Analysis Of Clinical Characteristics And Recurrence Factors Of Cushing’s Syndrome

Background:Cushing’s syndrome(CS)is a rare endocrine disorder,which is a general term for the overproduction of glucocorticoids by the adrenal glands due to various etiologies.According to the level of Adrenocorticotropic Hormone(ACTH),CS can be divided into ACTH-dependent and non-ACTH-dependent.ACTH-dependent CS mainly includes Cushing’s disease(CD),ectopic ACTH syndrome(EAS),and ACTH-independent CS mainly includes adrenal adenoma.The annual incidence of Cushing’s syndrome is 2-3 per1 million people,and the low incidence has led to a paucity of data on the disease,making it difficult to analyze differences between etiologies.Currently,there are limited data on the demographic characteristics and etiological classification of CS patients,and fewer studies in China have compared in detail the clinical characteristics,biochemical indices,glucose and lipid metabolism,and hormonal alterations of CS patients with different etiologies,and many controversial issues remain to be elucidated by more research data.Moreover,there are limited data from our studies on relapse factors in patients with CS of different etiologies.The postoperative relapse rate of Cushing’s syndrome varies among different etiologies,and long-term follow-up studies have shown that the survival rate is significantly lower for those who relapse after surgery than for the remission group,so it is significant to study the relevant factors affecting relapse for early intervention in CS patients to prevent possible problems.Purpose:1.To analyze and compare the clinical characteristics of patients with Cushing’s syndrome of different etiologies,to gain a deeper understanding of the clinical features unique to Cushing’s syndrome,with a view to improving the accuracy of clinical typing diagnosis and to explore the mechanisms underlying the abnormalities of some biochemical indicators and hormone levels.2.To investigate the factors associated with postoperative recurrence in patients with Cushing’s syndrome and to provide ideas for early clinical intervention to prevent possible problems.Methods:According to the inclusion and exclusion criteria,202 patients with CS diagnosed at the First Hospital of Jilin University from December 2012 to December 2022 were collected as study subjects.The clinical data of the patients were obtained by checking the case management system,and the basic information included: gender,age,height,weight,BMI,systolic blood pressure,diastolic blood pressure,duration of disease,clinical characteristics,and first diagnosis symptoms.Clinical information: blood routine,coagulation routine,ion,liver and kidney function,thyroid function,sex hormone,cardiac index and other related laboratory indicators.According to the different etiologies of CS,they were divided into three groups: Cushing’s disease,adrenal adenoma,and ectopic ACTH syndrome.SPSS 26.0 was used for statistical analysis.The measurement data conforming to normal distribution were expressed as mean ± standard deviation,and those not conforming to normal distribution were described as median and interquartile spacing;the count data were expressed as frequency and percentage.If the numerical variables conformed to independence,normality,and chi-square,one-way ANOVA was applied for the comparison of multiple sample means,and if there was a difference in the overall group in multiple comparisons,the Bonferroni method was used for two-way comparisons;if the numerical variables did not conform to normality and chi-square,Kruskal-Wallis H test was applied for the comparison of multiple independent samples.The chi-square test was applied for the comparison of count data.Linear correlation analysis was used for correlation analysis of two variables,and Pearson correlation analysis was used if both variables met normal distribution,and Spearman correlation analysis was used if they did not.The risk factors affecting tumor recurrence in CS patients were analyzed by univariate and multifactorial Cox regression.p<0.05 was considered a statistically significant difference.Results:1.General:(1)Age characteristics: The median age of onset was 46(32,54)years in202 CS patients,with the highest median age of onset in the EAS group and the lowest median age of onset in the adrenal adenoma group;and the greatest number of patients were aged 40-49 years.(2)Gender characteristics: women accounted for 87.1% of all CS patients,and the CD group,adrenal adenoma group and ectopic ACTH syndrome group all had a high proportion of women,with 95.8% of women in the adrenal adenoma group,84.4% of women in the CD group,and 55.6% of women in the EAS group.(3)Disease duration characteristics: The median disease duration of CS patients was 12(12,36)months,with the shortest disease duration in the EAS group and the longer disease duration in the CD group.