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Background: Hypocalcaemia as a common complication after total thyroidectomy [23-40% in University Malaya Medical Centre (UMMC)] and could result in prolonged hospital stay. We compared the early hypocalcaemia rate between prophylactic infusion of calcium and placebo among post total thyroidectomy patients and to establish whether prophylactic intravenous infusion of calcium reduces the rate of hypocalcaemia in the first 48 hours after surgery. Methods: Patients undergoing elective total thyroidectomy in UMMC between June 2020-May 2022, were recruited and randomized to receive placebo or prophylactic calcium infusion. Both groups of patients received same dosages of post-operative prophylactic vitamin D and oral calcium. Early hypocalcaemia (within 48 hours) rate after surgery was the primary outcome and duration of hospital stay was the secondary outcome. The data collected was analysed using per-protocol analysis. Results: Thirty-four patients were randomized equally (1:1) into both arms. No differences in the early hypocalcaemia rate between the intervention and placebo arms (0% vs. 5.8%, P>0.05). The median serum calcium levels were comparable between the intervention and placebo arms at 6 hours (2.33 vs. 2.37 mmol/L, P=0.59) and 48 hours (2.26 vs. 2.23 mmol/L, P=0.19) post-surgery. However, the median serum calcium level at 24 hours was statistically significantly higher in the intervention arm than the placebo arm (2.31 vs. 2.22 mmol/L, P=0.02). Similar duration of hospital stay between the both groups (2 vs. 2 days, P=0.81). Conclusions: Routine prophylactic calcium infusion with oral calcium and vitamin D does not diminish the rate of early symptomatic hypocalcaemia post total thyroidectomy in a low-risk group. However, its usefulness needs to be further assessed in a large scale randomized controlled trial (RCT) incorporating more bigger population. Trial Registration: Registered on ClinicalTrials.gov (NCT04491357).

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INTRODUCTION: After total thyroidectomy (TT), postoperative hypoparathyroidism (PH) is the most frequent complication. Yet, management strategies for PH remain disputed. The aim of this study was to evaluate outcomes of a reactive supplementation in case of symptomatic PH. Additionally, risk factors for symptomatic PH and readmission due to PH were analyzed. MATERIALS AND METHODS: All consecutive patients who underwent TT or completion from 2017 to 2022 were considered for inclusion. During this period, a reactive to symptom vitamin-calcium supplementation was used. The primary outcome was the occurrence of severe PH after discharge resulting in readmission. RESULTS: Overall, 307 patients were included, of which 98 patients (31.9%) developed symptomatic PH including 43 patients before discharge. Independent risk factors for developing symptomatic PH were age (p = 0.010) and postoperative day 1 (POD1) PTH level (p < 0.001). Overall, 264 patients (86%) did not present PH before discharge and were discharged home. Among them, 55 patients (20.8%) experienced symptomatic PH, requiring readmission in 18 patients. The overall readmission rate owing to symptomatic PH requiring intravenous supplementation despite oral vitamin-calcium supplementation was 6.8% (n = 18). Independent risk factors for symptomatic PH-related readmission were age (p = 0.007) and POD1 PTH level (p < 0.001). Adequate cut-off values for predicting readmission were POD1 albumin-adjusted calcium = 2.1 mmol/l (Sensibility = 0.95, Specificity = 0.30) and POD1 PTH = 11.5 pg/ml (Sensibility = 0.90, Specificity = 0.71). CONCLUSION: Supplementing only symptomatic patients was safe and efficient. This attitude does not alter on morbidity, mortality or readmission rate which is in line with current literature.

Asunto(s)

Suplementos Dietéticos , Hipoparatiroidismo , Readmisión del Paciente , Complicaciones Posoperatorias , Tiroidectomía , Humanos , Tiroidectomía/efectos adversos , Hipoparatiroidismo/etiología , Femenino , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Factores de Riesgo , Readmisión del Paciente/estadística & datos numéricos , Calcio/sangre , Calcio/administración & dosificación , Adulto , Estudios Retrospectivos , Anciano , Vitaminas/administración & dosificación , Vitaminas/uso terapéutico

