History Of Hypocalcemia Research Articles

Who Keeps Changing My Results? - A Case of Heterophile Antibody Interference

Abstract Introduction/Objective Heterophile antibodies are known to cause interference in immunoassays leading to misleading results causing diagnostic confusion and unnecessary testing and/or treatment. Many clinically important analytes are tested using antibody-based assays, as such, these are prone to interference. Methods/Case Report We describe a case of a 73 year old male who was referred with history of hypocalcemia and his previous lab tests were suggestive for idiopathic hypoparathyroidism, Hashimoto’s disease and Addison’s disease raising physician concern for a possible Type 1 autoimmune endocrinopathy. One of his results (cortisol) was outside the analytical measurement range and hence the sample was diluted and tested again, but the result was much less than what was expected, prompting an investigation. Investigation for an interfering substance included serial dilution and analysis of the same sample for the same analytes by different methods (different immunoassay, mass spectrometry or both). Based on non-parallelism in serial dilution results, discordant results with other methods, and loss of interference after dilution it was determined that the most likely cause was a heterophile antibody. Results (if a Case Study enter NA) NA Conclusion Awareness of the possibility that interference by heterophile antibodies can lead to erroneous laboratory results is important to prevent unnecessary testing and inappropriate diagnosis/management.

A-099 Case Study of a Patient With Heterophile Antibodies Interfering with Both Competitive and Immunometric Assays

Abstract Background Immunoassay results may be affected by the presence of interfering substances including heterophile antibodies. These heterophile antibodies can cause either an increase or decrease in the result based on assay design and antibody target. We report a case study wherein we identified several analytes whose results were either increased or decreased by heterophile antibodies in a patient. Methods 74 year male presented to Endocrinology with history of hypocalcemia and his previous lab tests were suggestive for idiopathic hypoparathyroidism, Hashimoto’s disease and Addison’s disease raising physician concern for a possible Type 1 autoimmune endocrinopathy. Cortisol was ordered (for an ACTH stimulation test for adrenal insufficiency); upon testing the post-stimulation cortisol result was higher than the analytical measurement range (AMR), and so the sample was diluted 1:2 and repeated. The repeat cortisol result after correction for the dilution factor was well within the AMR and prompted an investigation for an interfering substance. Serial dilution of analytes was performed and send-out testing for the same with another immunoassay from a different manufacturer and/or mass spectrometry method where available were done. Results The results for most analytes did not match with the reference lab results. Serial dilution showed non-parallelism in the results. For most analytes, after dilution of the sample by 1:4 or 1:8 times, the interfering substance was diluted enough to obtain a result matching the reference lab result. Conclusions Based on non-parallelism in serial dilution results, discordant results with other methods, and loss of interference after dilution it was determined that the most likely cause was a heterophile antibody. Formal testing using blocking antibodies was not done as it seemed that the reference lab used did not run our method and their assays were not affected by this particular heterophile antibody. Analysis of the assay designs and analyte results showed that competitive assays showed falsely high results, while immunometric assays showed falsely low results. The physician was contacted and the case discussed in detail and it was recommended that further testing on this individual be sent out to a reference lab using the alternate method or to use mass spectrometry based assays for further testing if needed. Today, the patient continues to have low calcium, high phosphate and an undetectable PTH suggestive of idiopathic hypoparathyroidism but his other endocrine functions are within normal limits.

Risk factors and outcomes of pericardial effusion in cancer patients receiving PD-1 inhibitors

