Symptomatic Hypocalcemia Research Articles

Permanent postoperative hypoparathyroidism: an analysis of prevalence and predictive factors for adequacy of control in a cohort of 260 patients.

Recent guidelines for the treatment of hypoparathyroidism emphasize the need for long-term disease control, avoiding symptoms and hypocalcaemia. Our aim has been to analyze the prevalence of poor disease control in a national cohort of patients with hypoparathyroidism, as well as to evaluate predictive variables of inadequate disease control. From a nation-wide observational study including a cohort of 1792 patients undergoing total thyroidectomy, we selected 260 subjects [207 women and 53 men, aged (mean ± SD) 47.2±14.8 years] diagnosed with permanent hypoparathyroidism. In every patient demographic data and details on surgical procedure, histopathology, calcium (Ca) metabolism, and therapy with Ca and calcitriol were retrospectively collected. A patient was considered not adequately controlled (NAC) if presented symptoms of hypocalcemia or biochemical data showing low serum Ca levels or high urinary Ca excretion. Two hundred and twenty-one (85.0%) patients were adequately controlled (AC) and 39 (15.0%) were NAC. Comparison between AC and NAC patients did not show any significant difference in demographic, surgical, and pathological features. Rate of hospitalization during follow-up was significantly higher among NAC patients in comparison with AC patients (35.9% vs. 10.9%, P<0.001). Dose of oral Ca and calcitriol were also significantly higher in NAC subjects. In a subgroup of 129 patients with serum parathyroid hormone (PTH) levels available, we found that NAC patients exhibited significantly lower postoperative PTH concentrations than AC patients [median (interquartile range) 3 (1.9-7.8) vs. 6.9 (3.0-11) pg/mL; P=0.009]. In a nation-wide cohort of 260 subjects with definitive hypoparathyroidism, 15% of them had poor disease control. These patients required higher doses of oral Ca and calcitriol, had higher rate of hospitalization during follow-up and showed lower PTH concentrations in the postoperative period.

Calcilytic NPSP795 Increases Plasma Calcium and PTH in an Autosomal Dominant Hypocalcemia Type 1 Mouse Model.

ABSTRACTCalcilytics are calcium‐sensing receptor (CaSR) antagonists that reduce the sensitivity of the CaSR to extracellular calcium. Calcilytics have the potential to treat autosomal dominant hypocalcemia type 1 (ADH1), which is caused by germline gain‐of‐function CaSR mutations and leads to symptomatic hypocalcemia, inappropriately low PTH concentrations, and hypercalciuria. To date, only one calcilytic compound, NPSP795, has been evaluated in patients with ADH1: Doses of up to 30 mg per patient have been shown to increase PTH concentrations, but did not significantly alter ionized blood calcium concentrations. The aim of this study was to further investigate NPSP795 for the treatment of ADH1 by undertaking in vitro and in vivo studies involving Nuf mice, which have hypocalcemia in association with a gain‐of‐function CaSR mutation, Leu723Gln. Treatment of HEK293 cells stably expressing the mutant Nuf (Gln723) CaSR with 20nM NPSP795 decreased extracellular Ca2+‐mediated intracellular calcium and phosphorylated ERK responses. An in vivo dose‐ranging study was undertaken by administering a s.c. bolus of NPSP795 at doses ranging from 0 to 30 mg/kg to heterozygous (Casr +/Nuf ) and to homozygous (Casr Nuf/Nuf ) mice, and measuring plasma PTH responses at 30 min postdose. NPSP795 significantly increased plasma PTH concentrations in a dose‐dependent manner with the 30 mg/kg dose causing a maximal (≥10‐fold) rise in PTH. To determine whether NPSP795 can rectify the hypocalcemia of Casr +/Nuf and Casr Nuf/Nuf mice, a submaximal dose (25 mg/kg) was administered, and plasma adjusted‐calcium concentrations measured over a 6‐hour period. NPSP795 significantly increased plasma adjusted‐calcium in Casr +/Nuf mice from 1.87 ± 0.03 mmol/L to 2.16 ± 0.06 mmol/L, and in Casr Nuf/Nuf mice from 1.70 ± 0.03 mmol/L to 1.89 ± 0.05 mmol/L. Our findings show that NPSP795 elicits dose‐dependent increases in PTH and ameliorates the hypocalcemia in an ADH1 mouse model. Thus, calcilytics such as NPSP795 represent a potential targeted therapy for ADH1. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Clinical Application of Near-infrared Autofluorescence Detection of Parathyroid Glands in Thyroid Surgery

