ResearchPad - bone-and-mineral-metabolism https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[MON-372 Treatment-Resistant Vitamin D Deficiency: Is It a Vitamin D Binding Protein Issue?]]> https://www.researchpad.co/article/elastic_article_9553 Introduction

Vitamin D is present in free and bound forms; the bound form is complexed mainly to vitamin D binding protein (DBP). Vitamin D levels are affected by age, pregnancy, liver disease, obesity, and DBP mutations. We report a patient with treatment-resistant vitamin D deficiency suggestive of a DBP with abnormal vitamin D binding.

Clinical Case

A 58-year-old Pakistani male with a history of hypertension, sleep apnea and hypogonadism presented to endocrine clinic with symptoms including fatigue, generalized muscle cramps, and joint pain. Evaluation of common causes of fatigue, such as anemia, thyroid dysfunction and adrenal insufficiency were ruled out with CBC, thyroid hormone levels and ACTH stimulation test results all within normal ranges. A 25-OH vitamin D level was profoundly low (4.2 ng/ml; normal 30-100), and a 1,25-OH vitamin D level was undetectable (<8 pg/ml; normal 18-72), leading to a presumptive diagnosis of severe vitamin D deficiency. However, his calcium, phosphorus, alkaline phosphatase and kidney function were in the normal range. Furthermore, the absence of osteoporosis, fracture history, or kidney stones suggested adequate vitamin D action at target tissues; PTH levels were high-normal to minimally elevated, ranging 70-94 pg/ml (12-88pg/mL). Aggressive supplementation with vitamin D3 at 50,000 IU 3 times a week and 5,000 IU daily failed to normalize 25-OH vitamin D (ranged 4.6-10ng/ml; normal 30-100) and 1,25-OH vitamin D levels remained undetectable. Addition of calcitriol resulted in mild hypercalcemia and was discontinued. Malabsorption did not appear to be a contributing factor, as a negative tTG antibody (with normal IgA) excluded celiac disease. Vitamin D metabolites levels measured with mass spectrometry showed undetectable 25-OH vitamin D levels (D2 <4 ng/ml, D3 <2 ng/ml; total <6ng/ml; normal 20-50) and 1,25-OH vitamin D levels (<8 pg/ml). Urine N-telopeptide, 24-hour urine calcium (177mg; 100-240) and bone-specific alkaline phosphatase were all normal. Repeat testing over more than five years showed similar results. DBP levels of 269 ug/ml [104-477] excluded DBP deficiency.

Clinical Lesson

Vitamin D deficiency is increasingly part of routine testing in internal medicine and endocrinology clinics, as is repletion with high-dose vitamin D. However, in rare cases such as this, relying on 25-OH vitamin D levels can be misleading, and supplementation unnecessary or potentially harmful. Thus, treatment decisions should consider the full clinical context and further evaluation performed when warranted. This patient’s labs are suggestive of an abnormality in the DBP, supporting future examination using molecular testing.

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<![CDATA[MON-365 Novel Use of Abaloparatide to Augment Spinal Fusion in Patient Undergoing Cervicothoracic Revision Surgery]]> https://www.researchpad.co/article/elastic_article_8813 Objective To present a case of using Abaloparatide (PTHrP 1–34 analogue) to promote spinal fusion in a patient with history of cervical instability s/p multiple cervical operations with non-union. Case Presentation 66 year-old female with a history of multiple sclerosis, obesity and hypothyroidism underwent neurosurgical evaluation of neck pain. She was found to have cervical spinal stenosis causing neck pain, radiculopathy, motor deficits and ataxia. Initially underwent anterior cervical discectomy and fusion which temporarily alleviated symptoms before suffering nonunion. Subsequently underwent two additional surgeries which also eventually failed. She presented to our facility for revision corpectomy and spinal fusion. Given her history of nonunion, endocrinology was consulted for evaluation of metabolic bone disease. No known personal or family history of metabolic bones disease. No history of chronic steroid use. Initial endocrine evaluation excluded common pathologies. A decision was made to pursue anabolic osteoporosis therapy to attempt to augment the spinal fusion process. Patient started on Abaloparatide 80mcg daily 2 weeks post procedure with planned 12-week therapy course. Cervical CT at 3 and 6 months showed post-surgical cervicothoracic fusion with no signs of non-union. Discussion Abaloparatide is a 34 amino acid synthetic analogue of parathyroid hormone related peptide (PTHrP) which works by selectively activating PTH1 receptor found on osteoblasts. Currently anabolic therapies are only FDA approved for treatment of osteoporosis but there is reported off label use in cases of spinal fusions, arthroplasty and fracture healing. Studies have shown that presence of PTH and PTHrP are necessary for fracture healing. Animal studies have also shown that intermittent PTH promotes spinal fusion. This case represents a novel use for Abaloparatide to augment spinal fusion in a human clinical model. Conclusion Further studies are warranted to better understand mechanism of action, drug timing and duration for optimal treatment of anabolic therapies in bone fractures and healing. The use of anabolic therapies like Abaloparatide can be considered in patients undergoing spinal fusion surgery at high risk for non-union or undergoing revision for failed fusion.ReferencesO’Loughlin PF, Cunningham ME, Bukata SV et al. Parathyroid Hormone Augments spinal fusion, fusion mass, and fusion mass quality in a rabbit spinal fusion model. Spine 2009 January; 34: 121–130

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<![CDATA[MON-393 Evaluation of Bone Mass in Transgender Women After Gender Affirming Surgery - a Pilot Study]]> https://www.researchpad.co/article/elastic_article_8809 Estrogen deficiency is classically associated with bone loss in both men and women. In transgender women, after being submitted to gender-affirming surgery (GAS), the main goal of hormone therapy (HT) is to maintain the female phenotype and prevent the consequences of the orchiectomy-related hypogonadal state. The aim of this study was to evaluate the impact of GAS on bone mass in transgender women. A total of 142 trans women attending the outpatient Gender Identity Program were sequentially enrolled. Patients aged < 20 and > 60 years (n=15), with gluteal silicone prosthesis (n=26) and without FSH dosage after surgery (n=9) were excluded. Anthropometric evaluation, laboratory tests and dual-energy X-ray absorptiometry (DXA) were performed in all patients during the follow-up. In women undergoing CAS (CAS-Y), DXA was performed at least 12 months after surgery and with estrogen therapy. In the other women (CAS-N), tests were performed after at least 3 months of standardized treatment (estradiol plus spironolactone or cyproterone acetate). Patients with testosterone values still above the reference for women were not excluded as long as they were on regular HT. Ninety two trans women were included. Among them, 30 had performed CAS, and had DXA assessment performed 37 months (21-78) after surgery. The mean age and BMI were 37 years (33 - 46) and 24.9 kg/m² (23.1 - 27.5) in patients CAS - Y and 30 years (24 - 36) and 24.3 kg/m² (21.5 - 28.5) in patients CAS - N. Trans women CAS-Y were significantly older (p=0.000). No difference was observed regarding estradiol levels between the groups [105.7pmol/L (48.4-207.8) and 147.5 pmol/L (71.9-284.5), p=0.622]. Free androgen index (FAI) was significantly higher [0.45 (0.17 - 1.63) and 4.47 (0.70 - 36.4), p=0.002] and FSH significantly lower [60.4mIU/ml (37.9 - 75.6) and 2.6mIU/ml (0.6 - 4.4), p=0.000] in trans women CAS - N. BMD (g/cm²) and Z-score of lumbar spine, femoral neck and total femur did not differ significantly between the groups. Considering all participants, the lumbar spine BMD was negatively correlated with FSH levels (r=-0.343, p=0.005), which remained significant even after adjustments for FAI. When only CAS - Y trans women were considered, a negative correlation was found between FSH levels and lumbar spine (r=-0.598, p=0.001) and hip (r=-0.404, p=0.033) BMD. In a multiple regression model adjusted for age and surgery, women with FSH > 35 mIU/ml presented a prevalence rate ratio of 11.79 for low bone mass (p=0.040, IC 95% 1.19 - 124.39). The results of this pilot study in trans women show no difference in bone mass according to GAS status. However, long-term elevated FSH levels observed in some post GAS - trans women, even on HT, presented a negative association with bone mass. Further studies with greater sample sizes are needed to confirm the impact of GAS on bone mass and fracture risk.

