Infusion Of Calcium Gluconate Research Articles

7987 Ravenous Bone

Abstract Disclosure: Y. Oo: None. L. Srisawitri: None. P. Patel: None. M. Thein: None. Introduction Hungry bone syndrome ( HBS ) is the rapid drop in serum total calcium concentration of less than 2.1 mmol/L and/or prolonged hypocalcemia for more than 4 days postparathyroidectomy. It is more frequent in hemodialysis patients with secondary hyperparathyroidism (SHPT). The severe hypocalcemia after the parathyroidectomy is believed to be due to the increased usage of calcium by the starving bones. The key management is to replenish the severe calcium deficit aggressively. Clinical Case A 44-year-old Hispanic male patient with ESRD on hemodialysis was admitted for elective parathyroidectomy for SHPT from ESRD. The hospital course was complicated with profound hypocalcemia after the surgery. The pertinent lab results before surgery were total calcium level of 7.2 mg/dl ( normal 8.4 - 10.2 ), ionized calcium level of 4.9 ( normal 4.48 - 4.92 ), and PTH level of 2184 pg/ml (normal 15 - 65). After the parathyroidectomy, the ionized calcium level became 3.4 mg/dl and the PTH level trended down to 56 pg/ml. On the post-op day ( POD ) 1, the patient was started on calcitriol 1 mcg BID and calcium carbonate 600 mg QID and also got the hemodialysis with a high calcium bath. Even with the replacement, the calcium level kept worsening and calcium gluconate infusion was started on POD 4. On POD 5, calcium gluconate infusion was on hold as the ionized calcium was improved. On POD 7, calcitriol was increased to 2 mcg BID as ionized calcium was 3.2 mg/dl and restarted on calcium gluconate infusion. On POD 8, ionized calcium was 3.5 mg/dl, and calcium gluconate infusion was titrated down. On POD 9, as the total calcium level was 8.8 mg/dl, the calcium gluconate infusion was discontinued and he was discharged with calcium carbonate 1200 mg TID and calcitriol 2 mcg TID. Unfortunately, 13 days from the discharge date, he was readmitted with the volume overload, and on this second admission, the total calcium was 7 mg/dl and ionized calcium was 3.2 mg/dl. The calcitriol dose was increased to 2 mcg TID and the same dose of calcium carbonate which was 1200 mg TID. He got hemodialysis with a high calcium bath. After being treated for the volume overload, he was discharged with calcitriol 2 mcg TID and calcium carbonate 1200 mg TID and followed up with the endocrinology team in 2 weeks. Conclusion Even with the aggressive and constant replacement of calcium, the HBS cases are challenging in terms of achieving and maintaining a normal calcium level after surgery. We, the clinicians, need a better understanding of how to avoid the development of HBS or at least minimize the severity of hypocalcemia in the postoperative course and the ultimate management regimen to maintain the normal calcium level in both inpatient and outpatient settings. Presentation: 6/1/2024

8690 Severe Hypocalcemia Following Treatment with Venetoclax for AML

Abstract Disclosure: K. Ruddiman: None. C. Price: None. Background: Venetoclax is a chemotherapeutic agent which has known side effects of tumor lysis syndrome, but few reports of isolated hypocalcemia. Clinical case: A 73 year old male with medical history pertinent for myeloproliferative and myelodysplastic disease was admitted for evaluation of failure to thrive. Workup revealed progression to acute myeloid leukemia. Following treatment with decitabine 34mg/day for 5 doses and initiation of venetoclax 100mg daily, he developed progressive, severe, symptomatic hypocalcemia with positive Trousseau and Chvostek sign. The patient was normocalcemic prior to admission with serum calcium ranging between 8.6-9.7mg/dL. Corrected calcium at admission was 8.8mg/dL. Serum calcium decreased steadily following venetoclax, requiring repletion with 3 doses of calcium chloride and gluconate 1gm IV and initiation of oral calcium carbonate 1900mg TID. At its nadir, corrected calcium was 6.1mg/dL on day 19 of treatment with venetoclax despite oral and IV repletion. Further workup showed undetectable 25 hydroxy vitamin D, PTH 62pg/mL, normal range uric acid, low phosphorus (lowest 2.2mg/dL), mild hypokalemia (lowest 3.2mg/dL), and mild hypomagnesemia of 1.8mg/dL. GFR was >90mL/min. Hypocalcemia improved after 3 infusions of calcium gluconate 10gm IV in 1 L normal saline to 7.2mg/dL. Oral repletion with calcium carbonate was transitioned to calcium citrate due to concomitant PPI use. PO calcium citrate titrated to 2850 mg TID to target corrected calcium 7.5 - 8.5 and limit further need for diuresis following calcium gluconate infusions. Ergocalciferol 50,000 IU was given thrice weekly in addition to daily cholecalciferol 5,000 IU with improvement in 25 hydroxy vitamin D to 17ng/mL. This patient was suspected to have multifactorial etiology for hypocalcemia, secondary to undetectable 25 hydroxy vitamin D as well as diuresis with furosemide during the admission, but the most strongly attributed factor was initiation of venetoclax prior to development of progressive hypocalcemia. FDA prescribing information reports hypocalcemia as a side effect of venetoclax when used in treatment for CML, but in phase 2 and 3 studies of venetoclax used alone and in combination with low dose cytarabine to treat AML, no significant episodes of hypocalcemia were reported. Tumor lysis syndrome (TLS) is a known adverse effect of venetoclax in which hypocalcemia is an expected feature, however, this patient did not have laboratory to support this diagnosis. His other electrolyte deficiencies were mild and transient. Conclusion: While electrolyte abnormalities associated with TLS are an expected side effect of venetoclax, isolated severe hypocalcemia is a rarely reported side effect. Calcium should be closely monitored during treatment. Presentation: 6/1/2024

