Low 25-OH Research Articles

7752 Navigating Hypercalcemia in Pregnancy: A Case Report

Abstract Disclosure: J. Gabbay: None. S. Steinmetz-Wood: None. Introduction: Primary hyperparathyroidism (PHPT) in pregnancy is rare but presents many diagnostic and therapeutic challenges. Prompt diagnosis and treatment are important due to associated maternal and fetal risks, however evaluation of urine calcium to differentiate from Familial Hypocalciuric Hypercalcemia (FHH) becomes less reliable due to physiologic changes in pregnancy, sestamibi scans. CT scans require radiation, parathyroidectomy introduces surgical risk, and medical alternatives like bisphosphonates can interfere with fetal skeletal development. Clinical Case: A 24-year-old woman who presented to the emergency room for progressive nausea and abdominal pain was found to be pregnant with elevated serum calculated calcium to 11.4 mg/dL (2.84 mmol/L). She had a history of renal stones, longstanding hypercalcemia of unknown etiology and a remote family history of parathyroid “issues”. Follow up laboratory work showed a PTH of 75.8 pg/ml (8.04 pmol/L) with an elevated 24-hour urine calcium and a low 25OH vitamin D. Given her history of kidney stones and overt symptoms it was our clinical judgement that this was not a case of FHH. She was started on IV fluids twice weekly. After an unrevealing neck ultrasound, an MRI neck showed a 7 mm lesion along the posterior aspect of the left thyroid suggestive of a parathyroid adenoma. Sestamibi scan was avoided due to the risks of radiation to the developing fetus. Given the presumptive diagnosis of parathyroid adenoma, the lack of response to aggressive hydration, and the maternal and fetal risks of hypercalcemia during pregnancy, parathyroidectomy was pursued in her second trimester. Intra-operative inspection and biopsy showed the lesion to be only a lymph node. She underwent 4-gland exploration and the left inferior parathyroid gland, which appeared abnormal and enlarged, was removed. The intra-operative PTH dropped only from 98 to 80 (10.4 to 8.5 pmol/L). She otherwise had an unremarkable hospital course and at discharge her calcium was normal with an undetectable PTH, which can be an expected finding in pregnancy. On follow up she was feeling well with sustained normocalcemia and low PTH levels. Given the age at which her hyperparathyroidism started, she was referred to genetics for further evaluation. Clinical Lessons/Conclusion: There were significant biochemical and radiological limitations in the management of this case. Normally an inappropriately normal PTH with elevated serum calcium and normal urine calcium/creatinine clearance ratio confirms the diagnosis of PHPT, however in pregnancy it should be noted that FHH could also present with normal or elevated urine calcium due to absorptive hypercalciuria in pregnancy. Additional clinical history and reasoning was needed for management as well as a skilled surgeon, where preoperative localization was limited and was not ultimately helpful. Presentation: 6/2/2024

The impact of vitamin D status on lipid profiles and atherogenic dyslipidemia markers in children and adolescents with obesity

Background and aimAdequate serum vitamin D levels correlate with a more favorable lipid profile compared to deficient levels. Despite the well-established prevalence of vitamin D deficiency in children with obesity, studies investigating its influence on lipid profiles in this population are scarce. We explored the impact of vitamin D status on lipid profiles and markers of atherogenic dyslipidemia in a cohort of children and adolescents with obesity. Methods and resultsA total of 271 Caucasian children and adolescents with overweight/obesity and a control group of 54 pediatric patients with normal weight. All participants underwent outpatient visits for the assessment of clinical parameters and venous blood collection for biochemical analysis such as triglycerides (TG)/HDL-C ratio, LDL-C/HDL-C ratio, atherogenic index of plasma AIP), vitamin D level.Individuals with obesity displayed severe vitamin D deficiency (25-OH-D ≤10 ng/ml) at a higher frequency compared to those with normal weight (p = 0.03). In patients with overweight/obesity and low 25-OH-D levels show higher values of glycemia (p = 0.001), insulin resistance (HOMA-IR and TRYG p < 0.001), TG (p < 0.001), TG/HDL-C (p = 0.001), AIP (p < 0.001), SBP (p = 0.01), and DBP (p = 0.04). In normal-weight individuals with low 25-OH- D levels an increased values of glycemia (p = 0.01), insulin resistance (HOMA-IR p = 0.01 and TRYG p = 0.002), TG (p = 0.01), TG/HDL-C (p = 0.02), AIP (p = 0.01). A direct correlation between 25-OH-D levels and metabolic parameters is observed. ConclusionsA correlation between vitamin D levels and the lipid/atherosclerotic profile was recorded. Vitamin D deficiency may represent a preventable and easily treatable cardiometabolic risk factor, emphasizing the importance of early intervention and preventive measures.