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<![CDATA[MON-385 Insulin Resistance and Osteoporosis in People Living with HIV]]> https://www.researchpad.co/article/elastic_article_8808 The life expectancy of people living with HIV (PLHIV) increased considerably after the advent of antiretroviral therapy (ARV). Nowadays, it is almost the same as the general population. However, this increase in survival exposes PLVH to age-related morbidities, including chronic metabolic and bone diseases. PLHIV has a low bone mineral density (BMD) and a high prevalence of osteoporosis. Moreover, the frequency of diabetes mellitus (DM) seems to be twice the frequency of the general population. Insulin resistance and DM might be associated with bone diseases in PLHIV. Our study aim was to evaluate the association between insulin resistance and osteoporosis in PLHIV. We carried out a cross-sectional study at the municipality of Santa Maria, South Brazil. PLHIV age 50 yrs or over on treatment with ARV were included. All subjects registered to receive ARV in the university hospital during the period 2016 to 2018 were invited to participate. Those who accepted responded to a standardized questionnaire, performed a bone density scan and a lateral spinal X-ray, underwent peripheral blood collection, and had their weight and height measured. Insulin resistance was considered present when HOMA-IR> 2.7 (Gelonese, 2009). The TyG index was also calculated (VASQUES, 2011). Of the 101 PLHIV who agreed to participate, 84 underwent both insulin and BMD measurements. The prevalence of osteoporosis was 19%. Vertebral fractures were twice as frequent in individuals with osteoporosis (73.3% vs. 36.5%, p = 0.018). Participants with osteoporosis had lower BMI and triglyceride values than those without it. The frequency of insulin resistance calculated by HOMA-IR was 68.2%, and it was associated with glucocorticoid use, smoking, and BMI. HOMA-IR [4.8(6.6) vs. 8.68(9.6), p =0.013], and TyG [5.0(0.3) vs. 5.2 (0.4), p=0.029] mean values were lower in the group with osteoporosis; however, this association disappeared after correction for BMI in the logistic regression model. In conclusion, in our study, PLHIV with osteoporosis have lower insulin resistance than PLHIV without it. Nevertheless, this finding appears to be relating to a lower BMI. Further studies are needed to assess the effect of insulin resistance on fracture risk in PLVH.

GELONEZE, B. et al. HOMA1-IR and HOMA2-IR indexes in identifying insulin resistance and metabolic syndrome: Brazilian Metabolic Syndrome Study (BRAMS). Arq Bras Endocrinol Metabol. 2009 Mar;53(2):281-7

VASQUES, A. C. et al. Análise Crítica do Uso dos Índices do Homeostasis Model Assessment (HOMA) na Avaliação da Resistência à Insulina e Capacidade Funcional das Células-C Pancreáticas. Arq. Bras. Endocrinol. Metab., 2008;52/1:32-39.

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<![CDATA[SUN-333 Burosumab Improves Bone Density in Patients with X-Linked Hypophosphatemia]]> https://www.researchpad.co/article/elastic_article_8794 Background: X-linked hypophosphatemia (XLH) causes rickets in children and osteomalacia in adults due to lifelong renal phosphate wasting that is mediated by high circulating levels of FGF-23. Burosumab, is a recently approved fully human monoclonal antibody that blocks FGF23, thereby correcting the renal phosphate leak, improving mineral metabolism and reducing osteomalacia by 50-75% in adults [1]. Whether this results in measurable changes in skeletal mass and microarchitecture is unclear. Objective: We examined the impact of burosumab on regional bone mineral density (BMD) and trabecular bone scores (TBS) in study subjects involved in two phase III clinical trials of burosumab.

Methods: In these trails subjects received burosumab 1 mg/kg every 4 weeks. Some patients received placebo for the first 6 months of one trial so we considered their month 6 data as their baseline. Most of the patients had been treated at some point in the past with calcitriol and phosphorus. DXA and TBS were obtained at baseline and then after 6, 12 and 18-24 months of drug treatment. Paired t-tests and ANOVA were performed to assess changes in L-spine BMD, Total Hip BMD and TBS.

Results: 25 subjects with XLH (mean age 38.9 years, 56% female) were enrolled in these studies. Paired data were available in 23 subjects at 6 months, 15 subjects at 12 months and 18 subjects at 18-24 months. Compared to baseline, there were significant increases in L-spine BMD at all time points by paired analysis: 6 months (+6.0%, p=<0.0001), 12 months (+6.95%, p=<0.0001), 18-24 months (+6.13%, p=0.0005). Although there was no significant difference in total hip BMD at 6 months when compared to baseline, there were significant increases at 12 months (+6.72%, p=0.0005) and a further increase at 18-24 months (+10.02%, p=0.0029). When all available subjects were analyzed by one-way ANOVA, there was a significant effect of time of treatment on these regional BMD measurements. There was no change in trabecular bone score over the course of treatment.

Conclusion: Treatment with burosumab is associated with a marked improvement in BMD, particularly in the hip. Since the hip is a frequent site of fracture in XLH, the effect of burosumab at this site is of considerable clinical relevance. The lack of an effect on TBS may relate to the fact that this measurement is much less sensitive to therapeutic interventions than BMD assessed by DXA.

References:

[1] JBMR. 2019. https://doi.org/10.1002/jbmr.3843.

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<![CDATA[OR07-03 Continuous Subcutaneous Delivery of RhPTH(1-84) by Pump in Adults with Hypoparathyroidism]]> https://www.researchpad.co/article/elastic_article_8785 More than 80,000 people in the United States have hypoparathyroidism, a disease of low or absent parathyroid hormone (PTH) leading to hypocalcemia and hyperphosphatemia. Conventional treatment with oral calcium and active vitamin D increases serum calcium concentrations but does not replace the physiologic functions of PTH. Once-daily subcutaneous injections of recombinant human (rh) PTH(1-84) were recently approved for the treatment of hypoparathyroidism, but are not consistent in correcting biochemical abnormalities and alleviating symptoms for all patients. In cases in which single or multiple daily injections of rhPTH(1-84) are insufficient for controlling symptoms, continuous subcutaneous infusion via insulin pump is used as a therapeutic alternative. Pump therapy with PTH(1-34) has some support in the literature as an effective form of treatment for hypoparathyroidism.1However, the effects of pump therapy with rhPTH(1-84) in patients with hypoparathyroidism have not been reported. Five women with chronic postsurgical hypoparathyroidism who received treatment at three different endocrine outpatient clinics in the United States were transitioned from multiple daily injections of rhPTH(1-84) to continuous delivery of rhPTH(1-84) using the Omnipod insulin pump. The patients’ ages ranged from 27 to 60 years old and all had had hypoparathyroidism for at least 5 years. All of the patients were transitioned from conventional therapy with oral calcium and calcitriol to subcutaneous injections of rhPTH(1-84), and then switched to continuous subcutaneous administration using an insulin pump. In all five patients, increased serum calcium concentrations and decreased serum phosphate concentrations were observed with increased frequency of PTH administration. Serum calcium concentrations were within the normal to high-normal range and serum phosphate concentrations were in the normal range on pump therapy. Urinary calcium was well-controlled (<250 mg/day) in four of the five patients. All of the women reported a decrease in symptoms while receiving pump-administered rhPTH(1-84), including a lower incidence of fatigue, brain fog, tingling, and muscle cramps compared to standard therapy and daily injections. This is the first report of patients with hypoparathyroidism on long-term therapy with continuously infused subcutaneous rhPTH(1-84) using a pump. Pump therapy improved key parameters of mineral metabolism; normalizing serum calcium in all patients and urinary calcium in four out of five patients. Clinical trials with larger cohorts are needed to confirm the efficacy of this promising mode of administration of rhPTH(1-84). Reference: 1. Winer KK. Advances in the treatment of hypoparathyroidism with PTH 1-34. Bone. 2019;120:535-541.