The use of prophylactic infusion of calcium gluconate compared to placebo in reducing the rate of early hypocalcaemia after total thyroidectomy: a double-blinded, randomized controlled trial.

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

Sine-wave pattern in a case of severe hyperkalemia and end-stage renal failure from a hospital in a rural area: A case report and narrative review

Background: A sine-wave pattern in electrocardiography (ECG) is one of the manifestations of severe hyperkalemia and requires rapid medical intervention and urgent hemodialysis. This manifestation has high specificity for detecting hyperkalemia, and rapid medical intervention is required upon first medical contact. Case Description: A 60-year-old woman presents to the emergency room with generalized weakness that started around two days ago, and became increasingly more severe and noticeable to the point that the patient went to the emergency department. The patient initially was stable and experienced no other complaints including chest pain or dyspnea. A 12-lead ECG was obtained which showed the sine-wave morphology. Minutes later, the patient rapidly deteriorated and underwent cardiac arrest while waiting for lab results to confirm the hyperkalemia. The patient was resuscitated successfully and lab results confirmed potassium levels of 9.7mmol/L and a creatinine level of 9.55mg/dL (estimated GFR using CKD-EPI formula of 4 ml/min/1.73m2. The patient underwent potassium correction therapy with fast-acting insulin agents, dextrose and calcium gluconate infusions. A secondary ECG post ROSC and potassium correction therapy was taken, showing a reversal of the sine-wave pattern into an accelerated junctional rhythm with tall T waves. Chest X-ray was performed and showed cardiomegaly, and the patient was admitted into the ICU to undergo urgent hemodialysis. Conclusion: This case further emphasizes the importance of recognizing ECG manifestations of hyperkalemia and rapid management after recognition of said ECG patterns to prevent the clinical deterioration of the patient and potentially fatal outcomes should be undertaken as soon as possible.

Idiopathic Hypoparathyroidism Presenting with Erythrodermic Psoriasis and Fahr’s Syndrome: A Case Report

Idiopathic hypoparathyroidism may remain asymptomatic or present with hypocalcaemic neuromuscular manifestations. Dermatological manifestations like exfoliative dermatitis, pustular psoriasis and symmetrical brain calcification known as Fahr’s syndrome are uncommon in clinical practice. Even in absence of neuromuscular symptoms, hypocalcaemia associated with exfoliative skin lesions and symmetrical brain calcification should prompt investigation for hypoparathyroidism. A 40-year-old male presented with diffuse erythematous pruritic plaques and fever of 10 days duration. Auspitz sign was positive on examination. Investigations showed leucocytosis with neutrophilic predominance. He was admitted with a diagnosis of erythrodermic psoriasis with secondary infection. On the second day of admission he developed an episode of generalised tonic clonic seizure for the first time. Investigations into the cause of seizure revealed low serum calcium while computerised tomography of head revealed symmetrical calcification of bilateral basal ganglia. Further, he was found to have a low level of intact Parathyroid Hormone (PTH) level and hyperphosphataemia. Based on clinical, biochemical and radiological findings, a diagnosis of idiopathic hypoparathyroidism, psoriasis and Fahr’s syndrome was made. Serum calcium was corrected with infusions of calcium gluconate followed by oral calcium carbonate. The patient was kept under observation for seizure recurrence. Calcium and vitamin D supplements and hydrochlorothiazide were started and psoriasis treatment was continued. His skin lesions resolved over the next two weeks, serum calcium levels returned to normal level and no seizure episodes were reported over three months of follow-up.

