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Cushing syndrome (Cushing syndrome, CS) is hypercortisolemia caused by various causes that act on target organs and cause central obesity, hypertension, abnormal glucose metabolism, hypokalemia, and osteoporosis.
It is a typical syndrome.
The most common causes are Cushing's disease (CD) and ectopic ACTH syndrome (EAS), both of which are ACTH-dependent Cushing syndrome.
The effective differentiation of the two is of great clinical significance
.
According to European data, the annual incidence of CS is 2-3 per 1 million people, and the prevalence is about 0.
4 per 10,000 people
.
On September 11, 2021, the "Research Report on the Definition of Rare Diseases in China 2021" was released in Shanghai.
The report proposed for the first time the "Chinese Rare Diseases 2021 Definition", that is, "the incidence of neonates should be less than 1/10,000, and the prevalence Diseases with less than 1/10,000 and less than 140,000 patients" are listed as rare diseases
.
There is a lack of large-scale epidemiological data of CS in China.
If calculated according to the above-mentioned foreign data and compared with China's new definition of rare diseases, CS belongs to the category of rare diseases
.
The mortality rate of CS patients is four times higher than that of the normal population.
Because the most important and common complications are hypertension, diabetes, osteoporosis and metabolic syndrome, it increases the risk of cardiovascular disease and leads to Cushing’s syndrome.
Most of the deaths of patients with symptoms are due to cardiovascular and cerebrovascular events, venous thrombosis, and severe infections
.
In 1952, before effective treatment, the median survival time of CS patients was only 4.
6 years
.
However, when hypercortisolemia is relieved, the standardized mortality rate (SMR) is equivalent to that of the age-matched general population.
If patients with persistent moderate hypercortisolism still exist after treatment, SMR will increase compared with the general population.
3.
8-5 times
.
This means that once CS is identified and effectively treated in time, it can reduce the mortality rate by 80%, which is of great significance
.
Yesterday, a newly diagnosed case of ACTH-dependent Cushing syndrome was discharged from the hospital (full case information will be described in a follow-up public account article).
Although Cushing’s disease is highly suspected, the pituitary and chest imaging reports are negative, and the pituitary-enhanced MR is only Appearing to see the illusory "microadenoma" of about 2mm-after all, up to 40% of Cushing's disease patients have occult ACTH microadenoma, which may not be found even on pituitary MR performed at an experienced center
.
Therefore, the following can only rely on the "gold standard"-bilateral inferior petrosal venous sinus blood sampling (BIPSS) to further distinguish Cushing's disease from ectopic ACTH syndrome (EAS).
Because our hospital cannot carry out this procedure, we are referred for follow-up
.
The high-dose dexamethasone suppression test (HDDST) is a preliminary method recommended in China’s guidelines to distinguish Cushing’s disease from EAS, but due to its insufficient sensitivity/specificity and high potential risks (blood sugar, blood pressure, electrolytes, infection, thrombosis) ), prolonged hospital stay and medical expenses, large impact on the HPA axis and subsequent BIPSS examinations, and whether the cut-off point should be changed after HDDST and low-dose dexamethasone suppression test (LDDST) should be changed after the series connection, etc.
, make clinicians big heads
.
If HDDST is not needed, and Cushing’s disease can be distinguished from EAS only by the results of LDDST, then most of the above-mentioned concerns can be avoided and the problem can be solved at a much smaller price
.
On October 15-17, 2021, the 13th "Concord Clinical Endocrinology and Metabolism Forum" will be held in Beijing.
Professor Chen Shi from Peking Union Medical College Hospital will give a topic: Is the high-dose dexamethasone suppression test necessary? -New understanding based on clinical data
.
Starting from the origin of the dexamethasone suppression test (1960), he introduced the origin of the high-dose dexamethasone suppression test (HDDST) used in the identification of Cushing’s syndrome.
There are many problems in the current clinical practice of HDDST.
The correlation between the results of the Dexamethasone Suppression Test (LDDST) and HDDST, and then a study involving 298 patients with Cushing’s syndrome was used to explore whether LDDST could replace HDDST in the differential diagnosis of Cushing’s syndrome and give a better diagnosis The cut point optimizes the diagnosis path of Cushing’s syndrome.
Finally, it is concluded that HDDST is not sensitive and specific for distinguishing Cushing’s disease from EAS, and the optimal inhibition value is not 50%.
It is useful for distinguishing Cushing’s disease from EAS.
, LDDST’s diagnostic efficacy is better than HDDST, and the new process of using LDDST to replace HDDST in series with BIPSS is more convenient, safer, time-saving and money-saving
.
Small and high-dose dexamethasone inhibition test in our department Note: In this case, the inhibition rate of F and 24hUFC in LDDST is> 54%, and the inhibition rate of F in HDDST is> 82%.
According to previous research data, she has more than 80%-93.
1% The probability of Cushing’s disease is Cushing’s disease, while the probability of EAS is small, but the result of BIPSS is needed in the end
.
The basic principle of HDDST is that pituitary ACTH adenoma cells in Cushing’s disease remain partially sensitive to glucocorticoids, while neuroendocrine tumors (NETs) that cause EAS are completely resistant to exogenous glucocorticoid inhibition.