The purpose of this paper is to compare and analyze the advantages and disadvantages of near-infrared autofluorescence (NIRAF) imaging, nano-carbon negative imaging and conventional naked eye recognition technology in recognizing parathyroid glands during surgery, and to preliminary evaluate the effectiveness, safety and feasibility of NIRAF imaging in the recognition of parathyroid glands. The clinical trials retrospectively analyzed 36 patients, including 12 patients in Group A (NIRAF imaging group), 12 patients in Group B (nano-carbon negative imaging group), and 12 patients in Group C (conventional naked eye recognition group). The number of parathyroid glands recognized during surgery in Group A was more than that in Group B and C. The time taken to recognize parathyroid glands in Group A was shorter than that in Group B and C. There was no significant difference in the average calcium ion levels of the three groups A, B and C before surgery. After surgery, the average calcium ion level of Group A was not significantly different from that of Group B, but it was higher than that of Group C, and the difference was significant. The incidence of postoperative hypocalcemia in Group A was not significantly different from that in Group B, but it was lower than that in Group C. The incidence of postoperative symptomatic hypocalcemia in Group A was lower than that in Group B and C. Compared with traditional technology, NIRAF can recognize more parathyroid glands during surgery, take less time, and make the probability of postoperative hypocalcemia and symptomatic hypocalcemia lower during thyroid surgery. It needs noninvasive and simple operation. It is a kind of safe, effective and feasible parathyroid gland recognition technology, which is worth further exploration.

Severe, symptomatic hypocalcemia due to denosumab and vitamin d deficiency in a post–menopausal female with osteopenia

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

Semptomatik Hipokalsemi ve Nütrisyonel Rikets Nedenli Hastane Başvuruları: Göçmen Suriye’li Süt Çocuklarının Predominansı

Amac: Nutrisyonel rikets, buyume cagindaki cocuklarda D vitamini ve kalsiyum eksikligine bagli olarak gelisen epifizyal kikirdagin defektif mineralizasyonudur. Nutrisyonel riketsin onlenmesi icin D vitamini profilaksisi ulkemizde sut cocuklugu doneminde rutin olarak uygulanmaktadir. Ancak halen semptomatik hipokalsemi ve D vitamini eksikligi nedeniyle hastane basvurularinin olmasi dikkat cekicidir. Calismamizda bu olgularin ozelliklerinin ortaya konulmasi amaclanmistir. Gerec ve Yontem: Ocak 2018-Mayis 2018 tarihleri arasinda nutrisyonel rikets tanisi ile yatirilarak izlenmis olan 28 hastanin (9 kiz, 19 erkek) verisi retrospektif olarak incelendi. Olgularin basvuru anindaki antropometrik ve laboratuvar ozellikleri kaydedildi. Bulgular: Olgularin ortanca basvuru yasi 8,8 (1-35) ay idi. Olgularin %67,9’u Suriye gocmeni idi. Hastalarin %57,1’i hic D vitamini profilaksisi almamis, %42,9’u ise duzensiz almisti. Basvuru yakinmasi olgularin %50’sinde konvulsiyon gecirme, %28,6’sinda rikets bulgulari iken %21,4’unde ise ates, enfeksiyon vb. nedenlerden dolayi hastaneye basvuran hastalarda rastlantisal olarak hipokalsemi tespit edilmis olmasi idi. Ilk basvuruda ortanca kalsiyum 6,6 mg/dL; iyonize kalsiyum 0,85 mmol/L; fosfor 3,5 mg/dL; alkalen fosfataz 787 U/L; parathormon 241 pg/mL ve 25-hidroksi vitamin D 3,4 ng/mL saptanmisti. Olgularin %60,7’sinde hipofosfatemi, %3,6’sinda hiperfosfatemi mevcuttu. Tum olgular hastanede yatirilarak tedavi edilmis ve D vitamini eksikligine bagli nutrisyonel rikets tanisi almisti. Sonuc: Ulkemizde D vitamini profilaksisine ragmen halen nutrisyonel rikets gorulebilmekte ve kis-ilkbahar aylarinda hipokalsemik konvulsiyon nedeniyle hastane basvurularina yol acabilmektedir. Ozellikle gocmen Suriyeli sut cocuklarinda D vitamini destek programina uyumun artirilmasi nutrisyonel riketsin onlenmesi acisindan onemlidir.

Parathormone decline levels are better markers of symptomatic hypocalcemia following total thyroidectomy than parathormone alone.