Optimising Ovulation Induction in PCOS

Biochemical, Metabolic and Endocrine changes in PCOS result in reproductive impairment in women with PCOS. Controlled ovarian stimulation (COS) may be associated with • Unpredictable response • Response may be slow • Hyper-response - OHSS • Risk of Cyst Formation • Poor oocyte quality • Miscarriage • Cycle cancellation So, the ovulation induction protocol should be efficacious and safe resulting in a singleton live birth, minimising complications, and risks like ovarian hyperstimulation syndrome (OHSS), multiple pregnancies and cancellation of cycles. For this special consideration should be given to prediction of response, pre-treatment, choosing the right ovulation induction (OI) protocol with right dose and analogue, using GnRH agonist trigger instead of hCG, preventing late follicular phase rise in progesterone, or following the segmentation protocol. We can maximize the success rates by stimulation individualization based on age, AMH, AFC and amended further for BMI. AMH is considered as more sensitive marker to define follicle excess than AFC as it appraises more follicle classes - preantral and early antral. One should probably use mild stimulation protocols where gonadotropins are given in combination with oral ovulogens or the low dose step up protocol. It is essential that we use GnRH antagonist protocol and administer GnRH agonist if there is risk of OHSS. If segmentation protocol is used one could also use the progesterone primed ovarian stimulation instead of GnRG antagonist. One could reduce the incidence of OHSS by laparoscopic ovarian drilling and use of Metformin and aspirin before assisted reproduction. If the patient is at risk of developing OHSS during stimulation then one could administer cabergoline, intravenous infusion of calcium gluconate or albumin and methylprednisolone. But freezing all embryos and transferring them in a subsequent cycle increase the efficacy and reduce complications of ART in PCOS women. Elective single embryo transfer(eSET) should be the norm to reduce the multiple pregnancy rate. Conclusion Thus, in all ART cycles individualised COS with freeze all and eSET could help in increasing the success of ART and reducing stress and anxiety and complications in these women.

Clinical profile and outcome of patients of common krait bite with features of neurotoxic envenomation, treated with intravenous calcium gluconate infusion in conjunction with AVS, a tertiary care center-based study

Background: Snake bite is one of the most neglected diseases in South East Asian region. Common Krait (CK) (Bungarus caeruleus) is the deadliest snake found in the dry zones of India. With the polyvalent anti-venom serum (AVS) remaining the cornerstone of treatment of neurotoxic snake envenomation, there is no universally accepted treatment for CK envenomation-associated neuroparalysis, except supportive measures. Aims and Objectives: Our study was conducted to describe the epidemiology, define clinical features, study outcome, and apparent efficacy of calcium gluconate in preventing or reversing neuromuscular paralysis with respiratory failure in CK bite patients. Materials and Methods: This study is a prospective observational study done on 52 CK bite patients. Patients were enrolled according to inclusion and exclusion criteria and were treated with AVS and calcium gluconate infusion according to National Standard Guideline, 2016. Patients developing severe respiratory muscle paralysis were offered mechanical ventilation. Results: Patients developed ptosis and dysphagia, pain abdomen, cyanosis, paralysis of jaw and tongue, perioral numbness, altered sensorium, dysphonia, ophthalmoplegia, and paradoxical breathing. 21.15% of patients developed respiratory failure and needed ventilator support with average critical care unit stay of 3 days and average stay on a ventilator of 2 days. 3 patients expired (case fatality rate 5.77%). The average hospital stay was 3.33 days. Conclusion: Our study shows that early intervention in patients of CK bite with neurotoxic envenomation, with calcium gluconate infusion, leads to less mortality and morbidity compared to other relevant studies. Further large-scale studies are required for better understanding and implementation.

Denosumab-induced hypocalcemia post bariatric surgery—a severe and protracted course: a case report

