ResearchPad - bone-and-mineral-case-reports-ii Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[MON-372 Treatment-Resistant Vitamin D Deficiency: Is It a Vitamin D Binding Protein Issue?]]> 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.

<![CDATA[MON-365 Novel Use of Abaloparatide to Augment Spinal Fusion in Patient Undergoing Cervicothoracic Revision Surgery]]> 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

<![CDATA[MON-345 Hypercalcemia After Placement of Antibiotic-Loaded Calcium Sulfate Beads]]> 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


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.

<![CDATA[MON-341 New Diagnosis of Hypophosphatasia in a 79-Year-Old Woman with Low Bone Density]]> 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.


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.

<![CDATA[MON-376 Head to Toe Hyperparathyroidism - Impending Hyperparathyroid Crisis and Subsequent Crystal Arthropathies]]> 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.

<![CDATA[MON-344 Uncommon Etiology of Hypophosphatemia and Secondary Hyperparathyroidism: Ferric Carboxymaltose Infusion]]> 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

<![CDATA[MON-LB67 Bisphosphonate Related Ocular Inflammation]]> 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: ( 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. 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

<![CDATA[MON-370 Treatment of Parathyroid Storm in a Patient with Traumatic Brain Injury: A Reversible Comatose State]]> 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.


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.

<![CDATA[MON-343 The Mystery of Recurrent PTH-Independent Hypercalcemia with Severe Hypophosphatemia]]> Background

The differential diagnoses for PTH independent hypercalcemia with hypophosphatemia are broad. Careful history with systematic evaluation for possible etiologies is necessary for accurate diagnosis and timely therapeutic intervention.

Clinical Case

A 72-year old female was referred to our clinic for evaluation of hypercalcemia with low iPTH level. Review of lab workup over the past two years showed frequent occurrences of mild hypercalcemia, low iPTH and moderate to severe hypophosphatemia. She denied use of calcium, vitamin D, Vitamin A or herbal supplements and over the counter (OTC) medications. Age-appropriate cancer screening was up to date. She had no clinical evidence of granulomatous diseases or malabsorption syndrome. Labs revealed corrected calcium (cCa) 9.9 (8.5-10.5 mg/dL), iPTH 6.36 (12-88 pg/mL), phosphate 1.5 (2.5-4.5 mg/dl), magnesium 1.6 (1.8-2.7 mg/dl), 25-OH Vit D 30 (30-100 ng/mL), PTHrP 12 (14-27 pg/mL), 1,25 OH Vit D 32 (18-72 pg/ml), TSH 1.8 (03-5.6 uIU/mL), GFR 49 (>90 mL/min/1.73 m2) and bicarbonate 30 (23-31 mEq/L). FGF23, 1-mg ODST and SPEP were normal. 24-hour urine phosphate was 3 mg/24h, ruling out renal phosphate wasting.

Two months later, she developed myalgia and generalized weakness. Labs showed cCa 11.3mg/dl, iPTH 3.79 pg/ml, phosphate <1 mg/dl, magnesium 1.2 mg/dl, bicarbonate 33 mEq/L. She was hospitalized for severe hypophosphatemia. Here, she revealed she was intermittently taking a “milky” antacid obtained from Mexico, for her GERD. She required IV phosphate and magnesium replacement and her mineral abnormalities normalized within 24 hours. She was advised to stop use of OTC antacids and provided daily phosphate and magnesium supplementation. 4 weeks later, she developed recurrent hypercalcemia 10.4 mg/dl, hypophosphatemia 1.1 mg/dl and alkalosis with bicarbonate 35 mEq/L, which corrected with supervised phosphate and magnesium supplementation and restricted access to home OTC medications.


Milk-alkali syndrome, characterized by the triad of hypercalcemia, metabolic alkalosis and renal failure, has been classically associated with ingestion of large amounts of milk and absorbable alkali. Once a common cause of hypercalcemia, its incidence declined rapidly with advent of new therapies for PUD. Recently, this syndrome, now described as calcium-alkali syndrome (CAS) has re-emerged due to use of high dose calcium carbonate supplements and OTC antacids, with a prevalence of 9-12% among hospitalized patients with hypercalcemia.

We hypothesize our patient’s mineral abnormalities are explained by CAS. High doses of calcium from antacids can bind phosphate in the gut, leading to poor phosphate absorption and hypophosphatemia.


