Materiały źródłowe

• #1 Cushing Syndrome: Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/5497-cushing-syndrome

  Cushing syndrome can possibly be fatal if you dont get treatment. […] If left untreated, Cushing syndrome can also result in death. […] Your provider can and should treat Cushing syndrome. If its not treated, it can be fatal. […] Theres usually a cure for Cushing syndrome. Treatment may last for some time, even up to 18 months. […] Cushing syndrome can get worse without proper treatment. Be sure to stay in contact with your healthcare provider and report any new or worsening symptoms or any other concerns you may have. […] Generally, these will be able to cure Cushing syndrome and improve symptoms caused by hypercortisolism. […] However, theyre worth it because, with the right treatment, theres a cure for Cushing syndrome.

• #2 SciELO Brazil – A review of Cushing’s disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism A review of Cushing’s disease treatment by the Department of Neuroendocrinology of the Brazil

  https://www.scielo.br/j/aem/a/M4MndFQN6rfbzqJRkhyydvQ/?lang=en

  Cushing’s syndrome is associated with a high mortality risk. A meta-analysis has found a standardized mortality ratio (SMR) of 2.22 in patients with Cushing’s syndrome compared to the general population. The major causes of mortality in these patients are cardiovascular diseases, diabetes mellitus, and infections. The mortality rate is influenced by the disease activity. The SMR is higher in patients with persistent disease when compared to patients in clinical remission of the hypercortisolism: 5.50 vs. 1.20, respectively. […] Even after the resolution of hypercortisolism, there may not be a complete reversal of cardiovascular risk factors or, alternatively, a complete reversal may take more than 5 to 6 years to occur. […] To improve the prognosis of patients with Cushing’s syndrome and to help reverse morbidities, it is important to identify the disease and to achieve eucortisolism as soon as possible.

• #3 SciELO Brazil – A review of Cushing’s disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism A review of Cushing’s disease treatment by the Department of Neuroendocrinology of the Brazil

  https://www.scielo.br/j/aem/a/M4MndFQN6rfbzqJRkhyydvQ/?lang=en

  Cushing’s syndrome is associated with a high mortality risk. A meta-analysis has found a standardized mortality ratio (SMR) of 2.22 in patients with Cushing’s syndrome compared to the general population. The major causes of mortality in these patients are cardiovascular diseases, diabetes mellitus, and infections. The mortality rate is influenced by the disease activity. The SMR is higher in patients with persistent disease when compared to patients in clinical remission of the hypercortisolism: 5.50 vs. 1.20, respectively. […] Even after the resolution of hypercortisolism, there may not be a complete reversal of cardiovascular risk factors or, alternatively, a complete reversal may take more than 5 to 6 years to occur. […] To improve the prognosis of patients with Cushing’s syndrome and to help reverse morbidities, it is important to identify the disease and to achieve eucortisolism as soon as possible.

• #4 Determinants of Clinical Behavior and Prognosis in Cushing’s Disease: A Quest for Useful Biomarkers

  http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0034-83762022000500244

  Determinants of Clinical Behavior and Prognosis in Cushing’s Disease: A Quest for Useful Biomarkers […] Cushing’s disease (CD) is the most common cause of endogenous hypercortisolemia. The clinical management of this condition is complex and entails multiple therapeutic strategies, treatment of chronic comorbidities, and lifelong surveillance for recurrences and complications. […] The identification of robust, practical, and reliable markers of disease behavior and prognosis could potentially allow for a tailored and cost-efficient management of each patient, as well as for a reduction of the medical procedure-associated stress. […] Achieving prompt remission is, however, paramount, since untreated hypercortisolemia entails an estimated 5-year mortality of 50%. […] Chronic hypercortisolemia is detrimental and greatly impacts life expectancy. Indeed, standardized mortality ratios (SMRs) of 1.7-3.8 and of 1.6-1.9 have been estimated for patients with persistent hypercortisolemia or under remission, respectively. […] The increased mortality among CD patients is mainly due to cardiovascular complications, although infectious diseases and suicide also play a role. […] In patients under remission, increased mortality is associated with bilateral adrenalectomy and glucocorticoid replacement. […] In many cases, the cardiovascular, metabolic, and psychiatric comorbidities of CD persist even several years after remission has been achieved. […] The identification of reliable markers of disease behavior and prognosis could potentially allow for a tailored and cost-efficient management of each patient, as well as for a reduction of the medical procedure-associated stress. […] The clinical behavior of CD is highly variable and involves complex diagnostic studies, a combination of multiple therapeutic strategies, long-term management of comorbidities, and a lifelong risk for recurrence. The identification of practical, robust, and reliable markers of clinical behavior would be of great help in guiding the clinical management of these individuals.

• #5 SciELO Brazil – A review of Cushing’s disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism A review of Cushing’s disease treatment by the Department of Neuroendocrinology of the Brazil

  https://www.scielo.br/j/aem/a/M4MndFQN6rfbzqJRkhyydvQ/?lang=en

  Cushing’s syndrome is associated with a high mortality risk. A meta-analysis has found a standardized mortality ratio (SMR) of 2.22 in patients with Cushing’s syndrome compared to the general population. The major causes of mortality in these patients are cardiovascular diseases, diabetes mellitus, and infections. The mortality rate is influenced by the disease activity. The SMR is higher in patients with persistent disease when compared to patients in clinical remission of the hypercortisolism: 5.50 vs. 1.20, respectively. […] Even after the resolution of hypercortisolism, there may not be a complete reversal of cardiovascular risk factors or, alternatively, a complete reversal may take more than 5 to 6 years to occur. […] To improve the prognosis of patients with Cushing’s syndrome and to help reverse morbidities, it is important to identify the disease and to achieve eucortisolism as soon as possible.