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<![CDATA[OR07-06 The Roles of GNAQ and GNA11 in Calcium-Sensing Receptor (CaSR) Signalling]]> https://www.researchpad.co/article/elastic_article_8778 The G-protein subunits Gα 11 and Gα q, which share >90% peptide sequence identity and are encoded by the GNA11 and GNAQ genes, respectively, mediate signalling by the calcium-sensing receptor (CaSR), a class C G-protein coupled receptor (GPCR) that regulates extracellular calcium (Ca2+e) homeostasis. Germline Gα 11 inactivating and activating mutations cause familial hypocalciuric hypercalcaemia type-2 (FHH2) and autosomal dominant hypocalcaemia type-2 (ADH2), respectively, but such Gα q mutations have not been reported. We therefore investigated the DiscovEHR cohort database, which has exomes from 51,289 patients with matched phenotyping data, for such GNAQ mutations. The DiscovEHR cohort was examined for rare GNAQ variants, which were transiently expressed in CaSR-expressing HEK293A Gα q/11 knockout cells, and their effects on CaSR-mediated intracellular calcium (Ca2+i) release and MAPK activity, in response to increasing concentrations of extracellular calcium were assessed using a nuclear factor of activated T-cells response element (NFAT-RE) luciferase reporter construct and a serum response element (SRE) luciferase reporter construct, respectively. Responses were compared to those of wild-type (WT), inactivating FHH2-associated GNA11 mutations (Leu135Gln and Phe220Ser), and engineered GNAQ mutations that were equivalent to the FHH2-causing GNA11 mutations. Gα q/11 protein expression was confirmed by Western blot analysis. Six rare missense GNAQ variants (Arg19Trp, Ala110Val, Gln299His, Ala302Ser, Ala331Thr, Val344Ile) were identified in DiscovEHR individuals, all of whom had mean plasma calcium values in the normal range (8.30–10.00 mg/dL). Functional characterisation of all six Gα q variants showed no significant difference to WT Gα q responses, thereby indicating that these variants are unlikely to be disease-causing mutations. In addition, the FHH2-causing GNA11 mutations (Leu135Gln and Phe220Ser) had significantly reduced responses, compared to WT Gα 11; however, this could be compensated by WT Gα q. GNAQ Leu135Gln and Phe220Ser, in contrast to their Gα 11 counterparts, showed no differences in protein expression or signalling responses when compared to WT Gα q. Our study, which provides mechanistic insights into the differences between Gα q and Gα 11, indicates that Gα q, unlike Gα 11, does not play a major role in the pathogenesis of FHH2 or ADH2.

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<![CDATA[MON-345 Hypercalcemia After Placement of Antibiotic-Loaded Calcium Sulfate Beads]]> https://www.researchpad.co/article/elastic_article_8772 Calcium sulfate beads are used to fill bone voids in bone loss and nonunion, as well as in the management of bone and joint infections.1 Specifically, Stimulan® is an absorbed form of antibiotic-loaded calcium sulfate beads which delivers high local antibiotic concentrations for treatment of infection, but has also been associated with hypercalcemia in 5.4% of cases.1 Despite the significant morbidity associated with hypercalcemia, there is little published literature describing this important complication.

In our institution, five patients hospitalized between March 2019 and September 2019 with normal baseline calcium levels developed hypercalcemia as a complication of Stimulan® placement. Typically, 10 to 60 cc of Stimulan® were inserted in each surgery, with the exception of 120cc in one surgery. Three patients required a second surgery with antibiotic bead placement, and hypercalcemia occurred with both initial and subsequent surgeries. The onset of hypercalcemia varied from post-operative day one to four. The peak corrected calcium was 10.7-16.1 mg/dL which corresponded to ionized calcium of 1.57 to >2.20 mmol/L (normal 1.09-1.29 mmol/L). The patient with the highest bead volume had the highest calcium. Calcium peaked on post-operative days three to five. Patients were treated with intravenous fluids, furosemide, calcitonin and anti-resorptives including denosumab and zoledronic acid. Four patients required hemodialysis. Three patients required dialysis for symptomatic hypercalcemia and in one patient the indication was multifactorial. Calcium typically normalized by post-operative day 14 to 21, but hypercalcemia duration was unknown in two patients (one died; one had hypercalcemia on hospital discharge).

As illustrated in our cases, patients who develop hypercalcemia after their initial antibiotic bead placement may be at risk for recurrent hypercalcemia if additional surgeries use antibiotic beads. Higher bead volume may be associated with more significant hypercalcemia.1 Although previous cases have reported milder hypercalcemia, our cases demonstrate that hypercalcemia can be more severe and prolonged, necessitating dialysis in addition to traditional therapies. 1-3

References:

1.Kallala R, Harris WE, Ibrahim M, Dipane M, McPherson E. Use of Stimulan absorbable calcium sulphate beads in revision lower limb arthroplasty: Safety profile and complication rates. Bone Joint Res. 2018 Nov 3;7(10):570-579.

2.Kallala R, Haddad FS. Hypercalcaemia following the use of antibiotic-eluting absorbable calcium sulphate beads in revision arthroplasty for infection. Bone Joint J. 2015 Sep;97-B(9):1237-41.

3.Carlson Jr. CR, Markulis E, Thompson E, Havill J. A novel case of hypercalcemia following the use of calcium sulfate beads. Nephrol Open J. 2015; 1(1): 17-19.

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<![CDATA[SAT-379 Giant Parathyroid Adenoma]]> https://www.researchpad.co/article/elastic_article_8767 Giant parathyroid adenoma

Background: Primary hyperparathyroidism is the most common cause of hypercalcemia. On ultrasound PTH adenomas are typically homogenous, hypoechoic, oval or bean-shaped with peripheral vascularity.

Clinical Case: A 60 year old woman with a history of calcium oxalate nephrolithiasis presented with fatigue, worsening depression, body aches of 3 months duration. Labs showed a serum calcium 11.1 mg/dl (normal range 8.5–10.1 mg/dl), PTH 114.3 pg/ml (normal range 12–88 pg/ml), 25 OH Vitamin D 11 ng/ml (normal range above 29 ng/ml), alkaline phosphatase 137IU/L (normal range 27–120 IU/L), spot urine calcium 34.8 mg/dl, spot urine creatinine 92.1 mg/dl (estimated 24 hour urine calcium 415 mg/dl). She was started on Vitamin D 1000 IU daily. A PTH scan with SPECT/CT showed a right parathyroid adenoma and possible thyroid nodules. A neck ultrasound demonstrated a left 1.5 cm thyroid nodule and a right 3cm lesion. She underwent FNA of the left thyroid nodule and pathology was suggestive of a benign follicular nodule. She underwent parathyroid gland exploration with resection of the right lesion which was a 3.5 x 2.5 x 1.4 cm right superior 5.68 gm PTH adenoma. Postoperatively her serum calcium normalized to 10.1 mg/dl, PTH was 8.4 pg/ml, 25 OH vitamin D was 15 ng/ml. Her Vitamin D dose was increased.

