Persistent Hypercalcemia Research Articles

5117 Unusual Sarcoid Presentation as a Case of Hypercalcemia

Abstract Disclosure: M. Salim: None. A. Chauhan: None. S. Avula: None. A. Ahmed: None. K. Zekarias: None. Background: Hypercalcemia may arise from a variety of causes and can pose challenging diagnostic dilemma. Clinical Case: An 89-year-old male presented with worsening malaise related to persistent hypercalcemia. He reported productive cough, polyuria, polydipsia, generalized muscle weakness and weight loss. Physical exam was remarkable for upper and lower extremities weakness. Laboratory tests showed calcium 11.6 (8.8-10.2 mg/dL), phosphorus 2.8 mg/dL (2.5-4.5 mg/dL), albumin 4.2 g/dL (3.5-5.2 g/dL), parathyroid hormone (PTH) 10 pg/mL (15-65 pg/mL), parathyroid hormone-related protein (PTH-rp) 4.5 pmol/L (0.0-2.3 pmol/L), TSH 6.24 (0.30 - 4.20 uIU/mL), free T4 1.10 ng/dL (0.90-1.70 ng/dL), GFR 61 mL/min/1.73m2, 25 OH Vit D 31 ng/mL (20-75 ng/mL), vit D 1,25-dihydroxy 134 pg/mL (19.9-79.3 pg/mL), calcium urine/creatinine 0.54. Hypercalcemia was first noted 11 months before the visit with a level of 14.0 mg/dL (8.8-10.2 mg/dL), phosphorus 3.5 mg/dL, PTH 11, PTH-rp 1.4 pmol/L, 25 OH Vit D 62 ng/mL, Vit D 1,25-dihydroxy 90 pg/mL, angiotensin-1-converting enzyme 12 U/L (16-85 U/L), serum and urine electrophoresis showed no monoclonal gammopathy present, and tuberculosis interferon-gamma test negative. Autoimmune workup was unremarkable, except for weak positive anti-signal recognition particle (SRP) antibodies and anti-Mi-2 antibodies. CT chest/pelvis/abdomen demonstrated peripheral predominant reticular opacities suggestive of interstitial lung disease and no malignant findings. Treatment history included zoledronic acid 11 months before the visit. The patient was referred for a granulomatous disease workup.Upon one month follow-up, the hypercalcemia symptoms were worsening. Repeat calcium was 12.3 mg/dL and fungal serologies were negative. The patient was started on prednisone empirically. PET CT was ordered and revealed patchy inflamed musculature of extremities suspicious of dermatomyositis/polymyositis. Further labs showed unremarkable myomarker panel, u3-Hydroxy-3-Methylglutaryl Coenzyme A reductase (HMGCR) antibody, Anti-cN-1A antibody, ACE 53 U/L, creatine kinase 32 U/L (39-309 U/L), aldolase 5.4 U/L (1.2-7.6 U/L), soluble IL-2R 1,021 U/mL (137-838 U/mL), and lysozyme 3.89 ug/mL (<2.75 ug/mL). A muscle biopsy was done, which showed benign skeletal muscle with patchy myofiber atrophy, patchy interstitial fibrosis, and focal interstitial mild chronic inflammation with no evidence of sarcoid granulomas in the sample. One week lab follow-up post initiation of steroid showed calcium of 10.1 mg/dL and subsequently improvement in his overall labs. Working diagnosis of sarcoid myositis was made. Conclusion: This case report highlights the approach of diagnosing a rare case of hypercalcemia due to sarcoid myositis. In a highly clinical suspicious patient, PET CT scan might be a necessary modality for diagnosis. Presentation: 6/2/2024

8165 A Case Of Rhabdomyolysis-Induced Hypocalcemia And Hypercalcemia

Abstract Disclosure: A. Desai: None. A.L. Izzi: None. B. Flores Chang: None. A. Sajan: None. Introduction: Rhabdomyolysis is a syndrome characterized by muscle breakdown and the release of intracellular muscle contents into circulation. It is associated with electrolyte abnormalities and acute renal failure that can lead to prolonged hospitalization. We report a case of persistent hypercalcemia from recovery of acute renal failure and severe rhabdomyolysis. Case Description: A 47-year-old man with past medical history of polysubstance use initially presented with opiate-induced acute encephalopathy and respiratory failure. He developed severe rhabdomyolysis during the hospital course leading to acute renal failure requiring hemodialysis with hypocalcemia. The initial labs showed corrected calcium 6.2 mg/dL [9.2-11.0], ionized calcium 3.48 mg/dL [4.65-5.28], creatinine kinase level was >72,600 U/L [38-174], BUN 110 mg/dL [8-23], creatinine 7.8 mg/dL [0.6-1.2], and GFR 7 ml/min/BSA. His renal function improved over the next several days in the hospital. The serum creatinine improved to 4 mg/dL, BUN 49 mg/dL and GFR 20 ml/min/BSA respectively after couple of intermittent dialysis sessions. Six days after the last hemodialysis session, patient developed severe hypercalcemia with corrected calcium values ranging from 13.5 to 14.7 mg/dL and ionized calcium 7.41 mg/dL. Labs showed PTH 10 pg/mL [15-65], 1,25-dihydroxyvitamin D <10.0 pg/dL [21-65] and 25-OH Vitamin D levels 15.3 ng/ mL [30-96], which is consistent non-PTH medicated hypercalcemia. The 24-hour urine calcium was 696 mg [0-300 mg/24 hrs, 2900 cc]. PTH-related peptide was not collected. He was treated with intermittent doses of calcitonin and a single dose of pamidronate when the calcium levels were >13 mg/dL. Hypercalcemia resolved in eleven days after initially noted to have hypercalcemia. The corrected calcium improved to 10.1 mg/dL on the day of discharge. Discussion:Severe rhabdomyolysis is associated with acute kidney injury. The initial hypocalcemic phase during rhabdomyolysis is due to entry of calcium into damaged myocytes and deposition of calcium salts in damaged muscle. This is seen in the oliguric phase of acute kidney injury. After the recovery of rhabdomyolysis, the polyuric phase persists during renal recovery. During this time, up to one third of patients may have rebound hypercalcemia due to massive muscle calcium release. As per case reports the hypercalcemia phase lasts from 8 days to 3.5 months. In our case, the patient initially developed hypocalcemia in the oliguric phase of acute kidney injury from rhabdomyolysis. He developed hypercalcemia in the polyuric phase of renal recovery. The hypercalcemia resolved with intravenous hydration, calcitonin and pamidronate. Rhabdomyolysis is a rare cause for both hypocalcemia and hypercalcemia. Our case highlights the biphasic calcium response associated with rhabdomyolysis in the setting of renal impairment and recovery. Presentation: 6/1/2024