Background: We aimed to assess the predictive value of the absolute and relative intact parathormone (iPTH) decline levels as reliable markers of postoperative hypocalcemia. Materials & methods: iPTH levels were measured 4 h after surgery and the following morning after surgery (postoperative day 1). iPTH, absolute iPTH decline (ΔPTH) and relative iPTH decline (ΔPTH%) were calculatedand correlated withsymptomatic hypocalcemia. Results: Of the 95 patients, 20% of patients (n=19) developed symptomatic hypocalcemia. The ΔPTH (U=206; p<0.001) andΔPTH% (U=127; p<0.001) were significantly higher in patients with symptomatic hypocalcemia. A ΔPTH% of 20% (sensitivity of 84%; specificity of 91%); and an absolute iPTH decline of 3.75pg/ml (sensitivity of 74%; specificity of 87%) were highly predictive of symptomatic hypocalcemia. Conclusion: Postoperative ΔPTH and ΔPTH% have the potential to be predictors of symptomatic hypocalcemia following thyroidectomy and could facilitate a safe early discharge.

Effect of Preoperative Vitamin D Deficiency on Hypocalcemia in Patients with Acute Hypoparathyroidism after Thyroidectomy.

Postoperative hypoparathyroidism is a common complication of total or completion thyroidectomy. The association between preoperative vitamin D deficiency (VDD) and the development of more severe postoperative hypocalcemia is still unclear. Objectives. To evaluate the effect of preoperative VDD on severity of hypocalcemia in patients with hypoparathyroidism following thyroidectomy. Methods. Patients who developed acute hypoparathyroidism after total or completion thyroidectomy, defined as postoperative parathyroid hormone (PTH) level <15 pg/mL and albumin-adjusted calcium level <8.6 mg/dL, were prospectively recruited. Patients were divided into two groups according to their preoperative vitamin D status (VDD group: 25-hydroxyvitamin D (25(OH)D) level <20 ng/mL; non-VDD group: 25(OH) level ≥20 ng/mL). The primary outcome was severity of hypocalcemia in postoperative hypoparathyroidism. Significant hypocalcemia was defined as calcium level ≤7.5 mg/dL. Results. Forty-three patients (21 VDD, 22 non-VDD) were enrolled. Serum total albumin-adjusted calcium level was significantly lower in the VDD group (7.71 ± 0.5 vs. 8.16 ± 0.4 mg/dL, p < 0.01), and the incidence of symptomatic hypocalcemia was significantly higher in the VDD group (43% vs. 9%, p=0.01). The median maximal daily supplementary dose of elemental calcium was significantly higher in the VDD group (2,400 vs. 1,500 mg/day, p=0.02). Length of hospital stay was nonsignificantly longer in the VDD group (p=0.06). Preoperative vitamin D level <19.6 ng/mL could predict significant and symptomatic hypocalcemia in postoperative hypoparathyroidism with sensitivity of 90% and 82% and specificity of 70% and 69%, respectively. Conclusion. VDD is an independent risk factor for both significant and symptomatic hypocalcemia in hypoparathyroidism patients after thyroid surgery.

What is the experience of our patients with transient hypoparathyroidism after total thyroidectomy?

BackgroundWe sought to better understand the experience of patients with transient hypoparathyroidism using patient interviews and quality of life surveys. MethodsThis is a prospective analysis of 62 patients after total thyroidectomy at a high-volume institution. Semistructured patient interviews and quality of life surveys were conducted preoperatively and postoperatively at 2 weeks, 6 weeks, 6 months, and 1 year and compared based on postoperative parathyroid hormone levels. ResultsPostoperative parathyroid hormone levels were <10 pg/mL in 32% of patients (n = 20), 10 to 20 pg/mL in 19% (n = 12), and >20 pg/mL in 48% (n = 30). Hypocalcemic symptoms at 2 weeks were reported in 28 of 55 patients (51%), but patients felt “well prepared” and reported it “wasn’t a big deal.” If symptoms persisted at 6 weeks, they became more bothersome. At 6 months and 1 year, patients reported calcium supplementation prevented most symptoms and did not interfere with daily activities. Quality of life as measured by the European Organization for Research and Treatment of Cancer and the 12-Item Short Form Survey demonstrated a slight improvement at 1 year postoperatively regardless of parathyroid hormone level. ConclusionEarly postoperative transient hypoparathyroidism is common but when appropriately managed did not have a substantial negative impact on the overall quality of life.

Total Thyroidectomy as an Ambulatory Procedure in Community Practice.