Abstract 2565: Vitamin D deficiency and outcomes in prostate cancer patients: A real-world database

Abstract Introduction: Vitamin D is essential for many bodily functions, including bone health and the prevention of osteoporosis and rickets. In recent years, the importance of vitamin D metabolism in immune system regulation and cancer prevention has been studied with increased focus. With the advent of cancer immunotherapies this has become more important. Multiple recent publications document that vitamin D deficiency is prevalent in cancer patients. This has also been observed specifically in prostate cancer patients, with a high percentage of these deficient patients being of African- American ancestry. It has been theorized that high levels of vitamin D deficiency among African American prostate cancer patients could contribute to worse cancer outcomes and increased health disparities. However, routine vitamin D testing has not been commonly performed in the oncologic community. We hypothesized that deficient levels of vitamin D could lead to inferior prostate cancer outcomes in men with a wide range of ethnic and socio-economic backgrounds. In this project we recorded vitamin D levels in prostate cancer patients at a large community oncology group and evaluated them by stage, pathologic data, survival, race/ethnicity, and other clinical features. Methods: This study is a retrospective, observational study of the data from the electronic medical records of patients with prostate cancer who received vitamin D level testing at Florida Cancer Specialists &amp; Research Institute from 2008- 2023, throughout the state of Florida. All data used in this study will constitute secondary data, it will have been collected originally for clinical use in the general oncology practice setting. No date parameters or patient limits will be applied to this study, and all eligible patients are included. Results: 451 patients with prostate cancer had determination of vitamin D levels, out of a total of 27,772 prostate cancer patients in the database. 38% of the prostate cancer patients analyzed had low 25-OH vitamin D levels (&amp;lt;32 ng/ml). Patients with low vitamin D levels had an average Gleason score of 7.46. Patients with low vitamin D levels who died had an average survival of 144 months. Patients with low vitamin D levels who presented with localized disease had a 35% chance of eventually developing castrate-resistant disease. 45% of the low vitamin D group developed metastatic disease during their course of treatment. Further comparisons of vitamin D levels with pathologic data, survival/longevity, race/ethnicity, and clinical course will be evaluated and presented. Citation Format: Lowell L. Hart, James Reeves, Stacey Garofalo, William Amick. Vitamin D deficiency and outcomes in prostate cancer patients: A real-world database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2565.

Serum 25-Hydroxyvitamin D is Associated With Bone Microarchitecture and Strength in a Multiracial Cohort of Young Adults.

To determine whether 25-hydroxyvitamin D (25-OH D) levels are associated with bone outcomes in a multiracial cohort of young adults. This cross-sectional study included 165 participants (83 men, 82 women, 18-30 years of age) who self-identified as Asian, Black, or White. We measured bone microarchitecture and strength of the distal radius and tibia using high-resolution peripheral quantitative computed tomography. We used linear regression to estimate the association between 25-OH D (ng/mL) and bone measurements, adjusting for race, sex, age, weight, height, calcium intake, physical activity, and season. A total of 43.6% of participants were 25-OH D deficient (<20 ng/mL) with greater prevalence in Asian (38.9%) and Black (43.1%) compared with White (18.0%) participants (P < 0.001). At the distal radius, 25-OH D was positively associated with cortical area, trabecular density, cortical thickness, cortical porosity, and failure load (P < 0.05 for all). At the distal tibia, higher 25-OH D was associated with higher cortical area, trabecular density, trabecular number, failure load, and lower trabecular separation and cortical density (P < 0.05 for all). After multivariable adjustment, those with 25-OH D deficiency had generally worse bone microarchitecture than those with 25-OH D sufficiency. Black individuals had largely more favorable bone outcomes than Asian and White individuals, despite higher prevalence of 25-OH D deficiency. We found a high prevalence of 25-OH D deficiency in a multiracial cohort of young adults. Lower 25-OH D was associated with worse bone outcomes at the distal radius and tibia at the time of peak bone mass, warranting further attention to vitamin D status in young adults.

25-Hydroxylase vitamin D deficiency in 27 Saudi Arabian subjects: a clinical and molecular report on CYP2R1 mutations.

Vitamin D deficiency remains a major cause of rickets worldwide. Nutritional factors are the major cause and less commonly, inheritance causes. Recently, CYP2R1 has been reported as a major factor for 25-hydroxylation contributing to the inherited forms of vitamin D deficiency. We conducted a prospective cohort study at King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia, to review cases with 25-hydroxylase deficiency and describe their clinical, biochemical, and molecular genetic features. We analyzed 27 patients from nine different families who presented with low 25-OH vitamin D and not responding to usual treatment. Genetic testing identified two mutations: c.367+1G>A (12/27 patients) and c.768dupT (15/27 patients), where 18 patients were homozygous for their identified mutation and 9 patients were heterozygous. Both groups had similar clinical manifestations ranging in severity, but none of the patients with the heterozygous mutation had hypocalcemic manifestations. Thirteen out of 18 homozygous patients and all the heterozygous patients responded to high doses of vitamin D treatment, but they regressed after decreasing the dose, requiring lifelong therapy. Five out of 18 homozygous patients required calcitriol to improve their biochemical data, whereas none of the heterozygous patients and patients who carried the c.367+1G>A mutation required calcitriol treatment. To date, this is the largest cohort series analyzing CYP2R1-related 25-hydroxylase deficiency worldwide, supporting its major role in 25-hydroxylation of vitamin D. It is suggested that a higher percentage of CYP2R1 mutations might be found in the Saudi population. We believe that our study will help in the diagnosis, treatment, and prevention of similar cases in the future.