Various thresholds have been proposed in the literature.
, The percentage of urine or serum cortisol inhibition varies from 50% to 90%
.
However, some studies have shown that there is almost complete overlap between the responses of some EAS and ACTH adenomas, and insist that it is impossible to find a discrimination threshold, especially in well-differentiated neuroendocrine tumors
.
This lack of specificity may be due to the expression of glucocorticoid receptors in well-differentiated, usually hidden NETs
.
Some authors believe that the diagnostic performance of HDDST for Cushing’s disease is not better than that of LDDST.
Other authors believe that the combination of HDDST and CRH test is valuable.
In some studies, the combination of the two tests is better than the correct diagnosis of CRH test alone.
The rate is lower
.
Therefore, HDDST is controversial and even considered outdated by some experts
.
It is precisely because of its lack of sensitivity, specificity and many other shortcomings mentioned above, especially with the advancement and popularization of biochemical detection technology, BIPSS, and functional imaging technology, HDDST has disappeared in the diagnosis and treatment path of the new Cushing syndrome related guidelines.
No, it's like the prone position test disappears
.
Differential diagnosis of Cushing syndrome Note: Each branch point is associated with a test that will determine what the doctor will do next
.
No tests should be omitted from the evaluation, and no tests should be added to the evaluation
.
——Loriaux D Lynn,Diagnosis and Differential Diagnosis of Cushing's Syndrome.
[J] .
N Engl J Med, 2017, 376: 1451-1459.
Cushing syndrome diagnosis process Note: ACTH, corticotropin; CBG, corticosteroid Binding globulin; CRH, corticotropin releasing hormone; DST, dexamethasone suppression test; IPSS, infra petrosal sinus sampling; UFC, urinary free cortisol
.
*It is agreed that all lesions with a diameter of less than 6 mm should be examined by IPSS, and lesions with a diameter of ≥10 mm do not require an IPSS examination, but there are different opinions from experts on lesions with a diameter of 6 to 9 mm
.
†There is no clear consensus on this alternative, and further research is needed, which is indicated by the darker box
.
Green boxes indicate points to consider; darker colors indicate test paths with less verification
.
——Fleseriu Maria, Auchus Richard, Bancos Irina et al.
Consensus on diagnosis and management of Cushing's disease: a guideline update.
[J] .
Lancet Diabetes Endocrinol, 2021, undefined: undefined.
Is a high-dose dexamethasone suppression test necessary? New understanding based on clinical data Professor Chen Shi, Chinese Academy of Medical Sciences Peking Union Medical College Hospital Source: Endocrine regulator
It is a typical syndrome.
The most common causes are Cushing's disease (CD) and ectopic ACTH syndrome (EAS), both of which are ACTH-dependent Cushing syndrome.
The effective differentiation of the two is of great clinical significance
.
According to European data, the annual incidence of CS is 2-3 per 1 million people, and the prevalence is about 0.
4 per 10,000 people
.
On September 11, 2021, the "Research Report on the Definition of Rare Diseases in China 2021" was released in Shanghai.
The report proposed for the first time the "Chinese Rare Diseases 2021 Definition", that is, "the incidence of neonates should be less than 1/10,000, and the prevalence Diseases with less than 1/10,000 and less than 140,000 patients" are listed as rare diseases
.
There is a lack of large-scale epidemiological data of CS in China.
If calculated according to the above-mentioned foreign data and compared with China's new definition of rare diseases, CS belongs to the category of rare diseases
.
The mortality rate of CS patients is four times higher than that of the normal population.
Because the most important and common complications are hypertension, diabetes, osteoporosis and metabolic syndrome, it increases the risk of cardiovascular disease and leads to Cushing’s syndrome.
Most of the deaths of patients with symptoms are due to cardiovascular and cerebrovascular events, venous thrombosis, and severe infections
.
In 1952, before effective treatment, the median survival time of CS patients was only 4.
6 years
.
However, when hypercortisolemia is relieved, the standardized mortality rate (SMR) is equivalent to that of the age-matched general population.
If patients with persistent moderate hypercortisolism still exist after treatment, SMR will increase compared with the general population.
3.
8-5 times
.
This means that once CS is identified and effectively treated in time, it can reduce the mortality rate by 80%, which is of great significance
.
Yesterday, a newly diagnosed case of ACTH-dependent Cushing syndrome was discharged from the hospital (full case information will be described in a follow-up public account article).
Although Cushing’s disease is highly suspected, the pituitary and chest imaging reports are negative, and the pituitary-enhanced MR is only Appearing to see the illusory "microadenoma" of about 2mm-after all, up to 40% of Cushing's disease patients have occult ACTH microadenoma, which may not be found even on pituitary MR performed at an experienced center
.
Therefore, the following can only rely on the "gold standard"-bilateral inferior petrosal venous sinus blood sampling (BIPSS) to further distinguish Cushing's disease from ectopic ACTH syndrome (EAS).
Because our hospital cannot carry out this procedure, we are referred for follow-up
.