Clinical Lessons: A normal parathyroid gland typically weighs 30–60 mg and is 3–4 mm in size. The differential diagnosis for large parathyroid lesions is parathyroid carcinoma vs giant parathyroid adenoma. Although there is not a definitive size cutoff to define giant parathyroid adenomas, a size greater than 3.5 gm has been used (1). On ultrasound giant parathyroid adenomas are homogenous with smooth borders whereas parathyroid carcinomas are large lobulated heterogeneous hypoechoic lesions (2). A depth/width ratio on ultrasound may be the ultrasound parameter with greatest discriminatory capacity as a depth/width ratio greater than or equal to 1 had 94% sensitivity and 95% specificity for parathyroid carcinoma (2). Whether vitamin D deficiency is a risk factor for the development of large parathyroid glands is controversial as there has been conflicting data on this (1,3). Because there is no serum calcium level that distinguishes parathyroid carcinoma from a parathyroid adenoma neck ultrasound may be a helpful tool in evaluating these patients.

References:

1. Spanhemier PM, Stoltze AJ, Howe JR, et al. Do giant PTH adenomas represent a distinct clinical entity? Surgery. 2013 Oct; 154(4):714–719.

2. Hara H, Igarashi A, Yano Y, et al. Ultrasonagraphic features of PTH carcinoma. Endocr J. 2001 April 48(2):213–217.

3. Rao DS, Honasoge M, Divine GW, et al. Effect of vitamin D nutrition on PTH adenoma weight: pathogenetic and clinical implications. J Clin Endocrinol Metab. 2000 Mar 85(3): 1054–1058.

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<![CDATA[SUN-334 Real-World Clinical Profiles of Adults with Hypophosphatasia (HPP) from the Global HPP Registry]]> https://www.researchpad.co/article/elastic_article_8757 Hypophosphatasia (HPP) is a rare, inherited, metabolic disease caused by low activity of tissue non-specific alkaline phosphatase (TNSALP). HPP in adults has a heterogeneous clinical presentation, often with multiple musculoskeletal and systemic manifestations, which can lead to misdiagnosis and substantial delays in diagnosis. To better understand the most common clinical profile of adults with HPP, data from 270 adults with confirmed HPP diagnosis (≥18 year of age, low ALP and/or ALPL mutation) in the Global HPP Registry were analyzed. Most were women (75.2%) with a median age at enrollment into the registry of 50 years and a median ALP activity of 25 U/L (normal range: 40-150 U/L). Based on medical history, pain (74.8%), mostly described as chronic bone pain or generalized body pain, was the leading symptom reported. Dental manifestations, such as early loss of primary teeth, were reported in 60.4% of adults. Skeletal manifestations, such as recurrent and poorly healing fractures or pseudofractures, were observed in 47.8% of adults. A substantial proportion also reported fatigue (35.2%) and muscle weakness (26.3%). Of the adults who had quality of life data available, median (range) of SF-36v2 Physical Component Score was 42.4 (17.9, 63.3; n=203; population norm=50) and pain interference on the BPI-SF was 3.5 (0, 9.5; n=196; 0=does not interfere; 10=completely interferes). Most adults with available data (n=212) reported some disability on the HAQ-DI (66%). Of these 270 adults, 77 were treated with enzyme replacement therapy (asfotase alfa) while 193 had never received treatment. Demographics and baseline ALP activity were similar between ever and never treated adults. Treated patients had a higher occurrence of pain, dental issues, recurrent and poorly healing fractures or pseudofractures, fatigue, and muscle weakness compared with untreated patients. Generally, treated adults reported poorer quality of life before treatment initiation compared with untreated adults, though data were limited in treated adults. Of the patients treated, 61.0% had pediatric-onset HPP which likely reflects the indication for asfotase alfa in most countries; 29.9% had unknown onset. 57.5% of untreated adults had adult-onset HPP, 24.3% had pediatric-onset, and 18.1% has unknown onset. Pain, dental issues, fatigue, recurrent and poorly healing fractures or pseudofractures, and muscle weakness were the most frequently reported symptoms in both adults with pediatric- or adult-onset HPP. These results establish real-world clinical profiles of adults with HPP, both untreated and before treatment start. Similarities in clinical profiles between adults with pediatric-onset and adult-onset HPP suggest that the age at onset itself is of limited clinical utility; current clinical status and the degree of disability are likely more meaningful in making treatment decisions.

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<![CDATA[OR13-02 Treatment with Zoledronic Acid Subsequent to Denosumab Cannot Fully Prevent Bone Loss]]> https://www.researchpad.co/article/elastic_article_8733 Purpose: Treatment with denosumab (DMAB) decreases bone resorption and fracture risk. Following discontinuation, bone resorption increases, bone mass is lost and fractures have been reported. The aim of the study was to investigate if an infusion of zoledronic acid (ZOL) can prevent increases in bone turnover and bone loss in patients previously treated with DMAB and if the timing of the ZOL infusion is important. Methods: The study was a 2-year randomized, open label, interventional study in patients with osteopenia after DMAB treatment for an average of 4.6 years. ZOL was administrated 6 months (6M group, n=20) or 9 months (9M group, n=20) after the last DMAB injection or when bone turnover was increased (OBS group, n=20). Patients in the OBS and the 9M groups were monitored closely and if p-carboxy-terminal collagen crosslinks (CTX) increased > 1.26 ug/l (50% above the range for postmenopausal women and elderly men), if BMD decreased > 5% at the lumbar spine or total hip, or if a patient suffered a low energy vertebral or hip fracture, ZOL was administered. In the OBS group, ZOL was administered no later than month 6. The patients were monitored with DXA 6, 12 and 24 months after treatment. ZOL was re-administered if BMD decreased > 5% at the lumbar spine or total hip or if CTX increased above 1.26 ug/l. We report the outcome 12 months after the initial ZOL infusion. The study is ongoing. Results: A total of 60 postmenopausal women and men with a mean age of 67.7 (range 51-85) years were enrolled in the study. In the OBS group 1, 2, 6, 1 and 0 patients fulfilled the CTX or BMD criteria for treatment 1, 2, 3, 4 and 5 months after baseline. The remaining 10 patients were treated at month 6. In the 9M group 2 patients fulfilled the CTX criteria for ZOL treatment at month 2. A total of 10, 5 and 5 patients in the 6M, 9M and OBS groups, respectively were re-retreated. In the 6M group CTX decreased initially, but increased rapidly thereafter, and 6 months after ZOL, CTX was 0.60±0.08 g/L (mean±SEM). CTX increased rapidly in the 9M and OBS Groups before ZOL, was suppressed by ZOL but increased again thereafter; CTX was 0.47±0.05 μg/L and 0.47±0.05 μg/L 6 months after ZOL in the 9M and the OBS groups, respectively. Mean CTX was within the premenopausal reference range 12 months after ZOL in all 3 groups. From study baseline to twelve months after ZOL BMD at the lumbar spine had decreased by 4.8±0.7%, 4.1±1.1%, and 4.7±1.2% in the 6M, 9M and OBS groups, respectively (p≤0.002 for all without differences between groups) and at the total hip by 2.6±0.5%, 3.2±0.8%, and 3.6±0.8% in the 6M, 9M and OBS groups, respectively (p≤0.001 for all without differences between groups). The decline in BMD was more pronounced in the months before ZOL in the 9M and OBS groups whereas the decline was steadier in the 6M group. Conclusion: Treatment with ZOL irrespective of the timing did not fully prevent loss of BMD in patients with osteopenia.