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Proton pump inhibitors (PPIs) are one of the most frequently used medications worldwide. The side effects of this class of drugs have been widely studied. However, their impact on the electrolyte balance is frequently forgotten. Long-term PPI administration can lead to profound electrolyte disturbances, namely hypomagnesaemia as well as, secondary to very low magnesium levels, hypocalcaemia and hypokalaemia. In this paper we comprehensively review the complexity of the mechanisms contributing to electrolyte imbalance following PPI (proton pump inhibitors) by changing the pH in the intestinal lumen, interfering with the active cellular transport of magnesium regulated by the transient receptor potential melastatin cation channels TRPM6 and TRPM7. The accompanying hypomagnesaemia causes unblocking of the renal outer medullary potassium channel (ROMK), which results in increased potassium loss in the ascending limb of the loop of Henle. Hypokalaemia caused by hypomagnesaemia is resistant to potassium supplementation because the loss of this element in urine increases with the supply of potassium. Additionally, within the calcium-sensitive receptor (CASR), dissociation of magnesium from the alpha subunit of G protein caused by hypomagnesaemia increases its activity, leading to inhibition of PTH secretion and hypocalcaemia resistant to calcium supplementation. All this means that in some patients, chronic use of proton pump inhibitors by affecting the absorption of magnesium, may lead to life-threatening electrolyte disorders.

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Hipocalcemia , Hipopotasemia , Inhibidores de la Bomba de Protones , Inhibidores de la Bomba de Protones/efectos adversos , Humanos , Hipocalcemia/inducido químicamente , Hipopotasemia/inducido químicamente , Magnesio/metabolismo , Magnesio/sangre , Deficiencia de Magnesio/inducido químicamente , Femenino , Masculino

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PURPOSE: Thyroidectomy is the treatment of choice for malignant thyroid diseases as well as for benign conditions who cannot be treated medically. The most common complication following thyroidectomy is hypocalcaemia and hypoparathyroidism that usually results from accidental damage or removal of one or more parathyroid glands. Parathyroid gland autotransplantation has been one of the most common intraoperative strategies applied to tackle this problem. The aim of this study is to assess whether parathyroid auto trasnplantation is associated with a decrease in postoperative hypoparathyroidism following thyroidectomy. METHODS: We conducted a thorough systematic review and meta-analysis of relevant studies published up to February 2024 in MEDLINE, Scopus, Embase and Cochrane Library databases. We compared the incidence of postoperative hypoparathyroidism between the group of patients who underwent autotransplantation and the patients were the parathyroid glands were preserved in situ. A trial sequential analysis was performed subsequently to confirm the findings. RESULTS: Eighteen studies fulfilled all the inclusion criteria and were ultimately included in our study. The total number of patients was 8,182 with 4,029 receiving parathyroid gland autotransplantation. Autotransplantation was associated with a higher incidence of immediate (within 24 h) and transient hypoparathyroidism (RR 1.58, 1.45-1.73, CI 95%, p < 0.00 and RR 1.60, 1.47-1.76, CI 95%, p < 0.001, respectively). However, it did not affect the rate of permanent postoperative hypoparathyroidism (RR 0.85, 0.51-1.41, CI 95%, p = 0.54). The subsequent trial sequential analysis confirmed these findings. CONCLUSION: Parathyroid autotransplantation does not lead to a decrease in the rate of permanent post-thyroidectomy hypoparathyroidism. The most important factor to decrease its incidence remains the accurate identification and preservation of the parathyroid glands intraoperatively.

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INTRODUCTION: Postoperative hypocalcaemia is common after thyroidectomy. This study aimed to evaluate whether a standardised post-thyroidectomy protocol using prophylactic calcium and calcitriol reduces hypocalcaemia incidence after total thyroidectomy in children and adolescents. METHODS: A cohort children and adolescents ≤18 years of age undergoing total thyroidectomy between January 2016 and October 2022 in one institution were retrospectively identified and divided into pre-protocol and post-protocol groups. The primary outcome measure was hypocalcaemia (total serum calcium of <2.0 mmol/L; ionised serum calcium of 0.9 mmol/L). Secondary outcome measures were the occurrence of hypercalcaemia (serum Calcium >2.7 mmol/L; ionised calcium >1.31 mmol/L), length of hospitalisation and number of postoperative blood tests. RESULTS: There were 22 patients in each group (mean age 11.8; SD 4.3 years, female 36 %). The rate of hypocalcaemia was significantly higher in the pre-protocol group than the post-protocol group (54 % vs 13.6 %, p = 0.010). Patients in the pre-protocol group had more inpatient blood tests (mean 5.4; SD 3.2) than the post-protocol group (mean 3.3; SD 1.8, p = 0.011), although the total postoperative blood test count was similar between the groups. Six (13.6 %) patients developed hypercalcaemia. The rate of hypercalcaemia was similar between groups (pre-protocol 2, 9.1 %; post-protocol 4, 18.1 %; p = 0.664). Length of hospitalisation was similar between groups. CONCLUSION: Our standardized protocol decreased hypocalcemia and inpatient blood tests after total thyroidectomy in children. Future research should explore if incorporating preoperative calcium and calcitriol treatment, along with intraoperative PTH levels for risk management, can further reduce hypocalcemia rates in paediatric patients.

