In vivo treatment with calcilytic of CaSR knock-in mice ameliorates renal phenotype reversing downregulation of the vasopressin-AQP2 pathway.

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.

Identification of a Novel Homozygous Missense Mutation in the CLDN16 Gene to Decipher the Ambiguous Clinical Presentation Associated with Autosomal Dominant Hypocalcaemia and Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis in an Indian Family.

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.

Autosomal dominant hypercalciuric hypocalcaemia: the calcium-sensing receptor in renal calcium homeostasis and the impact of renal transplantation.

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.

Recurrent transient severe hypocalcaemia in two siblings with type 1 Bartter syndrome.

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.

Hypoparathyroidism after total thyroidectomy: reactive to symptoms supplementation.

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.

Thyroid surgery in the elderly: a surgical cohort.

PURPOSE: The need for thyroid surgery in the elderly is rising due to an ageing population, the liberal use of imaging studies, and the increasing prevalence of thyroid nodules and cancer with age. Data on surgical outcomes in this population are scarce and conflicting, but essential to assess safety of short-stay surgery. This study aims to compare surgical outcomes by age. METHODS: All consecutive patients undergoing thyroid surgery from January 2010 to July 2021 in a large tertiary referral centre for endocrine surgery were included in this surgical cohort. The indication for surgery, surgical morbidity (hypocalcaemia, bleeding, recurrent laryngeal nerve (RLN) palsy), and length of hospital stay were assessed in three age groups (young: 18-64y, older: 65-74y, and the elderly: 75 years and older). RESULTS: A total of 2,030 patients (1,499 young, 370 older, and 161 elderly) were included. The indication for surgery was significantly different, with the main indications in the elderly being multinodular goitre (70.2% vs. 47.7% in young patients) and thyroid cancer (9.9% vs. 7.0%). Reintervention for bleeding was more often required in the older (4.6%) and the elderly (2.5%) patients (vs. 1.4%). There was no difference in the proportion of hypocalcaemia or RLN palsy. The length of hospital stay was significantly longer in the elderly (length of stay longer than one day 43.5% vs. 9.8%). CONCLUSION: Thyroid surgery in patients aged 75 years and older is a safe procedure with morbidity comparable to younger patients. However, the risk of reintervention for bleeding is higher, rendering ambulatory surgery not advisable. TRIAL REGISTRATION: Researchregistry6182 on October 29th 2020, retrospectively registered.

Interaction between ferric carboxymaltose and denosumab causing severe hypocalcaemia and hypophosphataemia in a patient without chronic kidney disease.

Coadministration of ferric carboxymaltose and denosumab may cause hypocalcaemia and hypophosphataemia; however, this interaction is not well-described in the literature and has typically been described in patients with chronic kidney disease (CKD). We present a case of this interaction in a patient without preexisting CKD. We suggest the use of alternative iron preparations and an interval of at least 4 weeks between administrations.

The role of preoperative vitamin D and calcium in preventing post-thyroidectomy hypocalcaemia: a systematic review.

BACKGROUND: The thyroid gland plays an important endocrine function regulating metabolism, growth and development. A variety of benign and malignant conditions necessitate surgical removal of the thyroid gland, either in its entirety, or partially. Thyroidectomy is the most commonly undertaken endocrine surgery. Hypocalcaemia, occurring at a rate of approximately 25%, is the most common complication following total thyroidectomy. Hypocalcaemia can increase healthcare costs requiring further investigations, treatment and delaying discharge. Severe hypocalcaemia can be potentially life threatening. It has been demonstrated that routine post-operative supplementation with Vitamin D and calcium, can reduce post-operative hypocalcaemia, at present it is unclear whether preoperative supplementation has a similar effect. METHODS: This systematic review includes randomised controlled trials on human adult subjects, who received preoperative Vitamin D and/or calcium, and which studied the effect on post-operative hypocalcaemia following total or near total thyroidectomy. There were no restrictions in respect of post-operative supplementation regimen. Studies were limited to those published in English. RESULT: Seven of the eleven trials demonstrated a reduction in either laboratory or clinical hypocalcaemia with preoperative supplementation. This benefit was most likely to be seen when postoperative supplementation was performed on an as needed basis. IV calcium was required to treat resistant or severe hypocalcaemia, in five of the eleven trials, in each of these five trials, rates of IV replacement were lower in the preoperative supplementation group. CONCLUSION: The use of preoperative Vitamin D, with or without calcium, may provide a modest reduction in the incidence of laboratory and clinic hypocalcaemia following total or near total thyroidectomy. There is a trend toward a reduced requirement for IV calcium with preoperative supplementation. Larger robust randomised trials are needed to provide a definitive answer. Preoperative supplementation can be considered in patients undergoing total or near total thyroidectomy.