BackgroundProgrammed cell death 1 (PD-1) inhibitors can induce various adverse reactions associated with immunity, of which cardiotoxicity is a serious complication. Limited research exists on the link between PD-1 inhibitor use and pericardial effusion (PE) occurrence and outcomes. MethodsWe conducted a retrospective study at the First Affiliated Hospital of Xi'an Jiaotong University from 2017 to 2019, comparing cancer patients who developed PE within 2 years after PD-1 inhibitor therapy to those who did not. Our primary outcome was the all-cause mortality rate at one year. We applied the Kaplan-Meier method for survival analysis. Multivariate logistic regression was utilized to identify PE risk factors, adjusting for potential confounders. ResultsA total of 91 patients were finally included, of whom 39 patients had PE. Compared to non-PE group, one-year all-cause mortality was nearly 5 times higher in PE group (64.10% vs. 13.46%, P < 0.001). Patients who developed PE within 2 years of taking PD-1 inhibitors were significantly associated with increased all-cause mortality compared with those who did not (HR: 6.26, 95%CI: 2.70–14.53, P < 0.001). Multivariable logistic regression showed that use of sintilimab (OR: 14.568, 95%CI: 3.431–61.857, P < 0.001), history of lung cancer (OR: 15.360, 95%CI: 3.276–72.017, P = 0.001), and history of hypocalcemia (OR: 7.076, 95%CI: 1.879–26.649, P = 0.004) were independent risk factors of PE development in patients received PD-1 inhibitors therapy. ConclusionsIn cancer patients receiving PD-1 inhibitors, PE was associated with higher one-year mortality. Use of sintilimab, and history of lung cancer or hypocalcemia were linked to PE occurrence.

PREVALENCE AND PATHOPHYSIOLOGY OF POST-THYROIDECTOMY HYPOCALCAEMIA

Post-thyroidectomy hypocalcemia is a recognised and potentially significant complication arising from the surgical removal of the thyroid gland. The study's main objective is to find the prevalence and pathophysiology of post-thyroidectomy hypocalcemia. This prospective observational study was conducted in Civil Hospital Quetta from June 2021 to July 2022. A total of 162 patients undergoing thyroidectomy for various indications, including thyroid cancer, hyperthyroidism, and goiter, were enrolled in the study. Before surgery, baseline data were gathered, including demographic information, medical history, and preoperative serum calcium and parathyroid hormone (PTH) levels, from the 162 enrolled patients scheduled for thyroidectomy. Data were collected from 162 patients from both genders. The mean age of patients was 48.5 ± 8.2 years, with 70% female. The diagnoses included 40% with thyroid cancer, 30% with hyperthyroidism, and 30% with a large goiter. Preoperative serum calcium levels were 9.0 ± 0.5 mg/dL, parathyroid hormone (PTH) levels were 45 ± 9.80 pg/mL, and vitamin D levels were 25.5 ± 6.3 ng/mL. A history of hypocalcemia was noted in 5% of the participants. The mean serum calcium level was 9.0 mg/dL, with a standard deviation of 0.5. However, at 48 hours post-op, there was a decrease in the mean serum calcium level to 7.8 mg/dL, with a standard deviation of 0.7. It is concluded that the interaction between reduced serum calcium and parathyroid hormone levels highlights the immediate impact of surgery on calcium homeostasis.

Postoperative Hypocalcemia following Non-Cardiac Surgical Procedures in Children with 22q11.2 Deletion Syndrome.

The guidelines for management of children with 22q11.2 deletion syndrome (22q11DS) highlight the risk for developing hypocalcemia after surgery and recommend monitoring calcium perioperatively. Despite this guidance, little has been published on postoperative hypocalcemia and 22q11DS. Our goals were to evaluate the frequency of perioperative calcium monitoring and examine how often postoperative hypocalcemia was identified. This is a retrospective chart review of patients in our 22q Center’s repository. Inclusion criteria were a diagnosis of 22q11DS and a history of a non-cardiac surgical procedure. Data collected included all non-cardiac surgeries and perioperative calcium labs. In total, 68 patients were included and underwent 305 on-cardiac surgeries. Patients in only 17% of these surgeries had postoperative calcium testing, but of those tested, 58% showed hypocalcemia. Patients with history of hypocalcemia at the time of chart review undergoing non-cardiac surgeries were tested postoperatively 40% of the time; however, 67% of these had hypocalcemia. Similarly, for patients without history of hypocalcemia, postoperative testing occurred 60% of the time, with 52% of these having hypocalcemia. This study demonstrates that postoperative hypocalcemia in children with 22q11DS following non-cardiac surgeries is common and affects patients both with and without prior history of hypocalcemia. These data support establishing a protocol for perioperative testing/management of hypocalcemia for patients with 22q11DS.