ObjectiveIncreasingly, total thyroidectomy is offered as an ambulatory procedure. Most of the relevant outcomes research derives from academic centers, but most thyroid surgeries are performed in the community. The goal of this study is to evaluate the safety of total thyroidectomy performed as an ambulatory procedure in a community otolaryngology practice.Study DesignRetrospective review and national database analysis.SettingA single community otolaryngology practice.MethodsAdult patients undergoing total thyroidectomy by a single otolaryngologist between 2013 and 2019 were divided into 2 cohorts: planned ambulatory and planned admission. Charts were reviewed for demographics and surgical outcomes in the 2 groups. The Healthcare Cost and Utilization Project databases for New York and Florida between 2015 and 2016 were also analyzed to compare outcomes of thyroidectomy as an ambulatory surgery between different practice settings.ResultsA total of 99 total thyroidectomies were performed during the study time period; 66 of 99 (67%) were planned as ambulatory procedures and 33 of 99 (33%) were planned admissions. Five of the 66 (8%) planned outpatient surgeries required admission. Complications of vocal fold dysfunction, symptomatic hypocalcemia, and seroma formation were more commonly seen in the inpatient cohort. Only 2 ambulatory patients required admission after discharge. Nationally, odds of complication were higher for ambulatory total thyroidectomy at nonteaching practice sites, which is not duplicated in our study.ConclusionsAmbulatory total thyroidectomy can be undertaken safely in the community in carefully selected cases.

Effect of citrate on ionized calcium levels during plateletpheresis procedures

Plateletpheresis procedures are generally well tolerated by most of the donors and adverse reactions due to citrate are generally mild and easily managed. The most common apheresis‐related reaction is hypocalcemia due to citrate anticoagulation which reduces ionized calcium and magnesium levels. The levels of ionized calcium levels decrease continuously from the baseline levels till end of the procedure and restore to baseline values post‐procedure. Symptoms of citrate toxicity are dependent on various factors like rate of citrate administration, duration of citrate infusion, dilution of citrate in extracellular fluid, redistribution, rate of citrate metabolism and the rate of citrate excretion. Citrate metabolism occurs in the liver, kidney, and skeletal muscle. Donors generally tolerate up to 20% decreases in ionized calcium levels. Citrate related reactions are generally transient and selflimiting. Citrate reactions can be differentiated into mild, moderate and severe. Management of citrate reactions includes mostly procedural modifications and/or oral calcium supplementation and rarely may require intravenous calcium supplementation. In donors with citrate related hypocalcemic symptoms, unresponsive to calcium supplementation, measurement of ionized magnesium should be considered as citrate decreased the ionized magnesium levels too. Management of such donors should be done with supplementation with magnesium sulfate. Management of donor reactions will make donors experience more pleasant, thereby increasing donor return rate and maintain the donor pool.

Prophylactic Calcium and Vitamin D Supplementation to Prevent Hypocalcemia Post-Thyroidectomy

Background: Hypocalcemia is a common post-operative complication of Thyroidectomy. This study is aimed to evaluate and treat hypocalcemia after total thyroidectomy procedure with routine administration of oral calcium and vitamin D supplements. The aim of this study was to evaluate the clinical effectiveness of oral calcium and vitamin D administration in preventing hypocalcemia post-thyroidectomy. Subjects and Methods: This was a prospective randomized controlled study conducted on 50 patients undergoing total or near total thyroidectomy for benign or malignant disease over the period of one year from February 2017 to January 2018 at Department of General Surgery, Bhaskar Medical College, Yenkapally, Moinabad, Ranga Reddy District, Telangana, India. All the participants were randomly assigned to routinely receive or not receive oral calcium (3 g/d) and vitamin D (1 µg/d) for 2 weeks. Hypocalcemia symptoms and signs and total serum calcium levels were monitored and compared between the 2 groups. Data were presented in the form of statistical tables and charts. SPSS software version 20 was used for statistical analysis. Results: The hypocalcemic symptoms were minimal in the supplement group but more severe in the group not receiving the supplement. Serum calcium levels decreased in both groups after surgery but recovered earlier in the supplement group. Conclusion: In reducing the incidence and severity of hypocalcemia after total thyroidectomy, routine administration of supplements containing oral calcium and vitamin D has been effective.

A registry for patients with chronic hypoparathyroidism in Russian adults.

Hypoparathyroidism and pseudohypoparathyroidism are rare endocrine disorders, characterized by low serum calcium due to inappropriate parathyroid hormone (PTH) levels or resistance to its action. There is little epidemiological information regarding chronic hypoparathyroidism in Russia. This study aims to build a registry database of Russian patients with chronic hypoparathyroidism who were referred for hospital treatment in order to conduct initial analysis of clinical presentations and hospital management. The Italian registry model was taken to be able to integrate our data in the future. Two hundred patients with hypoparathyroidism (n = 194) and pseudohypoparathyroidism (n = 6) were enrolled over 2 years (2017–2019). The most frequent cause of hypoparathyroidism was neck surgery (82.5%, mostly females), followed by idiopathic hypoparathyroidism (10%), syndromic forms of genetic hypoparathyroidism (4.5%) and forms of defective PTH action (3%). Calcium supplements and alfacalcidol were prescribed in most cases. However, a minority of patients (n = 6) needed to receive teriparatide as the only way to maintain calcium levels and to prevent symptoms of hypocalcemia. Consequently, substitution treatment with parathyroid hormone should be available in certain cases of hypoparathyroidism. This database will be useful to estimate the potential requirement for recombinant PTH in Russia and standards for clinical and therapeutic approaches.

