Profound Hypocalcemia 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

HDR syndrome (hypoparathyroidism, deafness and renal dysplasia) Unveiled: A rare cause of profound hypocalcaemia and seizure

HDR syndrome (hypoparathyroidism, deafness and renal dysplasia) Unveiled: A rare cause of profound hypocalcaemia and seizure

APECED SYNDROME (FAMILY OBSERVATION)

Introduction: APECED (Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy) is an autosomal recessive disease characterized by the association of autoimmune endocrine involvement, mucocutaneous candidiasis and ectodermal tissue involvement. Observation: We report the case of 2 brothers from a 2nd degree consanguineous marriage with a history of 2 deaths in the siblings for whom the diagnosis of APECED syndrome was retained on clinical and biological criteria (genetic study in progress).The eldest had candidous onychomycosis of the hands and feet, generalized mucocutaneous candidiasis, profound hypocalcemia with tetany crisis, autoimmune hepatitis, Biermers anemia and ADDISONs disease. Meanwhile the youngest had onychomycosis, vitiligo, atrophy of the tongue, alopecia and adrenalinsufficiency. Discussion:Autoimmune polyglandular syndrome type 1 (APS-1) is classically characterized by at least two of the three components of Whitakers triad: chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and chronic adrenal insufficiency. If a sibling is affected, only one component of the triad is necessary to make the diagnosis. Conclusion: This syndrome requires a multidisciplinary approach, without forgetting the importance of genetic counseling for this autosomal recessive disease.

A profound hypocalcaemia following parathyroidectomy. A case report

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Hypocalcaemia and hypophosphataemia following denosumab and IV ferric carboxymaltose in an older patient with normal renal function

AbstractBackgroundSevere hypocalcaemia and hypophosphataemia following the co‐administration of denosumab and IV ferric carboxymaltose has previously been reported in the setting of chronic kidney disease and malignancy. Despite scarce evidence, there has been growing concern amongst clinicians of a possible drug interaction between denosumab and IV iron therapies. Although electrolyte abnormalities are well known side effects of these individual therapies, it is possible that co‐administration of the agents can exaggerate these effects and result in a potentially life‐threatening interaction.AimWe present a case of profound hypocalcaemia and hypophosphataemia following same day administration of denosumab and IV ferric carboxymaltose in a hospitalised older patient.Clinical detailsAn older female with normal renal function, serum calcium, phosphate and 25‐hydroxy‐vitamin D levels, and no history of malignancy was given denosumab 60 mg SC for secondary fracture prophylaxis following an acute osteoporotic fracture. On the same day, she received ferric carboxymaltose 1 g IV for treatment of iron‐deficiency anaemia.OutcomesFollowing a review of her pathology results during the inpatient hospital admission, profound hypocalcaemia and hypophosphataemia was identified 8 days after denosumab and ferric carboxymaltose administration. Despite supplementation, electrolyte abnormalities persisted for 12 days following administration.ConclusionAlthough the patient had no pre‐existing risk factors for developing electrolyte disturbance, profound hypocalcaemia and hypophosphatemia following denosumab and IV ferric carboxymaltose administration occurred, suggesting a possible interaction between the two therapies. Caution should be exercised by clinicians when these agents are co‐administered within a close timeframe.

EP.WE.103223-hour stay following total parathyroidectomy in renal patients

Abstract Aim Total parathyroidectomy in end-stage renal failure (ESRF), is an effective way to improve or stabilise calcium and parathormone levels and thus improve renal osteodystrophy. Previous BAEST guidelines were not in favour of true day-case neck surgery due to the risk of airway compromise from bleeding. Additionally, ESRF patients are at risk of profound hypocalcaemia after total parathyroidectomy. Patients undergoing total parathyroidectomy are prescribed Alfacalcidol 4mcg daily for 5 days prior to surgery. Following surgery under GA on a morning list, the potassium and calcium levels are checked in the afternoon. Calcium levels are then monitored daily for 3 days and subsequently when required. Oral Alfacalcidol is continued at the same dose until the nephrologists advise otherwise. Methods All ESRF patients undergoing total parathyroidectomy for secondary hyperparathyroidism were identified between 01/01/2005 and 31/12/2019 from a prospectively maintained electronic database. Demographics, biochemistry, length of stay (LoS) and outcomes were analysed. Results There were 43 (30 male) total parathyroidectomies. The median age was 53 (range 14 – 78), and median LoS 1 day (range 0 -13). 26 patients (60%) were discharged within 23 hours (26% were day-case). Prolonged stay was due to calcium replacement (n = 8) or dialysis (n = 4) requirements. Pre- and post-operative calcium values over 2.49mmol/L were significantly related to 23-hour stay (p = 0.010482 and p = 0.000263 respectively). No 30-day re-admissions were observed Conclusions Careful patient selection and adherence to a perioperative management protocol in total parathyroidectomy may enable early discharge within 23 hours. Preoperative calcium levels help predict this outcome.