The Unusual Suspect: Hypocalcemia in Preeclampsia After Magnesium Infusion

Background: Magnesium plays a vital role in calcium homeostasis. Magnesium sulfate is used in obstetric populations for the management of preeclampsia and eclampsia. Hypocalcemia secondary to iatrogenic hypermagnesemia is an uncommon complication. We report a case of symptomatic hypocalcemia due to hypermagnesemia. Clinical Case: A 26-year-old female with type 1 diabetes at 33 weeks gestation was admitted for preeclampsia. She had severe hypertension and proteinuria, and the decision to induce labor was made. She was started on a magnesium sulfate drip and remained on the drip for 33 hours. Magnesium levels peaked at 7.5 mg/dL (1.7–2.5 mg/dL). The magnesium drip was suspended after delivery. She complained of mild tingling and numbness in her hands, feet, and perioral area. Shortly after delivery, she had a pre-syncopal event. The laboratory evaluation revealed a calcium of 5.9 mg/dL (8.4–10.4) with an albumin of 2.2 g/dL (3.7–5.5), magnesium of 4.2 mg/dL, phosphorus 2.2 mg/dL (2.3–4.6) and GFR above 60 mL/min/1.73m2 . Spot urine calcium to creatinine ratio was 0.17 mg/dL. The 25-hydroxy vitamin D level was low at 12 ng/mL (20–100). The parathyroid hormone (PTH) level was inappropriately normal at 21.7 pg/mL (12–88). She had no history of hypocalcemia, and calcium level obtained six months before the presentation was normal. She received one calcium gluconate infusion, was then started on a continuous calcium gluconate infusion for symptomatic hypocalcemia. She also received oral supplementation of calcium and vitamin D. The calcium levels normalized within 24 hours as the hypermagnesemia resolved from the discontinuation of the magnesium drip. The subsequent PTH level was 38.8 pg/mL. She was discharged on vitamin D supplements. She had no recurrence of hypocalcemia. Conclusion: Our case highlights the effect of magnesium infusion on the parathyroid gland leading to profound symptomatic hypocalcemia. Magnesium plays an essential role in the secretion of PTH. Transient hypoparathyroidism can occur due to hypomagnesemia and hypermagnesemia (tocolytic therapy). In hypomagnesemia, the parathyroid gland secretes insufficient PTH, and the renal and skeletal response to PTH is reduced. In hypermagnesemia, the magnesium activates the extracellular calcium-sensing receptor, subsequently causing inhibition of the parathyroid gland. Amelioration of hypermagnesemia leads to the normalization of parathyroid function. Health care providers should be aware of this phenomenon, especially in the obstetric population receiving magnesium infusion. The monitoring of calcium levels may be necessary for this patient population. The laboratory testing should include magnesium in the evaluation of hypocalcemia.

Potential Clinical Predictors of Suspected Early and Late Onset Sepsis (EOS and LOS) in Preterm Newborns: a Single Tertiary Center Retrospective Study.

Neonatal sepsis represents one of the common diseases in the neonatal intensive care unit. Here we aim to evaluate the differences between a group of preterm newborns with sepsis and a control group in relation to clinical and laboratory variables. In addition, our goal is to establish potential predictors of early-onset sepsis (EOS) and late-onset sepsis (LOS). The study included 113 preterm newborns with sepsis (EOS-63.72%/LOS-36.28%). Laboratory deter-minations included full blood count, CRP, biochemical determinations, blood culture. The most important univariate neonatal predictors were gestational age (p < 0.001), surfactant adminis-tration (p < 0.001), mechanical ventilation (p < 0.001), heart failure (p < 0.001), a history of hypocalcemia (p = 0.037), Apgar score at 1 minute lower than 7 (p = 0.001), birth weight < 1,500 g (p = 0.005), number of hospi-talization days (p = 0.048), and number of weight recovery days < 10 (p < 0.05). The WBC and CRP parameters remained significant univariate predictors of sepsis on day 7 (p = 0.002; OR = 2.01 per 10,000 mm3 increase of WBC, 95% CI: (1.30; 3.09) and p = 0.001; OR = 4.27, 95% CI: (1.85; 9.88), respectively). Logistic regression anal-ysis showed maternal urinary tract infection (OR = 3.05), heart failure (OR = 5.28), the number of hospitalization days (OR = 1.09) and CRP (OR = 3.26) were significant independent risk factors for neonatal sepsis in preterms. The univariate predictors of EOS were gestational age (p = 0.002), birth weight (p = 0.014), 1-minute Apgar score (p = 0.012), maternal urinary tract infection (p = 0.008), surfactant administration (p < 0.001), heart failure (p < 0.001), and CRP level (p < 0.001). Surfactant administration (OR = 6.73) and CRP level (OR = 3.51) represent predictors of EOS in preterms according to the multivariate model. The univariate predictors of LOS were gesta-tional age (p = 0.001), birth weight (p = 0.048), 1-minute Apgar score (p = 0.001), surfactant administration (p < 0.001), hypocalcemia (p = 0.03), heart failure (p = 0.003), CRP level (p < 0.001), mechanical ventilation (p < 0.001), and the number of hospitalization days (p < 0.001). In the multivariate model, the number of hospitali-zation days (OR = 1.11) and heart failure (OR = 5.98) are independent predictors for LOS in preterms. The study confirms the presence of maternal urinary tract infection, hospitalization days, heart fail-ure, and CRP level as predictors of neonatal sepsis in preterms with differences between EOS and LOS.

