Plasma calcium concentration during detoxification predicts neural cue-reactivity and craving during early abstinence in alcohol-dependent patients

Recent studies on the pathophysiology of alcohol dependence suggest a link between peripheral calcium concentrations and alcohol craving. Here, we investigated the association between plasma calcium concentration, cue-induced brain activation, and alcohol craving. Plasma calcium concentrations were measured at the onset of inpatient detoxification in a sample of N = 115 alcohol-dependent patients. Alcohol cue-reactivity was assessed during early abstinence (mean 11.1 days) using a functional magnetic resonance imaging (fMRI) alcohol cue-reactivity task. Multiple regression analyses and bivariate correlations between plasma calcium concentrations, clinical craving measures and neural alcohol cue-reactivity (CR) were tested. Results show a significant negative correlation between plasma calcium concentrations and compulsive alcohol craving. Higher calcium levels predicted higher alcohol cue-induced brain response in a cluster of frontal brain areas, including the dorsolateral prefrontal cortex (dlPFC), the anterior prefrontal cortex (alPFC), and the inferior (IFG) and middle frontal gyri (MFG). In addition, functional brain activation in those areas correlated negatively with craving for alcohol during fMRI. Higher peripheral calcium concentrations during withdrawal predicted increased alcohol cue-induced brain activation in frontal brain areas, which are associated with craving inhibition and cognitive control functions. This might indicate that higher plasma calcium concentrations at onset of detoxification could modulate craving inhibition during early abstinence.Trial registration number: DRKS00003388; date of registration: 14.12.2011.

Hypocalcemia in the Critically Ill Pediatric Patients: A Review

Hypocalcemia is common in the critically ill pediatric patients. However, the diagnosis of hypocalcemia in this population is complicated by interpretation of the total plasma calcium concentration. These limitations are principally the result of the effects of hypoalbuminemia and disorders of acid-base balance on the total calcium concentration. Thus, measurement of ionized calcium can be critical in determining an individual’s true serum calcium status. In this review, we first described the regulation of normal calcium metabolism and then focus on the various etiologies of hypocalcemia, which are encountered in the pediatric critical care settings. The approach to the treatment of hypocalcemia and the current consensus on treatment of hypocalcemia in the critically ill pediatric patient is also presented. DS (Child) H J 2019; 35(2) : 156-161

Plasma Calcium Concentration Modifies the Blood Sodium During Hemodialysis: Lessons from Hard Water Syndrome

Introduction. Extracellular sodium (Na+) concentration is maintained within a tight physiological range due to hormonal control, that mainly modulates thirst, Na+ and water renal excretion. Extra-renal regulation of Na+ and water homeostasis is only partially understood. Recently it has been debated whether the osmotically inactive Na+ storage is fixed or variable. Methods. In the present study, fourteen End-Stage Renal Disease (ESRD) patients treated by chronic hemodialysis underwent by accident to a sharp increase in plasmatic calcium (Ca+2) levels due to the failure of the water control system, leading to the so-called hard water syndrome. The levels of plasmatic Ca+2 after 1 hr of hemodialysis were correlated with urea, Na+, potassium (K+) and creatinine levels. Eleven ESRD patients treated with hemodialysis under similar conditions were used as controls. Results. The hard water syndrome resulted in hypercalcemia, while mean plasma levels of Na+, K+ and urea were not different compared to controls. Plasma creatinine levels were slightly but significantly higher that control. A correlation analysis on the measured variables has showed a positive correlation between plasma Ca+2 and Na+ levels (Pearson=0.428, p=0.032), and the absence of any correlation with K+, creatinine and urea concentration. Conclusions. Our study suggests that acute changes in plasmatic Ca+2 levels may affect Na+ concentration in the absence of renal function; it is possible that hypercalcemia may trigger Na+ release from the osmotically inactive storage. These data further support previous observations on the interplay of sodium and calcium at extrarenal sites.

USE OF TERIPARATIDE IN A FOUR YEAR OLD PATIENT WITH AUTOSOMAL DOMINANT HYPOCALCAEMIA

AimWe report the effective use of the synthetic parathyroid hormone (PTH) teriparatide to treat a 4 year old boy with autosomal dominant hypocalcaemia.BackgroundAutosomal Dominant hypocalcaemia is characterised by hypocalcaemia with a lack of parathyroid hormone (PTH) response and inappropriately high urinary calcium excretion. It is caused by gain-of-function mutations in the extracellular calcium sensing receptor which then “over-reads” the extracellular fluid concentration of calcium resulting in suppression of PTH secretion. This then reduces PTH-mediated calcium reabsorption in the distal nephron. Treatment of hypocalcaemia with vitamin D analogues and calcium supplements results in further increases in urinary calcium concentrations, frequently causing nephrocalcinosis and progressive renal damage.Our four year old male patient presented in the neonatal period with seizures secondary to hypocalcaemia and low PTH levels. He suffered repeated seizures with associated tetany. Treatment with alfaclacidol and calcium supplements was able to provide seizure control, however episodes of tetany continued. A heterozygous, activating mutation of the extracellular calcium sensing receptor (c.2528C>A; p.Ala843Glu) was confirmed at age 2. The treatment caused significant hypercalciuria and nephrocalcinosis with a reduction in GFR to 73 ml/mim/m.2 Continuing this therapy would have resulted in end stage kidney disease requiring dialysis/transplantation. The decision was made to try treatment with PTH in order to raise the plasma calcium concentration while minimising the increase in urinary calcium excretion.Funding for treatment was approved by specialised commissioning and treatment was commenced at a dose of 0.4 microg/kg BD.AdministrationTeriparatide is only available in a prefilled pen (Forsteo®) delivering 20 microg in 80 microlitre per dose. Following discussions with the pharmacy team at Great Ormond Street Hospital for Sick Children a protocol was developed to allow these set doses to be diluted prior to administration. By diluting the 20 microg dose to 0.5 ml in a 1 ml syringe a solution containing 40 microg/ml was obtained.OutcomeTreatment was started at 3.66 years of age. Pre-treatment adjusted plasma calcium concentration was 1.96 mmol/L and the urinary calcium excretion was 0.11 mmol/kg/day (normal<0.1). After 5 days of treatment the patient felt very much better and had more energy. The adjusted plasma calcium concentration had risen to 2.09 mmol/L and the urinary calcium excretion had fallen to 0.045 mmol/kg/day.Over the following 9 months the dose of alfacalcidol was reduced from 600 nanograms per day to 300 nanograms per day and calcium supplements were reduced from 16 mmol four times per day to zero. The teriparatide dose was increased from an initial dose of 2 microgram twice daily to 6 microgram twice daily. The plasma calcium has remained above 2 mmol/L apart from a period where further weaning of the alfacalcidol dose was attempted.Rather to our surprise, the patient did not experience symptoms of hypercalcaemia with plasma calcium concentrations within the normal range. His muscle power and tone has increased.We conclude that teriparatide is a useful agent for treating patients with gain-of-function mutations of the calcium-sensing receptor/autosomal dominant hypocalcaemia