BackgroundDenosumab is known to cause abnormalities in calcium homeostasis. Most of such cases have been described in patients with underlying chronic kidney disease or severe vitamin D deficiency. Previous bariatric surgery could also contribute to hypocalcemia and deterioration in bone health.Case presentationWe present a case of a 61-year-old Malay female with worsening bilateral limb weakness, paresthesia, and severe carpopedal spasm a week after receiving subcutaneous denosumab for osteoporosis. She had a history of gastric bypass surgery 20 years ago. Post gastric bypass surgery, she was advised and initiated on lifelong calcium, vitamin D, and iron supplementations that she unfortunately stopped taking 5 years after surgery. Her last serum blood tests, prior to initiation on denosumab, were conducted in a different center, and she was told that she had a low calcium level; hence, she was advised to restart her vitamin and mineral supplements. Laboratory workup revealed severe hypocalcemia (adjusted serum calcium of 1.33 mmol/L) and mild hypophosphatemia (0.65 mmol/L), with normal magnesium and renal function. Electrocardiogram showed a prolonged QTc interval. She required four bolus courses of intravenous calcium gluconate, and three courses of continuous infusions due to retractable severe hypocalcemia (total of 29 vials of 10 mL of 10% calcium gluconate intravenously). In view of her low vitamin D level of 33 nmol/L, she was initiated on a loading dose of cholecalciferol of 50,000 IU per week for 8 weeks. However, despite a loading dose of cholecalciferol, multiple bolus courses, and infusions of calcium gluconate, her serum calcium hovered around only 1.8 mmol/L. After 8 days of continuous intravenous infusions of calcium gluconate, high doses of calcitriol 1.5 μg twice daily, and 1 g calcium carbonate three times daily, her serum calcium stabilized at approximately 2.0 mmol/L. She remained on these high doses for over 2 months, before they were gradually titrated down to ensure sustainability of a safe calcium level.ConclusionThis case report highlights the importance of screening for risk factors for iatrogenic hypocalcemia and ensuring normal levels before initiating denosumab. The patient history of bariatric surgery could have worsened the hypocalcemia, resulting in a more severe presentation and protracted response to oral calcium and vitamin D supplementation.

Iatrogenic calcinosis cutis in a preterm infant.

Extravasation phlebitis over the right forearm of a preterm newborn persisted beyond 3 weeks of limb care. The initial swelling evolved into a firm, non-tender, non-erythematous induration. The newborn was born as a singleton preterm birth at 32 weeks of gestation with a birth weight of 2.1 Kg (81 percentile) due to antepartum hemorrhage in a primigravida mother. The chart review suggested intravenous calcium gluconate infusion at 80 mg/kg per day for 2 days because of low ionized calcium (0.70 mmol/L) and seizures on day 2 of life.

Single stage chest wall soft tissue reconstruction with ipsilateral pectoralis major turnover flap, rhomboid skin flap, and inferior nipple transposition

Extravasation injury is a well-known complication of central venous catheter placement, with potential for extensive soft tissue necrosis. Here, we describe the case of a patient who developed a large right chest well soft tissue defect, due to a chest wall abscess from calcium gluconate infusion via a right internal jugular central venous catheter. After multiple debridements, the chest wall defect was reconstructed with a single stage ipsilateral pectoralis major turnover flap, rhomboid skin flap, and inferior nipple transposition to match the contralateral nipple. There was no further infection, no nipple necrosis, and patient regained full range of motion of the ipsilateral shoulder.

ODP076 A Unique Case of Iatrogenic Hypermagnesemia Induced Symptomatic Hypocalcemia

Abstract Introduction Magnesium plays a role in production, release, and end-organ responsiveness of parathyroid hormone (PTH) and calcium homeostasis. Hypomagnesemia has been well documented to cause hypocalcemia by impaired secretion of PTH or PTH resistance. Iatrogenic hypermagnesemia in pregnant patients receiving intravenous magnesium for suppression of premature labor and pre-eclampsia is an uncommon cause of hypocalcemia. We are reporting a case of symptomatic hypocalcemia caused by iatrogenic hypermagnesemia in post-partum mother, who had high PTH in contrast to previous case reports. CaseA 28-year-old G4P1122 female, postpartum day 16 was admitted for headache, slurred speech, and vomiting. She was found to have elevated blood pressures and was started on IV magnesium for postpartum preeclampsia. On her first day, she received a 4g bolus of magnesium sulfate followed by 2g as maintenance for seizure prophylaxis. The following morning, the patient awoke complaining of numbness/tingling in both arms and twitching in her face and eyelids. Later that day, she had developed bilateral spontaneous carpopedal spasm as well. Labs drawn at that time revealed ionized calcium 0.78mmol/L (1.18-1.32 mmol/L), corrected calcium 7.42mg/dL (8.5-10.1), vitamin D 25-OH 45ng/mL (30-100), PTH 149.1pg/mL (18.5-88), phosphorus 2.9mg/dL (2.3-4.6), GFR116mL/min (>60) and magnesium 3.5mg/dL (1.4-2.2). Patient was started on IV calcium gluconate infusion along with calcium carbonate 1g QID and vitamin D3 5000 units daily. By the evening of the second day, patient's carpopedal spasm and paresthesia completely resolved. Repeat labs demonstrated improved ionized calcium of 1.17mmol/L (1.18-1.32), corrected calcium of 9.78mg/dL (8.5-10.1), and magnesium of 1.5mg/dL (1.4-2.2). Patient was discharged on calcium carbonate 1g TID and Vitamin D3 5000 units daily. Patient self-discontinued calcium and vitamin D supplementation a week after discharge. Repeat labs one week later showed normal corrected calcium, magnesium, and PTH levels. Conclusion Our patient developed transient, symptomatic hypocalcemia with elevated PTH secondary to iatrogenic hypermagnesemia, which improved with intravenous calcium. Hypomagnesemia is a known cause of hypocalcemia, but hypermagnesemia is a significantly less recognized etiology. Hypermagnesemia can cause low PTH due to activation of calcium sensing receptors resulting in inhibition of PTH secretion. Hypermagnesemia can also blunt the peripheral effect of PTH and promote hypercalciuria. Previous studies showed PTH can peak by the end of magnesium infusion but still result in hypocalcemia, although this is an uncommon clinical presentation. Our case highlights this aspect of elevated PTH after the completion of IV Magnesium infusion but still unable to correct hypocalcemia due to PTH resistance from hypermagnesemia. This calls attention to another underrecognized sequalae of hypermagnesemia: blunting of peripheral tissues response to PTH. Clinicians should be aware of development of hypocalcemia with both hypo- and hypermagnesemia as well as the underlying pathophysiology. Presentation: No date and time listed