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<![CDATA[MON-341 New Diagnosis of Hypophosphatasia in a 79-Year-Old Woman with Low Bone Density]]> https://www.researchpad.co/article/elastic_article_8724 Introduction: Hypophosphatasia is a rare metabolic bone disease caused by one of several mutations in the ALPL gene which encodes tissue nonspecific alkaline phosphatase (ALP). It is usually diagnosed in childhood and can have a heterogenous clinical presentation depending on the extent of enzyme deficiency. Here we report the oldest known patient with hypophosphatasia.

Clinical Case: A 79-year-old woman with a history of medullary thyroid cancer (MTC) in remission, was referred to our metabolic bone disease clinic for the evaluation and treatment of osteopenia. She had suffered from numerous musculoskeletal complaints for several years and had received a diagnosis of polymyalgia rheumatica. However, her symptoms persisted despite a six month trial of prednisone. Although she had developed dental caries at a young age, she denied premature tooth loss. Her family history was significant for arthralgias and vertebral disc disorders in multiple family members, including both her children. Her mother carried a diagnosis of rheumatoid arthritis and osteoporosis. The only pertinent physical exam finding was short stature (Height -4’6”). A DEXA scan was performed using a Hologic unit and revealed a T Score of -1.0 at the L-spine and -1.9 at the femoral neck. A FRAX score predicted a 14% risk of major osteoporotic fracture and 4% risk of hip fracture.

Laboratory data revealed: Serum Calcium 9.3 (8.5-10.5 mg/dL), Albumin 4.3 (3.5-5.0 g/dL), ALP 21 (<130 U/L), Vitamin D 25OH 46.2 (>30 ng/ml), Intact PTH 28.3 (15.0-65.0 pg/ml), Vitamin B6 87.7 (2-21 ng/ml).

On review of her medical record, low ALP levels ranging between 20-30 U/L were noted to be present for the last twenty years. Given her history of musculoskeletal complaints, short stature, elevated Vitamin B6 and low ALP, genetic testing for hypophosphatasia was performed. Her results confirmed a known pathogenic mutation in the ALPL gene.

Conclusion: This case highlights the importance of reviewing ALP levels and relevant patient history to rule out hypophosphatasia prior to initiating therapy for osteoporosis. This condition is often unrecognized. Bisphosphonates, which are often the first line of treatment in osteoporosis, are contraindicated in hypophosphatasia as they can increase the risk of atypical fractures.1 Teriparatide may improve bone density depending on the extent of ALP deficiency. Asfotase alfa is a new agent that is currently available for the management of certain cases of hypophosphatasia.

References:

1.”Atypical femoral fractures”during bisphosphonate exposure in adult hypophosphatasia; Sutton,RA; Mumm,S;Coburn SP; Ericson,KL; Whyte, MP; Journal of Bone and Mineral Research 2012 May;27(5):987-94.

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<![CDATA[MON-376 Head to Toe Hyperparathyroidism - Impending Hyperparathyroid Crisis and Subsequent Crystal Arthropathies]]> https://www.researchpad.co/article/elastic_article_8715 The myriad of presentations associated with PHP are well established, however gout is not commonly associated with this disease. Additionally, it is unusual to see multiple threatening and potentially debilitating complications occur concurrently in one patient.

An asymptomatic elderly male with hypertension presented to the PCP for the first time and was found on routine blood work to have a serum creatinine of 4.03 mg/dl, a serum calcium of 12.1mg/dl, and a PTH of 831.7ng/L. Subsequent Tc-99 Sestamibi scanning suggested that the source was both a single right inferior parathyroid adenoma and an ectopic mediastinal adenoma. At the initial encounter the patient’s hypercalcemia was treated with IV fluid resuscitation and calcitonin then subsequently cinacalcet. Renal ultrasound at that time showed normal sized kidneys with several cysts, and phosphate levels ranged from 2.0-3.9 mg/dl (range 2.5-4.5mg/dl. The patient’s serum calcium was controlled at 10.44mg/dl, and his renal function improved to a serum creatinine of 3.08mg/dl. Prior to discharge patient developed acute left knee pain, and was found to have an inflammatory arthritis, with urate crystals seen. The patient was diagnosed with an acute gout flare, which responded well to colchicine and was discharged. The patient eventually underwent parathyroidectomy, which showed a large 4cm left superior parathyroid as well as a large right superior parathyroid gland extending into the mediastinum. Pathology was consistent with parathyroid hyperplasia. After surgery, the patient developed hungry bone syndrome, with an admitting serum level calcium of 6.05mg/dl, serum magnesium of 2.00mg/dl, serum phosphorus of 2.8mg/dl, and serum potassium of 5.1mg/dl, with clinical features of tetany and weakness that resolved after two days with calcium and calcitriol administration. He again had an acute monoarticular arthritis prior to discharge that had both urate and calcium pyrophosphate crystals in the joint fluid and again responded well to colchicine and glucocorticoids. He was eventually discharged on vitamin D and calcium supplementation, with cinacalcet and colchicine.

This case illustrates the multiple clinical teaching points that exist in primary hyperparathyroidism, including both types of presentation and potential complications. It also expresses the need to be vigilant of some rarer clinical features, such as potential hyperparathyroid crisis and multiple enlarged parathyroid glands. Physicians should also be wary of both gout and CPPD, as well as complications that occur post parathyroidectomy such as hungry bone syndrome.

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<![CDATA[MON-344 Uncommon Etiology of Hypophosphatemia and Secondary Hyperparathyroidism: Ferric Carboxymaltose Infusion]]> https://www.researchpad.co/article/elastic_article_8713 Background: Hypophosphatemia has been recognized as one of the side effect of intravenous ferric carboxymaltose infusion. This effect is thought to be secondary to fibroblast growth factor 23 (FGF 23) mediated renal phosphate wasting and associated with calcitriol deficiency and secondary hyperparathyroidism.

Clinical Case: A 76 years old male patient with medical problems including hypertension, type 2 diabetes mellitus, hyperlipidemia, paroxysmal atrial fibrillation, nephrolithiasis, spinal stenosis and chronic anemia was referred to endocrinology clinic for osteoporosis management. Bone density scan showed left femur neck T-score of -2.5 and L1-L4 lumbar spine T-score of 1.4. He reported pain on back and bilateral posterior thighs, difficulty with ambulation which were partly attributed to severe spinal stenosis that he was planned to have surgery for. Muscle strength was normal on examination. Laboratory studies were obtained for osteoporosis work up and showed: Calcium: 8.9 mg/dL (8.8-10.2 mg/dL), Creatinine: 0.77 mg/dL (0.74-1.35 mg/dL), GFR: 88 mL/min/BSA, Albumin 4.5 g/dL (3.5-5.0 g/dL), 25-Hydroxy vitamin D: 26 ng/mL, Magnesium 1.8 mg/dL (1.7-2.3 mg/mL), 1,25 Dihydroxy Vitamin D 24 pg/mL (18-64 pg/mL), Phosphorus: 1 mg/dL (2.5-4.5 mg/dL), PTH 163 pg/mL (15-65 pg/mL), Hemoglobin 12.9 mg/dL (13.2-16.6 mg/dL). Due to hypophosphatemia tumor induced osteomalacia diagnosis was entertained and further work up was considered in this regard however later noted that patient received ferric carboxymaltose 750 mg infusion two times within last 3 weeks for iron deficiency anemia. Hemoglobin level was 8.6 mg/dL before the infusions. After oral phosphate replacement the phosphate level improved to 2.4 mg/dL. Serum FGF 23 level was measured and it was normal at 108 RU/mL (<180 RU/mL). He was then started on bisphosphonate treatment for osteoporosis.