Predictors of post-thyroidectomy hypocalcaemia: a systematic and narrative review.

Hypocalcaemia is the most common complication after total or completion thyroidectomy. This study assesses recent evidence on predictive factors for post-thyroidectomy hypocalcaemia in order to identify the patients affected and aid prevention. Two authors independently assessed articles and extracted data to provide a narrative synthesis. This study was an updated systematic search and narrative review regarding predictors of post-thyroidectomy hypocalcaemia using the Ovid Medline, Embase, Cochrane and Cinahl databases. Results were limited to papers published from January 2012 to August 2019. Sixty-three observational studies with a total of 210 401 patients met the inclusion criteria. The median incidence was 27.5 per cent for transient biochemical hypocalcaemia, 12.5 per cent for symptomatic hypocalcaemia and 2.2 per cent for permanent hypocalcaemia. The most frequent statistically significant predictor of hypocalcaemia was peri-operative parathyroid hormone level. Symptomatic hypocalcaemia and permanent hypocalcaemia were seen more frequently in patients undergoing concomitant neck dissection. Many factors have been studied for their link to post-thyroidectomy hypocalcaemia, and this study assesses the recent evidence presented in each case.

P1397LONG-TERM EFFICACY AND SAFETY OF ETELCALCETIDE IN HEMODIALYSIS PATIENTS WITH SEVERE SECONDARY HYPERPARATHYROIDISM

Abstract Background and Aims Currently the therapeutic strategies most frequently used in the treatment of secondary hyperparathyroidism (SHPT) are represented by vitamin D receptors activators (VDRAs) and cinacalcet. However, both drugs have side effects that limit their use. Recently, in the treatment of SHPT has been introduced the etelcalcetide, a second generation calcimimetic given intravenously (i.v.). This new route of administration could improve adherence to therapy and reduce gastrointestinal side effects. The aim of the study was to evaluate the efficacy and safety of the etelcalcetide in hemodialysis (HD) patients with SHPT inadequately controlled with traditional therapy (cinacalcet and/or VDRAs), or who had side effects with cinacalcet, or that were not adherent to cinacalcet therapy. Method For this purpose we have selected 28 HD patients with inadequate control of SHPT (PTH &amp;gt; 500 pg / ml; range 502-2148 pg/ml). Serum albumin-corrected calcium (sCa), phosphate (P), calcium–phosphate product (Ca x P), and PTH were assessed monthly. Baseline 19 patients were taking stable doses of active vitamin D analogs and all patients were taking phosphate binders. Etelcalcetide was administered three times a week after each hemodialysis session. The starting dose was 2.5 or 5.0 mg and then adjusted between 2.5 and 10.0 mg according to sCa and PTH levels. Treatment was temporarily withheld for sCa &amp;lt;7.5 mg/dl, or symptomatic hypocalcemia and was subsequently resumed at a lower dose. The primary endpoint was a PTH reduction &amp;gt; 30% compared to baseline levels. Results At present 12 months have passed since the beginning of etelcalcetide therapy. In most patients PTH levels were reduced immediately after the start of therapy. After 12 months we observed a reduction &amp;gt; 30% in 82% of patients, meanly -54% with a range between – 22% and – 81%. On average PTH levels decreased from 1167±444 to 558±310 pg/ml (P&amp;lt;.001). Serum calcium significantly reduced already after one month of therapy settling on stable levels from the third month onward, sCa decreased from 9.7±0.4 to 9.2±0.5 mg/dl (P&amp;lt;.01). However, the percentage of patients treated with calcium salts rose from 21% at baseline to 44% at F-U, mean dose at F-U 1.8 ± 0.9 g/d, while the percent of patients treated with VDRAs increased from 68% to 91%. Serum phosphate decreased from 6.4±1.4 to 4.6±1.3 mg/dl (P&amp;lt;.001), Ca x P decreased from 60±13 to 42±12 mg2/dl2 (P&amp;lt;.001). The median average dose of etelcalcetide at F-U was 6.2 ± 1.7 mg/HD, with a range of 2.5-10.0 mg/HD. Throughout the study, the only side effect was asymptomatic hypocalcemia that required the use of calcium salts. There were no gastrointestinal adverse effects. Conclusion Our results confirm that in hemodialysis etelcalcetide therapy is effective and safe in the control of SHPT refractory to conventional therapy over a 1-year treatment period.

P1420IS THE CHANGE FROM CINACALCET TO ETELCALCETIDE SAFE AND EFFECTIVE IN PATIENTS ON HEMODIALYSIS WITH SECONDARY HYPERPARATHYROIDISM?