PSAT189 Severe Hypocalcemia and Hypophosphatemia Associated with Denosumab use in a Chronic Myeloid Leukemia Patient on Imatinib

Abstract Background Hypocalcemia and hypophosphatemia are known side effects of Denosumab, especially in presence of risk factors including underlying chronic kidney disease, osteoblastic metastasis, high bone turnover states, vitamin D deficiency and preexisting hypocalcemia. We report a unique case of prolonged severe hypocalcemia and hypophosphatemia in a patient with CML on Imatinib, treated with Denosumab for osteoporosis. Clinical case A 73-year-old lady with history of CML, on Imatinib for 4 years and osteoporosis with a chronic L1 compression fracture treated with her second dose of Denosumab 3-months back, presented with complaints of numbness and tingling involving the entire body. Labs revealed severe hypocalcemia (calcium 5.6 mg/dL, ionized calcium 2.93 mg/dL), severe hypophosphatemia, (phosphorus of 0.5mg/dL) and a low normal magnesium level of 1.5mg/dL, with normal ALP, liver and kidney function parameters. Of note she had normal calcium, phosphorus and vitamin D levels before receiving denosumab. Further work-up revealed an elevated PTH level of 241 pg/mL, normal 25 hydroxy vitamin D level of 26.0 ng/ml, slightly low 1,25 (OH) vitamin D of 16pg/ml and an elevated FGF 23 of 299RU/mL (normal <180RU/mL). Her calcium and phosphorus levels remained suboptimal despite treatment with up to 24 grams of calcium carbonate supplementation daily, K-phos 1 packet QID and calcitriol 0.25 mcg TID. 24-hour urine calcium and phosphorus levels were low at 4mg/day and 0.2mg/day respectively. Fractional excretion of phosphate was 13.63%, suggesting renal phosphorus wasting, likely from an elevated FGF23. Bone scan showed no metastatic lesion. After discussion with oncology, Imatinib was held inpatient and she was started on intravenous calcium gluconate infusion, and continued on Calcitriol, vitamin D3 and K-phos supplementation. After receiving almost 18gm of calcium gluconate intravenously over 2 days, her hypocalcemia and hypophosphatemia resolved with improvement in symptoms. Conclusion Hypocalcemia is a recognized adverse effect of Denosumab that is seen in patients with underlying risk factors. Emerging data now suggests the deregulatory effect of long term Imatinib therapy on bone formation by inhibition of osteoclastic activity along with transient increase in osteoblastic activity leading to retention and sequestration of calcium and phosphate in bone, resulting in hypocalcemia and hypophosphatemia. Ours is the first reported case of severe hypocalcemia and hypophosphatemia observed in a CML patient on Imatinib after receiving Denosumab, with resistance to high dose oral calcium and phosphate supplementation, requiring intravenous supplementation and transient discontinuation Imatinib. The elevated FGF 23 likely played a key role in severe hypophosphatemia. This unique case addresses the prospect of occurrence of severe hypocalcemia and hypophosphatemia in patients on Imatinib receiving Denosumab, while questioning the possibility of potentiation of the osteoclast inhibitory effect of this medication when used in patients on long term Imatinib therapy. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Calcium gluconate infusion is not as effective as dopamine agonists in preventing ovarian hyperstimulation syndrome.