8120 Effective Management of Neonatal Hypercalcemia in Congenital Mesoblastic Nephroma: A Case Report on the Use of Calcitonin

Abstract Disclosure: C.S. Galvez: None. K. Rifai: None. C. Moorthy: None. S. Chheda: None. M. Zerah: None. Introduction: Pediatric patients with hypercalcemia of malignancy are typically treated with hyperhydration, loop diuretics and bisphosphonates. Calcitonin, a peptide functionally antagonizes the effects of PTH. Calcitonin has limited pharmacokinetic data in neonates, especially those with Congenital Mesoblastic Nephroma (CMN), making treatment challenging with unclear safety and efficacy parameters. We present the fourth published case describing the use of calcitonin for likely PTH-rP-mediated severe hypercalcemia in a neonate with CMN. Clinical Case: A 15-day-old late preterm male, presented with lethargy, poor feeds, severe failure to thrive and a large abdominal mass. The mother is a G4P4, with good prenatal care. On admission, the patient was hypertensive (138/84 mmHg) and appeared dehydrated. Physical examination revealed a firm mass in the right abdomen crossing the midline. Serum calcium levels were 13.5 mg/dL (normal 9.0-10.9 mg/dL), with an ionized calcium 1.71 mmol/L (normal 1.15 and 1.30 mmol/L). Abdominal ultrasound showed a large, 9.1 x 8 cm dominant solid right renal mass, most likely CMN, with left-sided medullary nephrocalcinosis. Cardiac Echo and EKG were within normal limits. The patient received hydration, nicardipine (titrated to decrease blood pressure by 10-15 mmHg per day) and furosemide at 1 mg/kg/day IV q6h. Due to the persistence of hypercalcemia after 24 hours of treatment (14.7 mg/dL serum calcium with ionize of 1.81 mmol/L), the patient received one dose of calcitonin (4 units/kg subcutaneously), resulting in a decrease in serum calcium to 11.5 mg/dL in 4 hours. The patient underwent a successful radical right uretero-nephrectomy, with post-surgery improvement of neurological, cardiovascular and electrolyte status. Unfortunately, PTH-rP sample was insufficient. Pathology reported CMN of the cellular type. CMN is a rare tumor with low malignant potential, representing approximately 3% of all pediatric renal tumors. It is the most common renal neoplasm diagnosed in the first 6 months of life. The most common symptom is an abdominal mass (76%), with hypertension (19%). Hypercalcemia was reported in only 4% which can be secondary to paraneoplastic secretion of PTH or PTH-rP. Conclusion: This case represents the fourth instance of calcitonin use in a neonate with CMN to manage persistent hypercalcemia. Subcutaneous administration of calcitonin at 4 units/kg proved effective with a short onset of action (within 2 hours) and duration of 6 to 8 hours, making it a viable alternative to bisphosphonates (action around 48 hours and duration of 7 to 14 days). Calcitonin's advantages include less significant side effects and a faster resolution of complications like "Hungry bone Syndrome." The flexibility of repeated dosing every 6 hours, with the option to increase the dose, if necessary, adds to its clinical utility. Presentation: 6/3/2024

Timing of parathyroidectomy after kidney transplantation: A cost-effectiveness analysis

IntroductionParathyroidectomy is the definitive treatment for tertiary hyperparathyroidism post-kidney transplantation. However, cinacalcet-based medical management is increasingly used as an alternative. The financial consequences of each treatment remain unclear. We aimed to identify the most cost-effective strategy for managing hyperparathyroidism from the kidney transplantation recipient's perspective. MethodsWe constructed a patient-level discrete event simulation model to compare parathyroidectomy and cinacalcet-based medical management. The effects of hyperparathyroidism on allograft survival and all-cause mortality were considered in the discrete event simulation model with a time horizon of 15 years. Our base case was a 55-year-old kidney transplantation recipient with persistent hyperparathyroidism and hypercalcemia. The primary outcome was the cost-effectiveness measured by cost per quality-adjusted life years. ResultsThe monthly out-of-pocket cost of cinacalcet ranged from $12 to $288, depending on insurance coverage, with a base case cost of $150. Our base case analysis showed that parathyroidectomy was the dominant treatment with lesser cost ($1,315 vs $7,147) and greater effectiveness (3.17 quality-adjusted life years and 2.92 quality-adjusted life years) than cinacalcet. One-way sensitivity analysis on the cinacalcet treatment duration showed that parathyroidectomy became more cost-effective at 9 months. Two-way sensitivity analysis on the cost of cinacalcet and the duration of treatment with cinacalcet showed that as the monthly cost of cinacalcet increases, the expense of cinacalcet-based medical management quickly exceeds the cost of parathyroidectomy. ConclusionParathyroidectomy becomes more cost-effective for kidney transplantation recipients with tertiary hyperparathyroidism when they require cinacalcet-based medical management for more than 9 months. As part of shared decision-making, it is important to discuss the financial costs involved in treating tertiary hyperparathyroidism.