Abstract Background and Aims Vitamin D analogues stimulate the absorption of calcium and phosphorus, while calcimimetics reduce parathyroid hormone (PTH) without calcium and phosphorus elevation, which reduces the risk of vascular calcification. However, the biggest problem of first-generation calcimimetics is the lack of adherence due to abandonment or non-compliance due to side effects and the high load of tablets taken by our patients. Method A prospective and exploratory 24-week study, which included 54 adult patients on chronic hemodialysis (3 times per week) with secondary hyperparathyroidism (PTH &amp;gt;=150 pg/ml). Thirty-three patients were converted from cinacalcet to etelcalcetide, due to the lack of adherence to cinacalcet treatment and the inability to increase the dose due to the side effects of cinacalcet. The remaining 21 patients started etelcalcetide without previously taking cinacalcet. The dose of etelcalcetide was done according to the baseline PTH value. PTH &amp;gt;150 and &amp;lt;=300 pg/ml, started with 5 mg of etelcalcetide per week, PTH &amp;gt;300 and &amp;lt;=500 pg/ml with 7,5 mg/week, PTH &amp;gt; 500 and &amp;lt;= 800 pg /ml with 10 mg/week, PTH &amp;gt;800 pg/ml with 15mg/week. Results In the first four weeks, calcium decreased significantly, but subsequently remained stable for the rest of the study. From the baseline to the 24-week, serum calcium 8.85 ± 0.85 vs. 8.43 ± 0.83 mg/dl (p &amp;lt;0.05), serum phosphorus 4.64 ± 1.46 vs. 4.51 ± 2.2 mg/dl (p&amp;gt; 0.05). PTH decreased significantly at the end of the study (718.4 ± 450 vs. 391.3 ± 232.7 pg/ml, p =0.03). PTH was reduced by 42% in the group that changed cinacalcet to etelcalcetide, and 50% in the group that did not take calciomimetics before the study. At the beginning of the study, 61.1% of our sample also maintained paricalcitol as a treatment for secondary hyperparathyroidism. At the end of week 24, 51.8% maintained paricalcitol but with a significant reduction of 36.8% of the dose of paricalcitol (3.22 ± 3.78 mg/week), without significant changes in the dose of etelcalcetide at the end of the study (9.5 ± 1.3 mg/week) . No symptomatic hypocalcaemia was recorded throughout the study. At week 12, the dose of etelcalcetide was reduced in 11% of patients and 7% at the end of week 24 due asymptomatic hypocalcemia. Conclusion Etelcalcetide showed a significant reduction in PTH with the optimization of therapeutic compliance. In our population, the use of paricalcitol was reduced by 30% due to a progressive increase in the dose of etelcalcetide, keeping calcium levels stable and safe. Asymptomatic hypocalcemia was the most observed side effect, but it is claimed that etelcalcetide has an even better safety profile than cinacalcet, with respect to digestive side effects. It is advisable to use Etelcalcetide by individualizing the dose in each patient, depending on their levels of PTH and calcium.

The effects of patient and disease-related factors on the quality of life in patients with hypoparathyroidism.

Hypoparathyroidism (HypoPT) is an orphan disease, which causes physical, emotional, and cognitive problems. We aimed to estimate the factors affecting the quality of life (QOL) of HypoPT patients. Basal characteristics, treatments, and laboratory results of the participants were recorded. QOL of the patients and controls were evaluated via the Short Form-36 (SF-36) survey. One hundred sixty HypoPT patients were compared with 148 controls. Patients had lower scores in all SF-36 domains than controls. Non-surgical patients had better scores in vitality and mental health compared with post-surgical ones. Males had higher scores in mental and physical health domains than females. Non-surgical patients had higher scores in mental health compared with post-surgical ones when calcium levels were between 8 and 8.9mg/dL. When we compared the patients with the pathological results, QOL scores of post-surgical patients with thyroid cancer were not different from the patients with thyroid nodular hyperplasia. HypoPT patients having an additional disease presented lower scores in physical functions and general health. Disease duration was found out positively correlated with vitality in non-surgical patients. While QOL is reduced in both post-surgical and non-surgical HypoPT groups, mental health seems to be less affected in non-surgical patients. Non-surgical patients might be tolerating hypocalcemia symptoms, lower calcium levels, and longer disease duration better than post-surgical ones. Having an additional disease affects the QOL negatively but having thyroid cancer may not change the QOL results of post-surgical patients.

Milk-alkali syndrome: a 'quick ease' or a 'long-lasting problem'.