Neuroendocrine Tumor Associated Severe Hypercalcemia of Pregnancy

Background: Literature of pregnancy associated neuroendocrine tumors is limited. We report an unusual case of severe hypercalcemia of pregnancy secondary to a neuroendocrine tumor. Clinical Case: A 43-year-old lady presented to our center in her 28th week of pregnancy with complaints of worsening nausea and epigastric pain over few days. She had developed gestational diabetes at 24 weeks for which she was taking insulin. On examination she was tachycardic, mildly confused with a distended abdomen. Serum chemistries revealed serum calcium of 15.9 mg/dL, elevated PTHrP of 64 pg/mL and low PTH of 2 pg/mL consistent with PTHrP mediated hypercalcemia. She had low 25-OH- vitamin D (15 ng/mL) with normal 1–25- OH vitamin D. An abdominal ultrasound showed a solid, heterogenous, soft tissue mass interposed between the left kidney and spleen measuring 11 x 9 x 12 cm. This was confirmed on Abdominal MRI, which also showed multiple large hepatic metastasis. Tumor biopsy with pathology confirmed well differentiated neuroendocrine tumor of gastric or pancreatic origin. Her hypercalcemia was initially treated with infusions of IV normal saline, furosemide diuresis, calcitonin 200 units SC 12 hourly and a single dose of dexamethasone 10 mg IV. Calcitonin and diuresis were discontinued after 5 days once calcium improved to 10 mg/dL. Oncology deferred treatment of the tumor until she had delivered. Patient was discharged with serum calcium of 10.7 mg/dL and counselled for plenty of oral hydration. She was readmitted with nausea, vomiting and serum calcium level of 15.1 mg/dL at 32 weeks gestation. She was again treated with a similar regimen of IV saline and furosemide along with calcitonin 480 units SC 12 hourly and prednisone 10 mg daily, but calcium levels remained high (13.6 mg/dL) despite aggressive treatment. Labor was induced at 33 weeks and she delivered a healthy boy through an uncomplicated vaginal delivery. Remarkably, her serum calcium normalized on day two post-partum and remained so throughout. Her serum calcium remains normal at 2 months post-partum (10.3 mg/dL, PTHrP 36 pg/mL, PTH 7 pg/mL) despite the presence of unresected tumor. She is planned to undergo surgical resection of the tumor and hepatic metastatic lesions. Conclusion: Clinicians must be aware that severe hypercalcemia may be the presenting manifestation of neuroendocrine tumors in pregnancy. In this case, we hypothesize a potential placental contribution to her elevated PThrP given resolution of hypercalcemia post-delivery. However, persistent elevated PThrP post-partum may also be physiologic or related to the abdominal tumor. A placental histopathological could be performed due to logistic reasons.

Ectopic Intact PTH Secretion Causing Humoral Hypercalcemia of Malignancy

Background: Tumor-generated ectopic intact PTH is difficult to diagnose and should be suspected in patients with apparent primary hyperparathyroidism but with normal parathyroid glands.Clinical Case: A 72-year-old man presented with symptoms of hypercalcemia including generalized weakness, polyuria, and polydipsia. Initial labs were consistent with primary hyperparathyroidism: calcium 12.1 mg/dL (n 8.6–10.3 mg/dL, albumin-corrected 12.5 mg/dL), intact PTH (iPTH) 115.6 pg/mL (n 10–65 pg/mL), low normal 25-OH vitamin D (25 ng/mL, n 25–100 ng/mL), and relatively high normal 1,25 dihydroxyvitamin D (52 pg/mL, n 18–78 pg/mL). 24-hour urine calcium was 381 mg/day (n 100–300 mg/day) and PTHrP was 1.6 pmol/L (n <4.2 pmol/L). Neck ultrasound demonstrated a 0.5 x 1 cm hypoechoic mass near right thyroid inferior pole, though sestamibi SPECT/CT scan did not reveal scintographic evidence of a parathyroid adenoma. He underwent subtotal parathyroidectomy with largest excised gland weighing 0.262 grams. The left inferior parathyroid gland appeared normal intraoperatively, thus was clipped and left in place. PTH decreased from 194 pg/mL to 98 pg/mL postoperatively. Pathological examination revealed three normocellular parathyroid glands with enlargement of only the right superior gland. Venous sampling of the parathyroid vasculature failed to identify the source of autonomous iPTH post operatively. Due to refractory hypercalcemia, cinacalcet was initiated. However, hypercalcemia as high as 12.6 mg/dl and hyperparathyroidism to 672 pg/mL persisted despite dose escalation. He eventually received pamidronate with subsequent transition to denosumab due to declining renal function. A 68Ga DOTATATE scan was performed to locate occult ectopic parathyroid, which reported multiple foci of presumed somatostatin receptor expression involving the liver and intra-abdominal lymph nodes without significant uptake in the neck concerning for metastatic disease. Liver lesion biopsy was consistent with pancreato-biliary adenocarcinoma. Surprisingly, the biopsy was negative for iPTH and neuroendocrine tumor markers on staining/immunohistochemistry. Given his poor prognosis and multiple comorbidities, the patient opted not to pursue any further workup or therapy for his malignancy.Conclusion: Occult malignancy should be suspected for a patient with persistent hyperparathyroidism after parathyroidectomy. Treatment of the malignancy may lead to an improvement in hypercalcemia and iPTH levels. Employment of iPTH mRNA testing or intra-abdominal venous sampling to prove ectopic iPTH secretion would be ideal, as iPTH staining could be falsely negative. Further testing was not completed as the patient declined further evaluation.