7-WEEK OLD MALE WITH TRUNCUS ARTERIOSUS AND ABNORMAL MISSOURI NEW BORN SCREENING TRECS

Introduction Immunological deficiencies associated with genetic defects, if identified earlier, may lead to targeted treatment resulting in improved management. Case Description A term 7-week old male with surgically repaired truncus arteriosus and history of hypocalcemia presents to Immunology Clinic for decreased newborn screening TRECs, Ct 37.39 (normal 3 (normal 3400-7600 mm3). Microarray analysis was normal. Physical exam demonstrated micrognathia and floppy pinnae. Additional evaluation revealed decreased CD3+ (1599 cells/mm3 (normal 2500-5500)), CD4+ (939 cells/mm3 (normal 1600-4000)) and naive CD4+CD45RA+ (732 cells/mm3 (normal 1200-2700)) T cells, normal immunoglobulin levels, and normal PTH level. Genetic testing demonstrated a heterozygous W303X nonsense mutation in the TBX1 gene, predicted to cause loss of normal protein function. The patient's father, who is a physician, had required cardiac surgery at 8 months of age for congenital hemitruncus; he has no other medical problems. Paternal FISH analysis was previously negative for chromosome 22q11 deletion. Further paternal genetic testing demonstrated the same heterozygous TBX1 mutation as the patient. Discussion DiGeorge Anomaly (DGA) is principally caused by heterozygous chromosome 22q11.2 deletion in 90% of subjects. Less frequently, TBX1 gene mutation leads to DGA. This patient had a cardiac defect, dysmorphic features, hypocalcemia, abnormal TRECs, and decreased T cells; whereas the father had only a cardiac defect. The spectrum of DGA is variable and not always detected by FISH or microarray. Therefore, TBX1 gene mutation should be examined in patients with DGA phenotype.

Association of hypocalcemia with congenital heart disease in 22q11.2 deletion syndrome.

Hypocalcemia is one of the cardinal features of the chromosome 22q11.2 deletion syndrome (22q11.2DS), the most common cause of DiGeorge syndrome. Hypocalcemia and other features of 22q11.2DS including congenital heart disease (CHD) are primarily ascribed to problems with morphogenesis and function of the pharyngeal arch system derivatives including the parathyroid glands, the aortic arch, and the cardiac outflow tract. In light of the aforementioned embryology, we hypothesized that hypocalcemia would be identified more frequently in those patients with 22q11.2DS and CHD. We conducted a retrospective IRB approved chart review on 1,300 subjects with 22q11.2DS evaluated at the Children's Hospital of Philadelphia. χ2 test was used to evaluate the statistical significance of differences in hypocalcemia between the two groups. Eight hundred fifty-two patients had calcium levels available for review. Of these, 466 (54.69%) had a history of hypocalcemia and 550 (64.55%) had CHD. Of those with CHD, 343 (62.36%) had a history of hypocalcemia, and of those without CHD, only 123 (40.73%) had a history of hypocalcemia. Thus, the frequency of diagnosed hypocalcemia was greater in patients with 22q11.2DS and CHD as compared to those without CHD (p < .001). We also analyzed age of onset of hypocalcemia and found that 66.47% of CHD/hypocalcemia group had neonatal/infantile hypocalcemia versus 43.09% in the non-CHD/hypocalcemia group. In our large cohort of patients with 22q11.2DS, the prevalence of diagnosed hypocalcemia is elevated among patients with CHD, in whom it is more likely to be diagnosed during the neonatal/infancy period.