SummaryWe report the case of a 65-year-old female who presented with symptomatic hypercalcaemia (corrected calcium of 4.57 mmol/L) with confusion, myalgias and abdominal discomfort. She had a concomitant metabolic alkalosis (pH 7.46, HCO3- 40 mmol/L, pCO2 54.6 mmHg). A history of significant Quick-Eze use (a calcium carbonate based antacid) for abdominal discomfort, for 2 weeks prior to presentation, suggested a diagnosis of milk-alkali syndrome (MAS). Further investigations did not demonstrate malignancy or primary hyperparathyroidism. Following management with i.v. fluid rehydration and a single dose of i.v. bisphosphonate, she developed symptomatic hypocalcaemia requiring oral and parenteral calcium replacement. She was discharged from the hospital with stable biochemistry on follow-up. This case demonstrates the importance of a detailed history in the diagnosis of severe hypercalcaemia, with MAS representing the third most common cause of hypercalcaemia. We discuss its pathophysiology and clinical importance, which can often present with severe hypercalcaemia that can respond precipitously to calcium-lowering therapy.Learning points:Milk-alkali syndrome is an often unrecognised cause for hypercalcaemia, but is the third most common cause of admission for hypercalcaemia.Calcium ingestion leading to MAS can occur at intakes as low as 1.0–1.5 g per day in those with risk factors.Early recognition of this syndrome can avoid the use of calcium-lowering therapy such as bisphosphonates which can precipitate hypocalcaemia.

OR07-01 Identification of the First Case of Acquired Autoimmune Parathyroid Hormone (PTH) Resistance Due to PTH1 Receptor (PTH1R) Autoantibodies

Background: Here we describe a patient who presented with symptomatic hypocalcemia and a biochemical picture suggestive of PTH resistance. PTH resistance is a hallmark of pseudohypoparathyroidism, a heterogeneous group of rare disorders caused by genetic or epigenetic alterations of PTH/PTHrP signaling. However, PTH receptor-related autoimmune etiology has not been identified as the underlying mechanism for PTH resistance. Here we describe the first case of acquired autoimmune PTH resistance that is secondary to PTH1R autoantibodies. Clinical Case: A 60-year-old African-American woman, who previously had normal calcium homeostasis, presented with acute, symptomatic hypocalcemia, hyperphosphatemia and markedly elevated serum PTH, consistent with parathyroid hormone resistance. She did not have other hormone resistance or a clinical phenotype suggestive of pseudohypoparathyroidism. Whole-exome sequencing and GNAS methylation analysis revealed no genetic or epigenetic defects of the PTH/PTHrP signaling pathway. Treatment with Calcitriol and Calcium supplements was initiated with good clinical response. Within 10 years of follow-up, the patient developed autoimmune hypothyroidism, alopecia and an unusual form of membranous glomerulonephritis, raising the suspicion for an autoimmune etiology for PTH resistance. Luciferase immunoprecipitation system assay identified antibodies against PTH1R with mapping to the N-terminal extracellular ligand-binding domain (amino acids 1- 178). Using an in vitro biological assay in GP-2.3 cells, we found that the antibodies derived from the patient’s serum blocked PTH downstream signaling via Gsalpha/cAMP/protein kinase A pathway in a concentration-dependent manner.The patient’s autoantibody profile led to the diagnosis of additional autoimmune diseases, including atrophic gastritis and Sjogren syndrome. Lymphocyte immunophenotyping using flow cytometry revealed an overall normal B and T cell profile, but with decreased frequencies and numbers of switched and non-switched memory B cell subsets and an increased frequency and number of the CD8+ naïve cell population. Genes associated with autoimmune inflammatory disorders were sequenced but no pathologic changes were detected. Conclusions: Identification of the first case of autoimmune PTH resistance secondary to PTH1R autoantibodies extends the etiologic spectrum of hypoparathyroidism and should be considered when a patient presents with findings consistent with pseudohypoparathyroidism, especially in the presence of additional autoimmune diseases.

SAT-077 Two Cases of Hypoparathyroidism Due to Activating Calcium Sensing Receptor Mutation