Hypercalcemia: A Metabolic Complication of an AIDS-Defining Illness

Abstract Background: Hypercalcemia may result from the activation of macrophages in granulomatous diseases with increased production of 1,25 dihydroxyvitamin D/calcitriol. Its occurrence in patients with human immunodeficiency virus-1 (HIV-1) infection may be atypical and signal major changes in immune status. We report on a patient with acquired immunodeficiency syndrome (AIDS) presenting with new-onset hypercalcemia after months of treatment for mycobacterium avium complex (MAC) infection and normal calcitriol levels. Clinical Case: A 37-year-old man on treatment for HIV-1 and disseminated MAC infection presented to the hospital 6 months after initial diagnosis with worsening headache, cough, and abdominal pain. On arrival he was afebrile and without palpable lymphadenopathy. He was found to have a high serum calcium (13.4 mg/dL, n 8.6–10.6 mg/dL) and acute kidney injury (AKI) (creatinine 4 mg/dL, n 0.6–1.25 mg/dL). His CD4 count had increased from 24 at time of diagnosis to 162 cells/μL (n 410–1,590 cells/μL); his HIV viral load was undetectable. Workup for hypercalcemia revealed an elevated phosphorus (5.2 mg/dL, n 2.5–5.0 mg/dL), low 25-OH vitamin D level (&amp;lt;13 ng/mL, n 25–80 ng/dL), low PTH (4.8 pg/mL, n 12–88 pg/mL), and calcitriol level of 31.4 pg/mL, n 19.9–73.3 pg/mL). Additional tests, including serum electrophoresis, thyroid stimulating hormone, and parathyroid hormone-related peptide levels, were unremarkable. The patient was diagnosed with hypercalcemia secondary to dysregulated calcitriol production in the setting of disseminated MAC and possible immune reconstitution. Hypercalcemia resolved with hydration and prednisone 20 mg daily. Patient was discharged with an 8-day prednisone taper, but readmitted to the hospital 3 weeks later with recurrent hypercalcemia (13.8 mg/dL) and AKI. Urine calcium was found to be elevated (484 mg/24 hours, n100-300 mg/24 hours) and repeat calcitriol was 53.6 pg/ml. Patient was restarted on prednisone 40 mg daily with normalization of calcium within 5 days (calcium 10.3 mg/dL). Conclusion: Hypercalcemia due to increased calcitriol production in the setting of MAC infection, an AIDS-defining illness, may occur months after initiation of effective antibiotic and antiviral therapy and could represent a manifestation of immune reconstitution. The deleterious effects of excess calcitriol may be present even in patients with chronic vitamin D deficiency and a calcitriol level that inappropriately remains within the normal range.

Type 1 Familial Hypocalciuric Hypercalcemia Caused by p.M74L Variant in the Calcium Sensing Receptor (CASR) Gene

Background: Familial hypocalciuric hypercalcemia (FHH) is a rare cause of hypercalcemia caused by inactivating mutations in specific regions of chromosome 3 and 19. Most cases are due to inactivating mutations in the Calcium sensing receptor (CASR) which is encoded by the gene located on the long arm of chromosome 3 (3q 21.1). FHH is characterized by hypercalcemia, an inappropriately normal to elevated serum PTH level, hypocalciuria, and a family history of hypercalcemia. Several mutations in the CASR gene have been described in literature. However, the p.M74L variant in the CASR gene has an extremely low frequency of occurrence in population databases such as the genome aggregation database (gnomAD)1. Clinical Case: A 67 years old woman with a past medical history of hypertension, dyslipidemia, type 2 diabetes mellitus, and chronic kidney disease presented for an evaluation of a long standing history of hypercalcemia. Patient reported non-specific symptoms including chronic fatigue and arthralgias. She denied a history of renal stone or chronic use of lithium. She distinctly recalled that her mother and maternal grandmother had high blood calcium levels. Review of old records showed an elevated corrected calcium level of 11.3 mg/dl, which was elevated since at least October 2013 (no medical records prior to October 2013 were available) which persisted to-date. Patient underwent work-up which revealed a high corrected serum calcium of 10.4 (8.6–10.0mg/dl), high serum PTH of 101 (15–65 pg/ml), an extremely low 24hr urine calcium of <9.2 (100–300 mg/24hr) with corresponding urine volume of 1150 cc and urine creatinine of 1392 (740–1570 mg/24hr), low 25-OH vitamin D of 20.6 (30–100 ng/ml), and a low eGFR of 47 ml/m/1.73. SPECT parathyroid gland was negative. FHH was suspected and subsequent CASR gene analysis panel showed a heterogenous DNA sequence change at nucleotide position c.220 in exon 3 of the CASR gene (c.220A>C). This nucleotide change results in an amino acid change from methionine (M) to leucine (L) at position 74 in the CASR protein (p.M74L). Conclusion: We report a case of a p.M74L variant in the CASR gene which is an extremely uncommon mutation in the CASR gene1. Our case supports the current limited evidence that p.M74L variant in the CASR gene can cause FHH.