Persistent mild hypercalcaemia in an infant with pseudohypoaldosteronism and the diagnostic challenges faced

Persistent mild hypercalcaemia in an infant with pseudohypoaldosteronism and the diagnostic challenges faced

Timing of parathyroidectomy for tertiary hyperparathyroidism after kidney transplant

BackgroundParathyroidectomy has been shown to be superior to medical management in treating hypercalcemia and preserving renal allograft function in patients with tertiary hyperparathyroidism after kidney transplant. Despite this evidence, parathyroidectomy remains underused. We aimed to evaluate outcomes in patients with tertiary hyperparathyroidism after kidney transplant based on management strategy (cinacalcet or parathyroidectomy) and optimal timing of parathyroidectomy. MethodsData from TriNetX Dataworks included adult kidney transplant patients diagnosed with tertiary hyperparathyroidism between 1998 and 2021. Patients who underwent parathyroidectomy were compared with those receiving cinacalcet. Subgroups based on parathyroidectomy timing after transplant were analyzed (within 6 months, 6 months to 1 year, and between 1 and 3 years). Descriptive statistics and relative risks were calculated using TriNetX Live. ResultsPatients receiving cinacalcet (n = 162) had a 77% higher risk of persistent hypercalcemia and a 73% higher risk of elevated parathyroid hormone levels than those who underwent parathyroidectomy (n = 338) within 3–10 years after the index event (start of cinacalcet or surgery). Parathyroidectomy performed 1 year after transplant (n = 132) was associated with a 57% lower risk of kidney stone formation and patients were 2 times more likely to maintain normal glomerular filtration rate than parathyroidectomy performed 1–3 years after transplant (n = 57). Even earlier parathyroidectomy (within 6 months of kidney transplant, n = 55) showed a 62% lower risk of persistent hypercalcemia, hyperphosphatemia, and kidney stone formation than surgery between 6 months and 1 year after transplant (n = 77). ConclusionParathyroidectomy is more effective than cinacalcet in managing tertiary hyperparathyroidism after kidney transplant. In addition, opting for early parathyroidectomy (within 6 months after transplant) could enhance long-term outcomes.

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.

Surgical strategy in lithium-associated hyperparathyroidism: A population-based study.

The extent of parathyroidectomy (PTX) recommendation in patients with lithium-associated hyperparathyroidism (LAH) remains controversial. The primary objectives of this study were to analyze extent of surgery, complications, and long-term outcomes. A population-based study, including all primary hyperparathyroidism (PHPT) patients who underwent PTX in Sweden between 2008 and 2017. Data on exhibited lithium prescriptions, morbidity, surgical approach, and outcomes were collected from relevant national registers and the Scandinavian Quality Register of Thyroid, Parathyroid, and Adrenal Surgery. Patients with lithium exposure before PTX were defined as having LAH. Descriptive summary statistics and regression models were used to evaluate differences in comorbidities, surgical approach, and outcomes between LAH and PHPT not exposed to lithium (non-LAH). Lithium exposure was significantly more common among PHPT (n=202, 2.3%) than in controls (n=416, 0.5%); OR 5.0 (95% CI 4.2-5.9). The risk of LAH correlated to the length of lithium exposure. In the LAH-group, the surgical procedures were more extensive and associated with a higher risk of postoperative bleeding, wound infections, persistent hypercalcemia, and hypocalcemia that remained after adjustment for the higher percentage of multiglandular disease. However, the cumulative risk of re-admission for PHPT was similar the first years after PTX and primarily elevated for patients with >5years duration of lithium exposure prior to surgery. The findings support the perception of LAH as a complex entity. We recommend a functionally oriented approach, aimed to obtain and maintain normocalcemia for as long as possible, minimizing the risk of permanent hypoparathyroidism, and accepting some risk of recurrence.

МЕТАБОЛИЧЕСКИЕ РЕАКЦИИ ОРГАНИЗМА ЗДОРОВОГО ЧЕЛОВЕКА В ДИНАМИКЕ ЭКСПЕРИМЕНТА SIRIUS-21

The SIRIUS-21 study was designed as a 240-day isolation of healthy volunteers in controlled environment simulating a piloted mission to the Moon including operator's activities in lunar orbit and on the surface. The investigation involved an international crew of two women and 3 men at the age of 29 to 44 years. The object was metabolic reactions of healthy bodies to the simulated conditions. Crew members demonstrated a moderate stress reaction characterized by inhibition of the gastrointestinal tract secretory activity, reduction of glycolysis intensity, persistent hypercalcemia, a more intensive creatine kinase system functioning as a buffer, deficit of macroergic compounds, magnesium and essential microelements. On day 7 post isolation, the stress symptoms showed a partial leveling. Hard physical training had both the positive and negative effects on metabolism dynamics. The preventive purpose of training was to normalize the content of essential microelements in blood and suppress atherogenesis; however, training had also the negative effect of inducing hypohydration. In future isolation studies it would be appropriate to optimize training protocols and enhance the program of countermeasures to the negative effects of simulated factors.