Profound Hypocalcemia Following Thyroidectomy for Graves’ Disease

Abstract Introduction: While transient parathyroid insufficiency is not an uncommon complication of thyroidectomy, severe and prolonged hypocalcemia attributed to a combination of post-surgical hypoparathyroidism, hungry bone syndrome (HBS) and hypovitaminosis D is unusual. Clinical Case: A 17-year-old female from a remote community in Australia with Graves’ disease, complicated by exophthalmos and atrial flutter, underwent total thyroidectomy due to challenges with medication adherence leading to persistent thyrotoxicosis. FT4 was >150 pmol/L (normal 10–20 pmol/L) almost two years after diagnosis. Pre-operatively, she received Lugol’s iodine, carbimazole and beta-blockade. The operation was uncomplicated and three parathyroid glands were preserved. Within six hours of thyroidectomy, she developed symptomatic hypocalcemia with corrected calcium 1.9 mmol/L (7.6 mg/dL) (normal 2.2–2.65 mmol/L). PTH level was 0.8 pmol/L (normal 1.4–9.0 pmol/L). Magnesium and phosphate levels were initially normal but hyperphosphatemia developed the following day. 25-OH vitamin D was low (29 nmol/L, normal 50–150 nmol/L) and was corrected with high dose cholecalciferol. Despite use of continuous intravenous calcium gluconate in addition to oral calcium carbonate, as well as both intravenous and oral calcitriol and magnesium, urinary calcium excretion remained undetectable. Teriparatide 20 mcg BD was commenced on post-operative day 14 with no demonstrable improvement in serum calcium. Less than 48 hours after cessation of parenteral calcium on day 18 post-operation, corrected calcium and ionised calcium declined to 1.47 mmol/L (5.9 mg/dL) and 0.46 mmol/L (normal 1.15–1.33 mmol/L) respectively, prompting recommencement of calcium infusion. Her remarkably high requirement for calcium replacement with negligible urinary calcium excretion for at least one month in spite of parenteral calcium infusion for a total of three weeks’ duration is highly suggestive of HBS which became evident due to post-surgical hypoparathyroidism. She had elevated ALP (618 U/L, normal 35–140 U/L) and increased bone resorption marker (N-telopeptide/creatinine 262 nmol BCE/mmol, normal <100 nmol BCE/mmol), with osteopenia at lumbar spine (Z-score -1.7) and femur (Z-score -1.3). Additionally, vitamin D deficiency is likely to have contributed to the severity of hypocalcemia. 60 days after surgery, she was still requiring calcium carbonate 2500 mg QID (4 g/day elemental calcium) and calcitriol 1 mcg TDS. Her phosphate level had normalised and ALP gradually declined to 241 U/L. Clinical Lesson: This case highlights the importance of attaining euthyroid status as early as possible pre-operatively to allow near-complete reversal of thyrotoxicosis-induced osteodystrophy, as indicated by normalisation of serum ALP, and ensuring vitamin D levels are replete prior to thyroidectomy for Graves’ disease.

