Iv Calcium Research Articles

Uso de calcio por vía intravenosa en urgencias para tratar pacientes con hiperpotasemia e intoxicación por digoxina y su impacto en la evolución a corto plazo

ObjetivesPatients with digitalis intoxication (DI) and hyperkalaemia are frequently encountered in the emergency department (ED). This alteration may require intravenous (iv) calcium, but its administration has been considered to increase cardiotoxicity and mortality in patients with DI. We studied the effect of iv calcium on mortality and 30-day readmission in patients with hyperkalaemia and DI. MethodsA retrospective, multicentre, retrospective cohort study including all patients with DI and hyperkalaemia from 2004 to 2023 seen in 6 hospital emergency departments. Two cohorts were created according to iv calcium administration, and demographic, clinical, electrocardiographic and outcome variables (mortality, readmission and combined event at 30 days) were collected. Results117 patients with ID and hyperkalaemia were collected and 29% were administered iv calcium. Seventy-eight point 6percent were women, with a median age of 82.8 years. Cardiological symptoms were present in 57.3%, 47% digestive and 37.6% neurological. Cardiac arrhythmia was present in 86.3%, the most frequent type being slow supraventricular arrhythmia in 76.1%. The presence of cardiological symptoms (76.5% vs. 49.4, P=.007), arrhythmias (97.1% vs. 81.9%, P=.037), and higher levels of creatinine (70.6% vs. 42.2%, P=.005) and serum potassium (94.1% vs. 31.3%, P<.001) was more frequent in the group receiving iv calcium. An association was found between the administration of iv calcium An association was found between calcium administration and the combined event at 30 days (ORa 3.11, 95% CI:1.02-9.53), but this increase was at the expense of more readmissions (ORa 3.58, 95% CI, 1.04-12,33), with no relationship found with mortality at 30 days (ORa 0,75, 95% CI: 0.18-3.09). ConclusionCalcium administration in hyperkalaemia and ID is not associated with short-term mortality.

1246: CALCIUM CHANNEL BLOCKER TOXICITY TREATED WITH METHYLENE BLUE AND LIPID EMULSION: A RARE SURVIVOR

Introduction: Calcium channel blocker (CCB) toxicity due to intentional overdose (OD) is associated with high morbidity and mortality. Depending on the CCB subclass, symptoms can include altered mentation, hypotension, and bradycardia. The lack of formally recognized guidelines in the treatment of CCB toxicity can complicate management. Description: A 67-year-old female with history of depression was admitted to the ICU after suicidal ingestion of thirty amlodipine 5 mg tablets for shock refractory to volume resuscitation and vasopressor support. Initial vitals were reported as blood pressure 55/29, pulse 86, respirations 18, pulse oximeter 94% on room air, Glascow coma scale of 13 with stuporous mentation. Despite fluids, initiation of norepinephrine, intravenous (iv) calcium and glucagon, her shock persisted. Toxicology was contacted and recommended high dose iv insulin and dextrose which transiently improved blood pressures, however low mean arterial pressures (MAP) necessitated initiation of vasopressin and epinephrine drips. Methylene blue was started, followed by escalation to iv lipid emulsion (ILE) therapy. With this regimen, distributive shock and mentation improved. With time, vasopressor support was weaned and the patient made a complete recovery from severe CCB toxicity. Discussion: Conventional treatment with iv calcium, glucagon, atropine, cardiac pacing and pressors often fail to improve the hemodynamics associated with intentional CCB OD. Adjunct therapy with insulin may improve cardiac myocyte contractility and methylene blue is postulated to improve distributive shock via inhibition of nitric oxide synthase but current literature lacks case control data. ILE therapy should also be considered early in the treatment course and utilized with the guidance of a toxicologist as ILE is not without risk of complications including but not limited to acute pancreatitis, fat embolism, cardiac arrest, kidney injury, ARDS, seizure, and coagulopathy. Despite its growing utility in the treatment of lipophilic drug toxicity, most studies with CCB OD are case reports and based on animal studies rather than clinical trials. This case demonstrates the potential benefits of adjunct treatment with methylene blue and iv lipid emulsion to improve refractory distributive shock.