Conclusion: Hypophosphatemia and secondary hyperparathyroidism can be seen after ferric carboxymaltose infusion due to FGF-23 mediated mechanism. In literature various presentations were reported from transient- asymptomatic hypophosphatemia to severe acute symptomatic hypophosphatemia along with persistent hypophosphatemia with osteomalacia and fragility fractures due to recurrent ferric carboxymaltose infusions. Thus, one should keep this possible side effect in mind during evaluation of hypophosphatemia and osteoporosis.

References: 1. Wolf M, Chertow GM, Macdougall IC, Kaper R, Krop J, Strauss W. Randomized trial of intravenous iron-induced hypophosphatemia. JCI Insight. Dec 6 2018;3(23):e124486 2. Fang W, McMahon LP, Bloom S, Garg M. Symptomatic severe hypophosphatemia after intravenous ferric carboxymaltose. JGH Open. October 2019, volume 3, issue 5, P 438-440

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<![CDATA[MON-LB67 Bisphosphonate Related Ocular Inflammation]]> https://www.researchpad.co/article/elastic_article_8696 Introduction: Osteoporosis is a major public health problem, increasing in incidence with the growth of the aging population. It affects over 200 million women worldwide and is associated with fragility fractures leading to increased morbidity, mortality and poor quality of life (1). Bisphosphonates are among the most widely used first line forms of treatment for management of osteoporosis. They have a structure like pyrophosphate and inhibit bone resorption by attaching to hydroxyapatite binding sites on the bone in areas with active resorption.

While initiating treatment with bisphosphonates, endocrinologists generally discuss side effects including gastrointestinal symptoms related to gastroesophageal reflux disease and gastritis, acute phase reactions related to infusion of the bisphosphonates, musculoskeletal pain, hypocalcemia, osteonecrosis of the jaw, and atypical femur fractures. There are rare but severe side effects causing ocular inflammation related to bisphosphonate use - Bisphosphonate Related Ocular Inflammation (BROI). While these are rare based on few case reports, they are significant side effects, which if patients are not aware of or not addressed in timely manner can result in vision loss.

We report a clinical scenario of a patient who experienced bisphosphonate-related ocular inflammation.

Clinical History: 62-year-old female with cerebral palsy presented to the emergency room with 1 day of marked left eye redness and swelling. When the symptoms began, she felt that her eye was itchy. She had mild left eye discomfort. She did not perceive any decreased visual acuity. Patient had her first infusion of bisphosphonate, 4 days prior to the emergency room visit. On Exam: She was alert, no apparent distress, left eyelids were swollen, almost completely shut with minimal discoloration, there was underlying severe chemosis and conjunctival redness, pupils equal and round, visual acuity 20/100 OD and 20/100 OS. She was diagnosed with allergic conjunctivitis, and advised to apply Tobradex drops and Diphenhydramine, and to follow-up in eye clinic. Scleritis related to bisphosphonates was also considered as a possible cause of her symptoms. The patient called the endocrinologist about the eye symptoms the following day. The endocrinologist also raised the possibility bisphosphonate related ocular inflammation and advised to be seen in ophthalmology clinic urgently. The endocrinologist also communicated with the ophthalmologist indicating that her eye symptoms could be due to inflammatory response related to bisphosphonates and to consider starting systemic steroids.

The patient was seen in ophthalmology clinic the following day: The ophthalmology exam revealed severe orbital inflammation with conjunctival chemosis OS: Table 1.She was started on Prednisone 80mg a day with tapering by 10mg daily over the next 2 weeks. She was also advised to apply Durezol eye drops twice a day. She was referred to Oculoplastics for further evaluation. Table 1:

Oculoplastics evaluation next day Table 2: Revealed orbital inflammation with good initial response to steroids and advised to continue prednisone taper.

Table 2:

On the 2 weeks follow up: Table 3: Resolved orbital inflammation and was advised to stop prednisone

Table 3:

Clinical Discussion: Bisphosphonates are widely prescribed and effective forms of treatment for osteoporosis in preventing fractures. Ocular side effects are rare but reported over the past 2 decades (2). First time users of bisphosphonates are at a higher risk compared with nonusers (3).There is also an association of bisphosphonate-related ocular inflammation (BROI) with coexisting inflammatory conditions that associated with ocular inflammation, such as rheumatoid arthritis, ankylosing spondylitis, psoriasis, inflammatory bowel disease, systemic lupus erythematosus or sarcoidosis (4,8).Symptoms related to BROI typically occur within 24 to 72 hours of the bisphosphonate exposure but can range between few hours to 3 years. Those who receive systemic bisphosphonates present earlier compared to orally administered bisphosphonates (5,6,7). In prior case reports, patients presented with flu like symptoms, lasting for lasting for 24 to 72h prior to onset of orbital disease (5). The range of ocular inflammation is variable, and can include conjunctivitis, uveitis, scleritis, episcleritis and keratitis. The symptoms can be unilateral or bilateral. Discontinuation of bisphosphonates is necessary for resolution of ocular inflammation (7).The postulated cellular mechanism causing BROI is as follows: Bisphosphonates are secreted into the lacrimal system, and induce an inflammatory response resulting in release of cytokines that results in ocular inflammation: Fig 1: (9).

Fig 1: It is unclear as to why BROI is a rare side effect, though related to release of inflammatory reactants, which are also responsible for the more common flu like side effect. The risk of BROI is increased in those with associated inflammatory condition (arthritis or inflammatory bowel disease). It is possible that in individuals susceptible to inflammatory disorders, there is pre-existing infiltration of the lacrimal gland with mononuclear cells which causes a robust local inflammatory response to bisphosphonate treatment in the eye.

Our patient with cerebral palsy and learning disability, was taken to the emergency room within few hours of onset symptoms and signs of ocular inflammation. Though she was diagnosed with severe orbital inflammation, she did not express eye pain, which is commonly seen in scleritis. Through multidisciplinary teamwork between the emergency physician, endocrinologist, ophthalmologist and oculoplastic specialists, she was promptly started on systemic steroids and her symptoms resolved completely with no vision loss.

While considering bisphosphonates as an option for osteoporosis treatment, the endocrinologist should discuss the rare but serious complications of BROI. With use of bisphosphonates in the aging population to treat osteoporosis, specific attention should be given to underlying eye disease, inflammatory conditions, and cognition.

References: 1. IOF statistics: (https://www.iofbonehealth.org/epidemiology). 2. Clark EM, Durup D. Inflammatory eye reactions with bisphosphonates and other osteoporosis medications: what are the risks?. Ther Adv Musculoskelet Dis. 2015;7(1):11–16. doi:10.1177/1759720X145664243. Etminan M, Forooghian F, Maberley D. Inflammatory ocular adverse events with the use of oral bisphosphonates: a retrospective cohort study. CMAJ. 2012;184(8):E431–E434. doi:10.1503/cmaj.1117524.French DD1, Margo CE. Postmarketing surveillance rates of uveitis and scleritis with bisphosphonates among a national veteran cohort. Retina. 2008 Jun;28(6):889-93. doi: 10.1097/IAE.0b013e31816576ef.