AM833, a Long Acting Amylin Analogue Induces Hypocalcemia in Young Rats via a Calcitonin Receptor Mediated Mechanism

Abstract Amylin is a peptide hormone that is co-secreted with insulin from pancreatic β-cells. It is member of the calcitonin family and activates amylin receptors (AMYRs) in the calcitonin receptor (CTR) family. During recent years, several AMYR agonists have been in clinical development for treatment of diabetes and obesity. In contrast to pramlintide, which is a short acting amylin analogue approved for use in combination with meal-time insulin in patients with diabetes, the more recent development candidates have been dual acting analogues activating both the CTR and the AMYRs. In rodents the CTR plays a significant role in calcium homeostasis, while in humans this has been associated with little long-term effect on the plasma calcium levels (Ganong, 1993; Longo et al., 2011); Rodents are usually chosen as first choice pre-clinical models for in vivo testing and introducing acute and profound hypocalcaemia can lead to general neurological and neuromuscular disturbances, which can be challenging in clinical development programs. AM833 (NNC0174-0833) is a long acting acylated dual acting amylin analogue activating both CTR and AMYRs. When combined with the long acting GLP-1 analogue semaglutide for weight management, both preclinical studies in rat models of obesity and clinical trials in humans with obesity have demonstrated significant weight loss potential. In young rats aged 7–9 weeks, single sc dose of 3–300 nmol/kg AM833 induced a reduction of total and ionized calcium of 40–50% from baseline with lowest level around 12 hours after dosing. A similar response was seen after administration of salmon calcitonin which also activates both CTR and AMYRs. Tachyphylaxis was introduced, with no effect on calcium found after sub chronic daily treatment for 2 weeks. Age played a key role in the sensitivity to calcium lowering with almost no effect found in 11 months old rats. When administering AM1213 (NNC0174-1213), a selective AMYR agonist with little activation of the CTR, no or little calcium lowering of around 10% was seen. These data indicated that the calcium lowering properties are CTR mediated. The induction of hypercalcemia was a rodent specific phenomenon as no calcium lowering outside of normal range was seen in young dogs and rabbits. Clinical data confirmed that CTR induced calcium lowering was not human relevant, but these data showed that understanding physiology and pharmacology in the animal models of investigation as well as human translational relevance is of outmost importance in the progress of an early development program.

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 Hypocalcemia Secondary to Infection With SARS-CoV-2 Virus

Background: A Case of Hypocalcemia Secondary to Infection with SARS-CoV-2 Virus.Clinical Case: A 40 year-old obese male presented to the emergency department with a five day history of nausea, vomiting, shortness of breath, and nonproductive cough. Symptoms progressed culminating in a single episode of pre-syncope leading to his seeking medical care. Positive testing for the presence of SARS-CoV-2 as well as findings from computed tomography of the patient’s chest led to a diagnosis of COVID-19 and the patient’s admission to a COVID-19 ward, where treatment with dexamethasone, doxycycline, and 2 L oxygen via nasal cannula began. Blood testing on admission revealed profound hypocalcemia (6.2 mg/dL total and 3.5 mg/dL ionized) as well as newly diagnosed diabetes mellitus type 2 (T2DM) (HbA1c 13.0% on admission). Further electrolyte disturbances noted were consistent with his history of vomiting and untreated T2DM. Thyroid stimulating hormone and thyroxine levels showed primary hypothyroidism, but the patient’s parathyroid hormone level (16.5 pg/mL) was inappropriately normal. No other causes for hypocalcemia were identified. The patient’s hypocalcemia was treated with intravenous calcium gluconate and rose consistently through day six of hospitalization. Calcium fell sharply between day six and seven (7.6 mg/dL to 7.3 mg/dL) coinciding with worsening respiratory symptoms and requiring a doubling of oxygen dose from 2 to 4 L with subsequent improvement in hypocalcemia once underlying pulmonary function improved. Discussion: SARS-CoV-2 infection presenting with hypocalcemia has been well documented without definitive explanation [1]. Further, while the precise mechanism of SARS-CoV-2 virion export is unclear, the patient’s worsening hypocalcemia, respiratory symptoms, and concurrent presumable increased viral load suggests this is caused by a calcium-dependent exocytotic process [2]. 1: Marazuela, M., Giustina, A. & Puig-Domingo, M. Endocrine and metabolic aspects of the COVID-19 pandemic. Rev Endocr Metab Disord 21, 495–507 (2020). https://link.springer.com/article/10.1007/s11154-020-09569-22: Fehr A.R., Perlman S. (2015) Coronaviruses: An Overview of Their Replication and Pathogenesis. In: Maier H., Bickerton E., Britton P. (eds) Coronaviruses. Methods in Molecular Biology, vol 1282. Humana Press, New York, NY. https://link.springer.com/protocol/10.1007%2F978-1-4939-2438-7_1.