HYPERTENSIVE CRISES AT THE EMERGENCY ROOM - HOW DO WE TREAT IN THE REAL-WORLD SETTINGS?

Objective: Hypertension (HTN) is a major public health problem and blood pressure (BP) control rates have remained poor worldwide leading to an increasing number of presentations at the Emergency Department (ED) for high BP. Until recently, the management of HTN crises was poorly addressed in the guidelines and therefore unstandardized in the clinical practice. The aim of the current study is to describe the pattern of anti-HTN drug therapy in the ED of a tertiary care emergency hospital. Design and method: We retrospectively analysed all the charts of patients presenting at the ED of a tertiary care emergency hospital during 1 month (March 2018). We retrieved complete demographic, clinical and treatment approach data from the ED charts of patients presenting for HTN defined as BP => 140/90 mmHg. We defined a hypertension emergency (EMG) as BP => 180/120 mmHg with acute HTN-mediated organ damage (HMOD) and HTN urgency as BP =>180/120 without HMOD (URG). In all other cases BP => 140/90 mmHg was referred to as elevated BP (EBP). Results: From 5898 patients presented at the ED in 1 month, we studied 293 pts evaluated for HTN (4.96%). While EBP is treated with anti-HTN drugs in only a quarter of patients, most of those presenting with EMG or URG receive treatment. Diuretics remain the most used anti-HTN drug (47.4 % of all pts), more used in URG then in EBP. The second most used anti-HTN drugs are ACEI (angiotensine converting enzyme inhibitors) (21.8% of all pts). Intravenous nitroglycerine is less used even though 19.4% of EMG pts receive it in comparison with only 2.8% of URG pts. See table. Conclusions: Hypertensive disease remains one of the main causes for ED presentation. Management is still suboptimal however with a high use of diuretics contrary to the current recommendations. ACEIs are the second choice while nitroglycerine is the third, being used mostly in EMG cases. Other recommended drug classes are underutilized however in our ED iv calcium channel blockers (CCB), iv beta blockers and urapidil are mostly unavailable.

Short-Term Safety of Zoledronic Acid in Young Patients With Bone Disorders: An Extensive Institutional Experience.

Zoledronic acid (ZA) is increasingly used in young patients with bone disorders. However, data related to the safety of ZA administration in this population are limited. The study aimed to characterize the short-term safety profile of ZA and identify risk factors for ZA-related adverse events (AEs) in young patients. This was a retrospective chart review of inpatients and outpatients less than 21 years old who received at least one ZA infusion between July 2010 and January 2014 at The Children's Hospital of Philadelphia. Eighty-one patients (56% male; median age, 12 y; age at first infusion, 0.5 to 20 y) with diverse skeletal disorders received a total of 204 infusions. The most common indications were osteoporosis (33% of cohort) and osteogenesis imperfecta (27.2%). The median ZA dose was 0.025 mg/kg (interquartile range, 0.025-0.05); the median dosing interval was 6 months (range, 1 to 25.6 mo). AEs were mild and more common after the first ZA infusion in patients with no previous bisphosphonate exposure: hypophosphatemia (25.2% of infusions), acute phase reactions (19.1%), and hypocalcemia (16.4%). Symptomatic hypocalcemia requiring iv calcium occurred after two infusions. ZA dose was significantly associated with hypophosphatemia, but not other AEs. Hypocalcemia was more common in patients with high bone turnover as assessed by preinfusion alkaline phosphatase levels. AEs were not associated with diagnosis, baseline serum calcium, or calcium/calcitriol supplementation. Acute AEs related to ZA infusion in youths are common, occur principally after the first ZA infusion in bisphosphonate-naive patients, and are typically mild and easily managed. Future prospective studies are needed to determine the potential long-term risks, as well as benefits, of ZA therapy in the pediatric population.

