Comparison of 12-month follow-up of biochemical markers associated with bone turnover in menopausal women with subclinical hypercortisolism and postmenopausal women with normal cortisol axis

Introduction and Purpose: Adrenal incidentaloma (AI) are masses that are not related to the adrenal gland and detected during cross-sectional imaging performed for another reason. It is seen in 5% of computed tomography (CT) scans taken for another reason. Situations that need to be investigated in AIs; malignancy and the presence of an autonomous hormone-producing mass. AI lesions are benign tumour about 80 percent. Benign lesions consist approximately 75% of nonfunctional adrenal adenomas (NFAs). Cortisol-secreting adenomas constitute 12% of benign lesions. Cortisol-secreting adenomas are divided into two as overt Hypercortisolemia and Subclinical Hypercortisolemia (SCS). SCS is characterized by changes in the HPA axis without clinical signs and symptoms (buffalo hump, moon face, abdominal purple striae, proximal myopathy, easy bruising) due to excess cortisol in patients with an incidentally detected adrenal mass. SCS patients are at increased risk of metabolic problems, cardiovascular morbidity, and osteoporotic fractures. Osteoporosis: It occurs when the balance between formation and resorption is disturbed. It disrupts the microarchitecture of bone tissue and causes low bone mass. It is a disease that is silent, caused by mild trauma or causes bone fracture without trauma. The osteoporosis diagnostic method is DXA. It may also be helpful to examine bone biomarkers (osteocalcin, PINP, CTX). SCS patients have an increased risk of osteoporosis and related fractures. It is aimed to monitor the effect of 1 mg DST value on bone biomarkers and fracture in SCS patients at 12-24 months intervals. Materials and Method: This study was planned as a prospective study with case-control groups. An additional tube of blood was taken and centrifuged together with the blood taken during routine examinations of postmenopausal female patients who are currently under follow-up due to adrenal adenoma in the endocrinology outpatient clinic between 07.06.2018 and 10.08.2021. It was aliquoted and stored in a -80 degree freezer. The patients were divided into two groups which are 1 mg DST≤1.8 µg/dl (NFA) and 1 mg DST>1.8 µg/dl (SCS). Standard osteoporosis screening, which should be done in all postmenopausal women, was performed. Treatment was started with the patients who had a t score of <-2.5 in DXA examination. The same procedures were repeated at the visit 12-24 months later during the routine follow-up of the patients. The blood concentrations of the biomarkers to be used in the study were measured by standard ELISA methods. The results were recorded in the SPSS program and analysed. Statistical significance level was determined as p<0.05. Findings: There are 82 of postmenopausal female patients which were followed up for AI were included in the study. 56.1% of the patients were followed up due to 1 mg DST value ≤ 1.8 µg/dl which is NFA. 43,9% of the patients were followed up due to 1 mg DST> 1,8 µg/dl which is SCS. The age range of the patients was between 45-79 years. At the second visit, patients of 63 were asked to come. There were seen result of 1 mg DST in patients of 59 who came to the second visit. At the first visit. 2 patients had vertebral fractures, 1 patient had hip fractures, and 3 patients had non-vertebral-hip fractures. Patients of 13 were diagnosed with osteoporosis during the first visit. Patients of 6 were followed up for NFA and patients of 7 for SCS. The relationship between CTX, PINP, osteocalcin values and 1 mg DST value was analysed with descriptive statistics (Levene test) and there is no statistical significantly result were found. When the results of CTX, PINP, and osteocalcin values at 1st and 2nd visits were evaluated by paired t-test, there is no statistical significantly difference was found. Factors that affect the risk of fracture were compared by using logistic regression. It was determined that worsening of fracture risk was associated with age, smoking, BMI, and an increase in 1 mg DST value of regardless of the follow-up period. In the long term, the risk of fracture increases 1.98 times for every 1 µg/dl increase in the 1 mg DST value. The risk was found to increase cumulatively. Result: In this study, it was observed that the risk of fracture was associated with age, smoking, BMI, and an increase in 1 mg DST value of regardless of the follow-up period. It was determined that the risk of fracture increased 1.98 times for every 1 µg/dl increase. When the effect of bone turnover biochemical markers (CTX, PINP, osteocalcin) was evaluated according to the 1 mg DST value, there is no statistical significantly result was found. Therefore, bone biochemical markers are not recommended for evaluation of osteoporosis in SCS patients. In addition, there is no significant difference was found in bone biochemical markers in the 12–24 months follow-up period, and it is not recommended to be used in the follow-up period. Keywords: Adrenal incidentaloma, osteoporosis, subclinical Cushing's Syndrome, fracture risk