A Woman and Her Father with Calcium-Sensing Receptor Mutation and Autosomal Dominant Hypocalcemia

ABSTRACT Objective: To discuss the case of a woman and her father with autosomal dominant hypocalcemia (ADH), a rare disorder caused by an activating mutation of the calcium-sensing receptor (CaSR). Methods: Previous ADH case reports were obtained by Medline search and from an updated CaSR database. Results: A 37-year-old female presented with intermittent leg cramps and hypocalcemia. Her father had been previously diagnosed with asymptomatic hypocalcemia at age 54. Genetic analysis in both individuals revealed identical missense mutations in nucleotide c.2489G>A that resulted in a glycine to aspartic acid change at codon 830 (G830D) in the CaSR. Conclusion: The same mutation of the CaSR gene was identified in a woman and her father. This warrants the need for genetic testing in adults with mild hypocalcemia and a family history of hypocalcemia.

Clinical manifestations and frequency of hypocalcemia in 22q11.2 deletion syndrome.

This study investigated the evolution of hypocalcemia with age and its associated risk factors in patients with 22q11.2 deletion syndrome (22qDS) and congenital heart defects. A retrospective review of the medical records of 16 22qDS patients (nine female, seven male; age range, 20.5-43 years) was performed. The frequency of hypocalcemia, as well as the clinical course of the disease and the presence of other phenotypes, were investigated. Ten of the 16 patients (62.5%) had a history of hypocalcemia. Among the 10 patients, the first onset of hypocalcemia occurred in the following developmental periods: neonatal stage, n = 1; early childhood, n = 3; late childhood, n = 2; adolescence, n = 2; and adulthood, n = 2. Neonatal hypocalcemia was observed in one patient, but it was transient. Two patients had sustained hypocalcemia after cardiac surgery. Hypocalcemia in one patient was transient following cardiac surgery, but it recurred during early adulthood. One patient developed hypocalcemia at 43 years of age. Thymus defect tended to be correlated with history of hypocalcemia (P = 0.09). This condition was often transient (60%) and was triggered by physical stress, such as intracardiac surgery. In 22qDS patients, hypocalcemia was often mild and transient during childhood, but it may recur in adulthood. Routine clinical measurement of serum calcium is recommended, particularly in 22qDS patients with thymic defect or in patients who are under physical stress.

Parathyroid hormone reserve in 22q11.2 deletion syndrome

ObjectiveWe hypothesized that most patients with 22q11.2 deletion and a history of hypocalcemia have inadequate parathyroid function, manifested by intact parathyroid hormone levels below normal. We aimed to evaluate intact parathyroid hormone levels both during normocalcemia and at hypocalcemia, in this population. Study DesignRetrospective chart review of 103 patients with 22q11.2 deletion born since 1997 and cared for at the Children's Hospital of Philadelphia. Calcium and intact parathyroid hormone drawn simultaneously were recorded, along with clinical presentation at hypocalcemia. ResultsForty-seven simultaneous Ca/intact parathyroid hormone values were available. Seventy-nine percent of calcium levels and 81% of parathyroid hormone levels were within normal range. There were 19 patients with a history of symptomatic hypocalcemia, for whom any available simultaneous Ca/parathyroid hormone levels, before, during, or after hypocalcemia were analyzed. In this subgroup, 59% of calcium and 76% of parathyroid hormone levels were normal. None had an intact parathyroid hormone of >39.2 pg/mL at hypocalcemia. Seventy-three percent of hypocalcemic events had a precipitating stressor. ConclusionsHypoparathyroidism in 22q11.2 deletion is mild, manifesting as a phenomenon of decreased parathyroid hormone reserve. Subjects are normocalcemic most of the time, but are unable to mount elevated intact parathyroid hormone levels, and therefore unable to correct hypocalcemia, in response to stressors.