Primary Hyperparathyroidism due to Ectopic Intrathymic Parathyroid Adenoma in A Child: A Case Report

Primary hyperparathyroidism (PHPT) is a rare endocrine disorder in children and adolescents. Surgery is curative in most pediatric patients with PHPT. PHPT due to ectopic parathyroid adenoma (EPA) presents the difficulty of their exact topographic diagnosis and there is no consensus for the optimal imaging modality. The 99mTc-sestamibi (99mTechnetium -labeled methoxy-isobutyl-isonitrile) scintigraphy appears to be the best exam to establish a topographic diagnosis of parathyroid adenoma. Herein, we present the case of a 14-year-old girl with the diagnosis of PHPT with bone involvement. Parathyroid scintigraphy (dual-phase and dual tracer subtraction imaging), has shown an abnormal tracer uptake in the anterior mediastinum. Computed tomography (CT), has confirmed the mediastinal seat of the adenoma, measured 40 x 24.6 mm, repressing the thymus. An adenectomy was performed using video-assisted mini-thoracoscopic surgery. Histological findings have shown intrathymic ectopic parathyroid adenoma. After surgery, the patient had profound and persistent hypocalcemia as a result of extensive remineralization in a relation to Hungry Bone Syndrome (HBS). Through this clinical report, we insist on the importance of preoperative localization of parathyroid adenoma to select the surgical approach and to avoid failed cervicotomy especially in cases of ectopic adenomas.

Role of Bisphosphonates in The Prevention of Postoperative Hungry Bone Syndrome in Primary Hyperparathyroidism: A Meta-Analysis and Need for Randomized Controlled Trials.

Dear Editor,Hungry bone syndrome (HBS) is a clinico-biochemical entity characterized by the development of profound and prolonged hypocalcemia associated with hypophosphatemia, hypomagnesemia, and rising alkaline phosphatase which follows curative parathyroidectomy for severe primary and secondary hyperparathyroidism. The prevalence of HBS after parathyroidectomy in primary hyperparathyroidism (PHPT) is variable with several case series from Asia reporting remarkably higher prevalence rates of 24-87% 1.

LACK OF HUMAN THROMBOMODULIN GENE EXPRESSION IN LIFE SUPPORTING PIG-TO-BABOON CARDIAC XENOTRANSPLANTATION MODELS ACCELERATE ANTIBODY MEDIATED REJECTION

Introduction: Transplantation of organs from animals to humans (xenotransplantation) has been proposed to address the critical shortage of organs for transplantation. The use of genetically engineered organ xenografts, including knock-out (KO) of alpha 1-3 galactosyltransferase (GTKO) along with insertion of a human complement regulator genes (hCD46-human CD46, hDAF-human decay accelerating factor) and other cell surface carbohydrate KOs, has been helpful in circumventing acute and subacute rejection. However, thrombotic complications still remain. Xenografts with additional human transgenes, including human thrombomodulin (hTBM), have been generated to address this barrier. Here, we studied the importance of hTBM in preventing microvascular and intramural thrombosis and rejection by comparing two transplanted groups utilizing GE donors with or without hTBM. Methods: Specific pathogen-free baboons of either sex weighing 15-30 kg (2-3 years of age) were used as recipients. 6 to 8-week-old genetically modified pigs with hTBM (GTKO.hCD46.hTBM) or without hTBM (triple knock out-GTKO.B4KO.CMAHKO, with or without hCD46 and hDAF) were used as donors. Expression of transgenes were consistent and high level across all pigs. All animals were used in compliance with guidelines provided by the Institutional Animal Care and Use Committee (IACUC). Results: GTKO.hCD46.hTBM donors (n=4) were found to have no intracardiac thrombus with survival up to 30 days post-transplant, but one with ongoing survival at the time of this abstract submission. However, non-hTBM donors (n=2) had an average survival of 7 days and were found to have a large intracardiac thrombus burden with propagation into major vascular structures such as the aorta, pulmonary artery and coronary sinus. Gross examination of thrombi indicated acute and subacute components, suggesting early formation of the thrombus postoperatively. Additionally, early clinical signs of thrombus formation included profound hypocalcemia requiring continuous calcium infusions in the first 48-72 hours postoperatively. These phenomena were not prevented by continuous heparin infusion. Histologic myocardial examination revealed microscopic and macroscopic thrombotic phenomena, likely related to accelerated antibody mediated rejection in non-hTBM containing grafts. Conclusion: Non-hTBM containing xenografts exhibited accelerated antibody mediated rejection. While immunologic rejection has been circumvented with novel immunosuppression regimens and GTKO, it is likely that hTBM or other transgenes involved in regulation of coagulation, may be needed for prevention of thrombotic complications and accelerated antibody mediated rejection.

