Calcifediol Rather Than Cholecalciferol for a Patient Submitted to Malabsortive Bariatric Surgery: A Case Report

Vitamin D deficiency following malabsorptive bariatric surgery can lead to osteomalacia. We report a patient with severe vitamin D deficiency following malabsorptive bariatric surgery successfully treated with calcifediol but not cholecalciferol. A 40-year-old woman, submitted to biliopancreatic diversion 20 years before and chronically treated with 50,000 IU cholecalciferol weekly, was admitted to our Endocrine Unit because of severe lower back pain, muscle weakness, and generalized muscular hypotrophy, associated with hypocalcemia and elevated PTH levels. Initial evaluation revealed low serum albumin, low albumin-corrected serum calcium (7.36 mg/dL), high serum PTH (240 pg/mL), bone-specific alkaline phosphatase (125 μg/L) and 1,25-dihydroxyvitamin D (112 pg/mL) concentrations, undetectable serum 25-hydroxyvitamin D (<7 ng/mL), and evidence of reduced liver function. Bone mineral density was markedly low. Normocalcemia was initially restored with intravenous albumin and calcium gluconate. Treatment with calcitriol (0.5 μg three times daily) and oral calcium carbonate (1000 mg daily) was simultaneously started and cholecalciferol was replaced with calcifediol [125 μg (5000 IU) daily)]. During follow-up the calcifediol dose was progressively tapered to 25 μg (1000 IU) daily and the calcitriol dose was progressively reduced and finally withdrawn. Serum albumin and other biochemical parameters normalized, bone mineral density significantly increased, and the patient's clinical conditions progressively improved, with a substantial recovery of autonomy. Serum vitamin D binding protein at the last observation was in the normal range. Our data suggest that calcifediol might be more efficacious than cholecalciferol for prevention and treatment of vitamin D deficiency in patients treated by malabsorptive bariatric surgery

Normocalcemic primary hyperparathyroidism: a survey in a small village of Southern Italy

We investigated the prevalence of normocalcemic primary hyperparathyroidism (NPHPT) in the adult population living in a village in Southern Italy. All residents in 2010 (n=2045) were invited by calls and 1046 individuals accepted to participate. Medical history, calcium intake, calcium, albumin, creatinine, parathyroid hormone (PTH) and 25OHD were evaluated. NPHPT was defined by normal albumin-adjusted serum calcium, elevated plasma PTH, and exclusion of common causes of secondary hyperparathyroidism (SHPT) (serum 25OHD <30 ng/ml, estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m(2) and thiazide diuretics use), overt gastrointestinal and metabolic bone diseases. Complete data were available for 685 of 1046 subjects. Twenty subjects did not meet the inclusion criteria and 341 could not be evaluated because of thawing of plasma samples. Classical PHPT was diagnosed in four women (0.58%). For diagnosing NPHPT the upper normal limit of PTH was established in the sample of the population (n=100) who had 25OHD ≥30 ng/ml and eGFR ≥60 ml/min per 1.73 m(2) and was set at the mean+3s.d. Three males (0.44%) met the diagnostic criteria of NPHPT. These subjects were younger and with lower BMI than those with classical PHPT. Our data suggest, in line with previous studies, that NPHPT might be a distinct clinical entity, being either an early phenotype of asymptomatic PHPT or a distinct variant of it. However, we cannot exclude that NPHPT might also represent an early phase of non-classical SHPT, since other variables, in addition to those currently taken into account for the diagnosis of NPHPT, might cumulate in a normocalcemic subject to increase PTH secretion

AI-SCoRE (artificial intelligence-SARS CoV2 risk evaluation): a fast, objective and fully automated platform to predict the outcome in COVID-19 patients

Purpose To develop and validate an effective and user-friendly AI platform based on a few unbiased clinical variables integrated with advanced CT automatic analysis for COVID-19 patients' risk stratification. Material and Methods In total, 1575 consecutive COVID-19 adults admitted to 16 hospitals during wave 1 (February 16-April 29, 2020), submitted to chest CT within 72 h from admission, were retrospectively enrolled. In total, 107 variables were initially collected; 64 extracted from CT. The outcome was survival. A rigorous AI model selection framework was adopted for models selection and automatic CT data extraction. Model performances were compared in terms of AUC. A web-mobile interface was developed using Microsoft PowerApps environment. The platform was externally validated on 213 COVID-19 adults prospectively enrolled during wave 2 (October 14-December 31, 2020). Results The final cohort included 1125 patients (292 non-survivors, 26%) and 24 variables. Logistic showed the best performance on the complete set of variables (AUC = 0.839 +/- 0.009) as in models including a limited set of 13 and 5 variables (AUC = 0.840 +/- 0.0093 and AUC = 0.834 +/- 0.007). For non-inferior performance, the 5 variables model (age, sex, saturation, well-aerated lung parenchyma and cardiothoracic vascular calcium) was selected as the final model and the extraction of CT-derived parameters was fully automatized. The fully automatic model showed AUC = 0.842 (95% CI: 0.816-0.867) on wave 1 and was used to build a 0-100 scale risk score (AI-SCoRE). The predictive performance was confirmed on wave 2 (AUC 0.808; 95% CI: 0.7402-0.8766). Conclusions AI-SCoRE is an effective and reliable platform for automatic risk stratification of COVID-19 patients based on a few unbiased clinical data and CT automatic analysis

Parathyroid tumorigenesis

Primary hyperparathyroidism (PHPT) is a common endocrinopathy, mostly caused by a monoclonal parathyroid adenoma. This review primarily summarizes current knowledge concerning molecular pathogenesis of familial forms of primary hyperparathyroidism and sporadic (non familial) parathyroid tumors. The hereditary syndromes have been recognized as exhibiting Mendelian inheritance patterns and include multiple endocrine neoplasia types 1 (MEN 1) and 2A (MEN 2A), hereditary hyperparathyroidism- jaw tumor (HPT-JT) syndrome, familial isolated hyperparathyroidism (FIHP), familial hypocalciuric hypercalcemia (FHH) and severe neonatal hyperparathyroidism (NSHPT). Inactivating mutations of MEN1 tumor suppressor gene are responsible for MEN 1 in >90% of cases. MEN1 gene has also an established role in the pathogenesis of sporadic parathyroid adenomas. Allelic loss (LOH) of chromosome 11q13 occurs in about 30-40% and somatic mutation of MEN1 gene occur in about 12-20% of sporadic parathyroid adenomas. A mouse model of MEN1 deficiency causes a phenotype that includes the same range of major endocrine tumors as in MEN 1 patients, and exhibits multistage tumor progression with metastatic potential. Hormonal disturbances, such as abnormal PTH and insulin levels, were also observed in these mice. Mutations in a newly identified tumor suppressor gene, HRPT2, have been recently associated with the development of HPT-JT. HRPT2 mutations are also frequent in sporadic parathyroid carcinomas and central to their pathogenesis. MEN1 and HRPT2 genes mutations have also been found in a subset of FIHP families. FHH and NSHPT represent the mildest and severest variants of PHPT, respectively. Both cause hypercalcemia from birth and atypical PHPT that always uniquely persists after subtotal parathyroidectomy. Future identification of additional oncogenes and tumor suppressor genes will clarify the molecular basis of abnormalities of parathyroid proliferation and regulatory function and other specific features unique to the parathyroid tumorigenesis