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 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.

The Berkeley Girls with ADHD Longitudinal Study

2016 ◽  
Author(s):  
Elizabeth B. Owens ◽  
Christine A. Zalecki ◽  
Stephen P. Hinshaw
Keyword(s):  
Longitudinal Study ◽  
Recruitment Strategy ◽  
Term Outcome ◽  
Prospective Longitudinal Study ◽  
Long Term Outcome ◽  
Health Significance ◽  
Matched Comparison ◽  
Prospective Longitudinal ◽  
Girls With Adhd

We describe the initiation and evolution of the Berkeley Girls with ADHD Longitudinal Study, an ongoing prospective, longitudinal study of 140 girls diagnosed with ADHD when they were children during the late 1990s, as well as 88 matched comparison girls. Study rationale, design, procedures, recruitment strategy, and measures are described in detail. Primary psychosocial and neuropsychological findings during childhood, adolescence, and adulthood are summarized. Our initial findings regarding predictors of outcome are presented. Results are discussed in light of the existing literature regarding long-term outcome among children with ADHD. Overall, during childhood, adolescence, and young adulthood, in almost every psychosocial and neuropsychological domain we investigated, females with ADHD show sizable disadvantages and deficits relative to females without ADHD. Our findings affirm the public health significance of ADHD in girls, given the likelihood of persisting symptoms and (especially) impairment in crucial domains over the long-term.

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).

scholarly journals Neural systems predicting long-term outcome in dyslexia

2010 ◽  
Vol 108 (1) ◽  
pp. 361-366 ◽  
Author(s):  
Fumiko Hoeft ◽  
Bruce D. McCandliss ◽  
Jessica M. Black ◽  
Alexander Gantman ◽  
Nahal Zakerani ◽  
...  
Keyword(s):  
Reading Skills ◽  
Diffusion Tensor ◽  
Behavioral Measure ◽  
Support Vector ◽  
Behavioral Measures ◽  
Prospective Longitudinal Study ◽  
Long Term Outcome ◽  
Reading Gains ◽  
Prospective Longitudinal

Individuals with developmental dyslexia vary in their ability to improve reading skills, but the brain basis for improvement remains largely unknown. We performed a prospective, longitudinal study over 2.5 y in children with dyslexia (n = 25) or without dyslexia (n = 20) to discover whether initial behavioral or brain measures, including functional MRI (fMRI) and diffusion tensor imaging (DTI), can predict future long-term reading gains in dyslexia. No behavioral measure, including widely used and standardized reading and language tests, reliably predicted future reading gains in dyslexia. Greater right prefrontal activation during a reading task that demanded phonological awareness and right superior longitudinal fasciculus (including arcuate fasciculus) white-matter organization significantly predicted future reading gains in dyslexia. Multivariate pattern analysis (MVPA) of these two brain measures, using linear support vector machine (SVM) and cross-validation, predicted significantly above chance (72% accuracy) which particular child would or would not improve reading skills (behavioral measures were at chance). MVPA of whole-brain activation pattern during phonological processing predicted which children with dyslexia would improve reading skills 2.5 y later with >90% accuracy. These findings identify right prefrontal brain mechanisms that may be critical for reading improvement in dyslexia and that may differ from typical reading development. Brain measures that predict future behavioral outcomes (neuroprognosis) may be more accurate, in some cases, than available behavioral measures.

scholarly journals Selective Use of Bilateral Inferior Petrosal Sinus Sampling in Patients with Adrenocorticotropin-Dependent Cushing’s Syndrome Prior to Transsphenoidal Surgery

2008 ◽  
Vol 93 (12) ◽  
pp. 4624-4632 ◽  
Author(s):  
Sigrid Jehle ◽  
Jane E. Walsh ◽  
Pamela U. Freda ◽  
Kalmon D. Post
Keyword(s):  
Cushing’S Syndrome ◽  
Transsphenoidal Surgery ◽  
Remission Rate ◽  
Preoperative Evaluation ◽  
Cushing's Syndrome ◽  
Inferior Petrosal Sinus ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Inferior Petrosal Sinus Sampling

Context: Few data are available on the selective use of bilateral inferior petrosal sinus sampling (BIPSS) in the presurgical evaluation of patients with ACTH-dependent Cushing’s syndrome, so we investigated whether its use only in patients without a clear adenoma on magnetic resonance imaging and/or inconsistent biochemical testing affected remission and long-term outcome after surgery in patients with Cushing’s disease (CD). Setting: This was a retrospective review of patients treated for CD by one pituitary neurosurgeon at tertiary medical centers in New York City. Patients: A total of 193 consecutive adult patients who underwent initial transsphenoidal surgery (TS) for presumed CD between 1987 and 2005 were included. Main Outcome Measures: We examined preoperative pituitary imaging and biochemical data, results of BIPSS and surgical pathology, and outcome based on biochemical tests after initial TS and long term after subsequent therapies. Results: Remission rate after the first TS was 80.8% overall, 79.1% in the BIPSS group (n = 105), and 83.0% in the No-BIPSS group (n = 88). Recurrences occurred in 13.5% after the first TS at a mean of 4.8 ± 3.5 yr (range, 0.7–12.4 yr) with no difference between BIPSS and No-BIPSS groups. Long-term remission was achieved after surgeries and radiotherapy in 85% (86.7% of BIPSS group, 83.0% of No-BIPSS group). CD was ultimately confirmed in all but one patient in each group. Conclusions: Selective use of BIPSS in the preoperative evaluation of patients with presumed CD did not lead to misdiagnosis in the No-BIPSS group or adversely affect remission rates or long-term outcome.

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