Pembrolizumab with external radiation therapy effectively controlled TMB-high unresectable recurrent parathyroid cancer: a case report with review of literature.

Parathyroid cancer (PC) is extremely resistant to chemotherapy and radiotherapy (RT), but hormonally functional by producing excessive parathyroid hormone (PTH), causing remarkable hypercalcemia even in biochemical disease recurrence. Accordingly, management of hypercalcemia by calcimimetics and bisphosphonates has been main treatment for unresectable PC. Here, we report a case of unresectable tumor mutational burden (TMB)-high recurrent PC that has been effectively controlled by pembrolizumab (PEM) with RT. A 48-year-old male patient, with previous history of left single parathyroidectomy for primary hyperparathyroidism, underwent surgeries for recurrent hyperparathyroidism at 47 and 48 years of age, and was pathologically diagnosed with PC. He was referred to our hospital due to persistent hypercalcemia and elevated PTH. The recurrent tumors were identified in the superior mediastinum and radically resected, then the hyperparathyroidism was improved. A FoundationOne® CDx of the specimen called TMB-high. He demonstrated recurrent hyperparathyroidism at 49 years of age, and underwent a gross curative resection. However, hyperparathyroidism achieved only insufficient improvement, indicating biochemical residual cancer cells. PEM treatment was initiated in combination with RT to the left central-lateral neck and superior mediastinum. He successfully achieved evocalcet and zoledronate withdrawal, and the PTH level improvement was continuously observed for 8 months at present, with only grade 2 subclinical hypothyroidism. Interestingly, leukocyte fraction ratios were reversed corresponding to disease improvement. A combination of PEM and RT is a promising treatment of unresectable TMB-high PC. Recent evidence on the immunomodulatory effect of RT provides the rationale for the combination of RT and PEM.

A >50% Intraoperative Parathyroid Hormone Level Decrease Into Normal Reference Range Predicts Complete Excision of Malignancy in Patients With Parathyroid Carcinoma

IntroductionThe mainstay of successful treatment for parathyroid carcinoma remains complete surgical excision. Although intraoperative parathyroid hormone (ioPTH) monitoring is a useful adjunct during parathyroidectomy for benign primary hyperparathyroidism, its utility for parathyroid carcinoma remains unclear. MethodsA retrospective review of 796 patients who underwent parathyroidectomy with ioPTH monitoring for primary hyperparathyroidism revealed 13 patients with parathyroid carcinoma on final pathology from two academic institutions. A systematic review yielded 5 additional parathyroid carcinoma patients. Complete excision of malignancy, or operative success (eucalcemia ≥6 mo. after parathyroidectomy); operative failure (persistent hypercalcemia <6 mo. after parathyroidectomy); and perioperative complications were evaluated. Comparison of the >50% ioPTH decrease alone to >50% ioPTH decrease into normal reference range was analyzed using Chi-squared, Kolmogorov–Smirnov, Kruskal–Wallis tests. ResultsAll 18 parathyroid carcinoma patients achieved a >50% ioPTH decrease, and 14 patients also had a final ioPTH level decrease into normal reference range. 93% of patients who met normal parathyroid hormone reference range had operative success, whereas only two of the four (50%) patients with parathyroid carcinoma with a >50% ioPTH decrease alone demonstrated operative success. ConclusionsParathyroidectomy guided by a >50% ioPTH decrease into normal reference range may better predict complete excision of malignant tissue in patients with parathyroid carcinoma compared to >50% ioPTH decrease alone. IoPTH monitoring should be used in conjunction with clinical judgment and complete en bloc resection for optimal treatment and success.

Long-term effects of hypercalcemia in kidney transplant recipients with persistent hyperparathyroidism.

Hypercalcemia is highlyprevalent in kidney transplant recipients with hyperparathyroidism. However, its long-term impact on graft function is uncertain. We conducted a prospective cohort study investigating adverse graft outcomes associated with persistent hypercalcemia (free calcium > 5.2mg/dL in ≥ 80% of measures) and inappropriately elevated intact parathyroid hormone (> 30pg/mL) in kidney transplant recipients. Asymptomatic mild hypercalcemia was monitored unless complications developed. We included 385 kidney transplant recipients. During a 4-year (range 1-9) median follow-uptime, 62% of kidney transplant recipients presented persistent hypercalcemia. Compared to kidney transplant recipients without hypercalcemia, there were no significant differences in graft dysfunction (10% vs. 12%, p = 0.61), symptomatic urolithiasis (5% vs. 3%, p = 0.43), biopsy-proven calcium deposits (6% vs. 5%, p = 1.0), fractures (6% vs. 4%, p = 0.64), and a composite outcome of urolithiasis, calcium deposits, fractures, and parathyroidectomy indication (16% vs. 13%, p = 0.55). In a subset of 76 kidney transplant recipients, subjects with persistent hypercalcemia had higher urinary calcium (median 84 [43-170] vs. 38 [24-64]mg/day, p = 0.03) and intact fibroblast growth factor 23 (median 36 [24-54] vs. 27 [19-40]pg/mL, p = 0.04), and lower 25-hydroxyvitamin D levels (11.3 ± 1.2 vs. 16.3 ± 1.4ng/mL, p < 0.001). In multivariate analysis, pretransplant intact parathyroid hormone < 300pg/mL was associated with a reduced risk of post-transplant hypercalcemia (OR 0.51, 95% CI 0.32-0.80). Long-term persistent mild hypercalcemia (tertiary hyperparathyroidism) was frequent in kidney transplant recipientsin our series. This condition presented with lower phosphate and 25-hydroxyvitamin D, and higher urinary calcium and intact fibroblast growth factor 23 levels compared to kidney transplant recipients without hypercalcemia, resembling a mild form of primary hyperparathyroidism. Despite these metabolic derangements, the risk of adverse graft outcomes was low.