Parathyroid Hormone Resistance: An Uncommon Cause of Hypocalcaemia in an Adult Ghanaian Female.

BACKGROUND AND OBJECTIVE: Parathyroid hormone (PTH) resistance, the main biochemical feature of a rare group of disorders known as Pseudohypoparathyroidism (PHP) is an uncommon cause of hypocalcaemia. In addition to the biochemical abnormalities, some individuals with PHP may have features of Albright Hereditary Osteodystrophy (AHO). Being a rare disorder with a significant level of variation and overlap in its clinical presentation, diagnosis of PHP may be challenging in some clinical settings. This case report highlights the diagnosis of this rare disorder. CASE REPORT: A 20-year-old Ghanaian female who had been involved in a road traffic accident (RTA) was referred to the endocrine clinic after a computer tomography (CT) scan of her head revealed an incidental finding of multiple basal ganglia calcifications. Investigations revealed hypocalcaemia, hyperphosphatemia, and elevated intact PTH in the presence of normal levels of 25-hydroxyvitamin D and magnesium, and a normal kidney function. She also had phenotypic features of AHO. Findings suggested a diagnosis of PHP, however, the type could not be identified due to the unavailability of further testing. CONCLUSION: This report of a Ghanaian female with PTH resistance and features of AHO diagnosed at the age of 20 years, is expected to add to the existing literature and assist in increasing the level of awareness and facilitate the diagnosis of this disorder in our setting.

CONTEXTE ET OBJECTIF: La résistance à l'hormone parathyroïdienne (PTH), principale caractéristique biochimique d'un groupe rare de troubles connus sous le nom de pseudohypoparathyroïdie (PHP), est une cause rare d'hypocalcémie. En plus des anomalies biochimiques, certaines personnes atteintes de PHP peuvent présenter des caractéristiques d'ostéodystrophie héréditaire d'Albright (AHO). Étant un trouble rare avec un niveau significatif de variation et de chevauchement dans sa présentation clinique, le diagnostic de PHP peut être difficile dans certains contextes cliniques. Ce rapport de cas met en lumière le diagnostic de cette maladie rare. RAPPORT DE CAS: Une femme ghanéenne de 20 ans qui avait été impliquée dans un accident de la circulation routière (RTA) a été référée à la clinique endocrinienne après qu'une tomodensitométrie (TDM) de sa tête a révélé la découverte fortuite de multiples calcifications des ganglions de la base. Les examens ont révélé une hypocalcémie, une hyperphosphatémie et une PTH intacte élevée en présence de taux normaux de 25 hydroxyvitamine D et de magnésium et d'une fonction rénale normale. Elle avait également des caractéristiques phénotypiques d'AHO. La découverte a suggéré un diagnostic de PHP, mais le type n'a pas pu être identifié en raison de l'indisponibilité de tests supplémentaires. CONCLUSION: Ce rapport d'une femme ghanéenne présentant une résistance à la PTH et des caractéristiques d'AHO diagnostiquée à l'âge de 20 ans, devrait s'ajouter à la littérature existante et aider à accroître le niveau de sensibilisation et à faciliter le diagnostic de ce trouble dans notre contexte. Mots-clés: Hypocalcémie, Hormone parathyroïdienne, Ghana.

Presentation and management of hypoparathyroidism in a paediatric patient - a case report.