Asunto(s)

Calcitriol , Calcio , Protocolos Clínicos , Hipocalcemia , Complicaciones Posoperatorias , Tiroidectomía , Humanos , Hipocalcemia/prevención & control , Hipocalcemia/etiología , Hipocalcemia/epidemiología , Hipocalcemia/sangre , Tiroidectomía/efectos adversos , Tiroidectomía/métodos , Femenino , Niño , Masculino , Adolescente , Estudios Retrospectivos , Calcio/sangre , Calcitriol/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/diagnóstico , Hormonas y Agentes Reguladores de Calcio/uso terapéutico

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BACKGROUND: Iatrogenic hypoparathyroidism is a common cause of postthyroidectomy hypocalcaemia. It has varying incidence rates after neck surgery in Saudi Arabia, ranging from 0.07% to 65.30%. Hypoparathyroidism can manifest with a spectrum of symptoms, ranging from mild to severe and life-threatening. This study aimed to assess the rate and predictors of iatrogenic hypoparathyroidism after thyroid surgery and its natural course. METHODS: This retrospective cohort study used a data collection form to extract patient information from the electronic healthcare system (Best-Care) for patients treated from 2017 to 2022. Patients' demographics, surgical specifics and biochemical profiles were recorded for subsequent analysis. RESULTS: Among the 343 patients who underwent thyroidectomy, 130 (37.9%) developed hypoparathyroidism, primarily within the first day after surgery. Calcium or vitamin D supplementation before surgery did not significantly influence hypoparathyroidism development. Notably, extensive combined lymph node dissection was significantly associated with postoperative hypoparathyroidism development (p = 0.0004). More patients who underwent central and lateral lymph node dissection (n = 19, 79.17%) developed hypoparathyroidism than patients who underwent central (n = 18, 40.91%) or lateral (n = 8, 38.10%) dissection alone. Permanent hypoparathyroidism was observed in 40 patients (11.66%). CONCLUSION: This study revealed a high incidence of iatrogenic hypoparathyroidism and high rates of permanent hypoparathyroidism. Further research is warranted to better comprehend the risk factors and optimise management strategies for iatrogenic hypoparathyroidism. Overall, our findings emphasise the need for vigilant monitoring and effective management of patients undergoing thyroidectomy and the significance of postoperative replacement therapies.

Asunto(s)

Hipoparatiroidismo , Enfermedad Iatrogénica , Complicaciones Posoperatorias , Tiroidectomía , Humanos , Tiroidectomía/efectos adversos , Hipoparatiroidismo/etiología , Hipoparatiroidismo/epidemiología , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Hipocalcemia/etiología , Hipocalcemia/epidemiología , Anciano , Arabia Saudita/epidemiología , Incidencia , Estudios de Cohortes , Factores de Riesgo

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We determined the association between urine pH and blood acid-base indicators and assessed a urine pH cut-off value to predict severe metabolic acidosis under field conditions in cows fed acidogenic diets. Eighty-six cows were sampled for urine and blood. Urine pH was evaluated immediately after collection, and blood acid-base status was evaluated within 2 hours of collection using a portable blood analyzer. Twenty-five cows were classified as having severe metabolic acidosis (blood pH ≤ 7.4; bicarbonate < 24 mmol/L, base excess ≤ -0.5; PCO2 low to normal concentrations and urine pH between 4.88 and 5.71. There was a positive linear association between urine pH and blood pH (r = 0.46), and between urine pH and base excess (r = 0.74). The area under the ROC curve was 0.91 (CI 95 %= 0.84-0.96; good-excellent test). The optimal cut-off value for urine pH to categorize a cow with severe metabolic acidosis was 5.5 (94 % specificity and 72 % sensitivity). For each 0.1 unit of decrease in urine pH below 5.5, cows were 1.6 times (95 % CI= 1.3-2.1) more likely to exhibit a severe metabolic acidosis. We conclude that a urine pH of 5.5 or less is indicative of more life-threatening metabolic acidosis in dairy cows.