Paget’s Disease of Bone Affecting Site With Orthopedic Hardware

Introduction: Paget’s disease of bone is a focal disorder of accelerated bone remodeling which leads to bone hypertrophy, cortical expansion and abnormal bone architecture. Either a single bone (monostotic) or multiple bones (polyostotic) can be affected. Although it has been suggested to be caused by a chronic slow viral infection of the bone, a cause and effect relationship has not been clearly established. Therefore, the etiology of Paget’s disease remains an uncertain and controversial topic of discussion. Case Description: A 62-year-old African American male with a past medical history of a left tibial fracture presented with worsening left leg pain for the past 6 months. He denied any recent traumatic events, falls or strenuous physical activity. Since the pain started, his ambulation had been significantly affected requiring the use of a cane for gait stability. His left tibial fracture occurred over 20 years ago after landing on another person’s foot while playing basketball. It was surgically treated with intramedullary nailing and metal rod insertion into the canal of the tibia. Since then, he remained an active person with no physical limitations or ailments until the recent developments that brought him to clinic. A left leg CT-Scan ordered for evaluation of the tibial hardware revealed cortical thickening, marrow expansion and coarse trabeculae throughout the majority of the tibia consistent with Paget’s disease. The hardware was intact with no peri-hardware lucency to suggest loosening or infection. His laboratory workup showed a normal alkaline phosphatase level (94 U/L; normal range 40 - 115 U/L) and low 25-OH Vitamin D level of 14. A Radionuclide Bone Scan done for evaluation of location and extent of bone disease resulted in diffusely abnormal uptake present in the left tibia with no other locations of suspicious uptake. After his 25-OH Vitamin D levels were replenished, a dose of Zoledronic acid IV infusion was given with significant improvement of pain several months after. Discussion: Paget’s disease of bone is the second most common bone disease after osteoporosis. Affected skeletal sites develop a disorganized mosaic of woven and lamellar bone more susceptible to deformities and fractures than normal bone. It is often asymptomatic, but classical features include bone pain experienced either at rest or with motion, cutaneous erythema and warmth. The goal of medical therapy is to relieve symptoms and to prevent future complications with high potency bisphosphonates. Although it is well known that Paget’s disease increase the risk of fractures, this case brings up an interesting take about the possibility of fractures managed with hardware placement increasing the risk of Paget’s disease in the involved site.

Associations between second to fourth digit ratio, cortisol, vitamin D, and body composition among Polish children

Associations between body characteristics (body composition: fat mass, muscle mass, cell, and water mass as well as body proportion—BMI), the 2D:4D digit ratio, and the concentrations of cortisol and vitamin (25-OH)D among Polish children have not been studied before. A total of 133 (73 girls and 60 boys) healthy Polish children aged 7–11 years were examined. The investigation was divided into three parts: measuring (the length of the second and fourth fingers in both hands, body composition, and body height and mass), questionnaires (socioeconomic status), and laboratory investigations (25-OH vitamin D and cortisol concentrations in saliva measured with ELISA methods). Boys with digit ratios below 1 had lower vitamin D concentration than those with digit ratios equal to or higher than 1 (Z = − 2.33; p = 0.019). Only boys with the male-typical pattern of 2D:4D digit ratio tended to have a lower 25-OH vitamin D concentration in saliva. Thus, it might indicate an effect of prenatal programming on the concentrations of steroid hormones in later life. Neither vitamin D, 2D:4D digit ratio nor the cortisol level was associated with the body components or proportions. More studies are needed to evaluate the molecular and genetic background of this phenomenon.

Low serum 25-OH vitamin D levels are associated with increased D/P creatinine ratio in peritoneal dialysis patients

Low 25-OH vitamin D levels have been linked to peritonitis and cardiovascular mortality in peritoneal dialysis (PD) patients. In this study we aimed to investigate the association of 25-OH vitamin D levels with peritoneal membrane characteristics in chronic PD patients. Consecutive 103 PD patients were enrolled in this retrospective study. Peritoneal dialysate to plasma (D/P) creatinine increase more than 0.1 with time were accepted as significant according Roc curve analysis. Patients with and without an increase in the D/P creatinine ratio of 0.1 were classified as Group 1 and Group 2, respectively. The relationship between baseline 25-OH vitamin D and peritoneal membrane characteristics were investigated. Mean age of the patients was 53.4±14.9 years and duration of PD was 72.1±50.3 months. There were thirty (29.1%) patients in Group 1. The duration of PD [73.5 (52.3-133.8) vs 49.0 (33.5-94.0) months, p:0.008]; hemoglobin [11.4 (10.4-12.2) vs. 10.2 (9.4-11.0) g/dL, p:0.001]and PTH [500.5 (254.5-748.3) vs 329.0 (205.0-549.5)ng/mL, p:0.047] levels were significantly higher in Group 1, whereas 25-OH vitamin D levels [5.0 (3.0-9.3) vs 7.8 (4.5-11.1)μg/L, p:0.027] and CRP [4.0 (3.0-7.2) vs. 8.0 (3.0-13.5)mg/L, p:0.028] were significantly lower. Multivariate analysis revealed duration of PD [Exp(B):1.012 (95%CI:1.001-1.022), p:0.028]; hemoglobin [Exp(B):1.756 (95%CI:1.199-2.571), p:0.004]; C-reactive protein (CRP) [Exp(B):0.882 (95%CI:0.789-0.985), p:0.026] and 25-OH vitamin D [Exp(B):0.853 (95%CI:0.754-0.965), p:0.012] were independent predictors of an increase in D/P creatinine ratio in PD patients. Increased D/P creatinine ratio was negatively correlated with 25-OH vitamin D level (r: -0.217, p:0.028). Lower levels of initial 25-OH vitamin D were associated with an increase in D/P creatinine ratio over-time.

Relationship between microalbuminuria and metabolic parameters in a normotensive population with obesity