Effects of RANK-Ligand Antibody (Denosumab) Treatment on Bone Turnover Markers in a Girl With Juvenile Paget's Disease

Juvenile Paget's disease (JPD) is an extremely rare, yet painful and debilitating bone disease with onset occurring during early childhood. JPD can be caused by loss of function of osteoprotegerin, resulting in subsequent stimulation of osteoclasts via the receptor activator of nuclear factor-κB (RANK) pathway. Increased bone turnover and lack of bone modeling lead to severe deformities, frequent fractures, short stature, and loss of hearing. The treatment for JPD is challenging and has previously been based on administration of either calcitonin or bisphosphonates. However, with the development of denosumab, a receptor activator of nuclear factor-κB-ligand (RANKL) antibody, a treatment targeting the pathophysiology of JPD may be available. We report the effects of denosumab treatment on an 8-year-old girl with a severe form of JPD. Before starting the denosumab treatment regimen, the patient had been treated for 3.5 years with iv pamidronate. The administration of denosumab resulted in improved disease control compared with bisphosphonate, as assessed by monitoring markers of bone turnover. Alkaline phosphatase levels dropped within the normal range and remained at normal levels for 5 months after the final dose of denosumab. Additionally, bone pain was more efficiently controlled with denosumab. However, concomitant with the first injection, severe hypocalcemia developed, for which the patient was hospitalized and iv calcium supplementation was required for 13 days. Denosumab appears to be significantly effective for osteoclast inhibition for the treatment of JPD. However, in our patient, denosumab administration was associated with severe hypocalcemia, indicating that close monitoring of calcium levels is required during treatment.

Calcinosis Cutis Complicated by Compartment Syndrome Following Extravasation of Calcium Gluconate in a Neonate: A Case Report

Hypocalcemia most frequently occurs in premature neonates. It is usually treated by intravenous (iv) calcium supplementation. However, complications caused by extravasation of iv calcium gluconate include localized soft tissue calcification, necrosis, cellulitis, osteomyelitis, and even compartment syndrome. We present a rare case of iatrogenic calcinosis cutis complicated by compartment syndrome secondary to extravasation of iv calcium gluconate in a neonate. Emergent fasciotomy was performed twice for decompression of compartment syndrome. Histologic findings revealed necrosis and calcification. Appropriate antibiotics were administered to control secondary infection. To the best of our knowledge, there were no previous case reports of calcinosis cutis with compartment syndrome in infants. Although iatrogenic calcinosis cutis is generally a benign entity, the early recognition of the presentation of extravasation of calcium gluconate is important to avoid severe complications and possible medical malpractice disputes. This report aims to raise doctors' awareness of the presentation, course, and management of this relatively rare iatrogenic complication.

Procalcitonin and the Calcitonin Gene Family of Peptides in Inflammation, Infection, and Sepsis: A Journey from Calcitonin Back to Its Precursors

Calcitonin (CT) is a hormone that received its name because of its secretion in response to induced hypercalcemia and its hypocalcemic effect (1). It was shown to originate from the thyroid gland (2). More specifically, the hormone was revealed to be located within the thyroidal parafollicular cells, interspersed within and about the follicular epithelium (3–5). Subsequently termed C cells, they occur primarily in the central region of each lobe of the human thyroid gland (6, 7). These cells, which have CT-containing secretion granules, are neuroendocrine. Embryologically, they originate from the neural crest and migrate to the ultimobranchial glands (8). In mammals, the ultimobranchial glands fuse with the thyroid gland. It was the demonstration that medullary thyroid cancer (MTC) was a malignancy of the C cells (5, 9) that eventually led to the isolation of human CT from this tumor and the determination of its structure (10, 11). Simultaneously, the amino acid sequence of porcine CT was determined (12). Later, the development of immunoassays of serum CT in humans led to the observation that the level of this hormone was increased in the serum of patients with MTC (13–15) and to the demonstration that these levels were further augmented after iv calcium and/or pentagastrin administration (13, 16, 17). These findings had a great impact on the clinical diagnosis, the evaluation of efficacy of surgical extirpation, and the follow-up monitoring of MTC. Although RET germline mutation testing has replaced CT for the purpose of determining the presence of carriers of this tumor associated with multiple endocrine neoplasia type 2 (18, 19), the measurement of serum CT has become and has remained the classical clinical marker for MTC. Immature and mature CT