Predictive factors for persistent hypercalcemia following parathyroidectomy in patients with persistent hyperparathyroidism after kidney transplantation: a retrospective cohort study.

Surgery for irreversible hyperparathyroidism is the preferred management for kidney transplant patients. The authors analyzed the factors associated with persistent hypercalcemia after parathyroidectomy in kidney transplant patients and evaluated the appropriate extent of surgery. The authors retrospectively analyzed 100 patients who underwent parathyroidectomy because of persistent hyperparathyroidism after kidney transplantation at a tertiary medical center between June 2011 and February 2022. Patients were divided into two groups: 22 with persistent hypercalcemia after parathyroidectomy and 78 who achieved normocalcemia after parathyroidectomy. Persistent hypercalcemia was defined as having sustained hypercalcemia (≥10.3mg/dl) 6 months after kidney transplantation. The authors compared the biochemical and clinicopathological features between the two groups. Multivariate logistic regression analysis was used to identify potential risk factors associated with persistent hypercalcemia following parathyroidectomy. The proportion of patients with serum intact parathyroid hormone (PTH) level is greater than 65pg/ml was significantly high in the hypercalcemia group (40.9 vs. 7.7%). The proportion of patients who underwent less than subtotal parathyroidectomy was significantly high in the persistent hypercalcemia group (17.9 vs. 54.5%). Patients with a large remaining size of the preserved parathyroid gland (≥0.8cm) had a high incidence of persistent hypercalcemia (29.7 vs. 52.6%). In the multivariate logistic regression analysis, the drop rate of intact PTH is less than 88% on postoperative day 1 (odds ratio 10.3, 95% CI: 2.7-39.1, P =0.001) and the removal of less than or equal to 2 parathyroid glands (odds ratio 6.8, 95% CI: 1.8-26.7, P =0.001) were identified as risk factors for persistent hypercalcemia. The drop rate of intact PTH is less than 88% on postoperative day 1 and appropriate extent of surgery for controlling the autonomic function were independently associated with persistent hypercalcemia. Confirmation of parathyroid lesions through frozen section biopsy or intraoperative PTH monitoring can be helpful in preventing the inadvertent removal of a parathyroid gland and achieving normocalcemia after parathyroidectomy.

Surgical treatment of tertiary hyperparathyroidism: does one fit for all?

Tertiary hyperparathyroidism (3HPT) is defined as a condition of excessive autonomous excretion of intact parathyroid hormone (iPTH) with persistent hypercalcemia (>10.5 mg/dL) that lasts for more than 12 months after a successful kidney transplantation, in the context of a long course secondary hyperparathyroidism (2HPT). The chronic high levels of iPTH cause a worsening of graft function, accompanied by systemic symptoms of hypercalcemia. The only curative therapy is parathyroidectomy (PTX). It remains unclear whether total parathyroidectomy with autotransplantation (TPTX-AT) or subtotal parathyroidectomy (SPTX) lead to better outcomes. The aim of this retrospective, single-institution cohort study is to evaluate the rate of persistent or recurrent disease and postoperative calcium/iPTH disturbances in patients treated with TPTX-AT or SPTX for 3HPT. A single-center retrospective analysis of 3HPT patients submitted to TPTX-AT or SPTX between 2007-2020 with at least 24 months follow-up was conducted. The outcome parameters included persistence/recurrence of disease, incidence of transitory hypocalcemia, and temporary/permanent hypoparathyroidism. A cohort of 52 patients was analyzed and divided in two groups: 38 (73%) were submitted for TPTX-AT, and 14 patients (27%) were submitted for SPTX. The TPTX-AT population showed lower plasmatic calcium concentrations compared with the SPTX group during the entire follow-up period (p<0.001). There were eight cases (21%) of transitory hypocalcemia in the TPTX-AT group and none in the SPTX group, with p=0.065. Two cases (5%) of temporary hypoparathyroidism occurred in the TPTX-AT group and none in the SPTX group, with p= 0.530. There were no cases of permanent hypoparathyroidism and no cases of persistent disease. No statistical difference was assessed for the recurrence of 3HPT between the TPTX-AT group and the SPTX group (N=1, 3% vs N=1, 7%) (p=0.470). No significative difference was registered between the TPTX-AT and SPTX groups in terms of persistence/recurrence of disease, incidence of transitory hypocalcemia, and temporary/permanent hypoparathyroidism. Mean calcium levels iPTH values were statistically lower among the TPTX-AT group compared with the SPTX group while remaining always in the range of normality.