CAS is emerging as a frequent cause of hospital admissions for hypercalcemia. Severe hypophosphatemia can be a rare manifestation. Primary therapy is withdrawal of offending agent.

<![CDATA[MON-371 The Case of Dueling Femurs]]> Introduction: Paget’s disease of the bone is characterized by excessive osteoclastic bone resorption followed by formation of disorganized bone; which is often focal. Bone pain and deformities are common features and it often leads to complications such as pathological fractures, deafness or neurologic deficits. Elevated bone turnover markers and alkaline phosphatase reflect ongoing exaggerated bone resorption and osteoblastic activity. We present an unusual scenario of post-menopausal osteoporosis and Paget’s disease occurring in the same patient.

Clinical Case: 86-year-old female with history of Type 2 Diabetes Mellitus, Hypertension,

Hypothyroidism, degenerative joint disease of lumbar spine with prior interbody fusion and laminectomy was referred to our clinic by Orthopedics for evaluation of newly diagnosed Paget’s disease. 2 months ago, she noticed severe right hip pain limiting daily activities. She denied any history of falls, fractures or family history of Paget’s. Physical exam was notable for tenderness to right sacro-iliac joint and right femoral trochanteric region. Work up included MRI of Lumbar spine and Pelvis, Pelvis X-ray, DEXA scan and routine blood work.

Interestingly, her DEXA scan showed T score of +2.9 in Right hip and -3.1 in Left hip. On Pelvis X-ray cortical thickening, coarse trabecula and osteoarthritic changes were noted in right femur and hip, consistent with Paget’s disease. Left femur showed strikingly thinner cortices compared to the right, due to underlying osteoporosis. MRI of lumbar spine and pelvis was consistent with polyostotic Paget’s involving L3-L5, Sacrum and Right femur. Nuclear bone scan showed areas of uptake including anterior calvarium, lumbar spine, right hip, right femur, 8th rib, left mid tibia and 1st metatarsal of left foot. Since the distribution of uptake seemed atypical for Paget’s, a skeletal survey was obtained which was negative for bone lesions suggestive of malignancy.

Laboratory testing revealed serum calcium 9.8mg/dL(8.4–10.2), 25-Hydroxy Vitamin D 30ng/dL(20–30), PTH 45.6pg/mL (15–65), Alkaline Phosphatase 370U/L (35–104), Procollagen I intact N-terminal 516mcg/L (16–96) and N-Terminal Telopeptide (NTX) 126.4 nM BCE (6.2–19).

Patient received one dose of IV Zoledronic acid with modest improvement in hip and lower back pain. She continues to take Calcium carbonate 600mg twice daily and vitamin D3 1000IU once daily. We plan to see her in follow up in 3 months with repeat levels bone turnover markers.

Conclusion: This is a unique case of Paget’s disease and osteoporosis, two very different diseases of metabolic bone disorder spectrum found in one patient. Treatment of Paget’s disease is indicated for pain reduction, prevention of fractures and deformities and to prevent disease progression in weight bearing areas. Bisphosphonates can target pathology of both diseases by reducing osteoclastic bone resorption.

<![CDATA[MON-337 Peripheral Neurological Complications in Pregnancy- Is Idiopathic Transient Osteoporosis of Pregnancy Concerning?]]> Idiopathic transient osteoporosis of pregnancy (ITOP) is a rare and under-reported condition that has affected healthy pregnancies. ITOP usually presents in the final trimester of a normal pregnancy. Radiographic studies detect drastic loss of bone mass, elevated rates of turnover in the bone, and edema in the affected portion.

We present a 26-year-old previously healthy woman, who was admitted at 39 weeks of gestation with severe left hip pain and inability to walk for one month.The pain was constant, progressive, involving left lower limb, and associated with numbness and weakness. Neurological exam revealed diminished power in the left hip (motor power was 2/5), and inability to stand and walk due to pain in the left hip. She was unable to stand by herself. Investigations revealed anemia, low vitamin B12, low vitamin D and magnesium. Bilateral hip MRI showed increased T2WI signal in the left femoral head consistent with idiopathic transient osteoporosis of the left hip (ITOP). DXA scan showed bone mass density (BMD) below expected for age.The patient had induced vaginal labor without complication. The left hip pain improved after delivery. She was treated conservatively with Calcium, Magnesium and vitamin D. The patient symptoms completely resolved in 3 months post-delivery. DXA scan and Hip MRI at 1 year interval showed normal BMD and complete resolution of previous bone marrow edema and changes seen in MRI hip.

