their relationship with endocrine function.

scholarly journals Muscle strength in patients with acromegaly at diagnosis and during long-term follow-up

2017 ◽  
Vol 177 (2) ◽  
pp. 217-226 ◽  
Author(s):  
Laila Füchtbauer ◽  
Daniel S Olsson ◽  
Bengt-Åke Bengtsson ◽  
Lise-Lott Norrman ◽  
Katharina S Sunnerhagen ◽  
...  
Keyword(s):  
Body Composition ◽  
Muscle Strength ◽  
Grip Strength ◽  
Muscle Function ◽  
Cell Mass ◽  
Proximal Muscle ◽  
Long Term Follow Up ◽  
One Year

Objective Patients with acromegaly have decreased body fat (BF) and increased extracellular water (ECW) and muscle mass. Although there is a lack of systematic studies on muscle function, it is believed that patients with acromegaly may suffer from proximal muscle weakness despite their increased muscle mass. We studied body composition and muscle function in untreated acromegaly and after biochemical remission. Design Prospective observational study. Methods Patients with acromegaly underwent measurements of muscle strength (dynamometers) and body composition (four-compartment model) at diagnosis (n = 48), 1 year after surgery (n = 29) and after long-term follow-up (median 11 years) (n = 24). Results were compared to healthy subjects. Results Untreated patients had increased body cell mass (113 ± 9% of predicted) and ECW (110 ± 20%) and decreased BF (67 ± 7.6%). At one-year follow-up, serum concentration of IGF-I was reduced and body composition had normalized. At baseline, isometric muscle strength in knee flexors and extensors was normal and concentric strength was modestly increased whereas grip strength and endurance was reduced. After one year, muscle strength was normal in both patients with still active disease and patients in remission. At long-term follow-up, all patients were in remission. Most muscle function tests remained normal, but isometric flexion and the fatigue index were increased to 153 ± 42% and 139 ± 28% of predicted values, respectively. Conclusions Patients with untreated acromegaly had increased body cell mass and normal or modestly increased proximal muscle strength, whereas their grip strength was reduced. After biochemical improvement and remission, body composition was normalized, hand grip strength was increased, whereas proximal muscle fatigue increased.

scholarly journals Restoration of the coupling process and normalization of bone mass following successful treatment of endogenous Cushing’s syndrome: A prospective, long-term study

2006 ◽  
Vol 154 (1) ◽  
pp. 109-118 ◽  
Author(s):  
Cybèle Kristo ◽  
Rune Jemtland ◽  
Thor Ueland ◽  
Kristin Godang ◽  
Jens Bollerslev
Keyword(s):  
Bone Mineral Density ◽  
Lumbar Spine ◽  
Bone Mineral ◽  
Cushing’S Syndrome ◽  
Biochemical Markers ◽  
Cushing's Syndrome ◽  
Mineral Density ◽  
Long Term Outcome

Objective: Endogenous Cushing’s syndrome (CS) is associated with bone loss and an increased risk of fractures. However, the long-term outcome of treatment on bone health has not been adequately clarified. Design: We followed 33 patients with active CS prospectively before and twice after treatment (mean follow-up 33 (n = 25) and 71 months (n = 18), respectively). The patients were compared to age-, sex- and body mass index (BMI)-matched controls, also followed longitudinally. Methods: Bone mineral indices (bone mineral density (BMD), bone mineral content (BMC) and bone area) were evaluated in the lumbar spine (LS), femoral neck (FN), and total body (TB) by dual-energy X-ray absorptiometry (DXA). Biochemical markers of bone turnover were assessed by serum levels of osteocalcin and C-terminal telopeptides of Type-1 collagen (CTX-1). Results: Mann–Whitney rank sum tests showed that BMD of the LS, FN and TB was reduced by 14.8% (P < 0.001), 15.7% (P < 0.001), and 9.2% (P < 0.001) in CS vs. controls at baseline, with markedly reduced serum osteocalcin (P = 0.014) and increased CTX-1 (P = 0.012) levels, but no correlation between markers. At first follow-up, BMD was increased in LS (7.9%, P < 0.001) and FN (3.5%, P = 0.003) compared to baseline. The time-dependent rise in BMD (LS (r = 0.59; P = 0.002) and FN (r = 0.52; P = 0.007); Spearman’s rank correlation), in CS was paralleled by increased osteocalcin (275%, P < 0.001) and correlation between biochemical markers (r = 0.92, P < 0.001; Pearson’s correlation). TB BMD did not increase significantly before the second follow-up, when BMD Z-scores were normalized in all three compartments. Conclusion: Our observations demonstrate restoration of coupled bone remodeling and normalization of bone mineral density in all measured skeletal compartments of treated CS patients after prolonged recovery, first significant in predominantly trabecular bone (i.e. lumbar spine).

