Hypercalcemia In Patients Research Articles

7588 Coexistent Toxic Nodular Goiter And Primary Hyperparathyroidism (PHPT), A Combo With Diagnostic And Management Implications

Abstract Disclosure: D. Dave: None. A. Bhan: None. S.D. Rao: None. About 17-84% of patients with PHPT have concomitant thyroid disorders, but the prevalence of coexistent hyperthyroidism in PHPT varies 9-14 %. A vast majority had Graves’ disease with only 3 cases of toxic multinodular goiter (MNG) and PHPT reported in the literature as of 2022 ([1]). We present a rare case of coexistent toxic MNG and PHPT. Case Description: A 68y woman presented with recent 23 kg unintended weight loss and palpitations, but no other symptoms. Denied having kidney stones or fractures. On examination she had fine tremors of hands, MNG without exophthalmos. An ultrasound showed multinodular MNG with cystic lesions. A diagnosis of toxic MNG was made. Laboratory results were: TSH (<0.01 uIU/mL), free T4 1,68 ng/dL (normal: 0.61-1.44 ng/ml), high serum Ca (11.0 - 11.4 mg/dl) over 4y, but PTH was unavailable prior to the visit when it was 107 pg/ml and 89 pg/ml after 3 months of antithyroid therapy. Despite clinical and biochemical euthyroidism after 3 months, serum Ca and PTH levels remained high (11.4 mg/dl and 89 pg/ml respectively). Because she had pulmonary embolism a few years ago, we deferred parathyroidectomy until complete remission of hyperthyroidism. Discussion: Hypercalcemia is the biochemical hallmark of PHPT but can occur in 2-10% of patients with hyperthyroidism alone but only 1% of those will have coexistent PHPT. When these two conditions coexist, hypercalcemia is moderate to severe, and an occasional patient may present with hypercalcemic crisis (2). Prior to the availability of PTH assays, it was a challenge to diagnose coexistent PHPT. Hypercalcemia in hyperthyroidism responds to propranolol but not in PHPT, although the response is variable (3). With the availability of sensitive PTH assays, this maneuver is not necessary. In most cases, current PTH assays distinguish hypercalcemia of hyperthyroidism with suppressed PTH from coexistent PHPT in whom PTH level is non-suppressed or elevated. Monitoring serum Ca and PTH levels during therapy of hyperthyroidism would be useful as normalization of serum Ca and PTH has occasionally been reported (4). In our patient, serum Ca and PTH levels remained high with 3-months of methimazole and atenolol. The impact of both conditions on bone and mineral metabolism are profound, with fractures and kidney stones. Since kidney stones are uncommon in hyperthyroidism, presence of kidney stone in a hyperthyroid hypercalcemic patient should alert the possibility of PHPT. Similarly, significant decrease in bone density in such patient also raises the possibility of PHPT. Prompt diagnosis and appropriate treatment of both conditions is necessary to avoid irreversible complications.

Ratios of calcium to citrate administration in blood transfusion for traumatic hemorrhage: A retrospective cohort study.

Massive transfusion with citrated blood products causes hypocalcemia, which is associated with mortality. Recognition of this problem has led to increased calcium administration; however, the optimal dosing is still unknown. This retrospective, single-center study included level 1 trauma patients in 2019 and 2020 who underwent an operation within 12 h of arrival and received a transfusion. Preoperative and intraoperative administrations were totaled to calculate the ratio of administered calcium to the number of blood transfusions for each patient. The citrate content of each blood component was estimated to calculate a second ratio, the ratio of administered calcium to administered citrate. Receiver Operating Characteristic (ROC) curves were performed on both ratios to determine the optimal cutoff values for predicting severe hypocalcemia (ionized calcium <0.9 mmol/L) and hypercalcemia (>1.35 mmol/L) at the end of the intraoperative period. A total of 506 trauma activations were included, receiving a mean of 17.4 citrated blood products and 16.3 mmol of calcium (equivalent to 2400 mg of calcium chloride). No ratio was statistically significant in differentiating severely hypocalcemic patients from the rest. A calcium to blood ratio of 0.903 mmol of administered calcium per citrated blood product differentiated hypercalcemic patients from the rest. Quantifying received calcium and citrated blood products was insufficient to predict severe hypocalcemia, suggesting other contributions to hypocalcemia. We demonstrated an upper-limit ratio for calcium administration in traumatic hemorrhage; however, further studies are required to determine what calcium dosing regimen results in the best outcomes.

HTLV-1 infected T cells cause bone loss via small extracellular vesicles.