• #6 Predictors of Mortality and Long-term Outcomes in Treated Cushing’s Disease: A Study of 346 Patients

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3590483/

  Active Cushing’s disease (CD) confers a 4-fold increase in mortality and is associated with significant morbidities. […] Although excess mortality risk may persist even after CD treatment, predictors of risk in treated CD are not well understood. […] Long-term follow-up of a large cohort of treated patients with CD identified several novel predictors of mortality. […] These data illustrate the importance of early recognition and treatment of CD. […] Mortality data were available for all subjects, with a total of 31 deaths in 346 patients (9.0%) occurring by the end of the study period (December 2011). […] Among the entire cohort, the following variables increased the risk of death: exposure time to excess GCs, estimated by duration of preoperative symptoms until postoperative remission was achieved by any means, older age at diagnosis, and preoperative plasma ACTH concentration.

• #7 Predictors of Mortality and Long-term Outcomes in Treated Cushing’s Disease: A Study of 346 Patients

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3590483/

  Active Cushing’s disease (CD) confers a 4-fold increase in mortality and is associated with significant morbidities. […] Although excess mortality risk may persist even after CD treatment, predictors of risk in treated CD are not well understood. […] Long-term follow-up of a large cohort of treated patients with CD identified several novel predictors of mortality. […] These data illustrate the importance of early recognition and treatment of CD. […] Mortality data were available for all subjects, with a total of 31 deaths in 346 patients (9.0%) occurring by the end of the study period (December 2011). […] Among the entire cohort, the following variables increased the risk of death: exposure time to excess GCs, estimated by duration of preoperative symptoms until postoperative remission was achieved by any means, older age at diagnosis, and preoperative plasma ACTH concentration.

• #8 Predictors of Mortality and Long-term Outcomes in Treated Cushing’s Disease: A Study of 346 Patients

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3590483/

  Depression at presentation increased the risk of death among patients who achieved overall and immediate remission. […] Male sex increased the risk of death in the overall remission and immediate remission cohorts. […] Overall, our study has identified several predictors of mortality in patients with treated CD, including duration of exposure to excess GCs, preoperative ACTH concentration, and older age at diagnosis. […] Depression and male gender predicted mortality among patients who achieved remission.

• #9

  https://link.springer.com/article/10.1007/s42000-019-00163-z

  Multiple hormone secretion may indicate worse prognosis in patients with ectopic Cushings syndrome […] Twenty-one patients had multiple hormone secretion, which correlated with shorter overall survival (OS), p=0.012 (HR 2.4 (95% CI 1.24.9)) […] Multiple hormone secretion should be considered as a bad prognostic sign in ECS patients and should lead to intensified clinical management […] In this comprehensive cohort of patients with ACTH-producing NENs, we identified multiple hormone secretion as the strongest indicator of worse prognosis […] Patients with multiple hormone secretion had significantly shorter OS […] Multiple hormone secretion can also be found in thoracic NENs, leading to worse prognosis compared to that of patients with ECS only […] Presence of diabetes at diagnosis also had a negative impact on OS compared to non-diabetic ECS patients (33 vs. 104 months).

• #10

  https://link.springer.com/article/10.1007/s42000-019-00163-z

  Multiple hormone secretion may indicate worse prognosis in patients with ectopic Cushings syndrome […] Twenty-one patients had multiple hormone secretion, which correlated with shorter overall survival (OS), p=0.012 (HR 2.4 (95% CI 1.24.9)) […] Multiple hormone secretion should be considered as a bad prognostic sign in ECS patients and should lead to intensified clinical management […] In this comprehensive cohort of patients with ACTH-producing NENs, we identified multiple hormone secretion as the strongest indicator of worse prognosis […] Patients with multiple hormone secretion had significantly shorter OS […] Multiple hormone secretion can also be found in thoracic NENs, leading to worse prognosis compared to that of patients with ECS only […] Presence of diabetes at diagnosis also had a negative impact on OS compared to non-diabetic ECS patients (33 vs. 104 months).

• #11 Cushing’s Syndrome – Endotext – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK279088/

  Cushings syndrome results from chronic exposure to excessive circulating levels of glucocorticoids. […] In its severe form and when untreated, the metabolic upset of Cushing’s syndrome is associated with a high mortality. However, more subtle excesses of cortisol may also have significant effects on glycemic control and blood pressure, and may therefore be an important cause of morbidity. […] The prognosis is mainly a reflection of the underlying condition. The life expectancy of patients with non-malignant causes of Cushing’s syndrome has improved dramatically with effective surgical and medical treatments. […] Even when cured by strict criteria, Cushings disease may often recur over time. […] The prognosis of the potentially malignant causes of Cushing’s syndrome is more variable. Adrenal cancer associated with Cushing’s syndrome has an extremely poor prognosis. Tumors that produce ectopic ACTH tend to have a poorer prognosis, compared with tumors from the same tissue that do not produce ACTH.

• #12 Cushing’s Syndrome – Endotext – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK279088/

  Cushings syndrome results from chronic exposure to excessive circulating levels of glucocorticoids. […] In its severe form and when untreated, the metabolic upset of Cushing’s syndrome is associated with a high mortality. However, more subtle excesses of cortisol may also have significant effects on glycemic control and blood pressure, and may therefore be an important cause of morbidity. […] The prognosis is mainly a reflection of the underlying condition. The life expectancy of patients with non-malignant causes of Cushing’s syndrome has improved dramatically with effective surgical and medical treatments. […] Even when cured by strict criteria, Cushings disease may often recur over time. […] The prognosis of the potentially malignant causes of Cushing’s syndrome is more variable. Adrenal cancer associated with Cushing’s syndrome has an extremely poor prognosis. Tumors that produce ectopic ACTH tend to have a poorer prognosis, compared with tumors from the same tissue that do not produce ACTH.