IntroductionThe extracellular calcium-sensing receptor (CaSR) expressed mainly in the parathyroid gland and kidneys regulates calcium (Ca+2) homeostasis through parathyroid hormone (PTH) secretion. Activating mutations of CaSR can lead to autosomal dominant hypocalcemia and severe congenital hypoparathyroidism. Constitutively activated CaSR receptors blocks PTH release leading to hypocalcemia, hyperphosphatemia and decreased Ca+2 reabsorption from the kidney.Case 1:14 year old male presented for an evaluation of hypocalcemia and hyperphosphatemia found on routine blood work. He denied symptoms of hypocalcemia. He had normal vital signs, positive Chovstek sign but rest of exam was unremarkable. His lab results showed low Ca+2 8.1 mg/dl (8.6–10 mg/dl), high phosphorus 6 mg/dl (2.7–4.5 mg/dl) and inappropriately normal PTH 26.8 pg/ml (10–65 pg/ml). FISH was negative for DiGeorge. Genetic testing showed heterozygous CaSR gene mutation I822T, variant of uncertain significance. His father with primary hypoparathyroidism has the same CaSR gene mutation; mother is healthy and tested negative for this variant. Given the inheritance pattern of the mutation, it is likely a pathologic mutation. He is maintained on Calcium (1500 mg BID) and Calcitriol (0.5 mcg PO BID) and is doing well.Case 2:One day old premature 32-week old infant girl was found to have early onset neonatal hypocalcemia 6.1 mg/dl (6.2–11 mg/dl) during NICU admission for respiratory distress, inappropriately normal PTH 18.5 pg/ml and high phosphorus 8.8 mg/dl (4.6–7.9 mg/dl). She had no symptoms of hypocalcemia in the NICU or at home. She did not have any dysmorphic features. FISH was negative for DiGeorge. Genetic testing to sequence genes including AIRE, AP2S1, CASR, GNAS, HADHA, HADHB, PTH1R, SOX3, STX16, TBCE was done and revealed a novel heterozygous mutation in the CaSR gene for a missense variant c.2495T>C(p.lle832Thr) and STX16 c.644A>T, possibly benign variant. Unfortunately, the parents have not consented to testing yet. Further familial and functional characterization of this new variant is necessary to confirm its possible pathogenetic role in this hypocalcemic patient. Currently she is maintained on ergocalciferol 800 IU, calcitriol 0.25 mcg and sevelamer 3 packets daily and is doing well.Conclusion:In the workup for primary hypoparathyroidism without dysmorphic features and tests negative for DiGeorge, CaSR mutations should be investigated as part of the differential as we have identified variants in the CaSR gene in 2 children with asymptomatic hypocalcemia, one of which is a novel mutation which has never been reported before.

SAT-347 Diagnosis of Autosomal Dominant Hypocalcemia Type 1 Following the Initiation of Imatinib for Treatment of Chronic Myeloid Leukemia

Background: Autosomal Dominant Hypocalcemia Type 1 is an underdiagnosed condition due to the vast majority of patients being asymptomatic and having mild hypocalcemia. Imatinib has been associated with hypophosphatemia and hypocalcemia. Clinical Case: 69-year-old man who had a long history of asymptomatic mild hypocalcemia, calcium level of 7.9 mg/dL (8.4 – 10.2 mg/dL) diagnosed with chronic myeloid leukemia and developed symptoms of hypocalcemia within 2 months of treatment with imatinib. After the initiation of imatinib, his calcium reduced to 6.8 mg/dL (8.4 – 10.2 mg/dL) with a corresponding ionized calcium of 0.98 mmol/L (1.12–1.32 mmol/L) within 2 months. He developed tetany. With the reduced calcium level his PTH was unexpectedly low-normal at 34 pg/mL (16–62 pg/mL). He also had a higher than expected urinary calcium of 342 mg/24 hours. The PTH and 24-hour urinary calcium levels raised concern for an underlying diagnosis of autosomal dominant hypocalcemia type 1. His phosphorous was normal at 3.3 mg/dL (2.6–4.9 mg/dL). He never had hypophosphatemia, which is common with imatinib.After two doses of IV calcium and initiation of oral calcium replacement, 1000 mg BID, his level continued to be reduced with symptoms. Given his symptoms, laboratory results, and continued hypocalcemia he underwent genetic testing. Results of his genetic testing showed a p.Thr151Met mutation in the CASR gene consistent with autosomal dominant hypocalcemia type 1. With this diagnosis, there is concern for nephrolithiasis with over treatment. His symptoms resolved with treatment with calcium 1000mg TID, calcitriol 0.25 mg BID and vitamin D3 2000 IU daily. He has not developed nephrolithiasis and his urinary calcium increased to 424mg/24 hours. A thiazide diuretic is being considered to decrease urinary calcium excretion.He continues on imatinib with an excellent response to therapy. It is likely that the trigger for symptomatic severe hypocalcemia was initiation of imatinib superimposed on the hypocalcemia type 1. Possible mechanisms for this are decreased intestinal absorption, increased urinary loss, or decreased dissolution from bone. 1 These mechanisms are also associated with hypophosphatemia, which our patient did not have. Another possible cause could be an immune mediated destruction of the parathyroid gland, a rare finding seen with other tyrosine kinase inhibitors.2 Conclusion: This is the first reported case of imatinib triggering severe symptomatic hypocalcemia leading to the diagnosis of underlying autosomal dominant hypocalcemia type 1.