腺瘤型肾上腺源性皮质醇增多症不同病理类型的临床表现和激素谱特点

Clinical manifestations and hormonal profile characteristics of different pathological types of adrenocortical adenoma hypercortisolism

目的探讨不同病理类型腺瘤型肾上腺源性皮质醇增多症患者的临床表现和血清肾上腺皮质激素谱的特点。方法去回顾性分析2018年1月至2022年6月北京大学第一医院收治的68例肾上腺源性库欣综合征患者的病例资料,其中12例术后病理检查示皮质腺瘤存在明显嗜酸性变(嗜酸性变组),56例无明显嗜酸性变(无嗜酸性变组)。嗜酸性变组男1例,女11例;年龄(49.83±9.87)岁;体质量指数(BMI)(25.86±3.21)kg/m^(2);收缩压(140.25±20.72)mmHg(1mmHg=0.133 kPa),舒张压(91.00±14.87)mmHg;显性库欣综合征7例。无嗜酸性变组男14例,女32例;年龄(52.91±10.82)岁,BMI(26.06±3.57)kg/m^(2);收缩压(142.13±16.71)mmHg,舒张压(83.63±11.41)mmHg;显性库欣综合征16例。两组上述指标比较差异均无统计学意义(P>0.05)。实验室检查,嗜酸性变组和无嗜酸性变组的24:00时皮质醇分别为14.95(5.93,23.2)ng/dl和6.69(4.07,11.35)ng/dl(P=0.044),1mg过夜地塞米松抑制试验后皮质醇分别为20.19(11.29,26.92)ng/dl和5.94(2.68,12.90)ng/dl(P=0.005),8:00、16:00、24:00时促肾上腺皮质激素(ACTH)分别为2.08(1.02,2.90)pg/ml和8.37(2.30,11.67)pg/ml(P=0.006)、1.22(1.00,3.20)pg/ml和4.22(1.80,6.33)pg/ml(P=0.012)0.65(0,2.63)pg/ml和2.76(1.44,5.57)pg/ml(P=0.023),三酰甘油分别为1.92(1.31,2.50)mmol/L和1.31(1.04,1.80)mmol/L(P=0.026),差异均有统计学意义。靶器官损害方面,嗜酸性变组和无嗜酸性变组合并心室壁肥厚分别为6例和10例(P=0.017),主动脉夹层分别为1例和0例(P=0.030),合并4种以上靶器官损伤分别为4例和5例(P=0.024),差异均有统计学意义。通过液相色谱-串联质谱方法检测两组术前血清肾上腺皮质激素谱,比较两组肾上腺皮质激素谱的差异和激素比值的差异,将年龄、性别和有统计学差异的指标纳入多因素logistic回归模型,分析各项指标与嗜酸性变的相关性。结果两组的肾上腺皮质激素谱显示,嗜酸性变组和无嗜酸性变组的血清雌酮分别为20.27(13.49,39.81)pg/ml和12.59(8.08,21.18)pg/ml(P=0.034),11-羟雄烯二酮分别为692.34(536.19,1049.66)pg/ml和1157.60(710.78,1539.30)pg/ml(P=0.026),差异有统计学意义;其他各激素表达水平比较差异均无统计学意义(P>0.05)。激素比值比方面,嗜酸性变组和无嗜酸性变组的雌二醇/睾酮分别为0.14(0.08,0.62)和0.04(0.01,0.09)(P=0.008),雌酮/雄烯二酮分别为0.06(0.05,0.12)和0.04(0.03,0.06)(P=0.007),11-羟雄烯二酮/雄烯二酮分别为2.26(1.30,2.69)和4.03(2.48,5.25)(P=0.008),雌三醇/雌酮分别为0.10(0.03,0.29)和0.25(0.12,0.51)(P=0.016),雌三醇/雌二醇分别为0.22(0.03,0.30)和0.33(0.12,0.73)(P=0.032),差异均有统计学意义。多因素分析结果显示,雌酮(0R=1.04,95%CI1.01~1.07,P=0.009)、雌酮/雄烯二酮(0R=25008670.29,95%CI8.45~74015852572024.10,P=0.025)与嗜酸性变独立相关。结论病理检查提示有嗜酸性变的腺瘤型肾上腺源性皮质醇增多症患者的血清皮质醇自主分泌水平更高,下丘脑-垂体-肾上腺轴受抑制更明显,代谢紊乱和靶器官损害更显著,肾上腺皮质激素雌酮产生也更多。