• #13

  https://link.springer.com/article/10.1007/s12020-019-02036-2

  Cushings disease (CD) is a rare endocrine condition caused by a corticotroph pituitary tumor that produces adrenocorticotropic hormone. The current state of knowledge of CD treatment is presented in this article including factors that can be helpful in predicting remission and/or recurrence of the disease. […] The primary goals in CD treatment are quick diagnosis and effective, prompt treatment as the persistent disease is associated with increased morbidity and mortality. […] The remission rate after TSS (defined as undetectable serum cortisol in the immediate postoperative period 1.8g/dL) is reported from 45 to 95%. […] The recurrence rates are reported in 6-27% children after initial remission and these results differ from the recurrence rates in adults who more often relapse 3 to 47%.

• #14 Cushing’s Syndrome – Endotext – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK279088/

  Cushings syndrome results from chronic exposure to excessive circulating levels of glucocorticoids. […] In its severe form and when untreated, the metabolic upset of Cushing’s syndrome is associated with a high mortality. However, more subtle excesses of cortisol may also have significant effects on glycemic control and blood pressure, and may therefore be an important cause of morbidity. […] The prognosis is mainly a reflection of the underlying condition. The life expectancy of patients with non-malignant causes of Cushing’s syndrome has improved dramatically with effective surgical and medical treatments. […] Even when cured by strict criteria, Cushings disease may often recur over time. […] The prognosis of the potentially malignant causes of Cushing’s syndrome is more variable. Adrenal cancer associated with Cushing’s syndrome has an extremely poor prognosis. Tumors that produce ectopic ACTH tend to have a poorer prognosis, compared with tumors from the same tissue that do not produce ACTH.

• #15

  https://link.springer.com/article/10.1007/s12020-019-02036-2

  Cushings disease (CD) is a rare endocrine condition caused by a corticotroph pituitary tumor that produces adrenocorticotropic hormone. The current state of knowledge of CD treatment is presented in this article including factors that can be helpful in predicting remission and/or recurrence of the disease. […] The primary goals in CD treatment are quick diagnosis and effective, prompt treatment as the persistent disease is associated with increased morbidity and mortality. […] The remission rate after TSS (defined as undetectable serum cortisol in the immediate postoperative period 1.8g/dL) is reported from 45 to 95%. […] The recurrence rates are reported in 6-27% children after initial remission and these results differ from the recurrence rates in adults who more often relapse 3 to 47%.

• #16 SciELO Brazil – A review of Cushing’s disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism A review of Cushing’s disease treatment by the Department of Neuroendocrinology of the Brazil

  https://www.scielo.br/j/aem/a/M4MndFQN6rfbzqJRkhyydvQ/?lang=en

  However, it is known that even undetectable levels of serum cortisol are not a guarantee of long-term remission, and an important study observed recurrence in 20% of patients at 5 years, even among those with cortisol levels 2 g/dL. […] Another important finding is that 5.6% of patients present a gradual decline in cortisol levels after the first week (late remission). […] The rates of complications derived from microsurgery and endoscopic techniques are similar.

• #17

  https://link.springer.com/article/10.1007/s12020-019-02036-2

  The analysis by Lonser et al. of 200 children with CD (mean postoperative follow-up 6.8±4.7 yrs, range 0.3-21.3) has shown the following prognostic factors of CD recurrence: dural invasion or petrosal sinus invasion, older age at the time of disease symptoms (in contrast to younger in adults), no identification of adenoma during surgery and larger tumor diameter. […] In the analysis by Devoe et al. of 42 children (mean follow-up 7.2 yrs, range 1.5-13.6) with CD recurrence of the disease was correlated with a younger age at the time of surgery. […] The study by Batista et al. (72 children, follow-up 24-120 months) has shown the following factors associated with relapse: lack of histological confirmation of an adenoma, higher post-TSS serum cortisol or ACTH levels, a higher ACTH and cortisol responses to oCRH (CRH test performed after TSS), and glucocorticoid replacement for less than 6 months after surgery. […] The options of treatment for patients who do not achieve remission after TSS are: second pituitary surgery, pituitary radiotherapy, long-term medical therapy to control hypercortisolemia and bilateral adrenalectomy.

• #18

  https://link.springer.com/article/10.1007/s12020-019-02036-2

  The analysis by Lonser et al. of 200 children with CD (mean postoperative follow-up 6.8±4.7 yrs, range 0.3-21.3) has shown the following prognostic factors of CD recurrence: dural invasion or petrosal sinus invasion, older age at the time of disease symptoms (in contrast to younger in adults), no identification of adenoma during surgery and larger tumor diameter. […] In the analysis by Devoe et al. of 42 children (mean follow-up 7.2 yrs, range 1.5-13.6) with CD recurrence of the disease was correlated with a younger age at the time of surgery. […] The study by Batista et al. (72 children, follow-up 24-120 months) has shown the following factors associated with relapse: lack of histological confirmation of an adenoma, higher post-TSS serum cortisol or ACTH levels, a higher ACTH and cortisol responses to oCRH (CRH test performed after TSS), and glucocorticoid replacement for less than 6 months after surgery. […] The options of treatment for patients who do not achieve remission after TSS are: second pituitary surgery, pituitary radiotherapy, long-term medical therapy to control hypercortisolemia and bilateral adrenalectomy.