The high-dose dexamethasone suppression test (HDDST) is a preliminary method recommended in China’s guidelines to distinguish Cushing’s disease from EAS, but due to its insufficient sensitivity/specificity and high potential risks (blood sugar, blood pressure, electrolytes, infection, thrombosis) ), prolonged hospital stay and medical expenses, large impact on the HPA axis and subsequent BIPSS examinations, and whether the cut-off point should be changed after HDDST and low-dose dexamethasone suppression test (LDDST) should be changed after the series connection, etc.
, make clinicians big heads
.
If HDDST is not needed, and Cushing’s disease can be distinguished from EAS only by the results of LDDST, then most of the above-mentioned concerns can be avoided and the problem can be solved at a much smaller price
.
On October 15-17, 2021, the 13th "Concord Clinical Endocrinology and Metabolism Forum" will be held in Beijing.
Professor Chen Shi from Peking Union Medical College Hospital will give a topic: Is the high-dose dexamethasone suppression test necessary? -New understanding based on clinical data
.
Starting from the origin of the dexamethasone suppression test (1960), he introduced the origin of the high-dose dexamethasone suppression test (HDDST) used in the identification of Cushing’s syndrome.
There are many problems in the current clinical practice of HDDST.
The correlation between the results of the Dexamethasone Suppression Test (LDDST) and HDDST, and then a study involving 298 patients with Cushing’s syndrome was used to explore whether LDDST could replace HDDST in the differential diagnosis of Cushing’s syndrome and give a better diagnosis The cut point optimizes the diagnosis path of Cushing’s syndrome.
Finally, it is concluded that HDDST is not sensitive and specific for distinguishing Cushing’s disease from EAS, and the optimal inhibition value is not 50%.
It is useful for distinguishing Cushing’s disease from EAS.
, LDDST’s diagnostic efficacy is better than HDDST, and the new process of using LDDST to replace HDDST in series with BIPSS is more convenient, safer, time-saving and money-saving
.
Small and high-dose dexamethasone inhibition test in our department Note: In this case, the inhibition rate of F and 24hUFC in LDDST is> 54%, and the inhibition rate of F in HDDST is> 82%.
According to previous research data, she has more than 80%-93.
1% The probability of Cushing’s disease is Cushing’s disease, while the probability of EAS is small, but the result of BIPSS is needed in the end
.
The basic principle of HDDST is that pituitary ACTH adenoma cells in Cushing’s disease remain partially sensitive to glucocorticoids, while neuroendocrine tumors (NETs) that cause EAS are completely resistant to exogenous glucocorticoid inhibition.
Various thresholds have been proposed in the literature.
, The percentage of urine or serum cortisol inhibition varies from 50% to 90%
.
However, some studies have shown that there is almost complete overlap between the responses of some EAS and ACTH adenomas, and insist that it is impossible to find a discrimination threshold, especially in well-differentiated neuroendocrine tumors
.
This lack of specificity may be due to the expression of glucocorticoid receptors in well-differentiated, usually hidden NETs
.
Some authors believe that the diagnostic performance of HDDST for Cushing’s disease is not better than that of LDDST.
Other authors believe that the combination of HDDST and CRH test is valuable.
In some studies, the combination of the two tests is better than the correct diagnosis of CRH test alone.
The rate is lower
.
Therefore, HDDST is controversial and even considered outdated by some experts
.
It is precisely because of its lack of sensitivity, specificity and many other shortcomings mentioned above, especially with the advancement and popularization of biochemical detection technology, BIPSS, and functional imaging technology, HDDST has disappeared in the diagnosis and treatment path of the new Cushing syndrome related guidelines.
No, it's like the prone position test disappears
.
Differential diagnosis of Cushing syndrome Note: Each branch point is associated with a test that will determine what the doctor will do next
.
No tests should be omitted from the evaluation, and no tests should be added to the evaluation
.
——Loriaux D Lynn,Diagnosis and Differential Diagnosis of Cushing's Syndrome.
[J] .
N Engl J Med, 2017, 376: 1451-1459.
Cushing syndrome diagnosis process Note: ACTH, corticotropin; CBG, corticosteroid Binding globulin; CRH, corticotropin releasing hormone; DST, dexamethasone suppression test; IPSS, infra petrosal sinus sampling; UFC, urinary free cortisol
.
*It is agreed that all lesions with a diameter of less than 6 mm should be examined by IPSS, and lesions with a diameter of ≥10 mm do not require an IPSS examination, but there are different opinions from experts on lesions with a diameter of 6 to 9 mm
.
†There is no clear consensus on this alternative, and further research is needed, which is indicated by the darker box
.
Green boxes indicate points to consider; darker colors indicate test paths with less verification
.
——Fleseriu Maria, Auchus Richard, Bancos Irina et al.
Consensus on diagnosis and management of Cushing's disease: a guideline update.
[J] .
Lancet Diabetes Endocrinol, 2021, undefined: undefined.
Is a high-dose dexamethasone suppression test necessary? New understanding based on clinical data Professor Chen Shi, Chinese Academy of Medical Sciences Peking Union Medical College Hospital Source: Endocrine regulator