Objective To explore the clinical manifestations and characteristics of serum adrenal cortex hormone spectrum in patients with adrenocortical hypercortisolism with different pathological types of adrenal adenoma.Methods A retrospective analysis was conducted on 68 patients with adrenal Cushings syndrome who underwent surgical treatment in the Department of Endocrinology and/or Urology,Peking University First Hospital from January 2018 to June 2022.Among them,12 patients had obvious eosinophilic changes in pathology(eosinophilic group),and 56 patients had no obvious eosinophilic changes(non-eosinophilic group).Among eosinophilic group,one male and 11 females,age(49.83±9.87)years old,body mass index(BMI)(25.86±3.21)kg/m^(2),systolic blood pressure(140.25±20.72)mmHg(1 mmHg=0.133 kPa),diastolic blood pressure(91.00±14.87)mmHg,7 cases were overt Cushing's syndrome.Among non-eosinophilic group,14 males and 32 females,age(52.91±10.82)years old,BMI(26.06±3.57)kg/m^(2);ystolic blood pressure(142.13±16.71)mmHg,diastolic blood pressure(83.63±11.41)mmHg;16 cases of overt Cushings syndrome.There was no statistically significant difference in the above indicators between the two groups(P>0.05).In terms of laboratory tests,0:00 cortisol levels in the eosinophilic group and non-eosinophilic groups were 14.95(5.93,23.2)ng/dl and 6.69(4.07,11.35)ng/dl(P=0.044),the cortisol levels after 1mg dexamethasone inhibition test were 20.19(11.29,26.92)ng/dl and 5.94(2.68,12.90)ng/dl(P=0.005),and 8:00,16:00,and 0:00,ACTH levels were 2.08(1.02,2.90)pg/ml and 8.37(2.30,11.67)pg/ml(P=0.006),1.22(1.00,3.20)pg/ml,and 4.22(1.80,6.33)pg/ml(P=0.012),0.65(0,2.63)pg/ml,and2.76(1.44,5.57)pg/ml(P=0.023),serum triglyceride were 1.92(1.31,2.50)mmol/L and 1.31(1.04,1.80)mmol/L(P=0.026),and the differences were statistically significant.In terms of target organ damage,there were 6 cases and 10 cases(P=0.017)in the eosinophilic group and non eosinophilic group with ventricular wall hypertrophy,1 case and 0 cases(P=0.030)in the aortic dissection group,and 4 cases and 5 cases(P=0.024)with four or more types of target organ damage,respectively,with statistically significant dfferences.Two groups of preoperative serum adrenal cortex hormone profiles were detected by liquid chromatography tandem mass spectrometry.The dfferences in adrenal cortex hormone profiles and hormone ratios between the two groups were compared.Age,gender,and statistically significant indicators were included in a multivariate logistic regression model to analyze the correlation between each indicator and eosinophilic changes.Results Adrenal cortical hormone profile of the two groups showed that the serum estrone levels in the eosinophilic group and non-eosinophilic group were 20.27(13.49,39.81)pg/ml and 12.59(8.08,21.18)pg/ml(P=0.034),and 11-hydroxyandrostenedione levels were 692.34(536.19,1049.66)pg/ml and 1157.60(710.78,1539.30)pg/ml(P=0.026),with statistically significant dfferences;There were no statistically significant difference in the expression levels of other hormones(P>0.05).In terms of hormone ratio,the estradiol/testosterone ratios in the eosinophilic and non eosinophilic groups were 0.14(0.08,0.62)and 0.04(0.01,0.09)(P=0.008),the estrone/androstenedione ratios were 0.06(0.05,0.12)and 0.04(0.03,0.06)(P=0.007),the 11-hydroxyandrostenedione/androstenedione ratios were 2.26(1.30,2.69)and 4.03(2.48,5.25)(P=0.008),the estriol/estrone ratios were 0.10(0.03,0.29)and 0.25(0.12,0.51)(P=0.016),the estriol/estradiol were 0.22(0.03,0.30)and 0.33(0.12,0.73)(P=0.032),and the differences were statistically significant.The results of multivariate analysis showed that estrone(OR=1.04,95%CI 1.01-1.07,P=0.009)and estrone/androstenedione(0R=25008670.29,95%CI 8.45-74015852572024.10,P=0.025)were independently associated with eosinophilic pathology.Conclusions Adrenocortical hypercortisolism patients with eosinophilic pathology have higher levels of serum cortisol secretion,more pronounced inhibition of the hypothalamic pituitary adrenal axis,more significant metabolic disorders and target organ damage,and higher production of estrone.