Hypocalcemia and Parathyroid Function in Metastatic Prostate Cancer

To report the occurrence of hypocalcemia in a patient with metastatic prostate cancer, discuss its pathogenesis, and review the related medical literature. An 82-year-old man with a known history of prostate cancer was found to have a serum calcium level of 5.4 mg/dL during an admission to the hospital for small bowel obstruction. A thorough review of his medical history revealed a temporal relationship between the diagnosis of malignant disease and progressive hypocalcemia. A complete evaluation was performed, including laboratory and imaging studies, to ascertain the cause of the hypocalcemia. The patient had no history of hypocalcemia before the diagnosis of, and initiation of antiandrogen therapy for, advanced prostate cancer. Serum magnesium and phosphorus levels were within normal limits. The serum calcium level responded to therapy in the hospital but remained between 5.8 and 7.1 mg/dL. The parathyroid hormone level was normal, and the 25-hydroxyvitamin D value was low. A 24-hour urine collection showed substantially reduced calcium excretion, and a whole-body bone scan revealed widespread metastatic deposits. These findings were compatible with hypocalcemia related to prostate cancer and bone metastatic lesions. This case serves as a reminder that hypocalcemia can be a manifestation of prostate cancer metastatic to bone. In contrast to the occurrence of secondary hyperparathyroidism in this setting, however, this patient had normal levels of parathyroid hormone. Review of similar previous reports and the causes and implications of a possible functional hypoparathyroid state are discussed.

A novel mutation (E767K) in the second extracellular loop of the calcium sensing receptor in a family with autosomal dominant hypocalcemia

Autosomal dominant hypocalcemia resulting from gain-of-function mutations of the calcium sensing receptor (CASR) is a rare familial disorder that can become evident at any age. We report a novel mutation (E767K) of the CASR in a family with autosomal dominant hypocalcemia. Ten members of the family had a history of hypocalcemia. The index case exhibited marked hypocalcemia and seizures in the newborn period, while her father who also has hypocalcemia, was largely asymptomatic except for a myocardial infarction-like event at 21 years of age, a new presentation of the disorder. The E767K mutation, which resides in the second extracellular loop adjacent to the fifth transmembrane domain, co-segregated with hypocalcemia in these two individuals. Both subjects are heterozygous for the mutation. The proband is also heterozygous for the previously reported CASR polymorphism of G990R in the intracellular domain, while her father is homozygous. The co-segregation of this naturally occurring mutation with autosomal dominant hypocalcemia supports the previously reported experimental model in which it was proposed that the three acidic residues (767, 758, and 759) in exo-loop 2 in CASR help maintain an inactive conformation of the receptor.

Familial non-syndromic conotruncal defects are not associated with a 22q11 microdeletion

Molecular studies have shown microdeletions in region q11 of chromosome 22 in nearly all patients with DiGeorge, velocardiofacial and conotruncal anomaly face syndromes (DGS, VCFS and CTAFS, respectively) and in a high percentage of non-syndromic familial cases of conotruncal defects (CTD). CTD account for roughly a fourth to a third of all non-syndromic congenital heart defects (CHD), thus, 22q11 could harbor a major genetic factor of CHD. We searched for a 22q11 microdeletion in familial cases of non-syndromic CTD. Thirty-six cases of various isolated CTD, that is without history of hypocalcemia, immune deficiency, absent thymus, and dysmorphic appearance, were selected. With 48F8, a cosmid probe localized in the smallest deleted region of the DiGeorge critical region (DGCR), we found no deletions by fluorescence in situ hybridization in these 36 affected individuals of 16 families with recurrent CTD. Moreover, D22S264, a microsatellite localized at the distal part of the largest deleted region, was used to genotype the patients. Thirty-two patients out of 37 were heterozygous and hence not deleted at this locus, whereas 5 were uninformative. In conclusion, there are no large deletions in familial cases of various CTD, whether these defects are identical or not within a family. This result does not rule out other minor anomalies in this chromosomal region.

Spontaneous Return of Normocalcemia

A 58-year-old man was admitted to the hospital with the superior vena cava (SVC) syndrome. The patient had a 13-year history of hypocalcemia resulting from surgically induced hypoparathyroidism, which he controlled with calcium lactate. Nine months before admission, he discontinued his daily therapy and still remained in a normocalcemic state. After he had the SVC syndrome, a small-cell tumor of the lung was found. His serum calcium level decreased after radiation of the tumor mass, suggesting that the tumor may have been secreting a substance producing the normocalcemia. A substance was extracted from the tumor that reacted immunologically like parathyroid hormone.