Aim: Today, the second-most common cause of preventable death after smoking is obesity. Microalbuminuria is defined as an albumin to creatinine ratio (ACR) of more than 30 mg per gram of creatinine. Obesity increases microalbuminuria by affecting the kidneys.Methods: This study was carried out by retrospectively examining the files of obese [Body mass index (BMI) ≥30 kg/m2)] individuals between the ages of 18 and 65 with spot microalbuminuria test in urine who admitted to the obesity outpatient clinic of a tertiary hospital between January 2013 and June 2015. Four hundred ninety subjects were included in the study. The physical parameters, blood and urine tests of the subjects included in the study at the time of first admission to the obesity clinic were examined.Results: Microalbuminuria was positive in 5.7 % of the participants. The glycated hemoglobin (HbA1c) and uric acid levels for subjects in the microalbuminuria-positive group were higher than in the levels of subjects in the microalbuminuria-negative group [5.6 (5.8-5.5) vs 5.5 (5.7-5.2); P=0.012 and 5.2 (6-4.5) vs 4.7 (5.5-4.2); P=0.038, respectively]. In microalbuminuria-negative group, 25-hydroxyvitamin D3 (25-OH D3) levels were higher than in the microalbuminuria-positive group [12 (18-7.1) vs 8.4 (12.9-6.9); P=0.032]. Urine albumin to creatinine ratio was positively associated with BMI, fasting insulin (FI), Homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides (TG) and c-reactive protein (CRP).Conclusion: Obesity increases microalbuminuria by affecting the kidneys. Microalbuminuria is associated with insulin resistance, dyslipidemia and low 25-OH D3. Microalbuminuria must be checked in obese individuals. The prevalence of obesity should be reduced for a healthier life.

Low 25-OH vitamin D level are associated with increased postoperative acute kidney injury, broch pleural fistula after lung transplantation

Background: Vitamin D (Vit D) deficiency is found in over two-thirds of lung transplantation (LT) candidates, which is greater than in general population. In addition to bone metabolism, low serum level of 25-hydroxyvitamin D[25(OH)D] is known to be associat ed with higher incidence of infections, cancer, and cardiovascular disease. So, it is important to investigate association between Vit D level and post LT complications. Methods: In this single-center study, we reviewed 237 LT patients from January 2013 to July 2019 at Severance Hospital, Seoul, Korea. Thirty-nine patients were excluded due to missed level of preoperative Vit D. Enrolled patients were divided into Vit D defi ciency group (range, 0-10 ng/mL), Vit D insufficiency (range, 10-30 ng/mL), and Vit D sufficiency group (>30 ng/mL). Analysis of variance and chi-square tests were used for comparing variables. Results: Forty-nine patients (24.7%) were Vit D deficiency, 128 patients (64.6%) were Vit D insufficiency, and 21 patients (10.6%) were Vit D sufficiency. There were no significant differences between three groups with respect to age, sex, comorbidities, and primary lung disease. Low Vit D level was associated higher occurrence of postoperative acute kidney injury (AKI; deficiency vs. insufficiency vs. sufficiency, 10 [22.2] vs. 11 [9.5] vs. 1 [5.0]; P<0.05). Prevalence of broncho pleura fistula was higher in Vit D sufficiency group: deficiency vs. insufficiency vs. sufficiency, 0 (0.0) vs. 14 (10.9) vs. 0 (0.0); P=0.016. We further evaluate postop erative broch pleural fistula (BPF) in Vit D increase and Vit D decrease group within 6-month follow-up, and Vit D decrease group show high prevalence of BPF: decrease vs. increase, 9 (12.3) vs. 1 (1.1); P=0.002. Low Vit D level was also associated with post operative anxiety, but it was not statically meaning. Conclusions: Low 25-OH Vit D level is associated with increased incidence of post LT complications such as AKI, BPF, and anxi ety. Also, Vit D decrease during postoperative period showed higher incidence of BPF.

Vitamin D deficiency in children with bronchial asthma in southern Jordan: a cross-sectional study.

ObjectivesTo assess serum 25-hydroxycholecalciferol (25-OH vitamin D) levels in Jordanian children with bronchial asthma, and to examine correlations between 25-OH vitamin D levels and asthma severity and control.MethodsA cross-sectional study was conducted at the Paediatric Chest Clinic, Al-Karak Governmental Hospital, Southern Jordan, between May 2015 and February 2016. Serum 25-hydroxyvitamin D level was determined in children aged 1–14 years diagnosed with bronchial asthma (6–14 years) or recurrent wheezing episodes (<6 years). Asthma severity was determined based on the Global Initiative for Asthma assessment, the Asthma Control Test, and the Childhood Asthma Control Test. Demographic and clinical characteristics were compared between patients with low and normal 25-OH vitamin D levels, and correlations between asthma severity and 25-OH vitamin D level were assessed.ResultsOut of 98 included children, 25-OH vitamin D levels were deficient and insufficient in 41 (41.8%) and 34 (34.7%) children, respectively. Only 23 (23.5%) had sufficient 25-OH vitamin D levels. A significant correlation was found between severity of asthma symptoms and 25-OH vitamin D deficiency.Conclusion25-OH vitamin D deficiency is highly prevalent in Jordanian children with bronchial asthma and correlates significantly with asthma severity.

Vitamin D Insufficiency Reduces Grip Strength, Grip Endurance and Increases Frailty in Aged C57Bl/6J Mice.

Low 25-OH serum vitamin D (VitD) is pervasive in older adults and linked to functional decline and progression of frailty. We have previously shown that chronic VitD insufficiency in “middle-aged” mice results in impaired anaerobic exercise capacity, decreased lean mass, and increased adiposity. Here, we examine if VitD insufficiency results in similar deficits and greater frailty progression in old-aged (24 to 28 months of age) mice. Similar to what we report in younger mice, older mice exhibit a rapid and sustained response in serum 25-OH VitD levels to differential supplementation, including insufficient (125 IU/kg chow), sufficient (1000 IU/kg chow), and hypersufficient (8000 IU/kg chow) groups. During the 4-month time course, mice were assessed for body composition (DEXA), physical performance, and frailty using a Fried physical phenotype-based assessment tool. The 125 IU mice exhibited worse grip strength (p = 0.002) and inverted grip hang time (p = 0.003) at endpoint and the 8000 IU mice transiently displayed greater rotarod performance after 3 months (p = 0.012), yet other aspects including treadmill performance and gait speed were unaffected. However, 125 and 1000 IU mice exhibited greater frailty compared to baseline (p = 0.001 and p = 0.038, respectively), whereas 8000 IU mice did not (p = 0.341). These data indicate targeting higher serum 25-OH vitamin D levels may attenuate frailty progression during aging.