The aim of the study was to compare the effectiveness of calcium gluconate and cabergoline therapy in the prevention of ovarian hyperstimulation syndrome (OHSS). Eight hundred and forty-five women who underwent GnRH antagonist protocol and at high risk for developing OHSS were divided into two groups, those given cabergoline (n=435) or calcium gluconate (n=410). In cabergoline group, 0.5 mg of cabergoline was administered once daily p.o. starting on the day of ovulation trigger and continued until the following 8 days. In calcium gluconate group, intravenous calcium gluconate was administered daily for four days starting on the day of oocyte pickup (OPU). 10 ml of 10% calcium gluconate solution was dissolved in 200 ml of physiological saline and administered by intravenous route within 40 minutes. Infusion was started within the first 30 minutes following the OPU and continued on the 1st, 2nd and 3rd days after OPU. Mild OHSS was developed in 367 (89%) patients receiving calcium gluconate infusion, while 251 patients (57%) in the cabergoline group developed mild OHSS. The frequency of mild OHSS in the calcium group was significantly higher than the cabergoline group (p<.001). Moderate OHSS was observed in 32 people (7.8%) in the calcium gluconate group, while it was observed in 184 people in the cabergoline group (42.3%). Calcium gluconate infusion significantly reduced the development of moderate OHSS compared to cabergoline therapy (p<.001). Severe OHSS developed in 11 patients (2.7%) in the calcium gluconate group, while severe OHSS did not develop in those given cabergoline (0%, p<.001). Clinical pregnancy, live birth and abortion rates were similar in the two groups. When logistic regression analysis was performed, a significant correlation was found between age, BMI, AMH, the number of antral follicle count, OHSS history, paracentesis, progesterone on the day of hCG, 2 PN zygotes, and HbA1c levels and the development of OHSS. No correlation was found between the use of metformin or cetrotide and the development of OHSS. Calcium gluconate treatment is not effective in the prevention of OHSS.

Improving management of severe hypoparathyroidism: a case series.

Hypoparathyroidism is considered a rare endocrine disease. Despite being a deficiency of parathyroid hormone, the standard therapy is based on oral calcium and active vitamin D supplementation. This approach provides satisfactory management in most cases but may be inadequate for patients in the most complex spectrum of the disease. Other therapies are being explored, and among them, the use of recombinant human parathyroid hormone (PTH) has proved to decrease the requirements of calcium and active vitamin D to reach adequate therapeutic goals. We aimed to provide information on the effectiveness of the current recombinant parathyroid hormone analogs in the clinical management of difficult to control cases of hypoparathyroidism. We report our experience using teriparatide and PTH (1-84) through five complex cases of hypoparathyroidism of diverse etiologies. We describe each case and report the effectiveness of treatment in clinical practice. Four patients with postsurgical hypoparathyroidism and one patient with autoimmune hypoparathyroidism, all of them with suboptimal control under the standard treatment with calcium and calcitriol supplements or calcium gluconate infusion, are presented. They were all started on teriparatide or PTH (1-84), and all of them showed a diminishment of symptoms and were able to maintain normocalcemia without parenteral calcium despite a reduction of oral treatment. This article highlights the effectiveness and safety of hormonal replacement treatment in difficult to manage hypoparathyroidism and provides evidence which justifies its off-label prescription in the case of teriparatide. We consider that this treatment should be considered in cases in which standard treatment fails to reach adequate therapeutic goals.

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.

A Case of Vocal Cord Paralysis and Severe Hypocalcemia

Background: Tetany is the hallmark of hypocalcemia. Vocal cord paralysis is a rare presenting symptom of hypocalcemia, especially without signs of overt tetany or seizures. Clinical case: 18 year old man with history of iron deficiency anemia and dyslipidemia presented with aphasia, right sided upper and lower extremity weakness and facial tingling for 3 days. Physical exam was notable for aphasia, pallor, positive Chvostek and Trousseau sign. Admission labs showed BUN 127 mg/dL (n 8–26 mg/dL), creatinine 12.74 mg/dL (n 0.8–2.00 mg/dL), calcium 5.2 mg/dL (n 8.5–10.5 mg/dL), magnesium (1.8–2.4 mg/dL), phosphorus 10.3 (2.4–4.8 mg/dL), alkaline phosphatase 126 (8–120 U/L), albumin 3.3 g/dL (n 3.0–5.0 g/dL), 25 OH VitD3 9.1 ng/mL (n 30–80 ng/mL), PTH 594 pg/mL (n 15–65 pg.mL), COVID 19 PCR negative. Aphasia resolved with 1 gram calcium gluconate infusion. Patient underwent emergent hemodialysis. He was placed on calcium carbonate 1500 mg oral three times daily, calcitriol 1 mcg oral twice daily, ergocalciferol 50,000 IU weekly, sevelamer carbonate 1600 mg tablet three times daily. Kidney biopsy showed membranoproliferative pattern glomerulonephritis with C3 deposits. He was discharged on hemodialysis and referred to a transplant center. Conclusion: Vocal cord paralysis is rare in adults and mostly seen in patients with pseudohypoparathyroidism caused by hypomagnesaemia.2,3 Identifying vocal cord paralysis as an atypical presentation of hypocalcemia secondary to acute kidney failure requires prompt recognition and treatment.

