Characterization of vitamin D metabolism in active acromegaly in the setting of bolus (150,000 IU) cholecalciferol treatment.

PURPOSE: To reveal distinctive features of vitamin D metabolism in patients with active acromegaly compared to healthy individuals, particularly in the setting of cholecalciferol treatment. METHODS: The study group included 34 adults with active acromegaly, and the control group included 30 apparently healthy adults with similar age, sex, and BMI. All participants received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3, and 7 after the administration. All data were analyzed with nonparametric statistics. RESULTS: Patients with acromegaly had tendency to lower baseline 25(OH)D3 levels (p = 0.05) and lower 25(OH)D3 levels (p < 0.05) during the follow-up. They were also characterized by PTH suppression (lower baseline PTH levels and lower prevalence of secondary hyperparathyroidism), altered production of main vitamin D metabolites (higher 1,25(OH)2D3 and lower 24,25(OH)2D3 levels with corresponding lower 25(ОН)D3/1,25(ОН)2D3 and higher 25(ОН)D3/24,25(ОН)2D3 ratios) as well as concordant biochemical features (higher levels of serum phosphorus and albumin-adjusted calcium levels) throughout the study (p < 0.05). The acromegaly group showed an increase in DBP levels after cholecalciferol intake as opposed to the control group (p < 0.05) and had lower increase in free 25(OH)D levels (p < 0.05). Δ25(OH)D3 was similar between the groups (p > 0.05), showed a negative correlation with the disease activity markers-both IGF-1 levels (r = -0.44, p < 0.05) and fasting GH levels (r = -0.56, p < 0.05)-and lacked correlation with BMI in the acromegaly group (p > 0.05). CONCLUSION: Patients with active acromegaly have dysregulated vitamin D metabolism characterized by higher 1,25(ОН)2D3, lower 24,25(ОН)2D3 and altered DBP production. The response to vitamin D supplementation in acromegaly patients might be influenced by hormonal excess. Obtained results require reproducibility check and further study to develop specific clinical recommendations. TRIAL REGISTRATION: NCT04844164 (release date: April 9, 2021; retrospectively registered).

[Epidemiology, clinical manifestations and efficiency of different methods of treatment of acromegaly according to the United Russian Registry of Patients with Pituitary Tumors].

BACKGROUND: The registry is the main source of information about patients with acromegaly for assessing the quality of medical care, effectiveness of treatment, determining the compliance of real clinical practice with existing standards and patient management protocols. AIMS: To evaluate epidemiological, demographic and clinical characteristics of acromegaly in Russian Federation and effectiveness of treatment modalities. MATERIALS AND METHODS: The object of the study was the database of the united Russian registry of patients with pituitary tumors with specific analysis of patients with acromegaly only. We analyzed the data of 4114 patients with acromegaly stored on the online system in February 2019. RESULTS: Based on the data 32% of patients had complete clinical and laboratory remission of acromegaly; the percentage of patients with no remission was 68%, among them 22.5% had significant improvements in clinical symptoms and a decrease in growth hormone (GH) and insulin-like growth factor-1 (IGF-1) without IGF-1 normalization. The average age of patients at the onset of the disease was 42.7 years and at diagnosis – 45.8 years. The ratio of men to women was 1:2.6. In patients with acromegaly hypopituitarism was registered in 14.7% of cases and among them hypothyroidism (66%) and hypogonadism (52%) were registered more often. Among other complications the leading were diabetes mellitus (15.7%) and acromegalic arthropathy (15%). The proportion of patients receiving neurosurgical treatment increased from 35.7% to 49.6% in 2012–2019; the portion of patients undergoing radiation therapy decreased significantly from 17.7% in 2012 to 0.8% in 2019. Remission was achieved in 40.47% after neurosurgery and 28.95% after medical treatment as a first line therapy p<0.01. The number of patients receiving medical treatment at the time of the study was 1209. Among them 51% of patients treated with long-acting lanreotide and 24% receiving long-acting octreotide achieved remission (p<0.0001) CONCLUSIONS: The remission rate of acromegaly remains suboptimal despite increased surgical activity, which corresponds to global trends. Long-acting lanreotide was significantly superior versus long-acting octreotide in the rate of acromegaly remission, which does not correspond with clinical trials.

[Vitamin D metabolism in hypercorticism and acromegaly].

Due to the high prevalence of low vitamin D levels in the overwhelming majority of regions of the world and discovery of extra-skeletal effects of vitamin D, the issue of maintaining adequate levels of vitamin D in the blood remains extremely relevant, especially in people with high risk of severe deficiency. To date, few studies have been performed on the features of vitamin D metabolism in disorders such as hypercorticism and acromegaly. However, vitamin D deficiency in such patients, according to available literature, may be more widespread and more pronounced than in general population. It is now recommended to use standard prophylactic and therapeutic doses of vitamin D for the treatment of these diseases, which may not satisfy the therapeutic goals specific to each disease. This review provides information on normal vitamin D metabolism, as well as literature data on the possible relationship and mutual influence between these endocrinopathies and vitamin D metabolism.

Diagnostic performance of osteocalcin measurements in patients with endogenous Cushing's syndrome.

