Algorithm for the diagnosis of subclinical hypercortisolemia in patients with adrenal incidentalomas and their implementation in MS Excel environment
Authors: Tovkai O. A. , Tretyak O. E. , Kuts В. В. 
Published: April 2022

Objective — to optimize the diagnosis of subclinical endogenous hypercortisolemia and develop a diagnostic algorithm in patients with adrenal incidentalomas based on the analysis of anamnestic, clinical, instrumental and laboratory studies.
Materials and methods. The study of 310 patients operated for adrenal incidentalomas included a clinical assessment of the presence of components of the metabolic syndrome (obesity, hypertension, carbohydrate metabolism disorders, dyslipidemia) and indicators of hormonal activity of adrenal glands (plasma adrenocorticotropic hormone (ACTH) levels, daily cortisol excretion, cortisol levels after 1 mg dexamethasone suppressive test, aldosterone, renin levels). The examination was performed according to algorithm developed in accordance with the international clinical guidelines for the diagnosis of Cushing’s syndrome and recommendations for confirming autonomous cortisol production. To perform the analysis, patients were divided into groups according to the data of the pathohistological study after surgery: Group 1 included 244 patients (78.7 %) with hormonally active adenomas; Group 2 included 66 patients (21.3 %) who confirmed hormonally inactive formations. Laboratory tests included determination of cortisol, blood aldosterone with electrochemiluminescence analysis on an automatic analyzer immunoassay-photometer Cobas e411 (Roche Diagnostics, Germany); ACTH, plasma renin, cortisol in daily urine by enzyme immunoassay on an IEMs Reader MF&MULTISKAN device (ThermoLabsystems, Finland); MSCT NC (tomograph Toshiba Corporation, Japan). Pathomorphological examination of adrenal formations was performed by light microscopy. Statistical processing of the results was performed using parametric and nonparametric methods (student's t-criterion, Mann-Whitney criterion, chi-square criterion, Fisher angular transformation, Spearman rank correlation, ROC analysis). When constructing the diagnostic algorithm, an inhomogeneous sequential Wald procedure was used. For data accumulation and processing, we used the MS Excel 2013 program and its appendices, as well as the statistical analysis program StatPlus Pro v. 7 (Analyst Soft Inc., USA, license No. 21735752).
Results. Women prevailed in both groups. Comparative analysis proved a significant age difference: patients with hormonally active adenomas were older, most of these patients had hypertension (68.4 % vs. 36.4 %, p < 0.05) and DM2 — 27 % vs. 13.6 % (p < 0.05). Concomitant hyperaldosteronism was confirmed in 36 patients (22.5 %). There is a significant difference between the study groups in the indicators of lipid metabolism — cholesterol and low-density lipoproteins. According to the results of ROC analysis, the test using a cortisol level of 1 mg — DST has a sensitivity of 90 %, specificity of 74 % with a limit level of 1.7 mcg/dL. The second most important screening test for confirming subclinical hypercortisolemia was ACTH — at the limit level ≤ 10 pg/ml, it had a sensitivity of 80 %, specificity of 56 %; the indicator of daily cortisol excretion had a sensitivity of 71 %, specificity of 82 %. Using the method based on the heterogeneous sequential Wald procedure, an integral model was developed to confirm or exclude hypercortisolemia in a patient with incidentaloma. The assessment included indicators that demonstrate the highest clinical and laboratory diagnostic quality — age, presence of hypertension, DM2, overweight, dyslipidemia and laboratory indicators that have the highest sensitivity and specificity — cortisol 1 mg DST, ACTH, daily cortisol excretion. To automate a sequential procedure, a spreadsheet has been created in the MS Excel program using built-in mathematical and logical functions, which significantly simplified the decision-making procedure.
Conclusions. To confirm the presence of subclinical endogenous hypercortisolemia in a patient with one/two-sided adrenal incidentalomas, it is advisable to use an integral diagnostic algorithm, which includes the sum of anamnestic (age, gender), clinical (presence of hypertension, DM2) and laboratory (cortisol level 1 mg DST, ACTH, excretion of cortisol, glucose, cholesterol, LDL) indicators. The use of the developed diagnostic model makes it possible to confirm or exclude autonomous cortisol production in a patient with NC incidentaloma with a sensitivity of 94.9 % and a specificity of 83.3 %; the overall diagnostic effectiveness of the method (with 12 % of undefined diagnoses) is 84.9 %.