Hypocalcemia in critically ill patients

To review calcium regulation, causes of hypocalcemia during critical illness, clinical features and treatment of hypocalcemia, hemodynamic effects of calcium administration, calcium-catecholamine interactions, and the role of calcium in ischemic injury. Representative articles from the medical literature are used to support the discussion of selected aspects of calcium metabolism which are important to the practice of critical care medicine. Results from both animal and human investigations and both in vitro and in vivo studies are discussed. Circulating calcium levels are best measured using ionized calcium electrodes. Ionized hypocalcemia is common in critically ill patients and usually results from impaired parathyroid hormone secretion or action, impaired vitamin D synthesis or action, or calcium chelation/precipitation. Ionized hypocalcemia most commonly presents as cardiovascular or neuromuscular insufficiency. Mild ionized hypocalcemia (greater than 0.8 mmol/L) is usually asymptomatic and frequently does not require treatment. Moderate-to-severe ionized hypocalcemia is best treated with iv calcium in the critically ill patient. The majority of studies report no increase in cardiac output but a significant increase in BP after iv calcium administration. When administered with beta-adrenergic agonists, calcium frequently impairs their cardiovascular actions. Intracellular calcium dysregulation is common during ischemic and shock states. Agents which increase intracellular calcium may be harmful during cellular ischemia. Alterations in calcium regulation and calcium concentrations are common during critical illness. Optimal management of altered calcium concentrations requires an understanding of the pathophysiology behind these alterations.

Parathyroid Function in Normocalcemic Renal Transplant Recipients: Evaluation by Calcium Infusion*

The extent to which secondary hyperparathyroidism may involute remains poorly defined. Renal transplantation offers a clinical situation in which metabolic stimuli for hyperparathyroidism are removed. To examine whether hyperparathyroidism resolves after transplantation, we evaluated 11 renal transplant recipients who had been normocalcemic 6 or more months after transplantation using a sensitive 2-site immunoradiometric assay for intact serum PTH. Nine of the 11 had PTH concentrations within the normal range. Of these 9, 6 were found to have abnormal parathyroid function when challenged with an iv calcium infusion. The other 2 patients demonstrated significantly elevated basal PTH concentrations and elevated ionized calcium despite normal total serum calcium and albumin concentrations. In both, the PTH response to infused calcium was markedly abnormal, confirming hyperparathyroidism. The estimated renal threshold phosphate concentration was low in 4 of 9 patients with normal basal PTH concentrations and in both with elevated basal PTH. Bone mineral density, measured at the radius by single photon absorptiometry and at the spine by dual energy x-ray absorptiometry, was normal in 8 of the 9 transplant recipients who had normal basal PTH concentrations.

Recurring hypocalcemia of bovine parturient paresis is associated with failure to produce 1,25-dihydroxyvitamin D.