The aim of this study was to evaluate the diagnostic performance of osteocalcin (OC), as measured by automated electrochemiluminescence immunoassay (ECLIA), in identifying Cushing's syndrome (CS) in two separate populations: among obese and overweight subjects and among women of postmenopausal age with osteoporosis. Among the 106 referral patients with obesity, CS was confirmed in 42 cases. The patients of the referred population provided late-night salivary cortisol (LNSC), underwent low-dose dexamethasone suppression testing (DST) and were further evaluated until CS was pathologically confirmed. A threshold of OC-8.3 ng ml(-1) differentiated CS among obese and overweight subjects with a sensitivity of 73.8% (95% confidence interval (CI) 58.9-84.7) and a specificity of 96.9% (95% CI 89.3-99.1). The total area under the receiver operating characteristic curve (AUC) was 0.859 (95% CI 0.773-0.945), which was lower than LNSC or DST (P=0.01). In the retrospective portion of the study, the OC levels were evaluated in 67 subjects with newly diagnosed postmenopausal osteoporosis and in 23 patients (older than 45) with newly diagnosed CS and osteoporosis (presence of low traumatic fractures or T-score P-2.5). The diagnostic performance of OC for osteoporosis due to CS was within an AUC of 0.959 (95% CI 0.887-1.00). A threshold for OC of 8.3 ng ml-1 yielded a sensitivity of 95.4% (95% CI 78.2-99.2%) and a specificity of 98.5% (95% CI 92.0-99.7%). Thus, osteocalcin could be used in the diagnostic testing for endogenous hypercortisolism in patients referred to exclude CS and to identify CS among patients of postmenopausal age with osteoporosis.

The risk factors for fractures and trabecular bone-score value in patients with endogenous Cushing's syndrome.

UNLABELLED: In a cohort study of 182 consecutive patients with active endogenous Cushing's syndrome, the only predictor of fracture occurrence after adjustment for age, gender bone mineral density (BMD) and trabecular bone score (TBS) was 24-h urinary free cortisol (24hUFC) levels with a threshold of 1472 nmol/24 h (odds ratio, 3.00 (95% confidence interval (CI), 1.52-5.92); p = 0.002). INTRODUCTION: The aim was to estimate the risk factors for fracture in subjects with endogenous Cushing's syndrome (CS) and to evaluate the value of the TBS in these patients. METHODS: All enrolled patients with CS (n = 182) were interviewed in relation to low-traumatic fractures and underwent lateral X-ray imaging from T4 to L5. BMD measurements were performed using a DXA Prodigy device (GEHC Lunar, Madison, Wisconsin, USA). The TBS was derived retrospectively from existing BMD scans, blinded to clinical outcome, using TBS iNsight software v2.1 (Medimaps, Merignac, France). Urinary free cortisol (24hUFC) was measured by immunochemiluminescence assay (reference range, 60-413 nmol/24 h). RESULTS: Among enrolled patients with CS (149 females; 33 males; mean age, 37.8 years (95% confidence interval, 34.2-39.1); 24hUFC, 2370 nmol/24 h (2087-2632), fractures were confirmed in 81 (44.5%) patients, with 70 suffering from vertebral fractures, which were multiple in 53 cases; 24 patients reported non-vertebral fractures. The mean spine TBS was 1.207 (1.187-1.228), and TBS Z-score was -1.86 (-2.07 to -1.65); area under the curve (AUC) was used to predict fracture (mean spine TBS) = 0.548 (95% CI, 0.454-0.641)). In the final regression model, the only predictor of fracture occurrence was 24hUFC levels (p = 0.001), with an increase of 1.041 (95% CI, 1.019-1.063), calculated for every 100 nmol/24-h cortisol elevation (AUC (24hUFC) = 0.705 (95% CI, 0.629-0.782)). CONCLUSIONS: Young patients with CS have a low TBS. However, the only predictor of low traumatic fracture is the severity of the disease itself, indicated by high 24hUFC levels.

Diagnostic performance of late-night salivary cortisol measured by automated electrochemiluminescence immunoassay in obese and overweight patients referred to exclude Cushing's syndrome.

This study estimates diagnostic performance of late-night salivary cortisol (LNSC) as measured by automated electrochemiluminescence immunoassay (ECLIA), evaluates the clinical implication of two consecutive LNSC measurements, and compares its accuracy with enzyme-linked immunosorbent assay (ELISA) and serum cortisol after low-dose dexamethasone suppression test (DST) in obese and overweight patients referred for suspected Cushing's syndrome (CS). One hundred twenty three consecutive obese and overweight referred patients and 98 healthy volunteers provided two saliva samples collected at 23:00 using a Salivette (Sarstedt, Germany), assayed by ECLIA (Cobas e601) and ELISA. The patients underwent DST and were further evaluated until CS was pathologically confirmed (n = 45) or excluded. Diagnostic performance of LNSC was evaluated by receiver operating characteristic (ROC) analysis. The total areas under the curve (AUC) were calculated to compare the different tests. We found that a cut-off value of 9.4 nmol/l can differentiate CS among obese and overweight patients with sensitivity of 84.4 % (95% CI 71.2-92.2), specificity of 92.3 % (95% CI 84.2-96.4), and diagnostic odds ratio of 65.1 (95% CI 20.4-207.6). No difference was found between AUCs from the first, second, and the mean from the two LNSC measurements (ECLIA), LNSC (ELISA), or DST. The single LNSC (ECLIA) and DST improved the sensitivity and specificity for concordant results up to 100 and 97.4 %, respectively. In conclusion, due to its automation and its comparable diagnostic performance, ECLIA is preferable as a first-line LNSC screening test for CS. The initial use of single LNSC followed by DST provides better diagnostic performance for concordant results.