Adult T cell leukaemia (ATL), caused by infection with human T- lymphotropic virus type 1 (HTLV-1), is often complicated by hypercalcemia and osteolytic lesions. Therefore, we studied the communication between patient-derived ATL cells (ATL-PDX) and HTLV-1 immortalized CD4+ T cell lines (HTLV/T) with osteoclasts and their effects on bone mass in mice. Intratibial inoculation of some HTLV/T leads to a profound local decrease in bone mass similar to marrow-replacing ATL-PDX, despite the fact that few HTLV/T cells persisted in the bone. To study the direct effect of HTLV/T and ATL-PDX on osteoclasts, supernatants were added to murine and human osteoclast precursors. ATL-PDX supernatants from hypercalcemic patients promoted the formation of mature osteoclasts, while those from HTLV/T were variably stimulatory, but had largely consistent effects between human and murine cultures. Interestingly, this osteoclastic activity did not correlate with expression of osteoclastogenic cytokine receptor activator of nuclear factor kappa-B ligand (RANKL), suggesting an alternative mechanism. HTLV/T and ATL-PDX produce small extracellular vesicles (sEV), known to facilitate HTLV-1 infection. We hypothesized that these sEV also mediate bone loss by targeting osteoclasts. We isolated sEV from both HTLV/T and ATL-PDX, and found they carried most of the activity found in supernatants. In contrast, sEV from uninfected activated T cells had little effect. Analysis of sEV (both active and inactive) by mass spectrometry and electron microscopy confirmed absence of RANKL and intact virus. Viral proteins Tax and Env were only present in sEV from the active, osteoclast-stimulatory group, along with increased representation of proteins involved in osteoclastogenesis and bone resorption. sEV from osteoclast-active HTLV/T injected over mouse calvaria in the presence of low-dose RANKL caused more osteolysis than osteoclast-inactive sEV or RANKL alone. Thus, HTLV-1 infection of T cells can cause release of sEV with strong osteolytic potential, providing a mechanism beyond RANKL production that modifies the bone microenvironment, even in the absence of overt leukaemia.

A thorough evaluation for primary hyperparathyroidism: More than a stone's throw away

BackgroundPrimary hyperparathyroidism (PHPT) is a treatable cause of nephrolithiasis. However, PHPT is not consistently evaluated in nephrolithiasis patients. Symptoms of parathyroid disease were explored in relation to evaluation of PHPT in nephrolithiasis patients. MethodsPatients with nephrolithiasis on imaging between 2017 and 2021 were identified. Measurement of serum calcium levels after nephrolithiasis diagnosis was determined. Patients with hypercalcemia (≥ 10.2 ​mg/dL) were identified. Characteristics associated with parathyroid hormone (PTH) evaluation and specialist referral were assessed. ResultsOf 2264 nephrolithiasis patients with calcium levels measured, 383 (17.1 ​%) had hypercalcemia. Of those, 107 (27.9 ​%) had PTH levels drawn. PTH was more often assessed in patients with higher median calcium levels, recurrent nephrolithiasis, depression, and osteopenia/osteoporosis. PTH was elevated (>64 ​pg/mL) or non-suppressed (40–64 ​pg/mL) in 68 (63.6 ​%) patients. Of those, 31 (45.6 ​%) were referred to a parathyroid specialist. Referred patients had higher PTH and calcium levels than those without referral, and higher rates of osteopenia/osteoporosis. ConclusionsPTH evaluation in hypercalcemic nephrolithiasis patients was low. The majority of patients evaluated had elevated or non-suppressed PTH levels, but only a fraction were referred to a specialist.

Assessment of Vitamin D Status in Primary Hyperparathyroidism Patients: A Retrospective Study.

Primary hyperparathyroidism (PHPT), a condition that manifests in various clinical forms, is a significant health concern. Normocalcemic primary hyperparathyroidism (NPHPT) is characterized by normal calcemia despite elevated parathyroid hormone (PTH) levels. Vitamin D deficiency can contribute to the clinical spectrum and complexity of NPHPT. Low vitamin D levels can elevate PTH, making it difficult to distinguish between NPHPT and secondary hyperparathyroidism. Additionally, it might mask hypercalcemia, leading to an underestimation of the disease severity.Our study aims to shed light on these complexities by investigating normocalcemic and hypercalcemic PHPT patient's clinical, hormonal, and biochemical patterns, including their vitamin D status. Materials: In this retrospective study, we enrolled 60 PHPT patients with autonomous parathyroid function confirmed using a combination of ultrasonography, radionuclide scan, and parathyroid function index calculation. We evaluated the albumin-corrected calcemia, calciuria, PTH, 25(OH)D level, serum phosphate, bone mineral density, and major clinical symptoms (fracture, nephrolithiasis). A comparative analysis and a correlation study were performed between normo- and hypercalcemic and vitamin D-deficient and vitamin D-non-deficient groups. The median age was 62 years, 51.66% (31/60) being normocalcemic and 46.66% (29/60) presenting a deficient 25(OH)D level. In the group with 25(OH)D below 20 ng/mL, we observed a reduced level of albumin-corrected calcemia, without a significant increase of PTH compared to the adequate 25(OH)D level group. The frequency of the NPHPT and the risk of fracture were significantly higher in the deficient 25(OH)D group (20/60, 33.33%and8/60, 13.33%) than in the adequate one (11/60, 18.33% and 1/60, 1.66%) with OR=4.7 (p<0.004) and OR=9.7 (p<0.027), respectively. We also found a positive correlation between PTH and adenoma size, the parathyroid function index and adenoma size, as well as PTH and phosphate levels. However, the correlation between 25(OH)D and phosphate levels was negative and moderate (rho=-0.504, p<0.001), adding a new layer of complexity to our understanding of these relationships. Our study provided significant insight into the link between vitamin D status and normocalcemic PHPT. We found that vitamin D-deficient patients with normocalcemic PHPT have an increased fracture risk, which requires meticulous monitoring and possible supplementation with vitamin D. This should be done carefully to avoid exacerbating hypercalcemia or hypercalciuria. Further research is needed to refine these management strategies and deepen our understanding of the complex relationships between the analyzed parameters.