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Equilibrio Ácido-Base , Acidosis , Alimentación Animal , Enfermedades de los Bovinos , Dieta , Animales , Bovinos , Concentración de Iones de Hidrógeno , Acidosis/veterinaria , Femenino , Enfermedades de los Bovinos/sangre , Enfermedades de los Bovinos/orina , Alimentación Animal/análisis , Dieta/veterinaria , Orina/química

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Background: Coronavirus disease 2019 (COVID-19) infection has been associated with various endocrinopathies. Few literatures have reported cases of transient hypoparathyroidism in acute COVID-19 infections, or even exacerbation of hypocalcaemia in previously known hypoparathyroidism patients. The mechanism of hypocalcaemia in COVID-19 infection remains unclear. Case Description: Our patient is a young gentleman who was incidentally diagnosed with superior mesenteric artery (SMA) syndrome and symptomatic primary hypoparathyroidism while presenting with an acute COVID-19 infection. He initially presented with high-grade fever, followed by multiple episodes of vomiting and abdominal pain and subsequently hypocalcaemic symptoms such as tonic-clonic seizures and carpopedal spasms. A computed tomographic scan of his abdomen revealed a SMA syndrome while his blood investigation showed a parathyroid hormone (PTH)-dependent hypocalcaemia. His SMA syndrome was a result of severe malnourishment and improved with refeeding, but his primary hypoparathyroidism persisted despite having recovered for 6 months from the initial COVID-19 infection. There was no evidence to suggest a congenital cause of hypoparathyroidism. Conclusions: To the best of our knowledge this is the first case report that describe this unique case of persistent primary hypoparathyroidism related to COVID-19 infection. Parathyroid gland involvement in a COVID-19 infection is rare but not impossible. Further studies are needed to determine the mechanism and extent of damage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the parathyroid glands.

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BACKGROUND: One of the most common complications of total thyroidectomy is post-operative transient or persistent hypoparathyroidism that can cause symptomatic hypocalcaemia. To prevent this complication, shorten the period of hospitalization and reduce morbidity, routine supplementation of oral vitamin D and calcium has been suggested. This systematic review and meta-analysis aims to critically assess the association between pre-operative calcitriol supplementation and post-operative hypocalcaemia. METHODS: Randomized controlled trial studies were identified by searching PubMed, Scopus, and Google Scholar databases up to 30 March 2023. Screening of titles, abstracts, and full texts of articles were performed, and data were extracted for a meta-analysis. RESULTS: This meta-analysis includes data from nine randomized controlled trials with a total of 1259 patients but with significant heterogeneity. The results demonstrate that calcium levels were higher in patients who had pre-operative calcitriol supplementation, with a weighted mean difference (WMD) 0.18 (95% confidence interval (CI) = 0.00, 0.37). Pre-operative calcitriol supplementation did not lead to significant changes in parathyroid hormone (PTH) levels, with WMD -0.49 (95% CI: -1.91, 0.94). CONCLUSION: Pre-operative calcitriol supplementation leads to higher calcium levels, but the high heterogeneity of the included studies (79% to 98.7%) could affect the results.

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Introduction: The impact that vitamin D (vit D) has on a variety of medical conditions like diabetes, cardiovascular, oncological, and central nervous system disorders has been a topic of interest for many years now. It is well-known that vit D deficiency is substantially more common in epileptics than in healthy subjects. The current research was piloted to analyse the vit D levels of the blood in newborns with seizures, as well as mothers' vit D status included subjects. Materials and Methods: A cross-sectional examination was piloted at a tertiary care center, which had a neonatal intensive care unit (NICU). The subjects were neonates and their mothers. The levels of vit D were measured in term and late preterm newborns who had been brought to the NICU with convulsions. Term or late preterm infants who were healthy and hospitalized in the same hospital's postnatal unit as their mothers served as the controls for the study. Demographics, as well as the vit D levels of both the neonate and the mother, were estimated and compared and evaluated for any significance, keeping significance at less than 0.05. Results: Of the 72 neonates included, they were similarly distributed between the epileptic (37) and healthy subjects. (40) The mothersy subjects.cluded, they were sim D levels averaged 15.11 ded, they were similarly distributed b D levels of their newborns were 13.26 ± 5.12 ng/mL (P = 0.77). There was no significant variance between the healthy and epileptic neonates (P = 0.212). Conclusion: The current studyficant variance between the healthy and epileptic neonates (eptic with convulsions. Termserum vit D levels and epileptic activity in neonates. Nevertheless, the levels of the vitamin were < 20 ng/mL among all the neonates. Interventions to improve the vit D levels have to be implemented.