Hypoparathyroidism occurs due to insufficient parathyroid gland activity leading to abnormal calcium and phosphate levels. The presentation of hypoparathyroidism is rare in adults and mostly encountered in the paediatric population. We present a case of a 3.5-month-old male infant with the presenting complaint of an episode of afebrile generalized tonic-clonic seizure. Haematological, urinary, cerebro-spinal fluid and radiological investigations were unremarkable but a biochemical profile revealed hypocalcaemia, hyperphosphataemia and lowered vitamin D3 levels. Parathyroid hormone profile showed a decreased level, confirming diagnosis of hypoparathyroidism. Intravenous administration of calcium and magnesium in combination with oral activated vitamin D3 and phosphate binders managed to resolve symptoms and maintain normal levels. The rationale of this case is to confirm the necessity of early diagnosis to prevent irreversible sequelae of hypocalcaemia and regular monitoring of treatment to avoid side-effects of medication.

Daily v. weekly oral vitamin D3 therapy for nutritional rickets in Indian children: a randomised controlled open-label trial.

The aim of the study was to compare the efficacy of daily v. weekly oral vitamin D3 therapy in radiological healing of nutritional rickets. Children 6 months to 12 years (n 132) diagnosed with nutritional rickets were randomised into three groups (n 44): group A - 2000 IU daily vitamin D3 for 12 weeks, B - 60 000 IU weekly for 3 weeks, C - 60 000 IU weekly for 6 weeks. Serum calcium, phosphorus, 25-hydroxyvitamin D (25(OH)D), parathyroid hormone and X-ray score were estimated at baseline and 12 weeks (endline). The proportion of children who achieved complete radiological healing at endline was compared between three groups by χ2 and delta change in laboratory parameters by ANOVA (parametric data) or Kruskal Wallis test (non-parametric data), respectively. Baseline 25(OH)D ≤ 20 ng/ml was seen in 119 (90·2 %), hyperparathyroidism in 90 (68·8 %) and hypocalcaemia in 96 (72·7 %). A total of 120/132 children completed the study. Complete radiological healing seen in 30 (75 %) in group A, 23 (60·5 %) in group B and 26 (61·9 %) in group C; P = 0·15, with comparable endline X-ray scores; P = 0·31. The median (interquartile range (IQR)) delta X-ray score (baseline-endline) was 7 (4,9), 5 (2·25, 6) and 6 (4,7) in groups A, B and C, respectively; P = 0·019. Median (IQR) 25(OH)D endline levels in groups A, B and C were 50·0 (26·5, 66·5), 42·1 (28·4, 54·4) and 53·5 (33·7, 71·2) ng/ml, respectively; P = 0·045. Radiological scores were comparable at endline among daily and weekly vitamin D groups with greater change from baseline in daily supplemented group.

Prognosis assessment model based on low serum calcium in patients with acute pulmonary thromboembolism.

BACKGROUND AND OBJECTIVE: The pulmonary embolism severity index (PESI) and simplified PESI (sPESI) are recommended to recognize patients with acute pulmonary thromboembolism (PTE) with low prognosis risk, which is of great significance for treatment. This study aims to verify the influence of hypocalcaemia on the prognosis of patients with PTE and to establish a new prognosis assessment model. METHODS: This is an observational, multicentre study enrolling patients with PTE from February 2010 to June 2020 across 12 Chinese hospitals. Variables in PESI, serum calcium levels and patient survival status as of 5 July 2020 were collected. The area under the curve of the receiver operating characteristic curve, sensitivity, specificity and Youden index were used to evaluate model performance. RESULTS: In the cohort of 4196 patients with PTE, independent associations existed between hypocalcaemia and mid- and long-term mortalities (p <0.05). By including hypocalcaemia, the new 30-day death risk prediction rule, Peking Union Medical College Hospital rule (PUMCH rule), showed significantly higher specificity (0.622 [0.582, 0.661]; p <0.001) than the PESI (0.514 [0.473, 0.554]) and sPESI (0.484 [0.444, 0.525]) and similar sensitivity (0.963 [0.810, 0.999]; p = 0.161) with PESI (0.889 [0.708, 0.976]) and sPESI (0.963 [0.810, 0.999]) in the internal validation cohort. Well-performing predictive validity was also verified on a constructed external validation cohort. CONCLUSION: Hypocalcaemia is independently associated with mid- and long-term PTE mortalities. The PUMCH rule showed significantly higher specificity than the PESI and sPESI and similar sensitivity, which may be used as a prognostic assessment tool for patients with acute PTE.

