Pegvisomant and pasireotide in PRL and GH co-secreting vs GH-secreting Pit-NETs.

The objective of the study was to evaluate the efficacy of second-line therapies in patients with acromegaly caused by a growth hormone (GH) and prolactin (PRL) co-secreting pituitary neuroendocrine tumor (GH&PRL-Pit-NET) compared to their efficacy in patients with acromegaly caused by a GH-secreting pituitary neuroendocrine tumor (GH-Pit-NET). This is a multicenter retrospective study of patients with acromegaly on treatment with pasireotide and/or pegvisomant. Patients were classified in two groups: GH&PRL-Pit-NETs when evidence of hyperprolactinemia and immunohistochemistry (IHC) for GH and PRL was positive or if PRL were >200 ng/dL regardless of the PRL-IHC and GH-Pit-NETs when the previously mentioned criteria were not met. A total of 28 cases with GH&PRL-Pit-NETs and 122 with GH-Pit-NETs met the inclusion criteria. GH&PRL-Pit-NETs presented at a younger age, caused hypopituitarism, and were invasive more frequently than GH-Pit-NETs. There were 124 patients treated with pegvisomant and 49 with pasireotide at any time. The efficacy of pegvisomant for IGF-1 normalization was of 81.5% and of pasireotide of 71.4%. No differences in IGF-1 control with pasireotide and with pegvisomant were observed between GH&PRL-Pit-NETs and GH-Pit-NETs. All GH&PRL-Pit-NET cases treated with pasireotide (n = 6) and 82.6% (n = 19/23) of the cases treated with pegvisomant normalized PRL levels. No differences in the rate of IGF-1 control between pegvisomant and pasireotide were detected in patients with GH&PRL-Pit-NETs (84.9% vs 66.7%, P = 0.178). We conclude that despite the more aggressive behavior of GH&PRL-Pit-NETs than GH-Pit-NETs, no differences in the rate of IGF-1 control with pegvisomant and pasireotide were observed between both groups, and both drugs have shown to be effective treatments to control IGF-1 and PRL hypersecretion in these tumors.

T1DiabetesGranada: a longitudinal multi-modal dataset of type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1D) patients face daily difficulties in keeping their blood glucose levels within appropriate ranges. Several techniques and devices, such as flash glucose meters, have been developed to help T1D patients improve their quality of life. Most recently, the data collected via these devices is being used to train advanced artificial intelligence models to characterize the evolution of the disease and support its management. Data scarcity is the main challenge for generating these models, as most works use private or artificially generated datasets. For this reason, this work presents T1DiabetesGranada, an open under specific permission longitudinal dataset that not only provides continuous glucose levels, but also patient demographic and clinical information. The dataset includes 257 780 days of measurements spanning four years from 736 T1D patients from the province of Granada, Spain. This dataset advances beyond the state of the art as one the longest and largest open datasets of continuous glucose measurements, thus boosting the development of new artificial intelligence models for glucose level characterization and prediction.

Lower trabecular bone score in type 2 diabetes mellitus: A role for fat mass and insulin resistance beyond hyperglycaemia.

AIMS: To examine the clinical and biochemical determinants of trabecular bone score (TBS) in type 2 diabetes mellitus (T2DM) patients. METHODS: Cross-sectional observational study in 137 T2DM patients (49-85 years). Whole-body fat percentage was estimated using the relative fat mass (RFM) equation. Bone mineral density (BMD) and TBS were assessed using dual-energy X-ray absorptiometry and TBS iNsight Software respectively. RESULTS: T2DM patients showed significantly lower TBS values (P < 0.001) despite significantly higher lumbar spine BMD (LS-BMD) (P = 0.025) compared to controls. TBS values ​​were negatively correlated with body mass index (BMI) (P < 0.001), waist circumference (P < 0.001), and HOMA-2IR index (P = 0.004) and positively correlated with sex hormone-binding globulin (SHBG) (P = 0.01) and LS-BMD (P = 0.003). RFM was negatively associated with TBS in both males (P < 0.001) and females (P = 0.005). The multivariate analysis showed that RFM, HOMA2-IR (negative), SHBG, and LS-BMD (positive) were the variables independently associated with TBS. ROC analysis revealed RFM as the variable with the highest predictive value for risk of degraded bone microarchitecture. CONCLUSIONS: The adiposity estimated by RFM may negatively affect TBS and this relationship may be influenced by insulin resistance and SHBG. RFM could act as a key estimator of degraded bone microarchitecture risk in the T2DM population.

Osteoglycin as a Potential Biomarker of Mild Kidney Function Impairment in Type 2 Diabetes Patients.

Osteoglycin (OGN) could be a biomarker of mild kidney function impairment in type 2 diabetes (T2D). Our study aimed to determine the association between serum OGN and impaired kidney function risk in T2D patients and to analyze its potential role as an estimator of kidney disturbances in this population. This cross-sectional study included 147 T2D patients (65 ± 8 years, 58.5% males), and 75 healthy controls (63 ± 10 years, 36% males). Circulating OGN levels were determined by ELISA. Linear regression modeling was performed to determine the variables influencing circulating OGN, and an ROC curve was plotted to assess the usefulness of OGN as an estimator of diabetic kidney disease risk. Circulating OGN was significantly increased in T2D patients compared to controls (18.41 (14.45-23.27) ng/mL vs. 8.74 (7.03-12.35) ng/mL; p < 0.001). We found a progressive increase in serum OGN according to the severity of kidney impairment in T2D patients (normal kidney function: 16.14 (12.13-20.48) ng/mL; mildly impaired kidney function: 19.15 (15.78-25.90) ng/mL; moderate impaired kidney function: 21.80 (15.06-29.22) ng/mL; p = 0.006). Circulating OGN was an independent estimator of mildly impaired kidney function risk in T2D patients. We suggest that serum OGN could act as an albuminuria-independent biomarker of incipient kidney dysfunction in T2D patients.