This case report serves to highlight the effect of pregnancy on bone mass during third trimester which may result in transient osteoporosis of pregnancy leading to weakness and gait disturbance. Clinical symptoms can be misdiagnosed as a peripheral neurological complications instead of bone metabolism changes of pregnancy.

<![CDATA[MON-338 Severe Hypophosphatemia Induced by Intravenous Ferric Carboxymaltose Therapy for Iron Deficiency Anemia]]> Background: Ferric carboxymaltose (Injectafer), a newer intravenous iron agent permits larger iron concentrations to be delivered in fewer doses compared to traditional preparations of intravenous iron. However, ferric carboxymaltose has been shown to up-regulate fibroblast growth factor 23 (FGF23) which can result in severe hypophosphatemia. We present a case illustrating this phenomenon.

Clinical Case: A 48 year-old Caucasian female was admitted to the emergency department with complaints of gradual onset muscle weakness and severe exhaustion. Over the course of several months she noticed significant muscle weakness in all extremities.

Her co-morbidities included morbid obesity (status-post Roux-en-y bypass surgery), asthma, and hereditary angioedema. Due to her history of gastric bypass surgery, the patient required monthly iron sucrose infusions over the previous two years. Her regimen was changed to ferric carboxymaltose (Injectafer) about five months prior to the admission, receiving 750mg treatments twice monthly.

On admission, she was found to have severe hypophosphatemia of 1.5 mg/dL (2.1 – 4.7 mg/dL) with 25-OH vitamin D 21 ng/mL and PTH of 155 pg/mL. A random urinary phosphate was 72 mg/dL with a urine creatinine of 45 mg/dL, with calculated fractional excretion of phosphorus of 74%. Further diagnostic tests including EMG / nerve conduction studies, inflammatory markers, autoimmune workup, and creatine kinase were negative. She was found to have a ferritin of 2159 ng/mL (11 – 306 ng/mL) from previous baseline of 12.8 ng/mL with normal ESR and CRP. This was elucidated to be due to iron overload from IV iron infusions out of proportion to her needs. Therefore, ferrric carboxymaltose was discontinued. Her symptoms gradually improved with phosphorus and vitamin D supplementation. Two months later, when seen by Endocrinology, her ferritin was 1220 ng/mL, PTH 44 pg/mL, and phosphorus normalized to 2.6 mg/dL.

Conclusion: Ferric carboxymaltose can cause profound phosphaturia and hypophosphatemia by inhibiting the cleavage of intact FGF23 to the inactive form, a mechanism similar to autosomal dominant hypophosphatemic rickets. Previous clinical trials show the incidence of hypophosphatemia to be as high as 41-70%. We conclude that baseline phosphorus and vitamin D levels should be obtained prior to therapy and monitored closely during treatment.

Reference: Adkinson NF et al. Comparative safety of intravenous ferumoxytol versus ferric carboxymaltose in iron deficiency anemia: A randomized trial. Am J Hematol. 2018;93(5):683.

<![CDATA[MON-363 Massive Bony Exostoses and Diffuse Osteosclerosis Secondary to Hepatitis C: Case Report]]> Introduction:

Acquired osteosclerosis due to hepatitis C is a rare complication. While there are previously published case reports of this condition, to our knowledge this is the first case reported with diffusely increased osteosclerosis and prominent bony exostoses.

Clinical Case:

A 52-year old woman was evaluated in the Metabolic Bone Clinic for non-radiating left hip pain and visibly prominent hard, non-tender masses at the lateral aspect of her bilateral hips and proximal humerus. She denied history of fragility fractures, radiation exposure, risk factors for sexually transmitted diseases or substance abuse. Laboratory evaluation showed vitamin D deficiency with a value of 18 ng/mL (reference range: 25-100 ng/mL), elevated alkaline phosphate of 426 IU/L (reference range: 30-116 IU/L) and markedly increased serum C-telopeptide with a value of 1901 pg/mL (reference range: <1008 pg/mL). Plain radiographs showed multiple exostoses at the pelvis, hip, and shoulders. MRI showed extensive thoracic spine endplate sclerosis and increased sclerosis throughout the pelvis and proximal femurs. Massive calcifications adjacent to the greater trochanters were also identified. A total body bone scan revealed intensely increased uptake in multiple bones consistent with a “super scan.” Bone biopsy showed sclerotic bone with extensive remodeling. Computed tomography of the chest, abdomen, and pelvis was negative for malignancy. Given the symmetric nature of these lesions and diffusely increased uptake, the diagnosis of metabolic bone disease was considered. Further testing revealed hepatitis C Ab positivity confirmed with HCV Quant PCR 1553475 IU/mL (reference range: undetected). Pathologic findings were attributed to hepatitis C and treatment for hepatitis c was initiated with subsequent improvement in alkaline phosphate to 273 IU/L.

Clinical Lessons:

Osteosclerosis represents a little-known complication of hepatitis C. It is postulated that hepatitis C itself or other unknown agents may stimulate hepatic growth factors that increase osteoblast action. The radiographic and bone scan findings are classic for acquired osteosclerosis seen as increased cortical thickening with an intensely increased uptake in multiple bones. It frequently affects the lower extremity and this condition may take years to develop. Bone formation markers such as alkaline phosphate are typically elevated and bone biopsies show increased rates of remodeling as seen in our patient. While bisphosphonates may improve the serum markers for bone formation, they have not been shown to reverse or halt the progression of skeletal changes. Thus far, there has been a single case report showing improvement in sclerosis following treatment for hepatitis C with ribavirin and interferon. Natural history, progression and treatment of this condition have not been well established.

<![CDATA[MON-333 Cutaneous Skeletal Hypophosphatemic Syndrome (Cshs) Caused by Somatic HRAS p.G13R Mutation: Long Follow-Up of Two Brazilian Women]]> BACKGROUND CSHS refers to the association of epidermal nevus syndrome (ENS), skeletal dysplasia, and hypophosphatemic osteomalacia (OM) mediated by FGF23 resulting from post zygotic mutations in RAS signaling pathway, with known by relationship with human cancers. CLINICAL CASE Patient 1 presented ENS since birth at right hemibody. At 1.6-yr-old, she underwent treatment for a left inguinal rhabdomyosarcoma. At 3-yr-old, she had an atraumatic right femur fracture associated with muscle weakness, and laboratory data and X-rays suggesting OM. Phosphate and calcitriol were initiated, but with poor adherence, and no improvement; skeletal deformities got worse and the girl became wheelchair user at 13-yr-old. Skeletal CT scan at age 17 showed dysplastic lesions with lytic changes at right dimidium (skull, jaw, ribs, pelvis and femur) with systemic OM signs confirmed by bone biopsy. The progressive enlargement of the jaw lesion required surgical removal after 2 years; histopathology revealed giant cell tumor. Patient 2 also had congenital ENS on the right dimidium with complaint of bone pain and muscle weakness since 2-yr-old. She evolved with bone fractures and deformities at 4-yr-old, becoming wheelchair user after 2 years. Iliac crest biopsy confirmed OM, already suspected based on laboratorial and X-rays findings at age 7. She had few improvements with phosphate and calcitriol treatment also due to low compliance. During follow-up, symptomatic nephrolithiasis occurred and, in regions affected by EN, multiple basal cell carcinomas (BCCs) emerged requiring excisions. Skeletal CT scan at age 36 showed dysplastic lesions at right hemibody (skull, ribs, pelvis, and limbs) with diffuse bone rarefaction and signs of OM. Sanger sequencing of DNA from EN and jaw tumor samples of patient 1 and from EN and BCC samples of patient 2 disclosed heterozygous HRAS p.G13R mutation, and this mutation was absent in leukocytes DNA from both patients confirming CSHS mosaicism. Owing to the CSHS associated increase risk of cancer, screening with thyroid and breast ultrasound, mammography, CT of skull, chest, abdomen, and pelvis ruled out presence of tumors in patient 1. Patient 2 is waiting for similar screening. Nowadays, patient 1 is 25-yr-old and patient 2 is 36-yr-old; both women have maintenance of OM, characterized by persistent hypophosphatemia with elevated bone formation makers despite treatment with phosphate and calcitriol. CONCLUSION CHSC is a very rare syndrome with less than 10 cases with molecular characterization in literature. Although Collins et al suggest an age-dependent improvement in mineral abnormalities, we reported two women without OM recovery probably because of extensive bone dysplasia. These cases also reinforce association of CSHS with neoplasms, including first descriptions of patients with rhabdomyosarcoma and giant cell tumor of jaw and the longest follow-ups described until.