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Calcium-sensing receptors (CaSRs) are G protein-coupled receptors that help maintain Ca2+ concentrations, modulating calciotropic hormone release (parathyroid hormone (PTH), calcitonin and 1,25-dihydroxyvitamin D) by direct actions in the kidneys, gastrointestinal tract and bone. Variability in population calcium levels has been attributed to single nucleotide polymorphisms in CaSR genes, and several conditions affecting calcium and phosphate homeostasis have been attributed to gain- or loss-of-function mutations. An example is autosomal dominant hypercalciuric hypocalcaemia, because of a missense mutation at codon 128 of chromosome 3, as reported in our specific case and her family. As a consequence of treating symptomatic hypocalcaemia as a child, this female subject slowly developed progressive end-stage kidney failure because of nephrocalcinosis and nephrolithiasis. After kidney transplantation, she remains asymptomatic, with decreased vitamin D and elemental calcium requirements, stable fluid and electrolyte homeostasis during intercurrent illnesses and has normalised urinary calcium and phosphate excretion, reducing the likelihood of hypercalciuria-induced graft impairment. We review the actions of the CaSR, its role in regulating renal Ca2+ homeostasis along with the impact of a proven gain-of-function mutation in the CaSR gene resulting in autosomal dominant hypercalciuric hypocalcaemia before and after kidney transplantation.

Asunto(s)

Calcio , Homeostasis , Trasplante de Riñón , Receptores Sensibles al Calcio , Humanos , Receptores Sensibles al Calcio/genética , Femenino , Calcio/metabolismo , Hipocalcemia/genética , Hipocalcemia/etiología , Hipercalciuria/genética , Hipercalcemia/genética , Riñón/metabolismo , Mutación Missense , Nefrocalcinosis/genética , Fallo Renal Crónico/cirugía , Hipoparatiroidismo/congénito

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Wilson's disease (WD) encompasses diverse clinical symptoms involving the liver, nervous system, and kidneys. The fundamental cause of this condition is the build-up of copper in organs, mainly the hepatic and brain parenchyma. Here, we are reporting the hospital presentation of a male patient in his 20s who had been experiencing severe irritability, abdominal pain, distension, and yellowish discoloration of the skin for the previous 75 days. Upon examination of blood pressure, a refractory carpopedal spasm was found in him. In addition to Kayser-Fleischer (KF) rings in his cornea, he exhibited elevated 24-hour urine copper and serum ceruloplasmin (CP). He was diagnosed as a case of WD with a rare association of hypoparathyroidism.

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Although haemolysis is the most common source of preanalytical error in clinical laboratories, its influence on cattle biochemistry remains poorly understood. The effect of haemolysis and its clinical relevance were investigated in 70 samples in which haemolysis was artificially induced (by spiking with increasing amounts of haemolysate, yielding 0.0%, 0.2%, 0.5%, 1.0%, 2.5%, 5.0% and 10% haemolysis degree (HD)), focusing on key parameters for bovine metabolic health assessment, including albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), blood urea nitrogen (BUN), calcium (Ca), cholesterol, creatinine, creatine kinase (CK), gamma-glutamyl transferase (GGT), globulins, magnesium (Mg), phosphorus (P), total bilirubin (TBIL) and total proteins (TP). Preanalytical haemolysis significantly affected most (8 of 14) of the biochemical parameters analysed, leading to significant increases in concentrations of albumin (starting at 5% HD), cholesterol (at 5% HD) and P (at 10% HD) and to significant decreases in Ca (at 2.5% HD), creatinine (at 5% HD), globulins (at 10% HD), TBIL (at 2.5% HD) and TP (at 10% HD). Comparison of the present and previous data indicated that, for each parameter, the HD required to produce significant bias and the clinical relevance of over- and underestimation are variable and appear to depend on the analytical technique used. Therefore, different laboratories should evaluate the influence of haemolysis in their analytical results and provide advice to clinicians accordingly. Affected parameters should be interpreted together with clinical signs and other analytical data to minimize misinterpretations (false or masked variations). Finally, due to the significant impact on numerous parameters and the limited potential for correction, we recommend rejection of samples with >10% HD.