Usefulness of Trabecular Bone Score (TBS) to Identify Bone Fragility in Patients with Primary Hyperparathyroidism.

BACKGROUND: Patients with primary hyperparathyroidism usually show decreased bone strength that are often not well diagnosed by conventional Dual-energy X-ray absorptiometry (DXA). Trabecular Bone Score (TBS) is a new technique for assessing bone microarchitecture indirectly. This cross-sectional study evaluates the usefulness of TBS in patients with primary hyperparathyroidism in clinical practice. METHODOLOGY: Bone mineral density (BMD) by DXA and TBS values by TBS InSight® software were determined in 72 patients with primary hyperparathyroidism to analyze its relationship with fragility fractures. A receiver operating curve was performed to evaluate the usefulness of TBS as predictor of fragility fractures. FRAX index with and without adjustment by TBS was calculated. Additionally, longitudinal data of a subgroup of patients according to the therapeutic management were also evaluated. RESULTS: A total of 51.4% of the patients showed degraded microarchitecture while only 37.5% of them were diagnosed of osteoporosis by DXA. No significant correlation was found between TBS values and BMD parameters. However, TBS values were lower in osteoporotic patients compared to those classified as normal by BMD (1.16 ± 0.12vs 1.26 ± 0.17; p = 0.043) and in patients with fragility fractures compared to nonfractured patients (1.19 ± 0.03vs 1.24 ± 0.02, p < 0.001). The area under the curve for TBS performed better than the combination of femoral, hip and spine-BMD for prevalent fractures (0.714vs 0.679). TBS-adjusted FRAX was higher than nonadjusted model for both major osteoporotic and hip fracture (4.5% vs 3%; 0.9% vs 0.7%; p < 0.001). At follow-up, an improvement in TBS values was observed in treated patients (medical or surgical) vs nontreated close to significance (1.27 ± 0.10vs 1.24 ± 0.11, p = 0.074). CONCLUSIONS: TBS could be a useful tool to identify increased fracture risk in patients with primary hyperparathyroidism underdiagnosed by BMD. Moreover, FRAX adjusted by TBS could be a more robust tool for predicting the risk of osteoporotic fracture to help in therapeutic decisions in this population.

Serum levels of bone resorption markers are decreased in patients with type 2 diabetes.

Previous studies of bone turnover markers in diabetes are limited, and the results are conflicting. Our aim was to evaluate differences in bone turnover markers and i-PTH between T2DM and non-diabetes subjects. Cross-sectional study including 133 subjects (78 T2DM, 55 without diabetes). BMD were measured by dual X-ray absorptiometry. Bone turnover markers were determined in serum. Serum levels of bone resorption markers (CTX and TRAP5b) were lower in T2DM compared with non-diabetes subjects. There were no differences in bone formation markers. i-PTH serum levels were lower in T2DM: 38.35 ± 18.20 pg/ml versus 50.22 ± 18.99 pg/ml, P < 0.05. TRAP5b and CTX were positively correlated with i-PTH (CTX: r = 0.443, P < 0.001; TRAP5b: r = 0.180, P = 0.047). There was an inverse relationship between TRAP5b levels and diabetes duration (r = -0.269, P = 0.021). T2DM patients have lower levels of bone resorption markers, and i-PTH compared with subjects without diabetes. Lower levels of PTH may induce a low turnover state as reflected by lower levels of bone resorption markers, and this situation may influence the higher risk of fracture of T2DM.

Hiperplasia adrenal macronodular bilateral ACTH independiente y síndrome de Cushing subclínico / ACTH-independent macronodular adrenal hyperplasia and subclinical Cushing's syndrome

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Serum osteoprotegerin and sex steroid levels in patients with prostate cancer.

The relationship between sex steroids and osteoprotegerin (OPG) in patients with prostate cancer is not well established. Our aim was to evaluate serum OPG levels in patients with prostate cancer and its relationship with sex steroids, bone mineral density, bone turnover markers, and fractures. We performed a cross-sectional study including 91 patients with prostate cancer. We determined: bone mineral density by dual-energy x-ray absorptiometry, bone turnover markers, serum levels of sex steroids and osteoprotegerin, and prevalent radiographic vertebral fractures. Serum OPG levels were higher in patients with vertebral fractures (8.02 ± 2.0 vs 4.91 ± 0.28 pmol/L; P < .05). OPG level and the duration of hormonal therapy were related (r = 0.299, P = .004), but this association did not persist after adjustment for age. In patients without androgen deprivation therapy, serum OPG levels were correlated with the levels of total testosterone (r = 0.508, P = .001) and bioavailable testosterone (r = 0.311, P = .037). In patients receiving androgen deprivation therapy, serum OPG levels were correlated with levels of total estradiol (r = 0.199, P = .18), bioavailable estradiol (r = 0.37, P = .009), and free estradiol (r = 0.349, P = .016). In conclusion, in patients with prostate cancer treated with androgen deprivation therapy, serum OPG levels were correlated with the levels of total estradiol, bioavailable estradiol, and free estradiol. Our hypothesis is that in patients with androgen deprivation therapy, the higher relative estrogen levels could stimulate OPG production in response to the higher resorption state. Future prospective studies are needed to clarify the role of OPG in androgen deprivation therapy-mediated bone loss.