• #19 Prognostic usefulness of ACTH in the postoperative period of Cushing’s disease in: Endocrine Connections Volume 8 Issue 9 (2019)

  https://ec.bioscientifica.com/view/journals/ec/8/9/EC-19-0297.xml

  To analyze the usefulness of plasma ACTH in predicting CD remission after surgery and to evaluate the prognostic usefulness of ACTH measurement after the cortisol and ACTH nadir (48h prior to discharge). […] We propose an ACTH value 3.3pmol/L as a good long-term prognostic marker in the postoperative period of CD. Reaching the ACTH nadir in less time is associated to a lesser recurrence rate. […] Following transsphenoidal resection, we recorded significantly lower mean ACTH nadir values in patients without disease persistence, in those with early and late remission, and in those without CD recurrence, thus reinforcing the idea that the ACTH nadir levels may play a prognostic role in the early postoperative period. […] The time to ACTH nadir is therefore also of prognostic importance.

• #20 Prognostic usefulness of ACTH in the postoperative period of Cushing’s disease in: Endocrine Connections Volume 8 Issue 9 (2019)

  https://ec.bioscientifica.com/view/journals/ec/8/9/EC-19-0297.xml

  The ANN analysis for the prediction of late remission and recurrence showed a dominant influence of the ACTH values. […] The dynamics of changes in plasma ACTH values after adenoma resection could also be of prognostic value, though the available data are limited and contradictory. […] We propose an ACTH nadir of 15pg/mL (3.3pmol/L) as a good long-term prognostic indicator in CD following transsphenoidal surgery, referred to the prevention of recurrence. This same cut-off point is also applicable to the determination of ACTH before hospital discharge the present study being the first to describe its relevance in predicting late disease remission and the absence of recurrence after transsphenoidal removal of the adenoma.

• #21 Prognostic usefulness of ACTH in the postoperative period of Cushing’s disease in: Endocrine Connections Volume 8 Issue 9 (2019)

  https://ec.bioscientifica.com/view/journals/ec/8/9/EC-19-0297.xml

  To analyze the usefulness of plasma ACTH in predicting CD remission after surgery and to evaluate the prognostic usefulness of ACTH measurement after the cortisol and ACTH nadir (48h prior to discharge). […] We propose an ACTH value 3.3pmol/L as a good long-term prognostic marker in the postoperative period of CD. Reaching the ACTH nadir in less time is associated to a lesser recurrence rate. […] Following transsphenoidal resection, we recorded significantly lower mean ACTH nadir values in patients without disease persistence, in those with early and late remission, and in those without CD recurrence, thus reinforcing the idea that the ACTH nadir levels may play a prognostic role in the early postoperative period. […] The time to ACTH nadir is therefore also of prognostic importance.

• #22 Prognostic usefulness of ACTH in the postoperative period of Cushing’s disease in: Endocrine Connections Volume 8 Issue 9 (2019)

  https://ec.bioscientifica.com/view/journals/ec/8/9/EC-19-0297.xml

  The ANN analysis for the prediction of late remission and recurrence showed a dominant influence of the ACTH values. […] The dynamics of changes in plasma ACTH values after adenoma resection could also be of prognostic value, though the available data are limited and contradictory. […] We propose an ACTH nadir of 15pg/mL (3.3pmol/L) as a good long-term prognostic indicator in CD following transsphenoidal surgery, referred to the prevention of recurrence. This same cut-off point is also applicable to the determination of ACTH before hospital discharge the present study being the first to describe its relevance in predicting late disease remission and the absence of recurrence after transsphenoidal removal of the adenoma.

• #23 Determinants of Clinical Behavior and Prognosis in Cushing’s Disease: A Quest for Useful Biomarkers

  http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0034-83762022000500244

  Determinants of Clinical Behavior and Prognosis in Cushing’s Disease: A Quest for Useful Biomarkers […] Cushing’s disease (CD) is the most common cause of endogenous hypercortisolemia. The clinical management of this condition is complex and entails multiple therapeutic strategies, treatment of chronic comorbidities, and lifelong surveillance for recurrences and complications. […] The identification of robust, practical, and reliable markers of disease behavior and prognosis could potentially allow for a tailored and cost-efficient management of each patient, as well as for a reduction of the medical procedure-associated stress. […] Achieving prompt remission is, however, paramount, since untreated hypercortisolemia entails an estimated 5-year mortality of 50%. […] Chronic hypercortisolemia is detrimental and greatly impacts life expectancy. Indeed, standardized mortality ratios (SMRs) of 1.7-3.8 and of 1.6-1.9 have been estimated for patients with persistent hypercortisolemia or under remission, respectively. […] The increased mortality among CD patients is mainly due to cardiovascular complications, although infectious diseases and suicide also play a role. […] In patients under remission, increased mortality is associated with bilateral adrenalectomy and glucocorticoid replacement. […] In many cases, the cardiovascular, metabolic, and psychiatric comorbidities of CD persist even several years after remission has been achieved. […] The identification of reliable markers of disease behavior and prognosis could potentially allow for a tailored and cost-efficient management of each patient, as well as for a reduction of the medical procedure-associated stress. […] The clinical behavior of CD is highly variable and involves complex diagnostic studies, a combination of multiple therapeutic strategies, long-term management of comorbidities, and a lifelong risk for recurrence. The identification of practical, robust, and reliable markers of clinical behavior would be of great help in guiding the clinical management of these individuals.

• #24 Long-term outcome in patients after treatment for Cushing’s disease in childhood | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226033

  At the latest FU: 18 patients (62%) had long-term disease remission after TSS1, 2 patients (6.9%) after TSS2, 1 patient (3.4%) after the post-TSS radiotherapy (XRT) cycle and 3 patients (10.3%) after bilateral adrenalectomy (BA). […] CD recurrence can occur even after a long time post effective treatment. […] Long-term observation of patients after CD treatment in childhood indicates the presence of a large number of patients with hormonal pituitary deficits, as well as a significant problem of mood and cognitive disorders that may be the result of hypercortisolemia in the past.

