| Background and ObjectiveSubclinical Cushing syndrome(SCS)lacks typical clinical manifestations while exhibits mild autonomous cortisol secretion.It is more common in adrenal incidentalomas.Cushing syndrome caused by adrenal adenoma is the most common type of adrenal Cushing syndrome.These two adrenal adenomas differ not only in the level of secretion of cortisol,but also in clinical signs and symptoms,hormone levels,and disease prognosis.We conducted our study trying to investigate the differences of clinical features,more importantly,pathophysiologic mechanism of the two diseases.MethodsWe retrospectively collected medical records of patients with diagnosis of SCS or CS caused by adrenal adenoma(CS)between May 1994 and July 2018 in Sir Run Run Shaw College of Medicine Zhejiang University.Clinical data of patients was analyzed by correlation analysis.Immunohistochemistry was performed on the adrenal adenoma tissue of typical cases,and the different expressions of SF-1,StAR and CYP21A2 proteins in the two groups were compared.Results1.A total of 41 patients were enrolled,11 patients diagnosed with SCS,and 30 patients with CS caused by adrenal adenoma(CS).The majority of patients in two groups were female(9 cases and 29 cases,respectively).SCS patients were older than CS patients[(54.9± 10.1)yr vs.(40.4±11.2)yr,P 0.01]and had higher BMI[(26.73±3.62)kg/m2 vs.(24.96±4.51)kg/m2,p>0.05].In clinical manifestations,CS patients had more obvious symptoms and signs,such as moon face,facial plethora,buffalo hump and purple striae(P<0.05).In terms of related complications,both two groups of patients had different proportions of hypertension,abnormal glucose and lipid metabolism,abnormal bone metabolism or hypokalemia,the most common of which was hypertension.At the hormone level,both two groups of patients lost normal cortisol and ACTH circadian rhythm,and CS patients had significantly higher levels of cortisol,24 h UFC,and cortisol levels after LDDST and HDDST than those in patients of SCS(P<0.001),whereas ACTH levels in CS patients were greatly inhibited.In tumor entity,more adenoma was found in the left adrenal(53.7%vs.43.9%),and the tumor volume of the SCS patients was significantly smaller than that of CS patients[(2.21 ±0.35)cm vs.(3.04±0.6 7)cm,P<0.01].All SCS patients and 26 CS patients underwent adrenal adenoma resection,with varying proportions of adrenal insufficiency after surgery(54.5%vs.90.9%,P<0.05).Linear bivariate correlation analysis showed that the tumor volume was positively correlated with cortisol levels(P<0.05),and the correlation with plasma cortisol levels at 4 pm was the strongest.2.Immunohistochemical staining was performed on adrenal adenoma of all SCS cases and 12 typical CS cases.The results showed that SF-1 was mainly expressed in the nucleus,and the expression level was higher in adrenal adenoma of CS patients,but with no significant difference between the two groups(P>0.05).StAR and CYP21A2 were mainly expressed in the cytoplasm,and the expression level of CYP21A2 was higher in adrenal adenoma of SCS patients(P<0.001).Linear bivariate correlation analysis showed that the CYP21A2 expression level was negatively correlated with cortisol levels,24h UFC and tumor volume,and its correlation with tumor volume was the strongest.Furthermore,the expression of CYP21A2 was positively correlated with ACTH levels(P<0.01)and the expression level of StAR(P<0.05).ConclusionsAlthough the clinical manifestations of SCS are mild and not typical,its hormonal secretion lose circadian rhythm and may cause a series of metabolic abnormalities.In addition,a considerable proportion of patients develop adrenal insufficiency after surgery.Therefore,it is recommended to routinely screen SCS in patients with adrenal incidentalomas.The volume of adrenal adenoma may be correlated with cortisol levels.The pathogenesis of SCS and CS caused by adrenal adenoma are different at molecular levels involved in steroidogenic synthesis pathways. |
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