Impact of etelcalcetide on fibroblast growth factor-23 and calciprotein particles in patients with secondary hyperparathyroidism undergoing haemodialysis.

AIM: Recently, we demonstrated the efficacy of etelcalcetide in the control of secondary hyperparathyroidism (SHPT). This post hoc analysis aimed to evaluate changes in fibroblast growth factor-23 (FGF23) and calciprotein particles (CPPs) after treatment with calcimimetics. METHODS: The DUET trial was a 12-week multicenter, open-label, parallel-group, randomized (1:1:1) study with patients treated with etelcalcetide plus active vitamin D (E + D group; n = 41), etelcalcetide plus oral calcium (E + Ca group; n = 41), or control (C group; n = 42) under maintenance haemodialysis. Serum levels of FGF23 and CPPs were measured at baseline, and 6 and 12 weeks after the start. RESULTS: In the linear mixed model, serum levels of FGF23 in etelcalcetide users were significantly lower than those in non-users at week 6 (p < .001) and week 12 (p < .001). When compared the difference between the E + Ca group and the E + D group, serum levels of FGF23 in the E + Ca group were significantly lower than those in the E + D group at week 12 (p = .017). There were no significant differences in the serum levels of CPPs between etelcalcetide users and non-users at week 6 and week 12, while CPPs in the E + Ca group were significantly lower than those in the E + D group (p < .001) at week 12. CONCLUSION: Etelcalcetide may be useful through suppression of FGF23 levels among haemodialysis patients with SHPT. When correcting hypocalcaemia, loading oral calcium preparations could be more advantageous than active vitamin D for the suppression of both FGF23 and CPPs.

Hypocalcemic cardiomyopathy - A rare and reversible entity.

Calcium plays a vital key role in cardiac automatism and excitation-contraction coupling, with low serum levels associated with myocardial contractility compromise especially if myocardial sarcoplasmic reticulum is unable to maintain enough calcium content to initiate normal cardiac contraction. We present a 42-year-old woman with postsurgical untreated hypoparathyroidism and severe hypocalcaemia manifested as acute heart failure, without underlying known cardiac disease. Hypocalcaemia is a rare and potentially reversible cause of cardiomyopathy, with very few cases reported in the literature. Restoration to normal serum calcium levels usually leads to a rapid improvement of cardiac function. This rare case report highlights the importance of considering hypocalcaemia as a potentially reversible cause of severe cardiac dysfunction. Exclusion of hypocalcemia due to surgical hypoparathyroidism is mandatory in any individual with acute heart failure previously subjected to thyroidectomy.

Preoperative vitamin D level is significantly associated with hypocalcemia after total thyroidectomy.

BACKGROUND: To evaluate the association of preoperative vitamin D levels with postoperative hypocalcaemia after total thyroidectomy. METHODS: The medical records of patients who underwent total thyroidectomy between May 2020 and January 2022 and who had a documented preoperative serum 25-hydroxyvitamin D (25-OHD) concentration were retrospectively reviewed. Vitamin D levels were categorized into four groups: <10 ng/mL (severe vitamin D deficiency), 10-20 ng/mL (vitamin D deficiency), 20-30 ng/mL (vitamin D insufficiency), and > 30 ng/mL (vitamin D sufficiency). Multivariate logistic regression was performed to analyse the association of vitamin D levels with the risk of hypocalcaemia after controlling for potential confounding factors. RESULTS: A total of 196 patients were included in this study. Of these, 47 (24.0%) had preoperative 25-OHD < 10 ng/mL, 62 (31.6%) had 25-OHD of 10-20 ng/mL, 51 (26.0%) had 25-OHD of 20-30 ng/mL and the remaining 36 (18.4%) had 25-OHD > 30 ng/mL. The incidence of postoperative hypocalcemia was highest in the group of patients with severe vitamin D deficiency (42.6% and 23.4% for postoperative laboratory and symptomatic hypocalcaemia, respectively), followed by the group with vitamin D deficiency (29.0% and 16.1%), the group with vitamin D insufficiency (19.6% and 5.9%) and the group with vitamin D sufficiency (5.6% and 2.8%). Multivariate logistic regression indicated that the odds of postoperative laboratory hypocalcaemia for patients with severe vitamin D deficiency and vitamin D deficiency were 13.20 times (95% CI: 2.69-64.79, P < 0.01) and 6.32 times (95% CI: 1.32-30.28, P = 0.02) greater than for those with vitamin D sufficiency, respectively; while the odds of symptomatic hypocalcaemia for patients with severe vitamin D deficiency was 10.18 times (95% CI: 1.14-90.86, P = 0.04) greater than for those with vitamin D sufficiency. CONCLUSION: Preoperative vitamin D deficiency (< 20 ng/mL), especially severe vitamin D deficiency (< 10 ng/mL), is an independent predictive factor of postoperative hypocalcaemia after total thyroidectomy.