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Enfermedades de los Bovinos , Globulinas , Bovinos , Animales , Hemólisis , Creatinina , Colesterol , Calcio , Albúminas

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BACKGROUND: The most important factors affecting the development of postoperative hypocalcaemia (PH) include intraoperative trauma to the parathyroid glands, incidental parathyroidectomy (IP), and the surgeon's experience. In this study, we aimed to determine the incidence of IP, evaluate its effect on postoperative calcium levels and investigate the effect of surgeon experience and volume on IP incidence and postoperative calcium levels. METHODS: This retrospective study included 645 patients who underwent thyroid surgery at the Department of General Surgery, Kütahya Health Sciences University between September 2016 and March 2020. All patients underwent surgery at a single clinic by general surgeons experienced in thyroid surgery and their residents (3-5 years). RESULTS: Normal parathyroid glands were reported in 58 (8.9%) of 645 patients. In 5 (8.6%) of 58 patients the parathyroid gland was detected in the intrathyroidal region. PH developed in ten patients (17.2%) with incidental removal of the parathyroid glands. A statistically significant difference was found between the number of incidentally removed parathyroid glands and the development of hypocalcaemia (p<0.05). Normal parathyroid glands were reported in the pathology of 37 (7.9%) patients operated on by general surgeons and 22 (12.6%) patients operated on by their residents. PH developed in 39 (8.2%) patients operated on by general surgeons and in 8 (4.5%) patients operated on by their residents. CONCLUSIONS: We found that the complication rate during the resident training process was the same as that of experienced general surgeons. A thyroidectomy can be safely performed by senior residents during residential training.

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Hipocalcemia , Paratiroidectomía , Tiroidectomía , Humanos , Tiroidectomía/efectos adversos , Tiroidectomía/estadística & datos numéricos , Estudios Retrospectivos , Hipocalcemia/etiología , Hipocalcemia/epidemiología , Femenino , Paratiroidectomía/estadística & datos numéricos , Paratiroidectomía/efectos adversos , Persona de Mediana Edad , Masculino , Adulto , Anciano , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Incidencia , Hallazgos Incidentales , Competencia Clínica/estadística & datos numéricos , Glándulas Paratiroides/lesiones , Glándulas Paratiroides/cirugía , Calcio/sangre , Adulto Joven , Complicaciones Intraoperatorias/epidemiología , Complicaciones Intraoperatorias/etiología

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INTRODUCTION: Postoperative surgical hypoparathyroidism (PoSH) following thyroid surgery is an established complication. Several predictive factors have been identified including perioperative parathyroid hormone (PTH) levels. The aim of the study is to compare the drop in perioperative PTH to postoperative day 1 PTH in predicting hypocalcaemia and hypoparathyroidism. METHODS: Records of consecutive patients who had either total or completion thyroidectomy with or without central neck dissection in a 3-year period in a single thyroid surgery unit were accessed to retrieve data on demographics, pathology, surgery, perioperative biochemistry and management. RESULTS: Of 295 included patients, there were 227 (76.9%) females. Forty-five (15.3%) had completion thyroidectomy, and the rest had total thyroidectomy. Seventy-eight (26.4%) had concomitant central neck dissection. Sixty-four (21.7%) had hypocalcaemia on the day after surgery. Hypoparathyroidism persisted in 10.5% of patients at 6 months. Both day 1 PTH and a drop in PTH predicted day 1 hypocalcaemia (p < 0.001) and 6-month hypoparathyroidism (p < 0.001). The area under the receiver operating characteristic (ROC) curves for day 1 PTH and drop in PTH for the prediction of day 1 hypocalcaemia (0.729 vs 0.726, respectively) and for 6-month hypoparathyroidism (0.964 vs 0.958, respectively) were similar, albeit slightly better for day 1 PTH. CONCLUSIONS: Day 1 PTH is equivalent to (if not better than) drop in PTH in predicting short- and long-term PoSH. Preoperative PTH measurements may not be needed in the detection and/or management of PoSH after thyroid surgery.