Human Thrombomodulin Transgene Expression Prevents Intracardiac Thrombus in Life Supporting Pig-to-Baboon Cardiac Xenotransplantation

Transplantation of organs from animals to humans (xenotransplantation) has been proposed to address the critical shortage of organs for transplantation. The use of genetically engineered organ xenografts, including knock-out (KO) of alpha 1-3 galactosyltransferase (GTKO) along with insertion of a human complement regulator genes (hCD46, hDAF) and other cell surface carbohydrate KOs, has been helpful in circumventing acute and subacute rejection. However, thrombotic complications still remain. Xenografts with additional human transgenes, including hTBM, have been generated to address this barrier. Here, we studied the importance of hTBM in preventing coagulation by comparing two transplanted groups utilizing GE donors with or without hTBM. Specific pathogen-free baboons of either sex weighing 15-30 kg (2-3 years of age) were used as recipients. 6 to 8-week-old genetically modified pigs with hTBM (GTKO.hCD46.hTBM) or without hTBM (triple knock out-GTKO.B4KO.CMAHKO, with or without hCD46 and hDAF) were used as donors, provided by Revivicor. Expression of transgenes were consistent and high level across all pigs. All animals were used in compliance with guidelines provided by the Institutional Animal Care and Use Committee (IACUC). GTKO.hCD46.hTBM donors (n=3) were found to have no intracardiac thrombus with survival up to 30 days post-transplant. However, all non-hTBM donors (n=3) were found to have a large intracardiac thrombus burden with propagation into major vascular structures such as the aorta, pulmonary artery and coronary sinus. Gross examination of thrombi indicated acute and subacute components, suggesting early formation of the thrombus postoperatively. Additionally, early clinical signs of thrombus formation included profound hypocalcemia requiring continuous calcium infusions in the first 48-72 hours postoperatively. These phenomena were not prevented by continuous heparin infusion. Histologic examination revealed no signs of rejection. hTBM prevents intracardiac thrombus in this model. While immunologic rejection has been circumvented with novel immunosuppression regimens and GTKO, it is likely that hTBM or other transgenes involved in regulation of coagulation may be needed for prevention of thrombotic complications.

Fatal Hypocalcaemia Due to Hungry Bone Syndrome with Secondary Refractory HyperParathyroidism after Parathyroidectomy: A Case Report

IntroductionHungry bone syndrome (HBS) refers to the rapid, profound, and prolonged hypocalcaemia associated with hypophosphatemia and hypomagnesaemia, and is exacerbated by suppressed parathyroid hormone (PTH) levels, which follows parathyroidectomy in patients with severe primary hyperparathyroidism (PHPT) and preoperative high bone turnover. [1]Case reportThis report concerns a dialysed patient who underwent surgical treatment for secondary refractory hyperparathyroidism. Haemodialysis was carried out pre-operatively, and subsequently, a total parathyroidectomy with auto-transplantation of parathyroid tissue in the sternocleidomastoid muscle (SCM) was performed. Rapid and progressive hypocalcaemia symptoms developed during the second day postoperatively. Acute cardiac symptoms with tachyarrhythmia, haemodynamic instability and finally asystole occurred, which required cardiopulmonary resuscitation (CPR). The ionic calcium level was 2.2 mg/dL being consistent with a diagnosis of HBS. A second cardiac arrest unresponsive to CPR followed an initial period of normal sinus rhythm. Death ensued shortly after. Before death, the ionic calcium was 3.1 mg/dL.ConclusionHBS, after parathyroidectomy in patients with secondary hyperparathyroidism (SHPT), may be severe, prolonged and sometimes fatal. Generally, HBS symptomatology is that of a mild hypocalcaemia. It can, however, include heart rhythm disturbances with haemodynamic alterations requiring intensive care measurements and even cardiopulmonary resuscitation. A close clinical and laboratory post-parathyroidectomy monitoring of dialysed patients is of the utmost importance.