THU406 24-hydroxylase Deficiency, A Rare Cause Of Hypercalcemia

Abstract Disclosure: J. Hodge: None. M. Gortakowski: None. N. Barua: None. Background: 24-hydroxylase is encoded by CYP24A1 and functions to convert 1,25 dihydroxyvitamin D and 25-hydroxyvitamin D to their inactive metabolites[1]. 24-hydroxylase deficiency due to CYP24A1 variants is rare and clinical presentation is characterized by hypercalcemia, nephrolithiasis and nephrocalcinosis. Treatment may include thiazide diuretics, sodium cellulose phosphate and ketoconazole.[1] We present a case of hypercalcemia due to 24-hydroxylase deficiency. Clinical Case: A 56-year-old male with chronic kidney disease initially presented with hypercalcemia at age 48 to another institution. He was initially diagnosed with primary hyperparathyroidism in the setting of an inappropriately normal parathyroid hormone (PTH) with hypercalcemia. He subsequently had one parathyroid gland removed a year after diagnosis, then another two years later due to continued hypercalcemia. However, he continued to have persistent hypercalcemia, 10.9-12.7 mg/dL but now in the setting of low PTH. In addition, his 1,25 dihydroxyvitamin D was high normal and 25-hydroxyvitamin D was high off exogenous vitamin D supplementation, which raised the suspicion for 24-hydroxylase deficiency. He presented to our institution eight years later. Initial evaluation revealed, calcium 12.4 (8.6-10.5 mg/dL), phosphorous 2.9 (2.5-4.5 mg/dL), normal albumin, PTH 13 (15-65 pg/mL), 1,25 dihydroxyvitamin D 87.2 (19-79.3 pg/mL) and 25-hydroxyvitamin D 38.3 (20-50 ng/mL), 24hr urine calcium 0.23 (0.05-0.30 g/24hr), fractional excretion calcium 0.02. His 25-hydroxyvitamin D:24,25 dihydroxy vitamin D ratio was unable to be calculated, since 24,25 dihydroxy vitamin D was below the limit of quantification. He also had evidence of nephrocalcinosis on renal ultrasound. Evaluation of other causes of non-PTH mediated hypercalcemia included normal angio converting enzyme, PTHrP level, vitamin A level, SPEP and UPEP. Chest X-ray did not demonstrate any evidence of granulomatous disease. He has been managed conservatively for suspected 24-hydroxylase deficiency. He has been advised to limit calcium and vitamin D intake, as well as sun exposure, with close monitoring of his calcium levels. His calcium levels have ranged from 10.7-12.4 mg/dL and he has had one hospitalization in the setting of heart failure where his calcium levels improved with furosemide to 8.7-9.9 mg/dL. Conclusion: In patients with persistent non-PTH dependent hypercalcemia, 24-hydroxylase deficiency should be a differential diagnosis when other common causes are excluded.

SAT202 A Case Of Primary Hyperparathyroidism Secondary To Ectopic Intrathymic Parathyroid Adenoma

Abstract Disclosure: S. Pandiri: None. Introduction: Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia. Majority of cases are due to a single adenoma. In about 6-16% of cases, the parathyroid adenoma is in an ectopic location. Accurate preoperative imaging is key in localizing ectopic parathyroid adenomas. Clinical Case: 64 year old man with hypercalcemia was referred to endocrinology for further evaluation. His symptoms included fatigue, nausea, polydipsia and polyuria. There was no history of fractures, radiation therapy or family history of hypercalcemia. The patient’s past medical history is significant for nephrolithiasis, thyroid nodules and hypertension. He was started on Cinacalcet 30 mg, twice daily, by his primary care physician about 6 weeks prior to the initial visit. Physical exam was unremarkable. Lab studies were significant for elevated albumin-corrected calcium: 11.2 mg/dl (8.6-10.3 mg/dl), elevated PTH: 578.1 pg/ml (12-88 pg/ml), 25-OH vitamin D: 17 ng/ml (&amp;gt;30 ng/ml), phosphorus: 2 mg/dl (2.5-4.5 mg/dl) TSH: 0.54 mIU/L (0.40-4.50 mIU/L), 24 hr urine calcium: 429 mg (&amp;lt;250 mg/24 hr). The lab findings were consistent with hypercalcemia due to primary hyperparathyroidism. Neck Ultrasound showed bilateral thyroid nodules but no parathyroid adenoma. Tc-99m sestamibi scintigraphy was significant for 2.8 x 1.5 x 3.4 cm mass in the anterior mediastinum but did not show uptake in the neck. CT Neck showed a mass in the anterior mediastinum measuring 1.6 x 2.7 cm. Bone density was significant for osteopenia. He underwent robot assisted mediastinal mass excision two months after the initial evaluation. The pathology was significant for ectopic, intrathymic parathyroid adenoma, watery cell type with nuclear atypia, measuring 3.8 x 3.1 x 1.3 cm. Labs at the follow up visit showed normal albumin-corrected calcium of 8.6 mg/dl, improved PTH of 110.3 pg/ml. His symptoms improved significantly after surgery. Conclusion: This case demonstrates that preoperative localization of an ectopic parathyroid adenoma can prevent recurrent surgeries and persistent hypercalcemia. It is important for physicians to be aware of the various ectopic locations of parathyroid adenomas during the diagnostic workup of PHPT. Reference: Roy M, Mazeh H, Chen H, Sippel RS. Incidence and localization of ectopic parathyroid adenomas in previously unexplored patients. World J Surg. 2013 Jan;37(1):102-6. doi: 10.1007/s00268-012-1773-z. PMID: 22968537. Presentation: Saturday, June 17, 2023

THU461 Severe Hypercalcemia Associated With Perinatal Hypophosphatasia While Receiving Enzyme Replacement Therapy