Low 25OH Vitamin D Blood Levels Are Independently Associated With Higher Amyotrophic Lateral Sclerosis Severity Scores: Results From a Prospective Study.

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive degeneration of upper and lower motor neurons. Prognosis is highly variable, ranging from few months to more than 30 years. 25OH vitamin D (25OH VD) blood levels have been associated with worse prognosis of ALS, but these results remain in dispute. We addressed this controversy with a prospective study and multivariate analysis to study the influence of known clinical prognostic factors of the disease and 25OH VD levels on Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) severity score (ALS-SS), as defined by the monthly rate of decline of ALSFRS-R score, to identify the factors most closely linked to the risk of worsening of the disease.Results:This prospective cohort of ALS patients recruited 127 individuals, and 105 of them met inclusion criteria. Mean age of onset was 62.2 ± 12.1 years, 32% of subjects had bulbar onset, and gender ratio was 1.44 (male/female). Mean 25OH VD level was 26.8 ± 10.8 ng/ml and was similar between males and females. Patients with 25OH VD levels <15 ng/ml had significantly higher ALS-SS at inclusion (ALS-SSi) than those with normal levels (>30 ng/ml), p = 0.011. The study of ALS-SS as calculated at the end of follow-up (ALS-SSe) was not found correlated to initial 25OH VD levels (r = −0.19; p = 0.084). Univariate analysis showed that ALS-SSe correlated with 25OH VD levels, ALS duration at inclusion, slow vital capacity (SVC) at inclusion, and SVC loss. Multivariate model showed that 25OH VD levels were independently associated with ALS-SSe: r = −0.0125, p = 0.033. Log rank test with Kaplan–Meier curves did not show significant differences of survival between the groups defined by 25OH VD levels: <15, >15 and <30, and > 30 ng/ml, p = 0.88.Conclusions: This prospective study in ALS patients confirmed previous retrospective results: ALS-SSi is significantly higher in patients with severe VD deficiency. For the first time, multivariate analysis showed that 25OH VD level was an independent prognostic factor correlated to ALS-SSe, suggesting that discrepancies between previous works could be due to confounders. It would be important that the present work be replicated in larger samples to confirm the present findings.

SAT-366 Hypercalcemia Due to Castleman’s Disease

Castleman’s disease is a group of poorly understood lymphoproliferative disorders in which pro-inflammatory cytokines are hyper-produced, causing a constellation of symptoms. This patient was diagnosed with a rare subtype of idiopathic multicentric Castleman’s called TAFRO, which is a subclass characterized by thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O). This is a case of hypercalcemia likely secondary to Castleman’s disease. To our knowledge, only two such cases have been reported, and none with this rare subtype of the disease. The mechanism of hypercalcemia in Castleman’s disease is thought due to lymph node macrophages expressing vitamin D activating enzyme 25-hydroxyvitaminD 1-alpha-hydroxylase, and possibly due to increased bone-turnover from osteoclasts production by IL-6. The treatment is managing the primary cause of the disorder: high doses of systemic steroids, immunosuppressants and IL6-inhibitors. We present a case of a 53 year old Hispanic female with a PMH of type 2 diabetes mellitus. She had hypercalcemia with a corrected calcium 12 mg/dl and a normal PTH 16.2pg/ml, with low levels of 1,25-OH vitamin D 8.3pg/ml, and 25-OH vitamin D 16.6ng/ml. PTHrP was undetectable. Phosphorous was normal at 3.3 mg/dl. Given that the iPTH was low normal, and with low 25-OH and 1,25-OH vitamin D levels, primary hyperparathyroidism was thought unlikely. SPEP showed a chronic disease pattern. TSH was also noted to be normal. Quantiferon tuberculin test, HHV6, HHV8 and HIV were negative. IgG, IgA, IgM levels were normal. She also had elevated alkaline phosphatase at 108 U/L. No other bone markers were checked. After steroid therapy, her corrected calcium came down to 10.1. Her Castleman’s disease was diagnosed via histopathology of lymph node biopsy showing follicular hyperplasia with atretic germinal centers, penetrating blood vessels, expanded mantle zones, hypervascular interfollicular regions and intense interfollicular plasmacytosis consistent with Castleman’s disease. Initial CT Chest with contrast showed diffuse lymphadenopathy in the retropectoal, axillary, prevascular, pretracheal, paratracheal, and retroperitoneal regions. She had anasarca with ascites, requiring paracentesis with ascites fluid that was negative for malignancy. She was also diagnosed with acute thrombotic microangiopathy via kidney biopsy for workup of thrombocytopenia and acute renal injury. She was initially treated with PLEX and dexamethasone 40mg, then switched to methylprednisolone, was also tried on riuxamab and cylclosporine. She failed therapy with an IL-6 inhibitor, Siltuximab, due to pulmonary edema requiring hospitalization. Currently, she is on a drug holiday and will resume lower doses of cyclosporine. Clinicians should consider an underlying lymphoproliferative disorder in the differential for a patient with hypercalcemia.

SAT-359 Hypercalcemia - Is This Sarcoidosis, Hyperparathyroidism, or Both?