Parturient paresis (milk fever) is a hypocalcemic disorder caused by the onset of lactation in the dairy cow. In most cows a complete recovery follows a single iv calcium treatment to correct the acute hypocalcemia. However, about 20% of cows treated for parturient paresis experience recurring episodes of hypocalcemia (relapses) requiring further treatment. Analysis of plasma from 8 nonrelapsing parturient paretic and 11 relapsing parturient paretic cows revealed differences in plasma 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations before and during the development of hypocalcemia. In nonrelapsing cows, plasma 1,25-(OH)2D increased to 4- to 5-fold as plasma calcium concentrations declined during the first stage of parturient paresis. In relapsing cows, decreases in plasma calcium concentrations during the first stage of parturient paresis were accompanied by just a 2- to 2.5-fold increase in plasma 1,25-(OH)2D. Plasma 1,25-(OH)2D eventually increased 4- to 5-fold in the relapsing cows, but this response was delayed 24-48 h compared with the response in the nonrelapsing cows. Plasma PTH concentration profiles were similar in relapsing and nonrelapsing cows, suggesting that renal 25-hydroxyvitamin D 1 alpha-hydroxylase was temporarily refractory to stimulation by PTH in the relapsing cows. In both groups of cows recovery from parturient paresis began about 12-24 h after plasma 1,25-(OH)2D concentrations had increased 4- to 5-fold. These data imply that lack of production of 1,25-(OH)2D is an important factor in predisposing the cow to relapses of parturient paresis and is critical for recovery from the hypocalcemia associated with the onset of lactation.

Plasma calcitonin in primary hyperparathyroidism: failure of C-cell response to sustained hypercalcemia.

An acute increase in serum calcium stimulates calcitonin (CT) secretion, but the effects of chronic hypercalcemia are controversial. Histopathological studies have shown C-cell hyperplasia in primary hyperparathyroidism (1 degree HPT), although circulating levels of CT have been variously reported to be normal, elevated, or depressed. We reexamined this relationship using CT RIA in conjunction with a silica extraction technique that conveys improved sensitivity and specificity for monomeric CT. Nine men and seven women with surgically documented 1 degree HPT were studied preoperatively before and after a short calcium infusion (2 mg Ca/kg, for 5 min), as were 72 normal men and 76 normal women. Basal whole plasma immunoreactive CT and silica-extractable CT concentrations in 1 degree HPT were indistinguishable from normal, regardless of sex. In addition, the whole plasma and silica-extractable CT responses to calcium stimulation were normal or blunted in patients with 1 degree HPT. We conclude that hypercalcemia resulting from 1 degree HPT is not associated with augmented CT secretion in response to an iv calcium infusion.

Parathyroid hormone secretory responses to peroral phosphate and stimulability of serum levels of carboxyl-terminal flanking peptide (PDN-21) of the human calcitonin gene by calcium in normal subjects and osteoporotic patients.

The roles of calciotropic hormones in the pathogenesis and treatment of osteoporosis are not clearly understood. Here we have assessed serum levels of immunoreactive parathyroid hormone (PTH) and urinary cyclic AMP excretion before and after acute peroral phosphate administration in osteoporotic patients and normal subjects of the same age. In some osteoporotic patients serum levels of PTH were measured after prolonged (5 days) treatment with peroral phosphate. Serum levels of immunoreactive carboxyl-terminal flanking peptide (PDN-21) (katacalcin is a synonym) of the human calcitonin gene which are closely related to calcitonin levels were also measured before and after iv calcium injections (1). The diagnosis of osteoporosis was established on the basis of at least one vertebral compression fracture. Control subjects had normal serum levels of calcium, phosphate and creatinine, and they presented no history of renal, hepatic and intestinal disease. None of the subjects were treated with glucocorticoids or were alcoholics.

Diagnostic evaluation of measurements of carboxyl-terminal flanking peptide (PDN-21) of the human calcitonin gene in human serum.