Persisting Hypercalcemia and Hyperparathyroidism after Kidney Transplantation Have a Negative Impact on Graft and Patient Survival.

Hyperparathyroidism (HPT) with hypercalcemia, often deemed irreversible and detrimental to graft survival post-kidney transplantation (KT), prompts pre-transplant parathyroidectomy in hypercalcemic patients. In this retrospective analysis of 1212 kidney transplant recipients (KTRs) between 2006 and 2019, the incidence and effect of persistent HPT and hypercalcemia on graft and patient survival, and risk factors for persistence were analyzed until 60 months of follow up (FU). At KT, 5.7% (n = 69) had no HPT, 32.7% (n = 396) had HPT without hypercalcemia and 37.0% (n = 448) had HPT with hypercalcemia. At 2 years FU, 26.4% (n = 320) of patients had no HPT and 6% (n = 73) had HPT with hypercalcemia. Dialysis and dialysis duration were linked to HPT development, while dialysis, KT waiting time and donor type correlated with persisting hypercalcemia after KT. KTRs with normalized PTH and recovered hypercalcemia had improved death-censored graft survival (p < 0.001) and overall patient survival (p < 0.001). HPT with hypercalcemia is frequent at time of KT with normalization of PTH and calcium in a substantial proportion of patients after a KT. These findings question the routine pre-KT parathyroidectomy for suspected parathyroid autonomy. Persisting HPT, especially with hypercalcemia, adversely affects graft and patient survival, suggesting the need for more aggressive treatment of HPT, especially in cases of persisting hypercalcemia.

Comparison of Normocalcemic vs Hypercalcemic Primary Hyperparathyroidism in a Hypercalciuric Renal Stone Population.

Primary hyperparathyroidism (PHPT) is commonly diagnosed in the setting of hypercalcemia, whereas normocalcemic primary hyperparathyroidism (NHPT) may be misdiagnosed. Our objective was to compare patients with hypercalcemic hyperparathyroidism (HPHPT) vs patients with NHPT hypercalciuric renal stones. We took advantage of a routine calcium load test performed in patients with hypercalciuric renal stones to assess retrospectively among patients with PHPT the prevalence and characteristics of NHPT and HPHPT under a calcium-restricted diet. Among 1671 patients with hypercalciuria, 91 patients had a final diagnosis of PHPT (postload ionized calcium [iCa] > 1.31 mmol/L and parathyroid hormone [PTH] > 30 pg/mL). Prevalence of NHPT is 40% of all PHPT; however, according to total serum calcium, 4/35 NHPT and 7/56 HPHPT cases would have been misclassified in the other group. Eighteen of 35 NHPT and 40/56 HPHPT cases underwent parathyroidectomy. No significant characteristics relating to parathyroid weight, stone composition, or bone remodeling biomarkers were detected between groups. Although iCa is higher in HPHPT in the fasting state and after calcium load, we found no difference for calcium diet, 24-hour calciuria, or calcitriol. Renal calcium excretion postload increased by 303% in NHPT but only 176% in HPHPT (P = .01) likely explained by a lesser PTH decrease (P = .02). However, a strong negative association (P < .0001) detected between pooled preload and postload iCa and PTH only in the NHPT group suggests a persistent efficient PTH-CaSR control within the parathyroid glands in this group. Our data show the relevance of dynamic tests to unmask NHPT in patients with hypercalciuric renal stones.

Twenty-four hour Holter ECG in normocalcemic and hypercalcemic patients with hyperparathyroidism.

To investigate the occurrence of arrhythmias in patients with normocalcemic (NC) primary hyperparathyroidism (PHPT) compared to both hypercalcemic PHPT patients and control subjects by means of 24-h Holter ECG. Thirteen NCPHPT postmenopausal patients were enrolled and age-matched with 13 hypercalcemic PHPT patients and 13 controls. Every subject underwent basal ECG, 24-h Holter ECG and mineral metabolism biochemical evaluation. PHPT patients had higher mean serum calcium levels compared to both NCPHPT and controls; there was no difference in mean serum calcium levels between NCPHPT and controls. Both NCPHPT and PHPT patients had significantly higher mean PTH levels compared with controls. There were no differences in ECG parameters between the three groups, except for QTc interval. PHPT patients had normal QTc interval values, but significantly shorter mean values compared with those of controls and NCPHPT patients. During 24-h Holter ECG recording, 100% of PHPT patients had supraventricular premature beats (SVPBs), compared to 46% of NCPHPT (p = 0.005) and to 53% of controls (p = 0.01). PHPT patients experienced ventricular premature beats (VPBs) (69.2%) vs 15% of NCPHPT patients (p = 0.01) and 23% of controls (p = 0.04). There was no difference between NCPHPT and controls subjects concerning occurrence of both VPBs and SVPBs. NCPHPT patients did not experience an increased occurrence of arrhythmias compared to controls, while PHPT patients showed an increased occurrence compared to both controls and NCPHPT. Our findings are most probably related to the short QTc interval caused by hypercalcemia observed in PHPT patients, but not in NCPHPT.