• #25 Cushing’s disease: pathobiology, diagnosis, and management in: Journal of Neurosurgery Volume 126 Issue 2 (2017) Journals

  https://thejns.org/view/journals/j-neurosurg/126/2/article-p404.xml

  While many studies indicate that CD-associated mortality is returned to general population rates after biochemical remission, other studies have shown an elevated cardiovascular risk of death up to 5 years after successful biochemical remission. […] Patients with persistent CD after treatment suffer increased morbidity and mortality.

• #26 Cushing’s disease: pathobiology, diagnosis, and management in: Journal of Neurosurgery Volume 126 Issue 2 (2017) Journals

  https://thejns.org/view/journals/j-neurosurg/126/2/article-p404.xml

  While many studies indicate that CD-associated mortality is returned to general population rates after biochemical remission, other studies have shown an elevated cardiovascular risk of death up to 5 years after successful biochemical remission. […] Patients with persistent CD after treatment suffer increased morbidity and mortality.

• #27 Determinants of Clinical Behavior and Prognosis in Cushing’s Disease: A Quest for Useful Biomarkers

  http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0034-83762022000500244

  Determinants of Clinical Behavior and Prognosis in Cushing’s Disease: A Quest for Useful Biomarkers […] Cushing’s disease (CD) is the most common cause of endogenous hypercortisolemia. The clinical management of this condition is complex and entails multiple therapeutic strategies, treatment of chronic comorbidities, and lifelong surveillance for recurrences and complications. […] The identification of robust, practical, and reliable markers of disease behavior and prognosis could potentially allow for a tailored and cost-efficient management of each patient, as well as for a reduction of the medical procedure-associated stress. […] Achieving prompt remission is, however, paramount, since untreated hypercortisolemia entails an estimated 5-year mortality of 50%. […] Chronic hypercortisolemia is detrimental and greatly impacts life expectancy. Indeed, standardized mortality ratios (SMRs) of 1.7-3.8 and of 1.6-1.9 have been estimated for patients with persistent hypercortisolemia or under remission, respectively. […] The increased mortality among CD patients is mainly due to cardiovascular complications, although infectious diseases and suicide also play a role. […] In patients under remission, increased mortality is associated with bilateral adrenalectomy and glucocorticoid replacement. […] In many cases, the cardiovascular, metabolic, and psychiatric comorbidities of CD persist even several years after remission has been achieved. […] The identification of reliable markers of disease behavior and prognosis could potentially allow for a tailored and cost-efficient management of each patient, as well as for a reduction of the medical procedure-associated stress. […] The clinical behavior of CD is highly variable and involves complex diagnostic studies, a combination of multiple therapeutic strategies, long-term management of comorbidities, and a lifelong risk for recurrence. The identification of practical, robust, and reliable markers of clinical behavior would be of great help in guiding the clinical management of these individuals.

• #28 Determinants of Clinical Behavior and Prognosis in Cushing’s Disease: A Quest for Useful Biomarkers

  http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0034-83762022000500244

  Determinants of Clinical Behavior and Prognosis in Cushing’s Disease: A Quest for Useful Biomarkers […] Cushing’s disease (CD) is the most common cause of endogenous hypercortisolemia. The clinical management of this condition is complex and entails multiple therapeutic strategies, treatment of chronic comorbidities, and lifelong surveillance for recurrences and complications. […] The identification of robust, practical, and reliable markers of disease behavior and prognosis could potentially allow for a tailored and cost-efficient management of each patient, as well as for a reduction of the medical procedure-associated stress. […] Achieving prompt remission is, however, paramount, since untreated hypercortisolemia entails an estimated 5-year mortality of 50%. […] Chronic hypercortisolemia is detrimental and greatly impacts life expectancy. Indeed, standardized mortality ratios (SMRs) of 1.7-3.8 and of 1.6-1.9 have been estimated for patients with persistent hypercortisolemia or under remission, respectively. […] The increased mortality among CD patients is mainly due to cardiovascular complications, although infectious diseases and suicide also play a role. […] In patients under remission, increased mortality is associated with bilateral adrenalectomy and glucocorticoid replacement. […] In many cases, the cardiovascular, metabolic, and psychiatric comorbidities of CD persist even several years after remission has been achieved. […] The identification of reliable markers of disease behavior and prognosis could potentially allow for a tailored and cost-efficient management of each patient, as well as for a reduction of the medical procedure-associated stress. […] The clinical behavior of CD is highly variable and involves complex diagnostic studies, a combination of multiple therapeutic strategies, long-term management of comorbidities, and a lifelong risk for recurrence. The identification of practical, robust, and reliable markers of clinical behavior would be of great help in guiding the clinical management of these individuals.

• #29 SciELO Brazil – A review of Cushing’s disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism A review of Cushing’s disease treatment by the Department of Neuroendocrinology of the Brazil

  https://www.scielo.br/j/aem/a/M4MndFQN6rfbzqJRkhyydvQ/?lang=en

  Cushing’s syndrome is associated with a high mortality risk. A meta-analysis has found a standardized mortality ratio (SMR) of 2.22 in patients with Cushing’s syndrome compared to the general population. The major causes of mortality in these patients are cardiovascular diseases, diabetes mellitus, and infections. The mortality rate is influenced by the disease activity. The SMR is higher in patients with persistent disease when compared to patients in clinical remission of the hypercortisolism: 5.50 vs. 1.20, respectively. […] Even after the resolution of hypercortisolism, there may not be a complete reversal of cardiovascular risk factors or, alternatively, a complete reversal may take more than 5 to 6 years to occur. […] To improve the prognosis of patients with Cushing’s syndrome and to help reverse morbidities, it is important to identify the disease and to achieve eucortisolism as soon as possible.