Calcitonin and its carboxyl-terminal flanking peptide (PDN-21), also encoded by the calcitonin gene, were measured by RIA in unextracted serum of normal subjects and patients with primary hyperparathyroidism and surgically verified and suspected medullary thyroid carcinoma. Serum PDN-21 was detectable (greater than 0.005 ngeq/ml) in the large majority of normal subjects (92%), and the values increased significantly more in men than women (4.8- and 2.0-fold, respectively; P less than 0.01) in response to 1-min iv calcium injections. Calcitonin was detectable (greater than 0.025 ngeq/ml) in only 25% of normal subjects before iv calcium and became measurable after iv calcium in 88% of men and 41% of women. In patients with chronic hypercalcemia due to primary hyperparathyroidism, PDN-21 and calcitonin were within normal limits. In normal subjects, iv pentagastrin (0.5 microgram/kg BW) did not increase PDN-21, and calcitonin remained undetectable. In 41 medullary thyroid carcinoma patients, basal PDN-21 and calcitonin levels were increased similarly, and they were stimulated in response to iv calcium or iv pentagastrin. In 5 siblings of medullary thyroid carcinoma patients, PDN-21 and calcitonin were increased in response to iv pentagastrin, and we suspect C-cell hyperplasia or medullary thyroid carcinoma. In conclusion, a diagnostically useful RIA for the measurement of PDN-21 in unextracted serum which complements calcitonin measurements has been developed.

Reversible diminished calcitonin secretion in the rat during chronic hypercalcemia.

A transient increase in serum calcitonin (CT) concentration is induced by an acute iv calcium (Ca) load, whereas in the chronic hypercalcemic state, serum CT levels, as well as CT content of the thyroid, are equivocal. The secretion of CT was tested in three models of hypercalcemia in rats: tumor induced by the hypercalcemic Walker carcinosarcoma 256 (HWCS 256), chronic parenteral Ca administration, and chronic 1,25(OH)2D3 administration. In rats with HWCS 256, serum CT levels increased from basal values of 0.21 +/- 0.11 ng/ml to a maximum of 0.42 +/- 0.20 ng/ml on day 4 after tumor transplantation, 1 day before serum Ca increased. The serum CT levels declined again the following day (day 5). In thyroidectomized, parathyroid autotransplated rats with HWCS 256, serum Ca increased 1 day earlier than in intact rats. Substitution of CT by exogenous CT injections delayed the hypercalcemia for one day. Ca loading was followed by a decreased serum CT level (delta CT); the CT content of the thyroid fell from 9.4 +/- 1.1 ng/mg wet wt to 1.0 +/- 0.3 ng/mg wet wt. While hypercalcemia was present. Also chronic intraperitoneal Ca administration induced a decrease in the CT response to a Ca load (delta CT) and a decrease in thyroid CT content from 9.32 +/- 0.58 ng/mg wet wt to 3.84 +/- 0.33 ng/mg wet wt. These changes were no longer present 4 days after stopping Ca administration. In chronic hypercalcemia induced by 1,25(OH)2D3 administration, basal serum CT levels did not vary significantly, whereas serum Ca increased to 11.8 +/- 0.46 mg/dl on day 4. CT after an acute Ca load was diminished, as was CT content of the thyroid during 1,25(OH)2D3 administration. These changes were reversible after stopping 1,25(OH)2D3 administration. During chronic hypercalcemia a reversible exhaustion of CT content of the thyroid and a diminished CT response to acute Ca stimulation was observed, while basal serum CT levels remained unchanged.

Influence of Vitamin D Status on Insulin Secretion and Glucose Tolerance in the Rabbit*

The influence of vitamin D status on insulin secretion and glucose tolerance was studied by a longitudinal design in the rabbit. Intravenous glucose tolerance tests were performed in Dutch rabbits (n = 12) before and after nutritional vitamin D deficiency, characterized by an absence of circulating 25-hydroxyvitamin D3, a 50% decrease in 1,25-dihydroxyvitamin D3, and a 16% decrease in serum calcium concentrations. Glucose-induced insulin secretion was reduced by 41% as early as 2 months after the start of the vitamin D-deficient diet and was associated with an impairment of glucose tolerance. An iv calcium infusion restored the serum calcium concentration of the vitamin D-deficient rabbits (n = 5), but did not improve glucose-mediated insulin secretion. When these animals received a single ip injection of 100 ng 1,25-dihydroxyvitamin D3 10 h before the glucose test, their insulin responses significantly increased. Supplementation with 25-hydroxyvitamin D3 for 2 weeks in another group of rabbits (n = 4) resulted in marked improvement in glucose-stimulated insulin release and glucose tolerance. These results show that vitamin D affects glucose-induced insulin secretion by a mechanism that involves more than its regulating action on serum calcium concentration.