Rhabdomyolysis with Multiple Electrolyte Imbalances under Proton Pump Inhibitor Treatment after Total Thyroidectomy.

A 90-year-old man presented with muscle weakness, difficulty concentrating, and dysphagia. About eighteen months prior to presentation, lansoprazole had been initiated to prevent stress ulcers; he also had a history of total thyroidectomy due to papillary thyroid cancer ten years prior. Laboratory findings were as follows: K 2.4 mEq/L, Ca 3.7 mg/dL, Mg 1.3 mg/dL, CK 5386 U/L, and intact PTH (iPTH) 14 pg/mL. Rhabdomyolysis with multiple electrolyte imbalances under proton pump inhibitor (PPI) treatment was diagnosed. We initiated intravenous hydration and electrolyte supplementation with discontinuation of PPI. After discontinuing PPI, the patient's serum magnesium, potassium, and calcium levels normalised with oral vitamin D and calcium supplementation. PPIs can cause hypocalcaemia and hypokalaemia via hypomagnesemia; hypocalcaemia is also a common postoperative complication of thyroidectomy. Careful monitoring of electrolyte levels is required in patients with long-term PPI treatment, especially in post-thyroidectomy cases.

Maladaptation to the transition period and consequences on fertility of dairy cows.

After parturition, dairy cows undergo a plethora of metabolic, inflammatory, and immunologic changes to adapt to the onset of lactation. These changes are mainly due to the homeorhetic shift to support milk production when nutrient demand exceeds dietary intake, resulting in a state of negative energy balance. Negative energy balance in postpartum dairy cows is characterized by upregulated adipose tissue modelling, insulin resistance, and systemic inflammation. However, half of the postpartum cows fail to adapt to these changes and develop one or more types of clinical and subclinical disease within 5 weeks after calving, and this is escorted by impaired reproductive performance in the same lactation. Maladaptation to the transition period exerts molecular and structural changes in the follicular and reproductive tract fluids, the microenvironment in which oocyte maturation, fertilization, and embryo development occur. Although the negative effects of transition diseases on fertility are well-known, the involved pathways are only partially understood. This review reconstructs the mechanism of maladaptation to lactation in the transition period, explores their key (patho)physiological effects on reproductive organs, and briefly describes potential carryover effects on fertility in the same lactation.

Prepartum measurement of serum biomarkers reflecting osteoclastic and osteoblastic bone metabolism for predicting the risk of milk fever in dairy cows.