SAT-513 Cut To The Bone: Hypocalcemia From Hungry Bone Syndrome In A Dialysis Patient

Background: Hungry bone syndrome is a life-threatening complication focused on prevention following parathyroidectomy in ESRD patients, requiring pre-operative optimization of serum calcium levels Case: A 35-year-old male with a past medical history of HTN, polycystic kidney disease and ESRD on peritoneal dialysis presented with numbness around the mouth and fingers, diffuse body aches and generalized weakness. He underwent total parathyroidectomy for tertiary hyperparathyroidism three days prior to presentation at another medical facility. Physical exam was unremarkable. Labs were significant for profound hypocalcemia of 5.8mg/dl [8.6-10.3mg/dl] and ionized calcium of 0.59mmol/L [1.12-1.32mmol/L]. The diagnosis of hungry bone syndrome was made based on the clinical setting. He received massive doses of IV and oral calcium along with IV calcitriol. Calcium was also added to each bag of peritoneal dialysate. Serum calcium levels remained low for three days despite optimal therapy with improvement after day four of admission. On the day of discharge, the serum calcium level was 7.8mg/dl [8.6-10.3mg/dl] with complete resolution of symptoms. He was discharged on calcitriol and calcium carbonate. Discussion: Hungry bone syndrome is a life-threating complication of parathyroidectomy. It is characterized by a severe drop in serum total calcium concentration and prolonged hypocalcemia for more than four days post parathyroidectomy. Hypocalcemia is generally transient because the degree of bone disease is typically mild but in some cases, the postoperative hypocalcemia is severe and prolonged. This most often occurs in patients who have developed bone disease preoperatively due to a chronic increase in bone resorption induced by high levels of PTH. The focus of hungry bone syndrome should be on prevention with pre-operative management of serum calcium and vitamin D levels. IV Calcitriol 2mcg is administered at the end of dialysis beginning three to five days prior to surgery, continued post-operatively as well. 2-3g of oral calcium is started two days prior to surgery. Once the serum calcium levels are within the reference range, IV calcitriol can be switched to an oral formulation. Despite adequate pre-op management, the risk of developing hungry bone syndrome in ESRD patients is high, requiring aggressive calcium supplementation Conclusion: Correction of serum calcium levels within the reference range prior to parathyroidectomy in ESRD patient is imperative to reduce the incidence of hungry bone syndrome.

Pseudohypoparathyroidism and Cardiomyopathy: A Case Report with a New Perspective on the Cardiovascular-Endocrine Axis with Respect to Calcium Homeostasis.

Pseudohypoparathyroidism encompasses a group of heterogeneous disorders defined by targeted organ unresponsiveness to parathyroid hormone (PTH). With an estimated prevalence of approximately 0.79 per 100,000, this is an extremely rare group of genetic disorders. The documented phenotypic manifestations and complications of this condition include skeletal abnormalities, thyroid-stimulating hormone (TSH) resistance, growth hormone deficiencies and abnormalities in gonadotropic hormones. However, the cardiovascular effects of this condition have never been studied. To the knowledge of the writer, this is the first report of pseudohypoparathyroidism resulting in profound hypocalcaemia leading to heart failure in a previously healthy 22-year-old man with no known cardiac history. Following treatment with calcium replacement therapy, the patient’s cardiac function improved dramatically, demonstrating the seminal role played by serum calcium in myocardial contractility and its influence on cardiac function.LEARNING POINTSIn patients with heart failure, serum calcium must be measured, especially if the underlying aetiology of heart failure is unclear.In patients with heart failure, correction of calcium levels is an important aspect of management.Patients with pseudohypoparathyroidism should undergo cardiac evaluation, especially in the presence of symptoms such as peripheral oedema and dyspnoea on exertion.