• #30 Cushing’s disease: pathobiology, diagnosis, and management in: Journal of Neurosurgery Volume 126 Issue 2 (2017) Journals

  https://thejns.org/view/journals/j-neurosurg/126/2/article-p404.xml

  Cushing’s syndrome (CS) is caused by prolonged supraphysiological levels of circulating cortisol. […] If not effectively treated, CD is associated with hypertension, diabetes, obesity, osteoporosis, vascular disease, and shortened life span. […] Successful resection of a CD-associated ACTH-secreting pituitary adenoma results in immediate biochemical remission and preservation of pituitary function. […] Early identification of CD by clinical findings, endocrinological evaluation, and imaging studies is critical for diagnosis and effective surgical management. […] CD-associated morbidity includes cardiac and cerebrovascular events, immunosuppression, osteoporosis, psychiatric disturbances, and diabetes. […] Untreated CD has an estimated standardized mortality ratio (ratio of observed CD-related deaths to expected deaths in the general population) of 1.94.8.

• #31 SciELO Brazil – A review of Cushing’s disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism A review of Cushing’s disease treatment by the Department of Neuroendocrinology of the Brazil

  https://www.scielo.br/j/aem/a/M4MndFQN6rfbzqJRkhyydvQ/?lang=en

  Cushing’s syndrome is associated with a high mortality risk. A meta-analysis has found a standardized mortality ratio (SMR) of 2.22 in patients with Cushing’s syndrome compared to the general population. The major causes of mortality in these patients are cardiovascular diseases, diabetes mellitus, and infections. The mortality rate is influenced by the disease activity. The SMR is higher in patients with persistent disease when compared to patients in clinical remission of the hypercortisolism: 5.50 vs. 1.20, respectively. […] Even after the resolution of hypercortisolism, there may not be a complete reversal of cardiovascular risk factors or, alternatively, a complete reversal may take more than 5 to 6 years to occur. […] To improve the prognosis of patients with Cushing’s syndrome and to help reverse morbidities, it is important to identify the disease and to achieve eucortisolism as soon as possible.

• #32 Cushing’s disease: pathobiology, diagnosis, and management in: Journal of Neurosurgery Volume 126 Issue 2 (2017) Journals

  https://thejns.org/view/journals/j-neurosurg/126/2/article-p404.xml

  Cushing’s syndrome (CS) is caused by prolonged supraphysiological levels of circulating cortisol. […] If not effectively treated, CD is associated with hypertension, diabetes, obesity, osteoporosis, vascular disease, and shortened life span. […] Successful resection of a CD-associated ACTH-secreting pituitary adenoma results in immediate biochemical remission and preservation of pituitary function. […] Early identification of CD by clinical findings, endocrinological evaluation, and imaging studies is critical for diagnosis and effective surgical management. […] CD-associated morbidity includes cardiac and cerebrovascular events, immunosuppression, osteoporosis, psychiatric disturbances, and diabetes. […] Untreated CD has an estimated standardized mortality ratio (ratio of observed CD-related deaths to expected deaths in the general population) of 1.94.8.

• #33 Machine-learning based prediction of Cushing’s syndrome in dogs attending UK primary-care veterinary practice | Scientific Reports

  https://www.nature.com/articles/s41598-021-88440-z

  Cushings syndrome is an endocrine disease in dogs that negatively impacts upon the quality-of-life of affected animals. […] The findings of our study indicate that machine-learning methods could predict the future diagnosis of a practicing veterinarian. […] Obtaining a correct and timely diagnosis of Cushings syndrome is crucial for early commencement of appropriate treatment to improve the quality-of-life of affected dogs. […] The good performance of these models suggests that discrimination of dogs with and without Cushings syndrome can be correctly determined at the point of first suspicion based on these factors. […] The LASSO penalised regression model was the best performing model when applied to a held-out test dataset. […] The findings indicate machine-learning aided diagnosis could predict the diagnosis of a practising veterinarian and that utilising machine-learning methods as decision support tools, may contribute to improved diagnosis in Cushings syndrome in dogs.

• #34

  https://link.springer.com/article/10.1007/s12020-019-02036-2

  Cushings disease (CD) is a rare endocrine condition caused by a corticotroph pituitary tumor that produces adrenocorticotropic hormone. The current state of knowledge of CD treatment is presented in this article including factors that can be helpful in predicting remission and/or recurrence of the disease. […] The primary goals in CD treatment are quick diagnosis and effective, prompt treatment as the persistent disease is associated with increased morbidity and mortality. […] The remission rate after TSS (defined as undetectable serum cortisol in the immediate postoperative period 1.8g/dL) is reported from 45 to 95%. […] The recurrence rates are reported in 6-27% children after initial remission and these results differ from the recurrence rates in adults who more often relapse 3 to 47%.

• #35 Predictors of Mortality and Long-term Outcomes in Treated Cushing’s Disease: A Study of 346 Patients

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3590483/

  Active Cushing’s disease (CD) confers a 4-fold increase in mortality and is associated with significant morbidities. […] Although excess mortality risk may persist even after CD treatment, predictors of risk in treated CD are not well understood. […] Long-term follow-up of a large cohort of treated patients with CD identified several novel predictors of mortality. […] These data illustrate the importance of early recognition and treatment of CD. […] Mortality data were available for all subjects, with a total of 31 deaths in 346 patients (9.0%) occurring by the end of the study period (December 2011). […] Among the entire cohort, the following variables increased the risk of death: exposure time to excess GCs, estimated by duration of preoperative symptoms until postoperative remission was achieved by any means, older age at diagnosis, and preoperative plasma ACTH concentration.