<![CDATA[MON-374 Management of 1,25-dihydroxyvitamin D (1,25-OHD) Mediated Hypercalcemia of Unknown Etiology]]> Background: We describe the diagnostic dilemma and treatment challenges faced in a rare case of 1,25-OHD mediated hypercalcemia. Clinical Case: A 13 year old boy was admitted with severe hypercalcemia (calcium 15.5 mg/dl) in the setting of a non-specific rash, malaise, pancytopenia and acute kidney injury. He was incidentally also noted to have hypogammaglobulinemia a few months prior to presentation. Blood tests were suggestive of hypercalcemia mediated by 1,25-OHD (level >200 pg/ml; ref: 30-83 pg/ml). 25-hydroxy vitamin D was normal (29 ng/ml) and PTH was appropriately suppressed (<4 pg/ml). Workup for various etiologies including infectious, rheumatologic and oncologic diseases associated with ectopic production of 1,25-OHD was initiated. Hypercalcemia was initially managed with hyperhydration, furosemide and calcitonin. However after a brief period of improvement in hypercalcemia, levels started to rise again despite increasing calcitonin dose and frequency (secondary to tachyphylaxis). Kidney function also started to worsen. Extrarenal 1-alpha hydroxylase activity can be suppressed using steroid therapy, however it was contraindicated at the time given that malignancy and other infectious etiologies had not been excluded. At that point, a trial of zoledronic acid was done with subsequent resolution of hypercalcemia. However, this was only temporary given that the underlying disease process driving the production of 1,25-OHD had not been addressed. Various other treatment options were considered including a repeat dose of bisphosphonate, denosumab, ketoconazole and hydroxychloroquine, but since hypercalcemia was only mild, supportive measures were continued. An extensive workup revealed splenomegaly, lymphadenopathy, bilateral renomegaly and bilateral pulmonary ground glass opacities and nodules. Infectious workup and bone marrow biopsy were negative. Although non-specific, an elevated angiotensin converting enzyme (ACE) level (359 units/L; ref: 13-100 units/L) suggested an underlying granulomatous process. Renal biopsy showed non-caseating granulomas. The most likely unifying diagnosis was thought to be sarcoidosis, however presence of hypogammaglobinemia also raised suspicion for a granulomatous form of Common Variable Immunodeficiency (CVID) which, albeit rare, has previously been reported to be associated with hypercalcemia. Patient was started on empiric treatment with steroids and intravenous immunoglobulin following which calcium, 1,25-OHD and ACE levels normalized. Conclusion: Granulomatous form of CVID is a rare entity but should be considered in a patient presenting with 1,25-OHD mediated hypercalcemia and hypogammaglobulinemia. Treatment of this entity during an ongoing diagnostic workup can be challenging, particularly if the use of steroids is contraindicated due to potential interference with diagnostic investigations.

<![CDATA[MON-355 Charge Syndrome: Unusual Cause of Hypogonadism Leading to Osteoporosis]]> CHARGE syndrome is an unusual cause of hypogonadism; it is characterized by coloboma, heart defect, ateresia choanae, retarded growth and development, genital hypoplasia and ear anomalies. Two-thirds of affected patients have a mutation within the chromodomain helicase DNA-binding protein-7 gene, which is involved in embryonic development. The involvement of this gene in the pathogenesis of isolated idiopathic hypogonadotropic hypogonadism (HH) has been postulated. The reported incidence of this syndrome ranges from 0.1–0.2/10000 (1).