Asunto(s)

Hipocalcemia , Hipoparatiroidismo , Hormona Paratiroidea , Complicaciones Posoperatorias , Tiroidectomía , Humanos , Hipoparatiroidismo/etiología , Hipoparatiroidismo/sangre , Hipoparatiroidismo/diagnóstico , Hormona Paratiroidea/sangre , Femenino , Tiroidectomía/efectos adversos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/etiología , Hipocalcemia/etiología , Hipocalcemia/diagnóstico , Hipocalcemia/sangre , Adulto , Estudios Retrospectivos , Anciano , Periodo Posoperatorio , Curva ROC , Disección del Cuello/efectos adversos , Valor Predictivo de las Pruebas , Periodo Perioperatorio

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PURPOSE: Hypocalcaemia upon arrival (HUA) to hospital is associated with morbidity and mortality in the trauma patient. It has been hypothesised that there is an increased incidence of HUA in patients receiving prehospital transfusion as a result of citrated blood products. This research aimed to determine if there was a difference in arrival ionised calcium (iCa) levels in trauma patients who did and did not receive prehospital transfusion. METHODS: We conducted a systematic review and meta-analysis of patients with an Injury Severity Score (ISS) > / = 15 and an iCa measured on hospital arrival. We then derived mean iCa levels and attempted to compare between-group variables across multiple study cohorts. RESULTS: Nine studies reported iCa on arrival to ED, with a mean of 1.08 mmol/L (95% CI 1.02-1.13; I2 = 99%; 2087 patients). Subgroup analysis of patients who did not receive prehospital transfusion had a mean iCa of 1.07 mmol/L (95% CI 1.01-1.14; I2 = 99%, 1661 patients). Transfused patients in the 3 comparative studies had a slightly lower iCa on arrival compared to those who did not receive transfusion (mean difference - 0.03 mmol/L, 95% CI - 0.04 to - 0.03, I2 = 0%, p = 0.001, 561 patients). CONCLUSION: HUA is common amongst trauma patients irrespective of transfusion. Transfused patients had a slightly lower initial iCa than those without transfusion, though the clinical impact of this remains to be clarified. These findings question the paradigm of citrate-induced hypocalcaemia alone in trauma. There is a need for consensus for the definition of hypocalcaemia to provide a basis for future research into the role of calcium supplementation in trauma.

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High concentrations of urinary calcium counteract vasopressin action via the activation of the Calcium-Sensing Receptor (CaSR) expressed in the luminal membrane of the collecting duct cells, which impairs the trafficking of aquaporin-2 (AQP2). In line with these findings, we provide evidence that, with respect to wild-type mice, CaSR knock-in (KI) mice mimicking autosomal dominant hypocalcaemia, display a significant decrease in the total content of AQP2 associated with significantly higher levels of AQP2 phosphorylation at Ser261, a phosphorylation site involved in AQP2 degradation. Interestingly, KI mice also had significantly higher levels of phosphorylated p38MAPK, a downstream effector of CaSR and known to phosphorylate AQP2 at Ser261. Moreover, ATF1 phosphorylated at Ser63, a transcription factor downstream of p38MAPK, was significantly higher in KI. In addition, KI mice had significantly higher levels of AQP2-targeting miRNA137 consistent with a post-transcriptional downregulation of AQP2. In vivo treatment of KI mice with the calcilytic JTT-305, a CaSR antagonist, increased AQP2 expression and reduced AQP2-targeting miRNA137 levels in KI mice. Together, these results provide direct evidence for a critical role of CaSR in impairing both short-term vasopressin response by increasing AQP2-pS261, as well as AQP2 abundance, via the p38MAPK-ATF1-miR137 pathway. KEY POINTS: Calcium-Sensing Receptor (CaSR) activating mutations are the main cause of autosomal dominant hypocalcaemia (ADH) characterized by inappropriate renal calcium excretion leading to hypocalcaemia and hypercalciuria. Current treatments of ADH patients with parathyroid hormone, although improving hypocalcaemia, do not improve hypercalciuria or nephrocalcinosis. In vivo treatment with calcilytic JTT-305/MK-5442 ameliorates most of the ADH phenotypes of the CaSR knock-in mice including hypercalciuria or nephrocalcinosis and reverses the downregulation of the vasopressin-sensitive aquaporin-2 (AQP2) expression, providing direct evidence for a critical role of CaSR in impairing vasopressin response. The beneficial effect of calcilytic in reducing the risk of renal calcification may occur in a parathyroid hormone-independent action through vasopressin-dependent inhibition of cAMP synthesis in the thick ascending limb and in the collecting duct. The amelioration of most of the abnormalities in calcium metabolism including hypercalciuria, renal calcification, and AQP2-mediated osmotic water reabsorption makes calcilytic a good candidate as a novel therapeutic agent for ADH.