Effect of intravenous calcium on urinary cyclic adenosine-3',5'-monophosphate and hydroxyproline in children with hypoparathyroidism.

Abstract. The effect of iv calcium on the urinary excretion of total adenosine-3',5',-monophosphate (cAMP) and total hydroxyproline (OH-P) was investigated in 5 children with parathyroid hormone (PTH)-deficient and PTH-resistant hypoparathyroidism, two of them being normocalcaemic during the study, in comparison to 4 healthy and 8 epileptic children and adolescents. Eighteen mg/kg body weight calcium, infused over 3 h, induced a decrease of cAMP to (mean ± sd) 82.1 ± 2.5% of the baseline value in controls and to 69.8 ± 9.7% in epileptic patients with an inverse correlation to the relative increase of serum calcium after the infusion in both groups (r = −0.75, P &lt; 0.01). In contrast, the cAMP excretion increased after calcium load in the 5 hypoparathyroid children to 118.7 ± 14.9% of baseline despite a comparable serum calcium increase. OH-P decreased to (mean ± SD) 48.0 ± 6.8% of baseline in controls, 48.2 ± 12.7% in the epileptic patients and 39.4 ± 9.8% in the children with hypoparathyroidism, the differences between the three groups being statistically not significant. It is concluded that the simple measurement of urinary cAMP before and after calcium infusion may provide a diagnostic tool to identify hypoparathyroid patients even in the normocalcaemic state. In contrast, the measurement of the calcium-induced suppressibility of OH-P does not discriminate these patients from subjects with normal parathyroid function.

Parathyroid hormone response in newborn infants during exchange transfusion with blood supplemented with citrate and phosphate: effect of iv calcium.

Summary: We studied secretory parathyroid function in 16 newborn infants, aged 34–137 hr, before, during, and after exchange transfusion with a radioimmunoassay recognizing mainly intact human parathyroid hormone-(1–84) (hPTH-(1–84)). Before the exchange transfusion, serum calcium was normal or decreased, whereas parathyroid hormone (PTH) was within or above the range of normal adults. Serum PTH approached a maximum at decreased serum ionized and total calcium levels which were close to the normal range. During the early period of the exchange transfusion, serum ionized calcium was decreased as a result of the administration of considerable amounts of phosphate and citrate in the donor-blood and PTH was raised to levels seen in hypocalcemic infants before the exchange transfusion. Thereafter, serum ionized calcium remained low, whereas mean PTH concentrations were below basal levels. These inappropriately low PTH levels in relation to lowered serum-ionized calcium concentrations are probably the result of inadequate PTH secretion, which is enhanced by withdrawal of large amounts of presumably biologically active PTH-(1–84) during the exchange transfusion. Serum total calcium, on the other hand, was raised during the exchange transfusion probably as a result of calcium mobilization, and the net calcium balance expressed as the difference of calcium administered and in the withdrawn blood was negative. Even though serum ionized calcium decreased to levels below 2.5 mg/dl during the exchange transfusion, tetany was never observed, iv injections of calcium during the exchange transfusion caused temporary increases in total, but not in ionized calcium levels and shortening of Q-oTc intervals lasting for less than 1 min. We, therefore, advocate that iv calcium injections at regular time intervals during the exchange transfusion with donor blood preserved in citrate and phosphate should no longer be recommended as a prophylactic measure for preventing the decrease in serum-ionized calcium.Speculation: Parathyroid secretory function is inversely related to serum calcium concentrations in newborn infants. Serum PTH secretion is maximal at serum-ionized and total calcium concentrations close to the normal range despite further reduction to more markedly hypocalcemic levels. Transitory hypoparathyroidism occurs during exchange transfusion as a result of the removal of considerable amounts of biologically active PTH-(1–84).