A 24 year old female presented to our facility for further management of her HH and osteoporosis in the setting of her CHARGE syndrome. She was born full-term and diagnosed with this condition at the age of 6. Formal genetic testing as an adult demonstrated mutation within the CHD7 gene (chr 8:61,757,970). She had delayed puberty secondary to her hypogonadism; she was not treated with HRT as benefits were not considered significantly sufficient. She subsequently developed osteoporosis at the age of 20 which was treated at an outside facility with pamidronate IV Q4 months along with calcium and Vitamin D supplementation. Her initial Dual-energy X-ray absorptiometry (DXA) showed scoliosis in the lumbar spine [bone mass density (BMD): 0.514,osteoporosis by Z-score] with total hip showing BMD: 0.738,osteopenia by Z-score. Follow-up DXA after 3 years showed statistically significant improvement in bone mineralization of her L-spine [BMD: 0.595, +16%] and total hip [BMD: 0.777, +13.5%]. She presented to our facility in 2018 with labs showing normal calcium and 25-OH D; treatment with pamidronate was continued. She had a repeat DXA in 2019 which showed Z-scores of 0 in the left and right femoral necks. She was given the option of continued treatment for her osteoporosis versus monitoring and chose the latter with follow-up DXA.

Hypogonadotropic hypogonadism is associated with delays in puberty or pubertal arrest. Luteinizing Hormone Releasing Hormone and HCG tests should be performed within the four months of life or at puberty in cases of hypogenitalism. GH deficiency should be investigated as a cause for growth retardation with GH stimulation levels. Hormone replacement is often required at puberty for females and is indicated for prevention of osteoporosis. Radiological testing with DXA scan should be included. Early proper endocrinological assessment and management is essential for adequate sexual development in these patients; this leads to improved overall quality of life along with prevention of serious morbidities, including bone demineralization (2).

1. Blake K D, Prasad C. CHARGE syndrome. Orphanet Journal of Rare Diseases 2006, 1:34.

2. Foppiani L, Maffe A. CHARGE syndrome as unusual cause of hypogonadism: endocrine and molecular evaluation. Andrologia (2010). 42: 326–330.

<![CDATA[MON-356 Atypical Femur Fracture with Denosumab]]> Background: Osteoporosis (OP) is a systemic disease that is associated with increased risk for fractures. Anti-resorptive medications (ARM) are an effective modality for treatment and prevention of fractures in OP. Long-term use of ARM like bisphosphonates (BP) is associated with increased risk of atypical femoral fractures (AFF). Denosumab (DM) is monoclonal antibody that targets receptor activator of nuclear factor KB ligand (RANKL). A few cases of AFF with DM have been reported in patients who have previously been on long term BP therapy. We present a case where the patient had only received two zoledronic acid (ZA) infusions, last one three years prior to being initiated on DM and experienced AFF.

Case: 73-year-old postmenopausal woman presented to the emergency room with sudden onset pain in the right thigh. Patient was standing and reaching into her closet when she felt a snap in right thigh followed by inability to move the right leg or bear weight on it. X-ray of the right femur showed a displaced femoral shaft fracture with a short transverse fracture line and a spike, without comminution.

History was significant for OP for which she received raloxifene for a couple of years followed by ZA in 2013 and 2015 by her primary care. Fracture history was significant for a wrist fracture in 2015, and T12 and L1 fractures in 2017 from coughing while on Medrol dospak for an acute episode of bronchitis. In 2017, bone density showed L1-L4 T score of -2.0, the left total hip T score was -1.8 and left femoral neck T score was -2.5 consistent with OP. Work up for secondary causes of OP was unremarkable. Due to recent T12 and L1 compression fractures, she was recommended DM. She received DM in June 2018 as she was undergoing a dental implant followed by December 2018 and June 2019 and presented with the right femoral fracture in November 2019.

Past history was significant for idiopathic pulmonary fibrosis which had been relatively stable without need for long-term steroid therapy. History was negative for diabetes or kidney disease. Menarche was at age 14, menopause at 52 and she did not take any hormone replacement therapy.

She underwent surgical fixation with intramedullary rod. Due to concern about ARM associated sub-trochanteric fracture in the right femur, left femur was imaged. She had cortical beaking in the distal third of the left femur, and underwent prophylactic medullary nailing of the left femur as well.

Conclusion: AFF are an uncommon complication of ARM used for OP. Not many cases of AFF have been reported with the use of DM and most of the reported cases are associated with prolonged BP therapy. Our case is unusual in that AFF occurred in the absence of prolonged BP therapy and raises concern that a couple of ZA infusions in the past can also increase the risk of AFF. Clinicians need to have a high index of suspicion and may consider doing femur x-rays in patients who have previously been on BP prior to starting DM.