Hypercalcemia (HC) is a common clinical problem. Among all causes of HC, primary hyperparathyroidism (HPT) and malignancy are the most common, accounting for >90 % of cases. We present a case of HC in a patient attributed to long-standing history of Sarcoidosis (SC) and later found to also have HPT with Parathyroid Adenoma (PA) and Vitamin D Deficiency.A 64-year-old female presented to the emergency room for social needs. She had not received medical care for the past 10 years and had known history of SC, previously treated with prednisone and methotrexate. She also noted a long-standing history of elevated calcium (Ca) up to 11 mg/dL. She was fasting for the past 1 month for spiritual reasons and was not taking any medications or supplements. Initial labs were significant for Ca of 13.2 mg/dL, Albumin 4.4 g/dL, ionized Ca 1.43 mmol/L. Creatinine was 1.1. EKG revealed T-wave inversions in V1, 2, 3. She received IV fluids and Ca improved to 11 mg/dL. HC was attributed to known history of SC. However further evaluation revealed parathyroid hormone (PTH) level high at 156 pg/mL, 25-OH Vit D level low at 8.5 ng/mL with normal 1,25 hydroxy Vit D levels at 46 pg/mL. Parathyroid sestamibi scan revealed a left parathyroid adenoma. Surgery was deferred because patient was asymptomatic and did not meet criteria for parathyroidectomy. On discharge, Ca levels remained stable and she was started on Ergocalciferol 50,000 units weekly.HC can be either parathyroid mediated, non-parathyroid mediated, or due to medications. In primary HPT, the elevated PTH levels cause increased bone resorption through activated osteoclasts and increased intestinal Ca absorption. Malignancies involving solid tumors and leukemias can lead to HC through osteolysis and osteoclasts or PTH-related peptide. Thiazide diuretics increase renal Ca absorption that lead to mild HC which can be reversed when the medication is discontinued. Other endocrine disorders that can lead to HC include thyrotoxicosis-induced bone resorption, adrenal insufficiency and pheochromocytoma.Management of hypercalcemia depends upon the level of Ca. Mild HC (Ca < 12mg/dL) is usually asymptomatic and improves with hydration. Asymptomatic or mildly symptomatic patients with chronic moderate HC (Ca 12-14 mg/dL) may not require immediate treatment. Severe HC (Ca >14mg/dL) is treated with IV hydration with normal saline (NS), calcitonin and zolendronic acid. Administration of calcitonin and NS results in substantial reduction in Ca within 12-48 hours.Although, HC was initially attributed to SC, primary HPT and low 25-OH Vit D levels also contributed to HC in this patient. Thus, it is important to evaluate patients with known HC from sarcoid for other etiologies.

MON-925 A Wolf in Sheep’s Clothing: Intermittent Hypercalcemia from an Intrathyroidal Parathyroid Carcinoma

Parathyroid carcinomas have an estimated prevalence of <0.1% of all cancers and is found in <1% of patients with primary hyperparathyroidism (PHPT). While they frequently present with PTH- mediated hypercalcemia, they are often distinguished by severe hypercalcemia and markedly elevated PTH levels compared to their benign counterparts. Parathyroid cancers most often arise from existing parathyroid glands, making them identifiable with standard imaging modalities such as parathyroid sestamibi scan, thyroid ultrasound, and 4-D CT scan. There are reports of non-functioning parathyroid carcinomas, including those that are intrathyroidal. Most of the reported cases are found de novo. We present a case of an intrathyroidal parathyroid carcinoma with intermittent hypercalcemia. A 72-year-old man with a history of Graves’ disease and RAI ablation in the 1970’s was found to have hypercalcemia up to 14.1 mg/dL (8.5 - 10.1) with a PTH level of 223 pg/mL (14 - 64). He denied any constipation, bone pain, fractures, renal stones, or changes in mental status. Thyroid ultrasound demonstrated a 3.9 cm R lobe complex nodule reported as TI-RADS 4, and a hypoechoic 1.0 cm nodule in the L lobe. No definitive parathyroid adenoma was reported. A parathyroid sestamibi scan showed persistent uptake in area of the L 1.0 cm nodule favoring a PTH adenoma while the R nodule had initial radiotracer uptake with delayed washout but no technetium uptake. Laboratory evaluation demonstrated a 24-hour urinary calcium of 338 mg/24hr, low 25-OH vitamin D, and normal vitamin D 1,25 levels. Osteoporosis was diagnosed by BMD with T-score of -3.2 at the femoral neck. Repeat serum corrected calcium level was 9.7 mg/dL and PTH was 93 pg/mL. FNA cytology of the R thyroid mass was reported as benign thyroid tissue. Due to size of the R thyroid nodule, the patient underwent a R hemithyroidectomy with L parathyroidectomy. Intraoperative PTH levels decreased from 154 to 120 pg/mL after removal of L parathyroid adenoma; PTH level decreased further to 12.9 pg/mL after R hemithyroidectomy. Surgical pathology revealed 4.5 cm R parathyroid carcinoma without thyroid tissue with positive margins, and a hypercellular L parathyroid gland. PHPT resolved. After review of all aspects of the case and discussion with patient, the decision was made to monitor his calcium and PTH levels and repeat BMD 1 year from resection. This is an uncommon presentation of a rare endocrine malignancy. To our knowledge, there are few case reports of non-functional parathyroid carcinomas that were initially reported as thyroid cancer or benign thyroid tissue after biopsy. This report underscores the importance in keeping this rare diagnosis in the evaluation of PTH-mediated hypercalcemia.