Underdiagnosis of Hyperparathyroidism in Patients With Nephrolithiasis in a Community Setting.

Objective Untreated primary hyperparathyroidism (PHPT) has wide-ranging multisystemic effects. Recent studies based in the US have shown a less than 25% screening rate for PHPT. Our study aims to detect whether similar deficiencies exist in our community healthcare system while quantifying the prevalence of PHPT underdiagnosis and inadequate surgical referrals. Study design This retrospective quantitative study enrolled patients aged ≥18 years with imaged-confirmed nephrolithiasis at our healthcare facilities from 2017 to the present (n=2021). Patients with documented calcium levels and kidney/ureter stones were included. Descriptive and univariate analyses were performed. Results A total of 2021 subjects met the criteria to be enrolled in the study. 26.6% (n=537) of patients with nephrolithiasis had elevated calcium levels on record. 13.6% (n=73) of hypercalcemic patients were screened for PHPT with an intact parathyroid hormone (PTH). A majority (63%, n=46) of patients with intact PTH had PHPTdefined as PTH levels >55 pg/mL. Ultimately, only 19.6% (n=9) of patients with PHPT were referred for surgical intervention, and there was no significant difference in referral rate between patients with PHPT and those without (p=0.913). Conclusions PHPT is underdiagnosed in our community, leading to a significantly low rate of surgical referral and delay in management. Implementation of hospital protocols to aid in improving diagnosis and interventions could improve outcomes for PHPT patients.

Lithium-associated primary hyperparathyroidism:: An evaluation of screening and referral patterns in a southeastern veteran population

BackgroundLong-term lithium therapy has a well-established but under-recognized association with primary hyperparathyroidism. Rates of hypercalcemia, screening for primary hyperparathyroidism, and referral for parathyroidectomy were evaluated among United States veterans on long-term lithium therapy. MethodsPatients undergoing chronic long-term lithium therapy (>12 months) were identified from 1999 to 2022. Demographics, long-term lithium therapy duration, post-treatment calcium, parathyroid hormone, creatinine, and vitamin D levels were abstracted. Rates of screening for hypercalcemia (calcium ≥10.2 mg/dL), primary hyperparathyroidism (parathyroid hormone ≥30 pg/mL in the setting of hypercalcemia), referral for parathyroidectomy, and outcomes were evaluated. ResultsA total of 1,356 patients underwent long-term lithium therapy, 514 of whom received chronic long-term lithium therapy. Baseline characteristics of patients with and without post-treatment hypercalcemia were compared. Of 148 patients with post-treatment hypercalcemia, 112 (74.7%) underwent no further evaluation for primary hyperparathyroidism, while 36 (25.3%) patients had a parathyroid hormone level recorded. Although 33 (91.7%) hypercalcemic patients screened positive for primary hyperparathyroidism, only 5 (13%) were referred for parathyroidectomy. Of the 4 patients who underwent parathyroidectomy, mean calcium was 11.2 mg/dL (range 11.1–11.4), and mean parathyroid hormone was 272 pg/mL (range 108–622). Three patients were localized on preoperative imaging, 2 of whom underwent unilateral exploration with cure, with 1 experiencing recurrence at 31 months. The remaining patient who localized preoperatively underwent bilateral exploration and had 2 ipsilateral glands resected and persistence. The patient who did not localize preoperatively underwent bilateral exploration with 3 gland resection and cure. ConclusionsScreening for primary hyperparathyroidism and referral for parathyroidectomy are underutilized in United States veterans undergoing chronic long-term lithium therapy. Institutional protocols to standardize screening, surveillance, and referrals to endocrinology/endocrine surgery could benefit this population at increased risk for primary hyperparathyroidism.

FRI685 Denosumab Withdrawal Is Associated With Hypercalcemia In Adults With Osteoporosis And Bone Metastases

Abstract Disclosure: M.D. Patil: None. S. Thosani: None. R.L. Bassett Jr: None. Z. Wang: None. T.A. Guise: None. Denosumab (dmab) is useful to treat conditions associated with increased bone resorption such as osteoporosis (OP), bone metastases (BM), hypercalcemia of malignancy and giant cell tumor of bone. However, discontinuation of dmab therapy is associated with rebound phenomenon characterized by increase in bone resorption, bone loss and vertebral fractures. Rebound osteoclastic activity as well as osteocyte apoptosis-induced reduction in osteoprotegerin are some of the mechanisms proposed for this rebound phenomenon. Recently, case reports of hypercalcemia following dmab withdrawal have been reported, more frequently in the pediatric population. To understand the association of hypercalcemia following dmab withdrawal in adult patients we conducted a retrospective analysis of patients with OP and with BM. We included adult patients treated with dmab or zoledronate for diagnosis of either OP or BM. We excluded patients with history of hypercalcemia before starting on either of the monotherapies. Subsequently, patients who were found to have other etiologies for hypercalcemia, such as increased PTHrP or calcitriol, multiple myeloma, hyperparathyroidism, or combinations therin, were also excluded. Of the 6181 patients who received dmab treatment, 2004 had OP and 2326 had BM. Among these, 77 experienced hypercalcemia:16 patients had other etiologies for hypercalcemia; 36 patients with BM and 25 patients with OP had no cause for hypercalcemia other than dmab withdrawal. The incidence rates of hypercalcemia in dmab group of patients with OP and BM without any other established cause of hypercalcemia were 1.2% (25/2004) and 1.5% (36/2326) respectively. The median time from last dose of dmab to hypercalcemia was 191 days (95% CI: 182 -295) and 92 days (95% CI: 43 - 170) for patients with OP and with BM, respectively. Of the 4177 patients treated with zoledronate, 666 had OP and 1015 had BM and 16 patients had hypercalcemia. Of these 16 hypercalcemic patients, 6 patients had other etiologies of hypercalcemia; 9 patients with BM and 1 patient with OP had no other etiology for the hypercalcemia other than dmab withdrawal. The incidence rates of hypercalcemia in zoledronate group of patients with OP and BM without any other established cause of hypercalcemia were 0.15% (1/666) and 0.88% (9/1015), respectively. Thus, compared with treatment with zoledronate, treatment with dmab is more likely associated with hypercalcemia (p-value 0.006) in patients with OP and with BM when the drug is discontinued. This is the first study comparing hypercalcemia in context of treatment with dmab and zoledronate which demonstrates significantly higher incidence in adult patients treated with dmab. The results have significant implications for treatment of patients with diseases associated with increased bone resorption. Presentation: Friday, June 16, 2023