• #36 Determinants of Clinical Behavior and Prognosis in Cushing’s Disease: A Quest for Useful Biomarkers

  http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0034-83762022000500244

  Determinants of Clinical Behavior and Prognosis in Cushing’s Disease: A Quest for Useful Biomarkers […] Cushing’s disease (CD) is the most common cause of endogenous hypercortisolemia. The clinical management of this condition is complex and entails multiple therapeutic strategies, treatment of chronic comorbidities, and lifelong surveillance for recurrences and complications. […] The identification of robust, practical, and reliable markers of disease behavior and prognosis could potentially allow for a tailored and cost-efficient management of each patient, as well as for a reduction of the medical procedure-associated stress. […] Achieving prompt remission is, however, paramount, since untreated hypercortisolemia entails an estimated 5-year mortality of 50%. […] Chronic hypercortisolemia is detrimental and greatly impacts life expectancy. Indeed, standardized mortality ratios (SMRs) of 1.7-3.8 and of 1.6-1.9 have been estimated for patients with persistent hypercortisolemia or under remission, respectively. […] The increased mortality among CD patients is mainly due to cardiovascular complications, although infectious diseases and suicide also play a role. […] In patients under remission, increased mortality is associated with bilateral adrenalectomy and glucocorticoid replacement. […] In many cases, the cardiovascular, metabolic, and psychiatric comorbidities of CD persist even several years after remission has been achieved. […] The identification of reliable markers of disease behavior and prognosis could potentially allow for a tailored and cost-efficient management of each patient, as well as for a reduction of the medical procedure-associated stress. […] The clinical behavior of CD is highly variable and involves complex diagnostic studies, a combination of multiple therapeutic strategies, long-term management of comorbidities, and a lifelong risk for recurrence. The identification of practical, robust, and reliable markers of clinical behavior would be of great help in guiding the clinical management of these individuals.

• #37

  https://link.springer.com/article/10.1007/s12020-019-02036-2

  The analysis by Lonser et al. of 200 children with CD (mean postoperative follow-up 6.8±4.7 yrs, range 0.3-21.3) has shown the following prognostic factors of CD recurrence: dural invasion or petrosal sinus invasion, older age at the time of disease symptoms (in contrast to younger in adults), no identification of adenoma during surgery and larger tumor diameter. […] In the analysis by Devoe et al. of 42 children (mean follow-up 7.2 yrs, range 1.5-13.6) with CD recurrence of the disease was correlated with a younger age at the time of surgery. […] The study by Batista et al. (72 children, follow-up 24-120 months) has shown the following factors associated with relapse: lack of histological confirmation of an adenoma, higher post-TSS serum cortisol or ACTH levels, a higher ACTH and cortisol responses to oCRH (CRH test performed after TSS), and glucocorticoid replacement for less than 6 months after surgery. […] The options of treatment for patients who do not achieve remission after TSS are: second pituitary surgery, pituitary radiotherapy, long-term medical therapy to control hypercortisolemia and bilateral adrenalectomy.

• #38 SciELO Brazil – A review of Cushing’s disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism A review of Cushing’s disease treatment by the Department of Neuroendocrinology of the Brazil

  https://www.scielo.br/j/aem/a/M4MndFQN6rfbzqJRkhyydvQ/?lang=en

  The remission rate is lower than observed for the first surgery, ranging from 40% to 70%, a rate that is similar to that obtained with current medical treatment. […] The remission rate in patients submitted to BIPSS is also lower than that observed in visible microadenomas on MRI and ranges from 50% to 70%. […] Other predictive factors of a better surgical outcome include absence of invasion of the duramater or cavernous sinuses, histological confirmation of adrenocorticotropic hormone-positive adenoma, low serum cortisol levels during the postoperative period, and prolonged secondary adrenal insufficiency. […] A very important factor for the analysis of serum cortisol levels in the postoperative period is glucocorticoid replacement therapy. […] The most studied and utilized laboratory parameter is serum cortisol.

• #39 SciELO Brazil – A review of Cushing’s disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism A review of Cushing’s disease treatment by the Department of Neuroendocrinology of the Brazil

  https://www.scielo.br/j/aem/a/M4MndFQN6rfbzqJRkhyydvQ/?lang=en

  The remission rate is lower than observed for the first surgery, ranging from 40% to 70%, a rate that is similar to that obtained with current medical treatment. […] The remission rate in patients submitted to BIPSS is also lower than that observed in visible microadenomas on MRI and ranges from 50% to 70%. […] Other predictive factors of a better surgical outcome include absence of invasion of the duramater or cavernous sinuses, histological confirmation of adrenocorticotropic hormone-positive adenoma, low serum cortisol levels during the postoperative period, and prolonged secondary adrenal insufficiency. […] A very important factor for the analysis of serum cortisol levels in the postoperative period is glucocorticoid replacement therapy. […] The most studied and utilized laboratory parameter is serum cortisol.

• #40 SciELO Brazil – A review of Cushing’s disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism A review of Cushing’s disease treatment by the Department of Neuroendocrinology of the Brazil

  https://www.scielo.br/j/aem/a/M4MndFQN6rfbzqJRkhyydvQ/?lang=en

  The remission rate is lower than observed for the first surgery, ranging from 40% to 70%, a rate that is similar to that obtained with current medical treatment. […] The remission rate in patients submitted to BIPSS is also lower than that observed in visible microadenomas on MRI and ranges from 50% to 70%. […] Other predictive factors of a better surgical outcome include absence of invasion of the duramater or cavernous sinuses, histological confirmation of adrenocorticotropic hormone-positive adenoma, low serum cortisol levels during the postoperative period, and prolonged secondary adrenal insufficiency. […] A very important factor for the analysis of serum cortisol levels in the postoperative period is glucocorticoid replacement therapy. […] The most studied and utilized laboratory parameter is serum cortisol.