Cardiac, bone and growth plate manifestations in hypocalcemic infants: revealing the hidden body of the vitamin D deficiency iceberg

BackgroundWhilst hypocalcemic complications from vitamin D deficiency are considered rare in high-income countries, they are highly prevalent among Black, Asian and Minority Ethnic (BAME) group with darker skin. To date, the extent of osteomalacia in such infants and their family members is unknown. Our aim was to investigate clinical, cardiac and bone histomorphometric characteristics, bone matrix mineralization in affected infants and to test family members for biochemical evidence of osteomalacia.Case presentationThree infants of BAME origin (aged 5–6 months) presented acutely in early-spring with cardiac arrest, respiratory arrest following seizure or severe respiratory distress, with profound hypocalcemia (serum calcium 1.22–1.96 mmol/L). All infants had dark skin and vitamin D supplementation had not been addressed during child surveillance visits. All three had severely dilated left ventricles (z-scores + 4.6 to + 6.5) with reduced ejection fraction (25–30%; normal 55–70), fractional shortening (7 to 15%; normal 29–40) and global hypokinesia, confirming hypocalcemic dilated cardiomyopathy. They all had low serum levels of 25 hydroxyvitamin D (25OHD < 15 nmol/L), and elevated parathyroid hormone (PTH; 219–482 ng/L) and alkaline phosphatase (ALP; 802–1123 IU/L), with undiagnosed rickets on radiographs.One infant died from cardiac arrest. At post-mortem examination, his growth plate showed a widened, irregular zone of hypertrophic chondrocytes. Histomorphometry and backscattered electron microscopy of a trans-iliac bone biopsy sample revealed increased osteoid thickness (+ 262% of normal) and osteoid volume/bone volume (+ 1573%), and extremely low bone mineralization density. Five of the nine tested family members had vitamin D deficiency (25OHD < 30 nmol/L), three had insufficiency (< 50 nmol/L) and 6/9 members had elevated PTH and ALP levels.ConclusionsThe severe, hidden, cardiac and bone pathology described here exposes a failure of public health prevention programs, as complications from vitamin D deficiency are entirely preventable by routine supplementation. The family investigations demonstrate widespread deficiency and undiagnosed osteomalacia in ethnic risk groups and call for protective legislation.

Hypocalcaemia (puerperal tetany, milk fever, eclampsia) in a ferret (Mustela putorius furo)

Dyspnoea and/or collapse are not uncommon presenting signs for ferrets (Mustela putorius furo) brought in to the veterinary clinic. A 2-year-old female entire ferret was presented 3 weeks post-whelping with sudden onset collapse and dyspnoea. Blood glucose levels were found to be normal, however biochemistry analysis showed profound hypocalcaemia. Clinical signs resolved fully after the administration of calcium gluconate. This case report alerts the clinician to the clinical presentation and management of hypocalcaemia in the lactating ferret.

Parathyroidectomy in the Management of Secondary Hyperparathyroidism.

Secondary hyperparathyroidism develops in CKD due to a combination of vitamin D deficiency, hypocalcemia, and hyperphosphatemia, and it exists in nearly all patients at the time of dialysis initiation. There is insufficient data on whether to prefer vitamin D analogs compared with calcimimetics, but the available evidence suggests advantages with combination therapy. Calcium derangements, patient adherence, side effects, and cost limit the use of these agents. When parathyroid hormone level persists >800 pg/ml for >6 months, despite exhaustive medical interventions, monoclonal proliferation with nodular hyperplasia is likely present along with decreased expression of vitamin D and calcium-sensing receptors. Hence, surgical parathyroidectomy should be considered, especially if concomitant disorders exist, such as persistent hypercalcemia or hyperphosphatemia, tissue or vascular calcification including calciphylaxis, and/or worsening osteodystrophy. Parathyroidectomy is associated with 15%-57% greater survival in patients on dialysis, and it also improves hypercalcemia, hyperphosphatemia, tissue calcification, bone mineral density, and health-related quality of life. The parathyroidectomy rate in the United States declined to approximately seven per 1000 dialysis patient-years between 2002 and 2011 despite an increase in average parathyroid hormone levels, reflecting calcimimetics introduction and uncertainty regarding optimal parathyroid hormone targets. Hospitalization rates are 39% higher in the first postoperative year. Hungry bone syndrome occurs in approximately 25% of patients on dialysis, and profound hypocalcemia requires high doses of oral and intravenous calcium along with calcitriol supplementation. Total parathyroidectomy with autotransplantation carries a higher risk of permanent hypocalcemia, whereas risk of hyperparathyroidism recurrence is higher with subtotal parathyroidectomy. Given favorable long-term outcomes from observational parathyroidectomy cohorts, despite surgical risk and postoperative challenges, it is reasonable to consider parathyroidectomy in more patients with medically refractory secondary hyperparathyroidism.