5.Herrera I, Kam Y, Whittaker TJ, Champion M, Ajlan RS. Bisphosphonate-induced orbital inflammation in a patient on chronic immunosuppressive therapy. BMC Ophthalmol. 2019;19(1):51. Published 2019 Feb 14. doi:10.1186/s12886-019-1063-8 6. Ehsan Rahimy, Simon K. Law. Orbital inflammation after zoledronate infusion: an emerging complication.https://doi.org/10.1016/j.jcjo.2012.09.011 7. Frederick W. Fraunfelder, M.D Bisphosphonates and Ocular Inflammation. NEngJ Med 2003; 348:1187-1188. DOI: 10.1056/NEJM200303203481225 8.Pazianas M1, Clark EM, Eiken PA, Brixen K, Abrahamsen B. Inflammatory eye reactions in patients treated with bisphosphonates and other osteoporosis medications: cohort analysis using a national prescription database. J Bone Miner Res. 2013 Mar;28(3):455-63. doi: 10.1002/jbmr.1783.9.Keith Thompson and Michael J. Rogers. New Insights into Old Drugs. BoneKEy-Osteovision. 2006 August;3(8):5-13

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<![CDATA[SAT-405 Trabecular Bone Score (TBS) in Primary Hyperparathyroidism (PHP): A Useful Tool?]]> https://www.researchpad.co/article/elastic_article_8694 Background: PHP is a common disorder, and regardless of being an asymptomatic entity, often leads to bone loss and osteoporosis. TBS is a software-based assessment method of trabecular bone structure of the spine based on the analysis of pixels in dual energy x-ray absorptiometry (DXA) images. The aim of this study was to evaluate TBS measurements in combination with DXA values by searching for more accurate bone fragility risk assessment among PHP patients.

Methods: From June/2017 to January/2019, all patients who met the criteria for PHP diagnosis prior to surgery were selected to take part in this study. Control group was composed by non-family related healthy volunteers. Bone mineral density (BMD) by DXA (DXA; Hologic QDR 4500) at the lumbar spine, total hip, femoral neck, distal third of the non-dominant radius and TBS values by InSight were determined in 64 PHP patients and 63 controls. Total and ionized calcium, PTH, 25-hydroxyvitamin D (25(OH)D), creatinine, alkaline phosphatase, P1NP and CTX were measured in all patients and control group.

Results: Primary hyperparathyroidism patients presented significant lower BMD values in all evaluated sites compared to controls. TBS measurements were also statistically different among PHP patients and controls (mean TBS PHP=1233 vs TBS controls= 1280, p=0.044). Patients and controls didn’t differ in age, sex, menopausal state or BMI (body mass index). Osteoporosis diagnosis by DXA analysis was observed in 50% of PHP patients and in 26.6% of controls. Self-reported or image-diagnosed fracture occurred in 15 PHP (23.4%) patients and in 11 (17.5%) controls. Among these fractures, vertebral fracture account for 9 (14%) in PHP group and 4 (6.3%) in controls. ROC curve analysis showed that the TBS value < 1187 is associated to significant high risk of vertebral fracture (sensibility 87.5%, specificity 67.3%) among PHP patients.

Conclusion: TBS, used as a complement to DXA measurements, is a useful tool to better assess fragility risk among PHP patients.

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<![CDATA[MON-370 Treatment of Parathyroid Storm in a Patient with Traumatic Brain Injury: A Reversible Comatose State]]> https://www.researchpad.co/article/elastic_article_8691 Background:

Parathyroid storm, also known as parathyroid crisis, is a rare and under-recognized endocrine emergency due to severe hypercalcemia in patients with primary hyperparathyroidism. It is characterized by significantly elevated parathyroid hormone (PTH) levels even up to 20 times above the normal limit along with calcium levels >15 mg/dl, leading to multiorgan dysfunction, notably altered mental status and acute kidney injury. Risk of mortality is high without urgent parathyroidectomy. We describe a case of a patient with acute traumatic brain injury and parathyroid storm with PTH >1700 pg/ml (11-51) and Ca 15.4 mg/dl (8.6-10.4) in whom resection of a parathyroid adenoma reversed the comatose state.

Clinical Case:

Our patient is a 68 year-old male with no significant past medical history who sustained a fall off a 12-foot ladder complicated by right intracranial bleed s/p hemicraniectomy and multiple fractures, including left clavicle fracture with possible subclavian artery injury, left rib fractures, and right hip fracture s/p ORIF. The patient had a brief, partial improvement of mental status, followed by comatose state in the setting of rapidly rising calcium levels and acute kidney injury. In the setting of blood transfusions, the patient had an initial Ca of 8.8 mg/dl (8.6-10.4) on admission. The calcium levels rose over a week to 15.4 mg/dl with albumin of 2.4 g/dl (3.9-5.0), PTH levels from 953 pg/ml to >1700 pg/ml (11-51) after tracheostomy, and creatinine from 0.69 mg/dl to peak of 2.0 mg/dl (0.60-1.30). In spite of IV hydration, calcitonin, cinacalcet up to 90mg twice daily, pamidronate 60mg IV, and several sessions of hemodialysis, the patient’s calcium did not normalize, and the patient remained comatose. Other labs showed phosphorus nadir of 1.4 mg/dl (2.3-4.4), 25-OH VitD 13 ng/ml (20-50), 1,25-OH VitD 9.8 pg/ml (19.9-79.3), VitA 0.6 mg/L (0.3-0.9), PTHrP <2.0 pmol/L (0.0-2.3), normal SPEP/UPEP, and peak CK of 569 U/L (63-474). Sestamibi scan showed intense tracer uptake within a nodule near the suprasternal notch, and parathyroid 4D-CT showed a left 17mm pretracheal lesion with cystic degeneration along the superior margin of the manubrium. The patient subsequently underwent parathyroidectomy of an ectopic cystic mass with normalization of calcium and PTH levels. Pathology revealed a 0.8 gram, 1.5 x 1.0 x 0.3 cm enlarged, hypercellular parathyroid. The patient woke up from his comatose state immediately after surgery with progressive improvement in mental status back to baseline, other than left-sided weakness.

Conclusion:

Our case highlights the importance of surgical management as an effective cure for parathyroid crisis and underscores the associated critical and significant rise in calcium and PTH levels, which was resistant to medical treatment.