Patients with low IGF-I after curative surgery for Cushing’s syndrome have an adverse long-term outcome of hypercortisolism-induced myopathy

2021 ◽  
Author(s):  
Frederick Vogel ◽  
Leah Braun ◽  
German Rubinstein ◽  
Stephanie Zopp ◽  
Sarina Benedix ◽  
...  
Keyword(s):  
Grip Strength ◽  
Muscle Mass ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Curative Surgery ◽  
Prospective Longitudinal Study ◽  
Long Term Outcome ◽  
Igf I ◽  
Prospective Longitudinal

Background: Glucocorticoid excess leads to muscle atrophy and weakness in patients with endogenous Cushing’s syndrome. Insulin-like growth factor I (IGF-I) is known to have protective effects on muscle loss. We hypothesized that individual serum IGF-I concentrations might be predictive for long-term myopathy outcome in Cushing’s syndrome. Patients and methods: In a prospective longitudinal study of 31 patients with florid Cushing’s syndrome, we analyzed IGF-I and IGF binding protein 3 (IGFBP 3) concentrations at the time of diagnosis and following surgical remission over a period of up to three years. We assessed muscle strength by grip strength measurements using a hand grip dynamometer and muscle mass by bio-impedance measurements. Findings: Individual serum IGF-I concentrations in the postoperative phase were strongly predictive of long-term grip strength outcome (rs = 0.696, p ≤ 0.001). Also, lower IGF-I concentrations were associated with a lower muscle mass after three years (rs = 0.404, p = 0.033). While patients with high IGF-I SD scores (> 1.4) showed an improvement in grip strength within the follow-up period (p = 0.009), patients with lower IGF-I SD scores (≤ -0.4) had a worse outcome with persisting muscle dysfunction. In contrast, preoperative IGF-I concentrations during the florid phase of Cushing’s syndrome did not predict long-term muscle function outcome (rs = 0.285, p = 0.127). Conclusion: Lower individual IGF-I concentrations six months after curative surgery for Cushing’s syndrome are associated with adverse long-term myopathy outcome and IGF-I might be essential for muscle regeneration in the early phase after correction of hypercortisolism.

scholarly journals Mortality in Cushing's syndrome: systematic analysis of a large series with prolonged follow-up

2013 ◽  
Vol 169 (5) ◽  
pp. 715-723 ◽  
Author(s):  
G Ntali ◽  
A Asimakopoulou ◽  
T Siamatras ◽  
J Komninos ◽  
D Vassiliadi ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Large Series ◽  
Term Outcome ◽  
Term Survival ◽  
Systematic Analysis ◽  
Long Term Outcome ◽  
Mortality Ratio

ObjectiveIn this study, we aim to assess the long-term survival and causes of death in a retrospective cohort study on patients with all aetiologies of endogenous Cushing's syndrome (CS) (except adrenal cancer), presenting to two large tertiary endocrine referral centres, and to identify variables predicting mortality.Subjects and methodsThe records of all patients presenting with endogenous CS in the Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK and the Department of Endocrinology, ‘Evangelismos’ General Hospital, Athens, Greece between 1967–2009 (Oxford series) and 1962–2009 (Athens series) were reviewed. The standardised mortality ratio (SMR) was calculated for the Oxford series.ResultsIn total, 418 subjects were identified (311 with Cushing's disease (CD), 74 with adrenal Cushing's (AC) and 33 with ectopic Cushing's (EC)). In CD, the probability of 10-year survival was 95.3% with 71.4% of the deaths attributed to cardiovascular causes or infection/sepsis. SMRs were significantly high overall (SMR 9.3; 95% CI, 6.2–13.4, P<0.001), as well as in all subgroups of patients irrespective of their remission status. In AC, the probability of 10-year survival was 95.5% and the SMR was 5.3 (95% CI, 0.3–26.0) with P=0.2. Patients with EC had the worst outcome with 77.6% probability of 5-year survival.ConclusionsIn this large series of patients with CS and long-term follow-up, we report that in CD the mortality is significantly affected, even after apparently successful treatment. The SMR of patients with AC was high, but this was not statistically significant. The implicated pathophysiological mechanisms for these findings need to be further elucidated aiming to improve the long-term outcome.

scholarly journals Persistence of myopathy in Cushing’s syndrome: evaluation of the German Cushing’s Registry