Lithium related thyroid and parathyroid disease: Updated clinical practice guidelines are needed

ObjectiveThis study aims to estimate the prevalence of and determine physician approaches to the screening and management of lithium-associated thyroid and parathyroid disorders in British Columbia, Canada. MethodsSerum lithium and thyroid/parathyroid laboratory data were collected retrospectively for patients with lithium levels measured at seven BC hospitals between 2012 and 2021. A mail-out survey about screening and management of thyroid/parathyroid disorders in patients on lithium was sent to the ordering physicians of patients with abnormal results. Three months after, a follow-up questionnaire was sent to respondents, and the original survey was re-sent to non-responders. ResultsOf 4917 patients, 1.9 % had PTH (mean 22.33 ± 23.00 pmol/L) and 77.1 % had TSH (mean 3.61 ± 6.69 pmol/L) measured. Of 222 hypercalcemic patients (defined as any serum calcium or ionized calcium above the laboratory reference), 17.6 % had a PTH level measured. From 294 surveys sent to 214 physicians, the overall response rate was 31.6 % (n = 93) with twelve fully completed surveys. All twelve respondents monitored TSH levels every 6–12 months, and eight physicians monitored PTH and/or calcium at variable intervals. Two physicians routinely ordered both thyroid and parathyroid screening laboratory tests. Of the 80 non-respondents, limited patient contact was the most common reason for opting out (n = 27). ConclusionsOur results suggest biochemical screening for lithium-associated parathyroid disorders is less common than for thyroid disorders. There is insufficient data to determine the true prevalence of lithium-associated thyroid and parathyroid disorders. This highlights the need for updated clinical guidelines for management of lithium-associated thyroid and parathyroid disorders.

Improvement of hypertension control and left-ventricular function after cure of primary hyperparathyroidism.

Cardiovascular mortality is significantly higher in patients with primary hyperparathyroidism (PHPT) compared to the general population. The role of the renin-angiotensin-aldosterone system (RAAS) as a mediator of cardiovascular pathology in PHPT is unclear, as is the question whether successful parathyroidectomy (PTX) mitigates hypertension (HT), and left-ventricular (LV) dysfunction. In 45 consecutive, hypercalcemic PHPT patients (91% female, 20 normotensive, mean age 54.6 ± 14.6), laboratory examinations, and 24h ambulatory blood pressure monitoring (ABPM) were performed before, one and six months after successful PTX, while transthoracic echocardiography (TTE) pre- and six months post-PTX. Both in patients with normotension (NT) and HT, lower calcemia and parathyroid hormone (PTH) as well as higher phosphatemia were observed on follow-up, while B-type natriuretic peptide, aldosterone, plasma renin activity, and aldosterone-to-renin ratios were comparable. Six months post-PTX, only in patients with HT, median 24-hour SBP/DBP decreased by 12/6 mmHg, daytime SBP by 10, and nighttime DBP by 5 mmHg. Improvement in BP was observed in approximately 78% of patients with HT. Six months post-PTX, TTE revealed: 1) decrease in median LV mass index (by 2 g/m2) and end-diastolic dimension (by 3mm) among patients with HT; 2) normalization of global longitudinal strain in 22% of patients (comparable between those with NT and HT); 3) a mean 12.7% reduction in left-atrium volume index among patients with HT, which underlay normalization of indeterminate diastolic function in 3 out of 6 patients with HT, who exhibited it at baseline (dysfunction persisted in 2). PTX was shown to significantly reduce BP, LV hypertrophy and diastolic dysfunction parameters in PHPT patients with HT, and improve systolic function in all PHPT patients.