• #41 Determinants of Clinical Behavior and Prognosis in Cushing’s Disease: A Quest for Useful Biomarkers

  http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0034-83762022000500244

  Determinants of Clinical Behavior and Prognosis in Cushing’s Disease: A Quest for Useful Biomarkers […] Cushing’s disease (CD) is the most common cause of endogenous hypercortisolemia. The clinical management of this condition is complex and entails multiple therapeutic strategies, treatment of chronic comorbidities, and lifelong surveillance for recurrences and complications. […] The identification of robust, practical, and reliable markers of disease behavior and prognosis could potentially allow for a tailored and cost-efficient management of each patient, as well as for a reduction of the medical procedure-associated stress. […] Achieving prompt remission is, however, paramount, since untreated hypercortisolemia entails an estimated 5-year mortality of 50%. […] Chronic hypercortisolemia is detrimental and greatly impacts life expectancy. Indeed, standardized mortality ratios (SMRs) of 1.7-3.8 and of 1.6-1.9 have been estimated for patients with persistent hypercortisolemia or under remission, respectively. […] The increased mortality among CD patients is mainly due to cardiovascular complications, although infectious diseases and suicide also play a role. […] In patients under remission, increased mortality is associated with bilateral adrenalectomy and glucocorticoid replacement. […] In many cases, the cardiovascular, metabolic, and psychiatric comorbidities of CD persist even several years after remission has been achieved. […] The identification of reliable markers of disease behavior and prognosis could potentially allow for a tailored and cost-efficient management of each patient, as well as for a reduction of the medical procedure-associated stress. […] The clinical behavior of CD is highly variable and involves complex diagnostic studies, a combination of multiple therapeutic strategies, long-term management of comorbidities, and a lifelong risk for recurrence. The identification of practical, robust, and reliable markers of clinical behavior would be of great help in guiding the clinical management of these individuals.

• #42 Machine-learning based prediction of Cushing’s syndrome in dogs attending UK primary-care veterinary practice | Scientific Reports

  https://www.nature.com/articles/s41598-021-88440-z

  Cushings syndrome is an endocrine disease in dogs that negatively impacts upon the quality-of-life of affected animals. […] The findings of our study indicate that machine-learning methods could predict the future diagnosis of a practicing veterinarian. […] Obtaining a correct and timely diagnosis of Cushings syndrome is crucial for early commencement of appropriate treatment to improve the quality-of-life of affected dogs. […] The good performance of these models suggests that discrimination of dogs with and without Cushings syndrome can be correctly determined at the point of first suspicion based on these factors. […] The LASSO penalised regression model was the best performing model when applied to a held-out test dataset. […] The findings indicate machine-learning aided diagnosis could predict the diagnosis of a practising veterinarian and that utilising machine-learning methods as decision support tools, may contribute to improved diagnosis in Cushings syndrome in dogs.

• #43 Machine-learning based prediction of Cushing’s syndrome in dogs attending UK primary-care veterinary practice | Scientific Reports

  https://www.nature.com/articles/s41598-021-88440-z

  Cushings syndrome is an endocrine disease in dogs that negatively impacts upon the quality-of-life of affected animals. […] The findings of our study indicate that machine-learning methods could predict the future diagnosis of a practicing veterinarian. […] Obtaining a correct and timely diagnosis of Cushings syndrome is crucial for early commencement of appropriate treatment to improve the quality-of-life of affected dogs. […] The good performance of these models suggests that discrimination of dogs with and without Cushings syndrome can be correctly determined at the point of first suspicion based on these factors. […] The LASSO penalised regression model was the best performing model when applied to a held-out test dataset. […] The findings indicate machine-learning aided diagnosis could predict the diagnosis of a practising veterinarian and that utilising machine-learning methods as decision support tools, may contribute to improved diagnosis in Cushings syndrome in dogs.

• #44 Machine-learning based prediction of Cushing’s syndrome in dogs attending UK primary-care veterinary practice | Scientific Reports

  https://www.nature.com/articles/s41598-021-88440-z

  Cushings syndrome is an endocrine disease in dogs that negatively impacts upon the quality-of-life of affected animals. […] The findings of our study indicate that machine-learning methods could predict the future diagnosis of a practicing veterinarian. […] Obtaining a correct and timely diagnosis of Cushings syndrome is crucial for early commencement of appropriate treatment to improve the quality-of-life of affected dogs. […] The good performance of these models suggests that discrimination of dogs with and without Cushings syndrome can be correctly determined at the point of first suspicion based on these factors. […] The LASSO penalised regression model was the best performing model when applied to a held-out test dataset. […] The findings indicate machine-learning aided diagnosis could predict the diagnosis of a practising veterinarian and that utilising machine-learning methods as decision support tools, may contribute to improved diagnosis in Cushings syndrome in dogs.

• #45 Machine-learning based prediction of Cushing’s syndrome in dogs attending UK primary-care veterinary practice | Scientific Reports

  https://www.nature.com/articles/s41598-021-88440-z

  Cushings syndrome is an endocrine disease in dogs that negatively impacts upon the quality-of-life of affected animals. […] The findings of our study indicate that machine-learning methods could predict the future diagnosis of a practicing veterinarian. […] Obtaining a correct and timely diagnosis of Cushings syndrome is crucial for early commencement of appropriate treatment to improve the quality-of-life of affected dogs. […] The good performance of these models suggests that discrimination of dogs with and without Cushings syndrome can be correctly determined at the point of first suspicion based on these factors. […] The LASSO penalised regression model was the best performing model when applied to a held-out test dataset. […] The findings indicate machine-learning aided diagnosis could predict the diagnosis of a practising veterinarian and that utilising machine-learning methods as decision support tools, may contribute to improved diagnosis in Cushings syndrome in dogs.

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