2017 ◽  
Vol 176 (6) ◽  
pp. 737-746 ◽  
Author(s):  
Christina M Berr ◽  
Mareike R Stieg ◽  
Timo Deutschbein ◽  
Marcus Quinkler ◽  
Ralf Schmidmaier ◽  
...  
Keyword(s):  
Grip Strength ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome ◽  
Hand Grip Strength ◽  
Dominant Hand ◽  
Cross Sectional ◽  
Hand Grip ◽  
Biochemical Remission

Background Cushing’s syndrome (CS) is characterized by an excessive secretion of glucocorticoids that results in a characteristic clinical phenotype. One feature of clinical hypercortisolism is breakdown of protein metabolism translating into clinical consequences including glucocorticoid-induced myopathy. While surgery is effective in control of cortisol excess, the effect of biochemical remission on muscular function is yet unclear. Methods In a cross-sectional study we analyzed 47 patients with CS during the florid phase (ActiveCS). 149 additional patients were studied 2–53 years (mean: 13 years) after surgery in biochemical long-term remission (RemissionCS). Also, 93 rule-out CS patients were used as controls (CON). All subjects were assessed for grip strength using a hand grip dynamometer and underwent the chair rising test (CRT). Results Hand grip strength (85% vs 97% of norm, P = 0.002) and the CRT performance (9.5 s vs 7.1 s, P = 0.001) were significantly lower in ActiveCS compared to the CON group. Six months after treatment grip strength further decreased in CS (P = 0.002) and CRT performance remained impaired. The RemissionCS group (mean follow-up 13 years) had reduced hand grip strength (92% compared to normal reference values for dominant hand, P < 0.001). The chair rising test performance was at 9.0 s and not significantly different from the ActiveCS group (P = 0.45). Conclusion CS affects muscle strength in the acute phase, but functional impairment remains detectable also during long-term follow-up despite biochemical remission.

scholarly journals Long-term outcome of indigenous 177Lu-DOTATATE PRRT in patients with Metastatic Advanced Neuroendocrine Tumours: a single institutional observation in a large tertiary care setting

2021 ◽  
Vol 94 (1117) ◽  
pp. 20201041
Author(s):  
Keerti Sitani ◽  
Rahul V Parghane ◽  
Sanjay Talole ◽  
Sandip Basu
Keyword(s):  
Primary Tumour ◽  
Univariate Analysis ◽  
Tertiary Care ◽  
Previous History ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Wide Range ◽  
Grade 3

Objectives: Assessment of long-term outcome and toxicity of indigenous 177Lu-DOTATATE PRRT in patients of metastatic/advanced NETs in a large tertiary-care PRRT setting. Methods: A total of 468 metastatic/advanced NET patients (wide range of primary sites including CUP-NETs), who underwent at least two cycles of 177Lu-DOTATATE PRRT with available follow-up information, were included and analysed retrospectively in this study. In-house labelling of DOTATATE with 177Lu (direct route produced) was carried out in the hospital radiopharmacy and treatment administered in cycles (dose: 5.55 to 7.4 GBq per patient), at 10–12 weeks interval. The assessment of long-term outcome was undertaken under three broad headings: (a) Therapeutic response, (b) Survival outcome and (c) Toxicity assessment. The median point estimate with 95% CI for progression free survival (PFS) and overall survival (OS) were calculated by Kaplan–Meier method. Prognostic covariates for association with PFS and OS was investigated by Cox proportional hazards model (univariate and multivariate Hazard Ratios) and with disease control rate (DCR) by Chi-square test, with significant P value defined as <0.05. Results: Long-term outcome (follow-up ranging from 4 to 97.6 months; median period:46 months following first 177Lu-DOTATATE PRRT) results showed, (i) on symptomatic response evaluation scale, complete response (CR) in 214 patients (45.7%), partial response (PR) in 108 (23.1%), stable disease (SD) in 118 (25.2%), progressive disease (PD) in 28 (6%). (ii) Biochemical response evaluation showed CR in 52 (12%), PR in 172 (40%), SD in 161 (38%), and PD in 42 patients (10%). (iii) Molecular imaging response (by PERCIST criteria) showed CR in 29 (6%), PR in 116 (25%), SD in 267 (57%) and PD in 56 (12%) patients. (iv) On RECIST 1.1 criteria, CR was observed in 14 patients (3%), PR in 126 patients (27%), SD in 282 patients (60%) and PD in 46 patients (10%). The median PFS and OS were not reached at a median follow-up of 46 months. Observed PFS and OS at 7 years were 71.1% 95% CI (62.4–79.7%) and 79.4% 95% CI (71.4–86.9%) respectively. PFS was dependent on previous history of chemotherapy, baseline 68Ga-DOTATATE and 18F-FDG uptake, site of primary tumour, total cumulative dose and number of PRRT cycles on univariate analysis, whereas multivariate analysis showed significant association for previous history of chemotherapy, baseline 68Ga-DOTATATE and 18F-FDG uptake and number of PRRT cycles. The OS was dependent on baseline 68Ga-DOTATATE uptake, site of primary tumour, presence of bony metastatic disease, total cumulative dose and number of PRRT cycles on univariate analysis, whereas multivariate analysis showed significant association for bony metastatic disease and number of PRRT cycles. Transient haematological toxicity of Grade 1, Grade 2, and Grade 3 was found in 8 (1.7%), 1 (0.2%) and one patient (0.2%), respectively. Nephrotoxicity of Grade 1, Grade 2, Grade 3, and Grade 4 were seen in 16 (3.5%), 3 (0.6%), 2 (0.4%) and one patient (0.2%), respectively. On a separate sub-analysis of 322 NET patients with progressive disease at the initiation point of PRRT, overall response rates (CR + PR + SD) were 93.5%, 88.5%, 89.1 and 87.9% on symptomatic, biochemical, RECIST 1.1 and PERCIST criteria and PFS and OS at 7 years 68.3% and 79.2%, respectively. Conclusions: The present results demonstrate that 177Lu-DOTATATE PRRT improved symptoms and biochemical markers substantially in most of the NET patients, with disease stabilisation on both anatomical and molecular imaging in majority and response in a sizeable fraction. Additionally, the therapeutic protocol with lesser dose per cycle (mean 5.92 GBq/cycle) and prolonged duration (over 5 cycles and 1.5 years) in a metastatic NET setting proved equally efficacious (with superior PFS and OS rates) and relatively better tolerated with minimal toxicity. Advances in knowledge: The present work critically examines the long-term results, survival outcome and toxicity profile of the indigenous 177Lu-DOTATATE (produced through direct neutron activation of enriched 176Lu) in metastatic progressive NETs across a wide range of primary sites and malignancies. Such long-term outcome data establishes the favourable impact of PRRT in a wide patient base and also the therapeutic efficacy of the product.