Trauma-induced disturbances in ionized calcium levels correlate parabolically with coagulopathy, transfusion, and mortality: a multicentre cohort analysis from the TraumaRegister DGU®

BackgroundTo which extent trauma- induced disturbances in ionized calcium (iCa2+) levels have a linear relationship with adverse outcomes remains controversial. The goal of this study was to determine the association between the distribution and accompanying characteristics of transfusion-independent iCa2+ levels versus outcome in a large cohort of major trauma patients upon arrival at the emergency department.MethodsA retrospective observational analysis of the TraumaRegister DGU® (2015–2019) was performed. Adult major trauma patients with direct admission to a European trauma centre were selected as the study cohort. Mortality at 6 h and 24 h, in-hospital mortality, coagulopathy, and need for transfusion were considered as relevant outcome parameters. The distribution of iCa2+ levels upon arrival at the emergency department was calculated in relation to these outcome parameters. Multivariable logistic regression analysis was performed to determine independent associations.ResultsIn the TraumaRegister DGU® 30 183 adult major trauma patients were found eligible for inclusion. iCa2+ disturbances affected 16.4% of patients, with hypocalcemia (< 1.10 mmol/l) being more frequent (13.2%) compared to hypercalcemia (≥ 1.30 mmol/l, 3.2%).Patients with hypo- and hypercalcemia were both more likely (P < .001) to have severe injury, shock, acidosis, coagulopathy, transfusion requirement, and haemorrhage as cause of death. Moreover, both groups had significant lower survival rates. All these findings were most distinct in hypercalcemic patients. When adjusting for potential confounders, mortality at 6 h was independently associated with iCa2+ < 0.90 mmol/L (OR 2.69, 95% CI 1.67–4.34; P < .001), iCa2+ 1.30–1.39 mmol/L (OR 1.56, 95% CI 1.04–2.32, P = 0.030), and iCa2+ ≥ 1.40 mmol/L (OR 2.87, 95% CI 1.57–5.26; P < .001). Moreover, an independent relationship was determined for iCa2+ 1.00–1.09 mmol/L with mortality at 24 h (OR 1.25, 95% CI 1.05–1.48; P = .0011), and with in-hospital mortality (OR 1.29, 95% CI 1.13–1.47; P < .001). Both hypocalcemia < 1.10 mmol/L and hypercalcemia ≥ 1.30 mmol/L had an independent association with coagulopathy and transfusion.ConclusionsTransfusion-independent iCa2+ levels in major trauma patients upon arrival at the emergency department have a parabolic relationship with coagulopathy, need for transfusion, and mortality. Further research is needed to confirm whether iCa2+ levels change dynamically and are more a reflection of severity of injury and accompanying physiological derangements, rather than an individual parameter that needs to be corrected as such.Graphical

Missed Opportunities to Diagnose and Treat Tertiary Hyperparathyroidism After Transplant

IntroductionTertiary hyperparathyroidism (3HPT) is common after renal transplant. However, guidelines for diagnosis are not clear and few patients are treated surgically. This study aims to determine rates of diagnosis and treatment of 3HPT in renal transplant patients with hypercalcemia. Materials and methodsThis retrospective chart review identified all renal transplant recipients at a single tertiary care institution between 2011 and 2021. Patients with post-transplant hypercalcemia (> 10.2 mg/dL) were identified. The time in months of index hypercalcemia was noted. Measurement of parathyroid hormone (PTH) levels after index hypercalcemia was determined and noted as elevated if > 64 pg/mL at least 6 mo after transplant. Documentation of symptoms of hyperparathyroidism, a diagnosis of hyperparathyroidism in the electronic medical record, and medical or surgical management of patients with classic 3HPT (elevated calcium and PTH) were determined. ResultsOf 383 renal transplant recipients, hypercalcemia was identified in 132 patients. The majority of hypercalcemic patients had PTH levels measured (127, 96.2%). PTH was elevated in 109 (82.6%). Among the 109 patients with classic 3HPT, 54 (49.5%) had a documented diagnosis of hyperparathyroidism in the electronic medical record (P = 0.01). Kidney stones or abnormal DEXA scan were present in 16 (14.7%) and 18 (16.5%), respectively. Most patients were managed non-surgically (101, 92.6%); calcimimetics were prescribed for 42 (38.5%, P = 0.01). Eight (7.3%) patients with classic 3HPT were referred to a surgeon (P = 0.35); all were initially prescribed calcimimetics (P = 0.001). Conclusions3HPT is underdiagnosed in patients with elevated calcium and PTH levels post-transplant. A significant percentage of these patients go without surgical referral and curative treatment.

Risk of Hypercalcemia in the Elderly Patients with Hypervitaminosis D and Vitamin D Intoxication.