Pseudohypoparathyroidism and Idiopathic Hypoparathyroidism: Relationship between Serum Calcium and Parathyroid Hormone Levels and Urinary Cyclic Adenosine-3′,5′- Monophosphate Response to Parathyroid Extract*

Forty patients with hypocalcemia and/or Albright's hereditary osteodystrophy were studied. Based on the estimation of serum calcium and parathyroid hormone (PTH) levels as well as the urinary cAMP response to infusions with parathyroid extract, it was possible to classify all of the patients studied as cases with idiopathic hypoparathyroidism (n = 6, low PTH, normal cAMP response), pseudohypoparathyroidism (PHP) type I (n = 18, high PTH, low cAMP response) and type II (n = 2, high PTH, normal cAMP response), as well as pseudopseudohypoparathyroidism (n = 14, normal PTH, normal cAMP response). In three cases studied at the age of 12, 17, and 23 yr, the signs of Albright's hereditary osteodystrophy were not observed. PTH levels were unusually high for a given serum calcium concentration in some patients with PHP, the increased PTH levels were, however, normalized during iv calcium infusions. In two young children with PHP, a gradual increase of serum PTH levels occurred despite persistent normocalcemia over a period of 3 yr. This suggests that factors other than hypocalcemia or frequent small unobservable falls of the serum calcium concentration, such as a deficient formation of 1,25-dihydroxyvitamin D3, secretion of an abnormal PTH, or an abnormal metabolism of the hormone, may contribute to the secondary hyperparathyroidism in PHP.

Improvement and initial in vivo application of the radioimmunoassay of rat thyrocalcitonin.

Previously we reported a homologous radioimmunoassy for rat thyrocalcitonin (TCT) which was sensitive enough (2--3 ng/ml serum) to measure TCT in thyroid venous blood or thyroid gland extracts but could not detect TCT in peripheral blood even after provocative challenge with iv calcium. In the present study chicken antisera to rat TCT were developed which were sufficiently sensitive (120--240 pg/ml serum) to permit initial evaluation of changes in TCT in rat peripheral blood. The following results were observed: (1) Basal serum TCT in young male Holtzman rats was undetectable, being less than 120--240 pg/ml; (2) induction of marked hypercalcemia by iv calcium increased TCT to approximately 1000--3000 pg/ml within 5 min; (3) thyroid cautery increased TCT to approximately 1000 pg/ml in 5--15 min; (4) calcium gavage (12.2 mg Ca/100 g) produced modest hypercalcemia in 30--60 min and increased serum TCT to approximately 500 pg/ml; (5) injection of isoproterenol raised serum TCT detectably; (6) injection of large doses of gastrin or pentagastrin did not produce detectable increases in TCT 5 or 30 min later. The results show that suitable antisera to rat TCT can be developed in chickens and applied to the measurement, by radioimmunoassay, of elevated circulating levels of TCT in the rat.

The effect of calcium infusion and calcitonin on plasma phosphate in sham-operated and thyroparathyroidectomized dogs.

The effect of iv calcium infusion (1.6 mg Ca/min as acetate or chloride) on plasma phosphate concentration was studied in dogs. Comparisons were made between sham-operated (TI), thyroparathyroidectomized (TPTX), and TPTX dogs administered calcitonin (50 MRC U × 2) during the calcium infusion. In anesthetized animals infused with calcium, a rise in plasma phosphate values was seen only in TPTX dogs. Subcutaneous calcitonin administration prevented this rise in TPTX dogs. Saline-infused controls, and urinary excretion measurements support the conclusion that the effects observed did not result from the presence or absence of parathyroid hormone. The results of these experiments demonstrate that calcitonin, from either endogenous or exogenous sources, prevents or reduces the rise in plasma phosphate concentration which would otherwise occur following calcium infusion in this species. This study supports the recent finding in rats that an important previously unrecognized role of calcitonin may be to moderate...