Denosumab Induced Severe Prolonged Hypocalcemia in Metastatic Prostate Cancer

Background: Denosumab is a RANK-l inhibitor that, in addition to the treatment of osteoporosis, is used in patients with advanced cancer and metastatic bone disease to prevent skeletal-related events. Although denosumab is generally safe and effective, it can cause hypocalcemia which in some patients can be severe and life threatening. We present a case of severe prolonged hypocalcemia after a single dose of denosumab in a patient with metastatic prostate cancer. Case: A 78-year-old male with a past medical history of stage 4 prostate cancer on antiandrogen treatment with GnRH antagonist presented with severe hypocalcemia. Physical exam revealed a blood pressure 125/80 mm Hg, pulse 115 per min and weight 135 lb with negative Chvostek’s and Trousseau’s signs. The electrocardiogram showed supraventricular tachycardia with prolonged QTc interval of 503 ms (<430 ms). Labs showed serum calcium 4.9mg/dL (8.5–10.5), albumin 2.5g/dL (3.6–5.1), corrected calcium 5.7 mg/dL, ionized serum calcium 0.64mmol/L (1.05–1.3), creatinine 1.10mg/dL (0.7–1.2), eGFR >60, phosphorus 2.0mg/dL (2.5–4.5), magnesium 1.9 mg/dL (1.6–2.6), 25-OH vitamin D 29.7 ng/mL (30–100), 1,25 dihydroxy vitamin D 174 pg/mL (18–64), iPTH 244.0 pg/mL (11–68) and PSA 1860 ng/mL. Three weeks prior to presentation, the patient received 120 mg of subcutaneous denosumab. Pre-treatment serum calcium was 9.2 mg/dL (8.5–10.5), and Tc-99m bone scan showed multiple osteoblastic osseous metastatic lesions involving both axial and appendicular skeleton. The patient was diagnosed with denosumab-induced severe hypocalcemia and started on intravenous (IV) calcium gluconate infusion, oral phosphate 250 mg twice daily, and ergocalciferol 50,000 IU twice weekly. He required IV calcium gluconate up to 10 g per day in addition to oral calcium carbonate 2 g t.i.d. for 2 weeks to resolve hypocalcemia and normalize QTc interval. Patient was discharged to nursing home on calcium carbonate 2 g q.i.d. with IV calcium gluconate as needed to keep corrected calcium >8.0 mg/dL. After discharge he required up to 4 g of IV calcium and 8 g of oral calcium per day. Unfortunately, he presented again with severe hypocalcemia 5 weeks after discharge. In addition to current regimen of oral and IV calcium boluses, low dose calcitriol was started. We were only able to maintain his serum calcium>8.0 mg/dL by administering high daily dose of oral calcium carbonate 8 g /day and calcitriol 2 mcg daily. Due to poor prognosis, he was transitioned to hospice care and died 2 weeks later. Discussion: There are not many case reports on severe prolonged hypocalcemia secondary to denosumab in cancer patients but normal kidney function. Our patient remained on high dose of calcium even 101 days after denosumab administration. Reference: 1. Milat F et al. Prolonged hypocalcemia following denosumab therapy in metastatic hormone refractory prostate cancer. Bone. 2013 Aug 1;55(2):305–8.

Hypermagnesemia in a 20-month-old healthy girl caused by the use of a laxative: a case report

BackgroundHypermagnesemia can be a fatal condition and should be diagnosed early on. Most reports of hypermagnesemia have been of adults with impaired renal function. We describe the case of a pediatric patient without renal dysfunction who developed severe hypermagnesemia.Case presentationA healthy 20-month-old Asian girl presented to our emergency department with episodes of vomiting and a reduced level of consciousness. The neurological examination showed a symmetric decrease in muscle tone, and the deep tendon reflexes were decreased. On admission, her magnesium (Mg) level was 11.0 mg/dL after receiving magnesium oxide for 4 days because of constipation. She was immediately administered calcium gluconate infusion (3.9 mEq), and then was continuously infused with it (0.23 mEq/h) as a Mg antagonist to cardiac side effects. She was kept hydrated with 0.9% sodium chloride to maintain good urine output to excrete the Mg. The level of the serum Mg decreased to 2.4 mg/dL, enabling her to regain consciousness. During 5 years of follow-up, she was neurologically well, without the recurrence of hypermagnesemia.ConclusionsEven in the absence of significant renal dysfunction, the prescription of a laxative containing Mg for constipation can result in severe hypermagnesemia. In addition, the symptoms of hypermagnesemia are nonspecific, and early diagnosis is difficult unless it is actively suspected.

