Monitoring adrenal insufficiency through salivary steroids: a pilot study.

BACKGROUND: Various glucocorticoid replacement therapies (GRTs) are available for adrenal insufficiency (AI). However, their effectiveness in restoring glucocorticoid rhythm and exposure lacks adequate biochemical markers. We described the diurnal salivary cortisol (SalF) and cortisone (SalE) rhythm among different GRTs and analysed the associations between saliva-derived parameters and life quality questionnaires. METHODS: Control subjects (CSs, n = 28) and AI patients receiving hydrocortisone (HC, n = 9), cortisone acetate (CA, n = 23), and dual-release hydrocortisone once (DRHC-od, n = 10) and twice a day (DRHC-td, n = 6) collected 9 saliva samples from 07:00 to 23:00. Patients compiled Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, and Addison disease-specific quality-of-life questionnaires. SalE and SalF were measured by liquid chromatography-mass spectrometry. Exposure was monitored using SalE for HC and DRHC and SalF for CA. Area under the curve (AUC) was computed. Different GRTs were compared by Z-scores calculated from saliva-derived parameters. Questionnaire results predictors were evaluated with multiple regression analysis. RESULTS: Compared with controls, all GRTs resulted in glucocorticoid overexposure in the morning. Hydrocortisone, CA, and DRHC-td caused overexposure also in afternoon and evening. Compared with other treatments, CA determined increased Z-score-07:00 (P < .001), DRHC-td determined increased Z-score-AUC07:00→14:00 (P = .007), and DRHC-od induced lower Z-score-AUC14:00→23:00 (P = .015). Z-scores-AUC14:00→16:00 ≥ .619 best predicted questionnaire scores. CONCLUSIONS: None of the GRTs mimics normal glucocorticoid rhythmicity and exposure. SalE, SalF, and Z-score may be useful markers for monitoring and comparing different GRTs. Excess glucocorticoid in early afternoon best associated with depressive symptoms and worse life and sleep quality.

Mild autonomous cortisol secretion in adrenal incidentalomas and risk of fragility fractures: a large cross-sectional study.

OBJECTIVE: Mild autonomous cortisol secretion (MACS) has been associated with a higher prevalence of osteoporosis, although most data rely on single-center studies with limited sample size. We aimed to assess the prevalence of fragility fractures and contributing factors in a large cohort of patients with adrenal incidentalomas. DESIGN AND METHODS: Medical records of 1023 patients with adrenal incidentalomas from 1990 to 2019 were reviewed, and 735 patients were selected. Clinically obtained electronic radiological images closest to first endocrine evaluation, such as lateral views of spine X-rays or CT thoraco-abdominal scans, were reviewed to screen for asymptomatic morphometric vertebral fractures. Clinical fragility fractures, hormonal, and dual-energy x-ray absorptiometry (DXA) indices were also recorded. RESULTS: Four hundred seventy-four patients had nonfunctioning (NF) adrenal incidentalomas, 238 had MACS and 23 adrenal Cushing's syndrome (AC). Prevalence of fragility fractures was different (P = .018) between groups, respectively, 24.1% (NF), 34.0% (MACS), and 30.4% (AC), with significant difference between NF and MACS (P = .012). When analyzed separately by sex and menopausal status, this difference remained significant in postmenopausal women (P = .011), with a fracture prevalence of 22.2% (NF) and 34.6% (MACS). Fracture prevalence was similar in males. Women with MACS aged ≥65 years reported a 48.8% prevalence of fractures, as compared with 29.5% in NF (P < .01). In postmenopausal women, fragility fractures were associated with age (odds ratio [OR] 1.1, P < .001), smoking (OR 1.8, P = .048), and 1 mg-dexamethasone suppression test (DST) cortisol (OR 3.1, P = .029), while in men, only age was associated with fragility fractures. CONCLUSIONS: A considerable fracture burden was shown in postmenopausal women with adrenal incidentalomas and MACS, with clinical implications for the evaluation and management of bone metabolism.

Initial Ablation Ratio Predicts Volume Reduction and Retreatment After 5 Years From Radiofrequency Ablation of Benign Thyroid Nodules.

Background: Radiofrequency ablation (RFA) has gained ground as an effective and well-tolerated technique to treat benign thyroid nodules. Most of the available studies have described the short-term outcomes of RFA, whereas there is a limited number of studies evaluating long-term issues, such as regrowth and the likelihood of retreatments. In addition, risk markers of regrowth and retreatment remain to be defined. The initial ablation ratio (IAR) is an index that measures the amount of ablation after RFA, which has been associated with technique efficacy (i.e. volume reduction >50% after 1 year from the procedure). This study aimed at evaluating i) IAR reproducibility and ii) IAR predictive value for RFA 5-year outcomes. Materials and Methods: This is a retrospective single center study on patients with benign thyroid nodules treated with RFA and followed for 5 years after initial treatment. IAR interobserver reproducibility was evaluated with Bland-Altman method and Lin's concordance correlation coefficient (ρc). IAR predictive value for RFA 5-year outcomes was evaluated with linear and logistic regression models, as well as with Cox models, while receiver operating characteristic (ROC) analyses were used for cut-offs. Results: We selected 78 patients with 82 benign thyroid nodules. The procedure significantly reduced nodule volume and this reduction was generally maintained over time. Technique efficacy was achieved in 92% of patients, while 23% of nodules regrew and 12% of nodules were retreated. Median IAR was 83%. Lin's concordance and Pearson's correlation coefficients suggested a good interobserver reproducibility of this index, consistent with the limits of agreement of the Bland-Altman plot. IAR was significantly associated with technique efficacy, 1- and 5-year volume reduction ratio, and with the likelihood of a retreatment, but not with nodule regrowth. ROC analyses showed that IAR cut-off was 49% for technique efficacy and 73% for retreatment. Conclusions: Our results show for the first time that IAR is reproducible and that it predicts the volume reduction and the likelihood of a retreatment after 5 years from RFA.