Abstract Disclosure: M. Salama: None. P.J. Tebben: None. Introduction: Hypophosphatasia (HPP) is characterized by defective bone mineralization due to reduced function of tissue non-specific alkaline phosphatase (TNSALP) from pathogenic ALPL gene variants. Initial presentation varies according to the clinical phenotype. Hypercalcemia is more common in the perinatal and infantile forms and may be mitigated or prevented with enzyme replacement therapy asfotase alfa (AA). Here, we report a patient who developed severe hypercalcemia while receiving AA and describe our management strategy. Case: A now three-year-old girl with perinatal hypophosphatasia presented with severe hypercalcemia at 9 months of age. Her prenatal ultrasound was suggestive of a skeletal dysplasia. She was diagnosed with HPP shortly after birth and initiated AA on day two of life. She had normal calcium of 10.5 mg/dl at diagnosis. Phosphorus 9.3 mg/dl, total alkaline phosphatase &amp;lt;5 U/L, pyridoxal 5-phosphata (PLP) 974 mcg/L and phosphoethanolamine (PEA) 1084 nmoL/mg. Calcium dropped to 6.8 mg/dL after starting AA for which calcium supplementation was transiently utilized. At nine months of age, she developed severe hypercalcemia (15.8 mg/dl). Her phosphorus was 5.5 mg/dl, PLP 14 mcg/l and 25 hydroxyvitamin D 28 ng/ml. Parathyroid hormone and calcitriol were appropriately suppressed at &amp;lt;6.0 pg/ml and &amp;lt;8.0 pg/mL respectively. She was receiving 2 mg/kg of Asfotase three times weekly. Initial management included intravenous fluids and a reduction in dietary calcium intake by 50%. Within 2 days, calcium came down to upper normal for age at 11 mg/dL. AA dose was increased to 3 mg/kg three times weekly due to hypercalcemia and mildly worsening radiographs. Hypercalcemia recurred and initially responded to IV fluids and further dietary calcium reduction (low calcium formula (2.9 mg/ 5 fl oz)). Despite these measures, she required a third hospital admission when calcitonin 4 IU/kg every 12 hours was added to her restricted dietary calcium intake and AA therapy. On this regimen, her calcium normalized without recurrence of severe hypercalcemia. Over the subsequent eight months, calcium intake was slowly increased, and calcitonin tapered and discontinued with maintenance of calcium within the normal range. Conclusion: Hypercalcemia is common in infants with untreated, severe HPP and is likely mitigated for most when treated with AA. This case highlights the importance of monitoring calcium concentrations and intake in infants with HPP. Although calcitonin is generally not considered a long-term therapy for hypercalcemia, bisphosphonates may worsen the bone disease of HPP and should be avoided. This case demonstrates the utility of calcitonin therapy added to low calcium intake and maximal AA dosing to treat severe, persistent hypercalcemia in an infant with perinatal HPP. Presentation: Thursday, June 15, 2023

SAT250 A Case Of Hypercalcemia In Pregnancy - A Diagnostic And Management Challenge

Abstract Disclosure: W. Cheng: None. Y. Kuan: None. Hypercalcemia in pregnancy is rare and poses significant diagnostic and management challenges especially in a low resource setting. Although primary hyperparathyroidism (PHPT) is the main cause, physiological changes in calcium homeostasis make it difficult to distinguish from familial hypocalciuric hypercalcemia (FHH) unless genetic testing is done. Furthermore uncertainty exists on the safety of pharmacotherapy for hypercalcemia in pregnancy which if untreated, can be detrimental to both mother and child. Described herein a 17 year-old primigravida who presented at 32 weeks of gestation for asthma exacerbation precipitated by COVID-19 infection. She was incidentally found to have PTH-dependent hypercalcemia with albumin-corrected calcium 3.42 mmol/L [2.10-2.55] associated with raised intact parathyroid hormone (iPTH) 15 pmol/L [1.6 - 6.0] and deficient serum 25OH Vitamin D at 19.95 nmol/L [50-125]. She was given IV saline of 3-3.5L/day but to no avail as her serum calcium was persistently above 3 mmol/L with an episode of premature uterine contraction. Calcitonin was given in short courses and withheld once albumin-corrected calcium dropped below 3 mmol/L but rebound within three days. As bisphosphonates is contraindicated in pregnancy, we introduced cinacalcet, up to 75mg/day after discussion with the patient and her family. Meanwhile, investigations were done to ascertain underlying cause. Fractional urine calcium excretion ranged from 0.0068 (spot urine sample) to 0.0568 (24-hour urine sample). Ultrasound neck did not reveal enlarged parathyroid glands or an adenoma. Sestamibi scan was contraindicated in pregnancy. Genetic testing for FHH was too costly but all her first-degree relatives tested to have normocalcemia. Blood pressure remained normal throughout pregnancy. She was discharged with cinacalcet at calcium level of 2.7 mmol/L. However she defaulted follow-up and medications and presented at 36 weeks of gestation for preterm labour. She gave birth to a healthy, 2.46kg baby girl. The baby had neonatal jaundice but normal calcium level. Postpartum, the patient was asymptomatic despite persistent hypercalcemia 3.12 - 3.15nmol/L. As she was non-compliant to cinacalcet it was stopped and serum calcium did not worsen. Sestamibi scan is planned after she stops breastfeeding and a reassessment of the urine calcium once vitamin D is adequately replenished. She refused exploratory parathyroidectomy. She continued to be followed up at the endocrine clinic while her baby at primary care. Contraception is advised untill definitive diagnosis and treatment of hypercalcemia. This case illustrates the challenges in managing hypercalcemia in pregnancy and difficulty in distinguishing PHPT vs FHH without genetic testing. Presentation: Saturday, June 17, 2023