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<![CDATA[SAT-343 Diagnosis and Management of Pseudohypoparathyroidism Type 1B]]> https://www.researchpad.co/article/elastic_article_8686 Background: Pseudohypoparathyroidism (PHP) is a heterogeneous group of disorders characterized by end-organ resistance to PTH. Most subtypes are caused by pathogenic variants or epigenetic alterations in GNAS, which encodes the alpha subunit of the G protein regulating end-organ response to PTH. PHP type 1B (PHP1B) is caused by methylation defects in GNAS and presents with isolated renal PTH resistance. Clinical Case: A 29-year-old gentleman presented with intermittent muscle spasms, perioral and digital paresthesias, fatigue, and anxiety. Family history was notable for similar symptoms in his sister and nephew. Physical examination revealed normal stature, non-dysmorphic facies, and no soft tissue ossifications or skeletal anomalies. Chvostek sign was positive. Laboratory studies showed total calcium 6.0 mg/dL (n 8.6–10.0 mg/dL), phosphorus 6.8 mg/dL (n 2.5–3.5 mg/dL), creatinine 0.8 mg/dL (n 0.8–1.3 mg/dL), albumin 5.0 (n 3.5–5.0 mg/dL), PTH 231 pg/mL (n 15–65 pg/mL), total 25-hydroxyvitamin D 19 mg/mL (n 20–50 ng/mL), and 1,25-dihydroxyvitamin D 45 pg/mL (n 18–64 pg/mL). Additional endocrine testing showed TSH 6.4 mIU/L (n 0.3–4.2 mIU/L), free T4 1.1 ng/dL (n 0.9–1.7 ng/dL), and TPO antibody <0.3 IU/mL (n <9.0 IU/mL). Renal ultrasound was normal. CT head showed diffuse intracranial calcifications. He was diagnosed with PHP1B and started on calcitriol, cholecalciferol, and calcium carbonate. He declined genetic testing. Repeat laboratory studies were improved with total calcium 8.5 mg/dL, phosphorus 3.9 mg/dL, total 25-hydroxyvitamin D 49 mg/mL, PTH 124 pg/mL, and 24-hour urinary calcium 269 mg (n <250 mg). Conclusion: International consensus guidelines for the diagnosis and management of PHP and related disorders were recently published by Mantovani et al. in 2018. Proposed clinical and biochemical major criteria include PTH resistance, ectopic ossifications, early-onset obesity, TSH resistance, and Albright hereditary osteodystrophy (AHO; round facies, short stature, brachydactyly, developmental delay). Unlike PHP type 1A, PHP1B often presents later in life and features of AHO are usually absent, so diagnosis requires a high degree of clinical suspicion. It is recommended that patients with suspected PHP have molecular confirmation with sequencing, methylation, and/or copy number variant analysis of GNAS. Routine monitoring of calcium, phosphorus, and PTH levels and treatment with active vitamin D analogues with or without calcium supplements are advised to maintain normal calcium and phosphorus and PTH <2 times the upper limit of normal. Other recommendations include renal imaging for nephrocalcinosis, eye exam for cataracts, CT head imaging (in patients with neurological findings) for calcifications, regular dental care, and management of comorbid endocrinopathies. A multidisciplinary approach is needed in this complex, heterogeneous group of disorders.

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<![CDATA[SAT-333 Autoimmune Polyglandular Syndrome Type 1 in a Patient with Bipolar Disorder]]> https://www.researchpad.co/article/elastic_article_8682 Autoimmune Polyglandular Syndrome Type 1 (APS-1) is clinically defined as the presence of at least two components of the classic triad of hypoparathyroidism, adrenal insufficiency and mucocutaneous candidiasis. It is commonly seen amongst Finns, Sardinians and Iranian Jews and is a very rare condition, with a challenging set of management.

50-year old female with a known past medical history of Bipolar disorder, Primary Adrenal Insufficiency, Hypothyroidism, Alopecia was transferred from an acute psychiatric facility for medical clearance. Patient was noted to have findings initially suggestive of Subarachnoid Hemorrhage on a CT scan of the Head which was later deemed to be likely dystrophic calcification. During her stay on the medical floors, patient was found to be unresponsive and hypotensive, after a bout of agitation. She had to be urgently intubated and started on stress doses of steroids (Hydrocortisone 100 mg every 8 hours) and was upgraded to the Intensive Care Unit (ICU). Patient was eventually successfully weaned off the ventilator and steroid doses were slowly tapered. During her hospital course she was noted to have gradually decreasing Calcium levels, down to a corrected Calcium level of 7.6. Further workup for the hypocalcemia revealed a Vitamin D Level of 12, and Parathyroid Hormone (PTH) level of 0. Patient was subsequently started on adequate Calcium and Vitamin D supplementation for the same. After a few days when the family was located and contacted through social work support, and a more thorough history was obtained, it was found that one out of the patient’s three sisters had a similar constellation of deficiencies. Patient had previously been diagnosed with a polyendocrine syndrome, however she was irregular with her medication compliance and follow-up outpatient with her endocrinologist due to her persistent psychiatric issues and poor social support.

APS-1 is an autosomal recessive disorder caused by mutation in AIRE, the autoimmune regulator gene which is hypothesized to be playing an important role in the generation of regulatory T cells. Although the complete pathogenesis is unclear, mutation in generation of these regulatory cells leads to autoantibody formation. Hypoparathyroidism or Chronic persistent Mucocutaneous Candidiasis is usually the first manifestation seen during adolescence and adrenal insufficiency usually manifests later. A variation of other autoimmune syndromes can be observed, with Hypothyroidism, Type-1 Diabetes Mellitus and Primary Hypogonadism being a few of them. Treatment primarily involves replenishment of the hormones of the underperforming gland. Management of a complex syndrome like APS-1 in a patient with psychiatric disabilities can be challenging and needs a multi-disciplinary approach involving the endocrinologist, the primary care physician and the psychiatrist.

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<![CDATA[SAT-378 Posterior Reversible Encephalopathy Syndrome Associated with Malignant Hypercalcemia and Hypertension Due to Primary Hyperparathyroidism]]> https://www.researchpad.co/article/elastic_article_8680 Background

Posterior Reversible Encephalopathy Syndrome (PRES) is an acute neurological entity characterized by headache, altered mental status, visual loss and seizures. It can be triggered by multiple aetiologies including hypertension, eclampsia, cytotoxic and immunosuppressant drugs and, rarely, hypercalcaemia.

Case Report

A 64 years old woman presented with five weeks history of fatigue, poor appetite, dry mouth, constipation and abdominal discomfort and one-week history of nausea and vomiting. She was hypertensive at 177/88 mmHg with dry mucous membranes. Physical examination and neurological examination were unremarkable.

Laboratory investigation showed corrected calcium of 4.83 mmol/L (2.25-2.54) with

Ionized calcium of 2.62 mmol/L (1.15-1.27), parathyroid hormone (PTH) of 1330 ng/l (15-68), phosphate of 1.16 mmol/L(0.8-1.5), magnesium of 0.51 mmol/L (0.7-1.0) urea of 10.7 mmol/L (2.8-8.4), creatinine of 119 umol/L (49-90), potassium 3.4 mmol/L(3.5-5.1). She was aggressively rehydrated, commenced on Intravenous (IV) frusemide and was given IV zoledronic acid. Cinacalcet was commenced and titrated gradually up according to corrected calcium level (target corrected calcium level between 2.5-3.0 mmol/L).Electrolytes deficiencies corrected with replacement therapy.Ultrasound neck and parathyroid MIBG scan showed large 5.1cm heterogeneous lesion posterior to the right lobe of the thyroid extending inferiorly into the superior mediastinum consistent with parathyroid mass. Histology confirmed benign parathyroid adenoma.

38 hours after admission, the patient became intermittently confused and complained of visual symptoms followed by complete visual loss in the left eye. This was followed shortly by status epilepticus which required treatment with intravenous antiepileptic therapy and mechanical ventilation.Corrected calcium at that time was 3.82 mmol/L.Patient was noted to have left upper limb weakness.Computed tomography of the brain was normal and magnetic resonance imaging (MRI) of the brain showed bilateral symmetrical subcortical T2 hyper- intensities in the occipital- parietal lobes consistent with PRES.

By day five, corrected calcium was 2.52 mmol/L. On day six patient had successful parathyroidectomy. Post operatively PTH was 7.73 ng/L and corrected calcium 2.27 mmol/L. Repeated Brain MRI showed resolution of symmetrical subcortical T2 hyperintensities within both occipital lobes. She made a complete neurological recovery. DEXA scan showed osteoporosis (T score in left forearm of -3.8). She was commenced on bisphosphonate therapy.

In conclusion, we demonstrated hypercalcemia-induced PRES. This can be a life-threatening condition and can be reversed by proper treatment of hypercalcemia.

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