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Acuaporina 2 , Regulación hacia Abajo , Receptores Sensibles al Calcio , Vasopresinas , Animales , Acuaporina 2/metabolismo , Acuaporina 2/genética , Receptores Sensibles al Calcio/metabolismo , Receptores Sensibles al Calcio/genética , Ratones , Vasopresinas/metabolismo , Técnicas de Sustitución del Gen , Riñón/metabolismo , Riñón/efectos de los fármacos , Ratones Endogámicos C57BL , Masculino , Transducción de Señal , Fenotipo , Hipercalciuria/genética , Hipercalciuria/metabolismo , Hipercalciuria/tratamiento farmacológico , Calcio/metabolismo , Fosforilación , Hipocalcemia , Hipoparatiroidismo/congénito

RESUMEN

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHNNC) is a rare autosomal recessive renal tubulopathy disorder characterized by excessive urinary loss of calcium and magnesium, polyuria, polydipsia, bilateral nephrocalcinosis, progressive chronic kidney disease, and renal failure. Also, sometimes amelogenesis imperfecta and severe ocular abnormalities are involved. The CLDN-16 and CLDN-19 genes encode the tight junction proteins claudin-16 and claudin-19, respectively, in the thick ascending loop of Henle in the kidney, epithelial cells of the retina, dental enamel, etc. Loss of function of the CLDN-16 and/or CLDN-19 genes leads to FHHNC. We present a case of FHHNC type 1, which was first confused with autosomal dominant hypocalcaemia (ADH) due to the presence of a very low serum parathyroid hormone (PTH) concentration and other similar clinical features before the genetic investigations. After the exome sequencing, FHHNC type 1 was confirmed by uncovering a novel homozygous missense mutation in the CLDN-16 gene (Exon 2, c.374 T > C) which causes, altered protein structure with F55S. Associated clinical, biochemical, and imaging findings also corroborate final diagnosis. Our findings expand the spectrum of the CLDN-16 mutation, which will further help in the genetic diagnosis and management of FHNNC.

Asunto(s)

Hipocalcemia , Hipoparatiroidismo/congénito , Nefrocalcinosis , Humanos , Magnesio , Mutación Missense , Nefrocalcinosis/complicaciones , Nefrocalcinosis/diagnóstico , Nefrocalcinosis/genética , Hipercalciuria/complicaciones , Hipercalciuria/diagnóstico , Hipercalciuria/genética , Hipocalcemia/complicaciones , Hipocalcemia/diagnóstico , Hipocalcemia/genética , Mutación , Claudinas/genética

RESUMEN

Type 1 Bartter syndrome causes hypokalaemia and metabolic alkalosis owing to mutation in the SLC12A1 gene. Meanwhile, hypocalcaemia is rare in Bartter syndrome, except in type 5 Bartter syndrome. Herein, we describe two siblings with type 1 Bartter syndrome with recurrent transient severe hypocalcaemia. They each visited our hospital several times with chief complaints of numbness in the limbs, shortness of breath and tetany after stresses such as exercise or fever. Severe hypocalcaemia was also observed with a serum calcium level of approximately 6.0 mg/dL at each visit. The clinical symptoms and abnormalities in laboratory findings quickly improved with rest and intravenous treatment. In a steady state, no severe hypocalcaemia was evident, but serum intact parathyroid hormone (PTH) levels were high. In recent years, a large-scale study has revealed that type 1 and type 2 Bartter syndrome have high PTH values. In addition, there are reports that these patients develop hypocalcaemia due to PTH resistance. Therefore, our patient was also in a PTH-resistant state, and hypocalcaemia was thought to be exacerbated by physical stress. It is not well known that Bartter syndrome patients other than those with type 5 suffer from hypocalcaemia. And hypocalcaemia was not detected in normal examinations under steady-state conditions. Therefore, in patients with type 1 and type 2 Bartter syndrome, severe hypocalcaemia may occur, but may go unnoticed. When following up these patients, the attending physician must keep in mind that such patients are in a PTH-resistant state and that physical stress can cause severe hypocalcaemia.

Asunto(s)

Síndrome de Bartter , Hipocalcemia , Humanos , Hipocalcemia/etiología , Hipocalcemia/genética , Síndrome de Bartter/complicaciones , Síndrome de Bartter/diagnóstico , Síndrome de Bartter/genética , Hermanos , Hormona Paratiroidea , Miembro 1 de la Familia de Transportadores de Soluto 12