SAT-404 Neonatal Hypocalcemic Seizures in Offspring of a Mother with Familial Hypocalciuric Hypercalcemia Type 1 (FHH1)

Background: Familial hypocalciuric hypercalcemia type 1 (FHH1) is caused by loss-of-function mutations of the calcium-sensing receptor (CaSR), and considered to be a benign condition associated with mild-to-moderate hypercalcemia (1). However, the children of parents with FHH1 can develop a variety of disorders of calcium homeostasis in infancy. Objective: To further characterise the range of calcitropic phenotypes in the children of a mother with FHH1. Methods: We assessed a three generation FHH kindred by clinical, biochemical and mutational analysis following informed consent. Results: The kindred comprised a hypercalcemic male, his daughter who had hypercalcemia and hypocalciuria, and her four children, of whom two had asymptomatic hypercalcemia, one was normocalcemic, and one suffered from transient hypocalcemic seizures during infancy. The hypocalcemic infant had a serum calcium of 1.57 mmol/L (normal, 2.0-2.8) and PTH of 2.2 pmol/L (normal, 1.0-9.3) as a consequence of maternal hypercalcemia, and required treatment with I-V calcium gluconate infusions. Mutational analysis identified a novel heterozygous p.Ser448Pro CaSR variant in the hypercalcemic family members, but not in the children with hypocalcemia or normocalcemia. Three-dimensional modelling using a reported crystal structure of the dimeric CaSR showed the mutated Ser448 residue to be located in the CaSR extracellular domain, and predicted the p.Ser448Pro variant to disrupt a hydrogen bond interaction across the extracellular CaSR dimer interface. The variant Pro448 CaSR, when expressed in HEK293 cells, was shown to significantly impair CaSR-mediated intracellular calcium mobilisation and mitogen-activated protein kinase (MAPK) responses following stimulation with extracellular calcium, thereby demonstrating it to represent a loss-of-function mutation. Conclusion: These studies have identified a novel loss-of-function CaSR mutation which caused asymptomatic hypercalcemia in a mother and her children who had inherited the mutation. However, one child who did not inherit the mutation developed transient neonatal hypocalcemic seizures as a consequence of maternal hypercalcemia. These findings highlight the importance of assessing serum calcium and undertaking CaSR mutational analysis in the newborn offspring of a mother with FHH1. Reference: (1) Hannan FM, Kallay E, Chang W, Brandi ML, Thakker RV. The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases. Nat Rev Endocrinol. 2018; 15(1): 33-51.

Medical Management of Primary Hyperparathyroidism in Pregnancy: A Case Report and Brief Literature Review

There is no established standard of care for the medical management of primary hyperparathyroidism in pregnancy for those patients who are not surgical candidates. We present a case of primary hyperparathyroidism in the third trimester that was managed with cinacalcet and a literature review on the various modalities for the medical management of primary hyperparathyroidism in pregnancy. The primary aim of this case report is to document a case of hyperparathyroidism in pregnancy that was managed medically and to perform a brief systematic review of the literature available on the medical management of primary hyperparathyroidism in pregnancy. The secondary aim is to contribute to the literature available on the use of cinacalcet in pregnancy. A 37-year-old woman with untreated primary hyperparathyroidism presented at 32 weeks of gestation with hypercalcemia that was not amenable to surgical intervention. We treated her with increasing doses of cinacalcet with improvement in her serum calcium until developing pre-eclampsia which prompted emergent cesarean delivery of the infant. The neonate developed respiratory distress after delivery but did not develop hypocalcemia after birth. The neonate became transiently hypercalcemic in the setting of calcium gluconate infusions given to prevent hypocalcemia. The patient underwent surgical removal of a parathyroid adenoma and required calcium supplementation for 1 month afterwards. Hypercalcemic crisis during pregnancy is associated with significant maternal and fetal morbidity. There is limited information regarding the medical management of primary hyperparathyroidism due to the lack of high-powered studies and prospective studies owing to the relative rarity of the condition. No serious adverse maternal events were reported for either bisphosphonate or cinacalcet use. Adverse neonatal events include transient hypocalcemia of the infant with cinacalcet use and possibly low birth weight, infantile hypocalcemia, and shortened gestational periods with bisphosphonate use. J Endocrinol Metab. 2020;10(2):49-53 doi: https://doi.org/10.14740/jem624