SAT199 Intrathyroidal Parathyroid Adenomas: A Case Series

Abstract Disclosure: B.K. Bowens: None. D. LaChance: None. M.K. Shakir: None. T.D. Hoang: None. Background: Primary hyperparathyroidism (PHPT) is a relatively common condition which affects 1-7 people per 1000. However, intrathyroidal parathyroid adenomas (ITPA) have a prevalence of 1.3% to 6.7%. In this case series, we report 3 cases of ITPA. Case 1: 66-year-old male with a history of PHTP without intervention at initial diagnosis presented to Endocrinology several years after initial diagnosis due to an incidental thyroid nodule on routine CT lung cancer screening. Parathyroid hormone (PTH) level found to be 109.3 from a previous level of 80 (ref 10-55pg/mL) in the setting of mild hypercalcemia and osteopenia. Initial bedside thyroid ultrasound was suggestive of a right ITPA. Parathyroid scan, formal thyroid US and CT gated scan revealed a 1.5cm parathyroid adenoma (PA) posterior to the right superior aspect of the thyroid gland. Fine Needle Aspiration (FNA) was completed with PTH washout of 399.40 pg/mL. Right superior parathyroidectomy confirmed ITPA due to an intrathyroidal parathyroid adenoma Case 2: 44-year-old female presented with 9 months of fatigue and was diagnosed with PHPT. Her PTH level was 167 with a serum calcium of 10.9 (ref 8.5-10.4 mg/dL). CT SPECT with tech-99M sestamibi was positive for a right parathyroid adenoma. Explorative surgery did not localize parathyroid adenoma. Thyroid ultrasound revealed a 9mm hypoechoic lesion in the right inferior lobe with polar artery. FNA of this lesion was completed with PTH washout of 4737 pg/mL. Right hemi-thyroidectomy was completed with resolution of PHTP. Case 3: 54-year-old male with history of PHPT and carcinoma of the right kidney s/p nephrectomy presented with persistent hypercalcemia. Serum calcium of 10.2-11.0 mg/dL and PTH of 160-186 pg/mL. Thyroid US showed a 1.1cm hyperechoic, cystic nodule in the left inferior thyroid lobe. Sestamibi was consistent with ITPA. FNA of left thyroid mass with PTH washout of 2602 pg/mL. Parathyroidectomy with left thyroid lobectomy was completed with resolution of hypercalcemia. Discussion: PHPT is a common endocrinopathy with 85% of cases due to PAs, 15% due to parathyroid hyperplasia, and &amp;lt;1% due to carcinoma. ITPAs have an incidence of 1.3% to 6.7% and are due to improper embryologic migration. Sestamibi parathyroid scan allows for localization of PA and for minimally invasive procedures. Other imaging modalities include SPECT, US, SPECT-CT, and MRI. PTH washout with more than 101 pg/mL confirms the presence of parathyroid tissue or adenoma. Conclusion: This is a rare presentation of a common endocrinopathy. These patients were noted to have PHTP. Initial exploratory neck dissections did not localize. FNA and US were able to confirm IPTAs and hemi-thyroidectomy was needed for definitive management with resolution of PHTP. Presentation: Saturday, June 17, 2023

SAT246 Ectopic (Penile) Calcification in 1, 25 Vitamin D Induced Hypercalcemia

Abstract Disclosure: J. Berquist: None. D.S. Reddy: None. A 60-year-old male with a history of well controlled type 2 diabetes and HTN presented with acute renal failure (initial creatinine 19.9 mg/dL, GFR 11). Kidney biopsy during admission was consistent with acute tubular necrosis and mild diabetic nephropathy. Serum calcium was normal at that time. He received temporary dialysis and eventually discharged home with improved (though still elevated) creatinine. On follow up labs a month later, he was noted to have high serum calcium. He was temporarily lost to follow up and was readmitted four months later due to persistent severe hypercalcemia. Peak serum calcium on his new admission was 13.2 mg/dL. Phosphorus level three months prior was 5.9 mg/dL, though had now improved to 2.7 mg/dL. Other labs this admission include creatinine 2.54 and GFR 33 (which was consistent with previous months), PTH 11 pg/mL, 25-OH Vitamin D 10 ng/mL, 1,25-Dihydroxy Vitamin D elevated at 84.8 pg/mL and magnesium low at 1.5 mg/dL. SPEP and UPEP were both negative and PTHrP was not measured. Kappa/Lamda free light chain ratio was mildly elevated at 1.77 (0.26-1.65). QuantiFERON Gold, HIV, Beta-2 microglobulin, ANA, and flow cytometry were negative. He received calcitonin x 2, IVF, zoledronic acid, and denosumab (three days later), which improved his calcium to 11.5 by discharge 11 days later. He underwent a CT Chest/Abdomen/Pelvis, T spine, and L spine that were remarkable for multiple bilateral partially calcified pulmonary nodules and hepatic steatosis with splenomegaly. PET CT showed 20 hypermetabolic osseous lesions throughout axial skeleton, multiple pulmonary, liver, and splenic lesions and lymphadenopathy in the head, neck, chest, abdomen. There was also diffuse calcification of the penile corpora. Pathology via biopsies of a retroperitoneal lymph node as well as bone marrow showed non-caseating granulomas. Lastly, 1-2 months ago, he noticed pain and hardening of his penis. On exam, there is a deep firmness with palpation and distal penile tenderness. There are no cutaneous lesions on the penis or anywhere else on the skin. Calciphylaxis was a consideration, but isolated penile involvement is rare. Additionally, it is rare to develop calciphylaxis without end stage renal disease. A review of the literature showed many cases of penile calciphylaxis, though none were without cutaneous involvement. Sarcoidosis of the penis is also very rare and cases in the literature cite either a cutaneous or intraurethral lesion. This case appears unique in the findings of penile calcification palpable on exam and visible on imaging, without any cutaneous manifestations, in the setting of previous though recovered acute renal failure and 1, 25 Vitamin D-mediated hypercalcemia in sarcoidosis. Presentation: Saturday, June 17, 2023