We aimed to evaluate the risk of hypercalcemia in the elderly population with hypervitaminosis D and vitamin D intoxication. A total of 121 patients with a 25(OH) vitamin D level > 100 ng/mL from patients aged ≥ 65 years who applied to our hospital between 2014 and 2020 were included in this study. Sixty-nine patients with 25(OH) vitamin D levels of 100 - 150 ng/mL were determined as D hypervitaminosis; 52 patients with 25(OH) vitamin D levels > 150 ng/mL were determined as vitamin D intoxication. People with a calcium level above 10.2 mg/dL were considered as hypercalcemic patients. Of 121 patients with D hypervitaminosis and vitamin D intoxication, 103 (85.1%) were normocalcemic, and 18 (14.9%) were hypercalcemic. Hypercalcemia was detected in 9 out of 69 patients with hypervitaminosis D; 8 of them had mild hypercalcemia and 1 person had severe hypercalcemia. Hypercalcemia was detected in 9 of 52 patients with vitamin D intoxication; mild hypercalcemia was found in 7 people, moderate hypercalcemia in 1 person, severe hypercalcemia in 1 person. There was no statistically significant difference between the incidence of hypercalcemia in patients with D hypervitaminosis and vitamin D intoxication (p = 0.514). It was observed that a total of 3 (16.7%) of the hypercalcemic patients with D hypervitaminosis and vitamin D intoxication died. In the elderly population with hypervitaminosis D and vitamin D intoxication, most of the patients were seen as normocalcemic. However, severe hypercalcemia, which was life-threatening and resulted in death, was also observed. Using vitamin D in elderly patients should be performed according to the guideline recommendations. Calcium level and clinical findings should be checked during follow-up.

BIOCHEMICAL WITH NORMAL PARATHYROID HORMONE : A CASE REPORT

Normo-hormonal primary hyperparathyroidism(NPHPT) is an uncommon condition which has been increasing in last decade. This milder biochemical entity remains incompletely understood due to lack of long term health outcomes regarding management. NPHPT poses two challenges to the surgeon, rst is when to operate and second is the use of intra-operative parathyroid hormone assay to predict the success of surgery. Here we present a 53 year old lady who came with low back ache of more than 2 years duration. It is found to have elevated calcium levels and on further evaluation found to have high normal parathyroid hormone levels in two occasions. Pre operative localization studies were done by suspecting normo-hormonal hyperparathyroidism which showed concordant lesions in both ultrasound neck and Sestamibi scan. She underwent focused parathyroidectomy with intra-operative parathyroid hormone levels which dropped in to less than 30pg/ml. Postoperative calcium was within normal limits and she was symptomatically better. In patients with symptoms of hypercalcemia, elevated calcium levels and high normal intact parathyroid hormone levels should be considered as inappropriate and should lead to the suspicion of normo-hormonal hyperparathyroidism. Intra operative parathyroid hormone levels below 30pg/ml can be utilized as an indicator of successful operation in normo-hormonal hyperparathyroidism.In symptomatic hypercalcemic patients, even if the parathyroid hormones are high normal, a further investigation should be done to locate the parathyroid adenoma and surgery is the best cure

PSAT159 Does Untreated Hypercalcemia Affect Postoperative Joint Pain Following Hip and Knee Arthroplasty for Osteoarthritis? A Retrospective Case Cohort Study

Abstract Background/Objective Primary hyperparathyroidism (pHPT) is characterized by the excess secretion of parathyroid hormone (PTH), leading to hypercalcemia. pHPT is a known cause of joint pain, which is the key element in the decision regarding possible arthroplasty in patients with osteoarthritis (OA). The effect of hypercalcemia on arthroplasty outcomes has not been studied. This study investigates the association between preoperative hypercalcemia and postoperative outcomes following total knee (TKA) and total hip arthroplasty (THA). Methods A retrospective chart review was conducted on patients who underwent initial elective THA and/or TKA at an academic medical center between 2015-2019. Patient characteristics and outcomes were obtained. Hypercalcemia was used as a proxy for pHPT as PTH is not routinely obtained in the orthopedic setting. Patients with a preoperative serum calcium &amp;gt;10.2 mg/dL were matched (1: 2-1: 4) with nearest neighbor matching to patients with normal serum calcium based on age, sex, BMI, Charlson Comorbidity Index, American Society of Anesthesiologists class, type of surgery (hip or knee), and date of surgery. THA and TKA functional outcomes were measured at baseline and one-year postoperatively using patient-reported Hip Disability and Osteoarthritis Outcome Scores (HOOS JR) and Knee Injury and Osteoarthritis Outcome Scores (KOOS JR) surveys, respectively. A score of '0' represents total joint disability; '100' represents perfect joint health. Patients with incomplete HOOS JR or KOOS JR scores were excluded. Postoperative complications, readmissions, length of stay, and functional outcome scores were compared. Results Of 5215 patients identified, 269 (5%) were hypercalcemic. The final cohort included 495 patients (106 [21%] hypercalcemic cases, 389 matched controls). Of these, 223 patients underwent THA (46 [21%] cases; 177 controls) and 272 patients underwent TKA (61 [22%] cases; 211 controls). There were no differences in HOOS JR and KOOS JR scores between cases and controls at baseline (HOOS JR: 49.6±12.9 vs 52.8±13.3; KOOS JR: 52.5±12.1 vs 53.5±11.4) or at one-year postoperatively (HOOS JR: 83.6±16.2 vs 84.7±15.5; KOOS JR: 78.0±13.1 vs 75.5±15.3). There also were no differences in rates of postoperative complications, readmissions, or length of stay. Only 19/106 (18%) hypercalcemic patients had a PTH drawn, and of these, 9 (47%) had possible pHPT (PTH&amp;gt;40). Sub-analysis of these 9 patients demonstrated similar HOOS JR and KOOS JR scores to controls at both timepoints. Conclusion Patients with hypercalcemia undergoing arthroplasty have similar functional and postoperative outcomes as normocalcemic patients. Analysis of patients with possible pHPT was limited, as a PTH was obtained in &amp;lt;20% of patients with hypercalcemia. However, nearly 50% of these patients had possible pHPT. Therefore, we recommend that all patients being evaluated for arthroplasty have a calcium level checked, and if high, be evaluated for possible pHPT. Additional investigation is needed to determine the effect of pHPT on arthroplasty outcomes. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP564 Hypercalcemia in the Setting of HTLV-1 Infection and Normal PTHrP Levels