We investigated whether prepartum levels of serum bone biomarkers are related to the degree of parturient hypocalcaemia and risk of milk fever (MF) in dairy cows with advancing parity. A total of 58 late-pregnant cattle were assigned to four groups: nulliparous, primiparous, multiparous in the 2nd lactation and multiparous in the 3rd-5th lactation. The multiparous cows were further assigned to MF and non-MF groups according to the onset of MF. Serum samples were obtained from the cows during the 3 weeks prepartum to 5 d postpartum period for the measurement of serum calcium (Ca) and three bone biomarkers: tartrate-resistant acid phosphatase isoform 5b (TRAP5b), osteoprotegerin (OPG) and bone isoenzyme of alkaline phosphatase (ALP3). The ratios of OPG to TRAP5b (O/T ratio) and ALP3 to TRAP5b (A/T ratio) were calculated. The data from all cattle showed that the severity of hypocalcaemia at parturition increased with advancing parity/age. The MF cows had elevated serum TRAP5b activity and a decreased O/T ratio after parturition, suggesting an increased number of osteoclasts due to osteoclastogenesis, in response to severe hypocalcaemia. The MF cows showed lower serum ALP3 activity during the 3 weeks prepartum than the non-MF cows, therefore, prepartum osteoblast function was likely weak in the MF cows. During the 2-3 weeks prepartum, serum ALP3 activity and the A/T ratio had moderate associations with the serum Ca concentration at day 0 (day of calving) in the multiparous cows, and receiver operating characteristic curve analysis revealed that ALP3 activity had excellent ability to predict MF. In conclusion, prepartum serum ALP3 activity is a promising biomarker to predict MF in multiparous cows.

Early and late complications of thyroidectomy: A descriptive cohort study in Rawalpindi.

OBJECTIVE: To assess the epidemiology of thyroid disorders and early and late complications following thyroidectomy.. METHODS: The descriptive cohort study was conducted at the Benazir Bhutto Hospital, Rawalpindi, Pakistan, from April 2017 to Janurary 2020, and comprised of patients undergoing total and near-total thyroidectomy. Post-operative complications were noted, and patients were followed up after 6 months to assess long-term complications. Data was analysed using SPSS 22. RESULTS: Of the 75 patients, 70(93.3%) were females and 43(58.1%) were aged <40 years. The most common symptom was neck swelling with hyperthyroidism 20(41.7%) and pressure symptom 20(41.7%). Post-operative complications developed in 26(35.6%) patients, with symptomatic hypocalcaemia being the most common 10(13.7%), followed by hoarseness 6(8.2%). Biopsy results were available for 50(66.6%) patients. Benign pathology was present in 44(88%) patients and 6(12.0%) had malignancy. Follow-up data was available for 62(82.7%) patients among whom symptomatic hypocalcaemia was the leading complication in 33(53.2%), followed by permanent hoarseness in 6(9.7%). CONCLUSIONS: Symptomatic hypocalcaemia and hoarseness were found to be the most common post-operative and long-term complications of thyroidectomy.

The complex role of post-operative magnesium on the long term serum calcium and parathyroid hormone levels in patients undergoing total and near-total thyroidectomy.

Objective: To assess the role of hypomagnesaemia in the development of permanent hypocalcaemia following thyroidectomy. METHODS: The prospective cohort study was conducted from April 3, 2017, to January 2, 2020, at Surgical Unit 1, Benazir Bhutto Hospital, Rawalpindi, Pakistan, and comprised of patients of both genders undergoing total and near total thyroidectomy. Post-operative calcium and magnesium levels were noted, and the patients were followed up after 6 months and fasting serum calcium, magnesium and parathyroid hormone levels were checked. Signs and symptoms of hypocalcaemia were noted. Data was analysed using SPSS 22. RESULTS: Out of the 62 patients followed up, 57 (91.9%) were females and 5 (8.1%) males. The overall mean age was 38.5 ± 12.1 years Post-operative hypomagnesaemia was seen in 6(9.8%) patients and none developed follow-up hypocalcaemia. Post-operative magnesium levels were significantly negatively correlated with follow-up parathyroid hormone level (p=0.006). Fall in magnesium post-operatively and follow-up magnesium were positively correlated with follow-up parathyroid hormone (p<0.05). Permanent hypocalcaemia was seen in 7(11.4%) patients and it was significantly associated with pre-operative and post-operative calcium levels, post-operative symptoms of hypocalcaemia and readmission for hypocalcaemia after discharge (p<0.05). Follow-up hypomagnesaemia was significantly associated with follow-up hypocalcaemia (p=0.024) and follow-up symptoms of hypocalcaemia (p=0.031). Conclusion: Acute development of mild hypomagnesaemia post-operatively may be beneficial in early positive feedback for parathyroid hormone secretion. Hypomagnesemia 6 months after surgery may be involved in PTH organ resistance. The complex role of hypomagnesemia on PTH levels must be further explored.