scholarly journals Long-term outcome of profound hyponatremia: a prospective 12 months follow-up study

2016 ◽  
Vol 175 (6) ◽  
pp. 499-507 ◽  
Author(s):  
Bettina Winzeler ◽  
Nica Jeanloz ◽  
Nicole Nigro ◽  
Isabelle Suter-Widmer ◽  
Philipp Schuetz ◽  
...  
Keyword(s):  
Sodium Level ◽  
Medical Condition ◽  
Tertiary Care ◽  
Drug Induced ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Mortality And Morbidity ◽  
Follow Up Study

Background Hyponatremia is the most common electrolyte abnormality in hospitalized patients and given its impact on mortality and morbidity, a relevant medical condition. Nevertheless, little is known about factors influencing long-term outcome. Methods This is a prospective observational 12-month follow-up study of patients with profound hyponatremia (≤125 mmol/L) admitted to the emergency department of two tertiary care centers between 2011 and 2013. We analyzed the predictive value of clinical and laboratory parameters regarding the following outcomes: 1-year mortality, rehospitalization and recurrent profound hyponatremia. Results Median (IQR) initial serum sodium (s-sodium) level of 281 included patients was 120 mmol/L (116–123). During the follow-up period, 58 (20.6%) patients died. The majority (56.2%) were rehospitalized at least once. Recurrent hyponatremia was observed in 42.7%, being profound in 16%. Underlying comorbidities, assessed by the Charlson Comorbidity Index, predicted 1-year mortality (odds ratio (OR) 1.43, 95% confidence interval (CI) 1.25–1.64, P < 0.001). Furthermore, ‘s-sodium level at admission’ (OR 1.14, 95% CI 1.01–1.29, P = 0.036) and ‘correction of hyponatremia’ defined as s-sodium ≥135 mmol/L at discharge were associated with mortality (OR 0.47, 95% CI 0.23–0.94, P = 0.034). Mortality rate fell with decreasing baseline s-sodium levels and was lower in the hyponatremia category ≤120 mmol/L vs >120 mmol/L (14.8% and 27.8%, P < 0.01). Patients with s-sodium level ≤120 mmol/L were more likely to have drug-induced hyponatremia, whereas hypervolemic hyponatremia was more common in patients with s-sodium >120 mmol/L. Conclusion Hyponatremia is associated with a substantial 1-year mortality, recurrence and rehospitalization rate. The positive correlation of s-sodium and mortality emphasizes the importance of the underlying disease, which determines the outcome besides hyponatremia itself.

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