Abstract A 53 year old male with history of HTLV-1 infection associated myelopathy but with unknown mode of transmission, presented with acute on chronic bilateral lower extremity weakness and numbness with no other deficits. Examination revealed decreased strength (grade 1/5) in lower extremities with normal bulk, tone and sensations. Initial blood work revealed hypercalcemia with corrected Calcium of 16.2mg/dl(8.5-11.5), Phosphorus of 2.7mg/dl (2.5- 4.5) and Alkaline Phosphatase of 126mg/dl(20-140). Workup for hypercalcemia revealed Parathyroid hormone (PTH) level of 14pg/ml (10-65), 25 hydroxy vitamin D at 19.6 ng/ml(30-100), 1,25 dihydroxy vitamin D at 6.7pg/ml(19.9-79.3) and TSH of 1.265 microIU/ml(0.5-5). The Parathyroid hormone related protein(PTHrP) level was low at &amp;lt; 2pmol/L while Lactate Dehydrogenase (LDH) was 433U/L(100-220). Urine calcium creatinine ratio was 0.388. Reverse Transcriptase PCR was positive for HTLV-1 but negative for HTLV-2. Smudge cells and atypical lymphocytes were noted on peripheral smear. Imaging revealed generalized lymphadenopathy with splenomegaly but no spinal cord compression. Flow cytometry showed 7.8% atypical helper T cells, positive for CD3, CD4, CD5 and CD45. Clonal T cell receptor gene rearrangements were found, suggesting an underlying T cell neoplasm. Lymph node biopsy confirmed ATLL. He received treatment with fluids, Calcitonin and Denosumab after which serum Calcium levels fell (nadir 7.7mg/dl) and then normalized. He developed another episode of hypercalcemia 5 weeks later which was treated similarly. Discussion Human T cell Lymphotropic Virus-1 (HTLV-1) is a retrovirus causing asymptomatic infections, symptomatic systemic disorders and adult T cell Leukemia and lymphoma(ATLL). HTLV-1 infections, whether in asymptomatic or symptomatic patients, and ATLL are rare but important causes of hypercalcemia and hypercalcemic crises. Individuals with ATLL have the highest incidence of hypercalcemia(50-70%) among all hematologic malignancies. Hypercalcemia is a poor prognostic factor and predicts lower overall survival. It is caused by increased bone resorption, mediated by various factors with the largest role being played by Receptor Activator of Nuclear Factor Kappa B ligand (RANKL), followed by PTHrP, Interleukins, Macrophage Inflammatory Protein 1 alpha and gp 46. RANKL expression is increased upon transactivation by the viral TAX gene product and mediates conversion of osteoclast precursors to mature osteoclasts engaging in bone resorption. PTHrP expression is variable among patients, relating to levels of the TAX gene product that transactivates the PTHrP gene promoter. Thus, a low level, like in our patient, does not rule out HTLV infection as the cause of hypercalcemia. Management of hypercalcemia is in keeping with guidelines for management of other causes of hypercalcemia but may be better responsive to monoclonal antibodies against RANKL than bisphosphonates given the role of the ligand in mediating hypercalcemia in these cases. It can also be used in the setting of poor renal function, which is commonly encountered in hypercalcemic patients. Presentation: No date and time listed

Atorvastatin lowers serum calcium levels in lithium-users: results from a randomized controlled trial

BackgroundAlthough lithium is considered the gold-standard treatment for bipolar disorder (BD), it is associated with a variety of major endocrine and metabolic side effects, including parathyroid hormone (PTH) dependent hypercalcemia. Aside from surgery and medication discontinuation, there are limited treatments for hypercalcemia. This paper will assess data from a randomized controlled trial (RCT).MethodsThis is a secondary analysis of an RCT that explored the effects of atorvastatin (n = 27) versus placebo (n = 33) on lithium-induced nephrogenic diabetes insipidus (NDI) in patients with BD and major depressive disorder (MDD) using lithium (n = 60), over a 12-week period. This secondary analysis will explore serum calcium levels and thyroid stimulating hormone (TSH) measured at baseline, week 4, and week 12.ResultsAt 12-weeks follow-up while adjusting results for baseline, linear regression analyses found that corrected serum calcium levels were significantly lower in the treatment group (mean (M) = 2.30 mmol/L, standard deviation (SD) = 0.07) compared to the placebo group (M = 2.33 mmol/L, SD = 0.07) (β = − 0.03 (95% C.I.; − 0.0662, − 0.0035), p = 0.03) for lithium users. There were no significant changes in TSH.ConclusionIn lithium users with relatively normal calcium levels, receiving atorvastatin was associated with a decrease in serum calcium levels. Although exciting, this is a preliminary finding that needs further investigation with hypercalcemic patients. Future RCTs could examine whether atorvastatin can treat PTH dependent hypercalcemia due to lithium and other causes.