(4)Etiological distribution characteristics: CD was the most common,accounting for 60.40%,followed by adrenal adenoma,accounting for 35.15%,and EAS was the least common,accounting for only 4.45%.2.Clinical manifestations: hypertension was the most common clinical symptom of Cushing’s syndrome,71.78% of patients had hypertension,followed by centripetal obesity,71.29% of patients showed centripetal obesity;the clinical manifestations of patients with different types of CS differed,centripetal obesity was the most common clinical symptom of adrenal adenoma,hypertension was the most common clinical symptom of CD and EAS;comparison between groups showed The percentage of patients with symptoms of centripetal obesity was higher in the adrenal adenoma group than in the CD and EAS groups,and the percentage of patients with diabetes mellitus,edema,infection,and weakness was higher in the EAS group than in the CD and adrenal adenoma groups.3.First diagnosis symptoms: The first diagnosis symptoms of CS patients are mostly elevated blood pressure,centripetal obesity,fatigue,edema,weight gain,menstrual disorders,physical examination,polycystic appearance,petechiae and hypertrichosis.4.Analysis of routine blood characteristics: absolute values of lymphocytes,eosinophils,red blood cells and hemoglobin were lower in the EAS group than in the CD and adrenal adenoma groups,and absolute values of neutrophils were higher than in the CD and adrenal adenoma groups;49.1% of patients with Cushing’s syndrome had increased absolute values of neutrophils,26.9% had decreased absolute values of lymphocytes,and 35.9% had decreased absolute values of eosinophils.Absolute values decreased.Correlation analysis showed that cortisol levels were positively correlated with absolute neutrophil values and negatively correlated with absolute lymphocyte values and absolute eosinophil values.5.Ion characteristics analysis: blood potassium,blood chloride,and blood calcium were lower in the EAS group than in the CD and adrenal adenoma groups;41.9% of patients with Cushing’s syndrome had hypokalemia and 15.0% had hypophosphatemia.Correlation analysis showed that cortisol levels were negatively correlated with blood potassium,blood chloride,and blood phosphorus.6.Analysis of liver and kidney function characteristics: total protein,albumin and globulin were lower in the EAS group than in the CD and adrenal adenoma groups,and total bilirubin and urea were higher than in the CD and adrenal adenoma groups.There was no significant correlation between each biochemical index and cortisol level.7.Analysis of glycolipid metabolic characteristics: CS patients had abnormal glycolipid metabolism with a median Hb A1 c of 6.95(5.95,8.48)%;there were no significant differences between the three groups comparing fasting glucose,Hb A1 c,cholesterol,triglycerides,LDL cholesterol,and HDL cholesterol.Diabetes mellitus was diagnosed in 35.15% of the total population and hyperlipidemia in 62.1% of the patients.Correlation analysis showed a positive correlation between cortisol levels and fasting glucose,with no significant correlation with lipid levels.8.Analysis of thyroid axis,gonadal axis and growth hormone axis characteristics:comparison between the three groups showed that FT3 levels were lower in the EAS group than in the CD and adrenal adenoma groups,LH levels were lower in the EAS group than in the adrenal adenoma group,and testosterone levels were lower in the adrenal adenoma group than in the CD and EAS groups;cortisol levels were negatively correlated with TSH,FT3,FSH and LH.9.Cortisol levels: blood cortisol levels and 24-hour urinary free cortisol levels were significantly different among the three groups,with the highest blood and urinary cortisol levels in the EAS group and the lowest blood and urinary cortisol levels in the adrenal adenoma group;in ACTH-dependent Cushing’s syndrome,cortisol levels were positively correlated with ACTH levels.10.Analysis of structural and functional characteristics of the heart: troponin,creatine kinase isoenzyme,and left ventricular mass index were higher in the EAS group than in the CD and adrenal adenoma groups,and pro-BNP,right ventricular internal diameter,septal thickness,and left ventricular end-diastolic diameter were higher in the EAS group than in the CD group.22.4% of patients with Cushing’s syndrome had structural cardiac abnormalities,11.2% of CS patients had centripetal remodeling,and 5.6% had centrifugal hypertrophy.5.6% showed centripetal hypertrophy and 5.6% showed centrifugal hypertrophy.11.Risk factors affecting recurrence: The overall recurrence rate of Cushing’s syndrome caused by pituitary tumors and adrenal adenomas was 24.2%;patients in the adrenal adenoma group had a longer recurrence time than the CD group,the recurrence time in the <50 years age group was longer than that in the ≥50 years age group,and the recurrence time in the tumor ≥1 cm group in the CD group was longer than that in the tumor <1 cm group.Age,preoperative cortisol levels,postoperative cortisol levels,and absolute neutrophil values were strongly associated with postoperative recurrence,and etiology was an independent predictor of tumor recurrence in patients with CS.Conclusions:1.Cushing’s syndrome caused by different etiologies had significant differences in general conditions,clinical manifestations,first diagnosis symptoms,blood routine,ions,liver and kidney function,glycolipid metabolism,thyroid axis and gonadal axis.2.Cortisol levels in patients with Cushing’s syndrome are positively correlated with absolute neutrophil values and fasting glucose;negatively correlated with absolute lymphocyte values,absolute eosinophil values,blood potassium,blood chloride,blood phosphorus,TSH,FT3,FSH and LH;not significantly correlated with blood lipid levels and liver and kidney function indicators.3.Cushing’s syndrome affects the structure and function of the patient’s heart,and some patients will have structural changes of the heart.4.Age,preoperative cortisol level,postoperative cortisol level,and absolute neutrophil value are closely associated with postoperative recurrence,and etiology is an independent predictor of tumor recurrence in patients with CS.