<![CDATA[MON-354 Hypocalcemia: Hypoparathyroidism or Calcium Chelation in a Transfusion-Dependent Patient?]]> Transfusion-associated hemochromatosis (TAH) can result in multiple endocrinopathies. Timely diagnosis and treatment can prevent life-threatening consequences. Here we report a misdiagnosed case of a transfusion-dependent 32 yo female with severe hypocalcemia.


Patient is a 32 yo female with Diamond-Blackfan anemia requiring chronic blood transfusions every 2-3 weeks. She has a history of non-compliance with iron chelation therapy, and as a child was diagnosed with TAH complicated by pancreatic diabetes, GH deficiency, hypogonadotropic hypogonadism, and primary hypothyroidism. In 2014, patient was evaluated for bilateral calf pain and found to have low calcium (6.9mg/dL) and elevated phosphorus (6.4mg/dL). She was started on calcium carbonate and calcitriol, but subsequently lost to endocrine follow up. During that time, calcitriol was discontinued, and she was treated with calcium alone for presumed hypocalcemia due to transfusion-related calcium chelation.

In 8/2019, patient was seen in the ED for symptomatic hypocalcemia (Ca 6.2mg/dL, PTH 3pg/mL, vitamin D 25-OH 43.5ng/mL and ferritin 1147ng/mL). She was not taking medications for her other endocrinopathies at that time, with TSH 104, estradiol <30, FSH <1, IGF-1 11. MRI confirmed no pituitary abnormality. She was evaluated by Endocrinology and diagnosed with hypoparathyroidism. She was started on calcium carbonate and calcitriol with stabilization of calcium levels, restarted on levothyroxine and discussion of estrogen replacement was started. She is not currently requiring insulin for treatment of her diabetes.


Patients with TAH develop organ damage from iron deposition in a pattern similar to hereditary hemochromatosis, with preferential deposition in the gonadotrophs and lactotrophs leading to hypogonadism and hypoprolactinemia. Primary hypothyroidism, GH deficiency and primary hypoparathyroidism are rare by comparison. Our patient is unique in her wide range of endocrinopathies.

More importantly, this case highlights that failure to recognize these endocrinopathies can lead to inappropriate management and increased morbidity to patients. Despite frequent contact with the health care system for management of her anemia, her endocrine labs were not consistently monitored, leading to the false diagnosis of calcium chelation for her hypocalcemia and treatment with calcium replacement alone. A correct diagnosis of primary hypoparathyroidism due to iron deposition ensured proper treatment with both calcium and calcitriol in this patient’s case.


Hypocalcemia associated with transfusion may be due to TAH or calcium chelation. It is important to recognize the rare case of primary hypoparathyroidism when present, in addition to other endocrinopathies, to ensure patients receive appropriate treatment.

<![CDATA[MON-364 Severe Postoperative Encephalopathy in a Patient with Oncogenic Osteomalacia and Neurofibromatosis Type 1]]> Background: Acute hypophosphatemia superimposed on chronic phosphate depletion results in decline in intracellular ATP and 2,3-diphosphoglycerate levels, affecting virtually all organ systems. It can lead to metabolic encephalopathy, impaired myocardial and diaphragmatic contractility, skeletal and smooth muscle dysfunction, increase in erythrocyte rigidity leading to hemolysis, and increased risk for postoperative morbidity and mortality. Risk of symptomatic hypophosphatemia may be greater in patients with urinary phosphate wasting syndromes hospitalized for intercurrent illness. Tumor-induced (oncogenic) osteomalacia (TIO) is a rare paraneoplastic disorder associated with mesenchymal tumors caused by tumor production of fibroblast-derived growth factor-23 (FGF-23). FGF-23 impairs transport of phosphorus in renal tubules, inhibits renal 25(OH)-1-α-hydroxylase activity, causing decreased levels of calcitriol, leading to hyperphosphaturia, hypophosphatemia and osteomalacia. We present a case of a patient with underlying TIO who presented with acute hypophosphatemia following hip surgery.

Case: 50-year-old woman with Neurofibromatosis type-1(NF-1) complicated by TIO, presented after a fall resulting in left femur fracture requiring surgery. During her initial management in an outside hospital for 4 days and following transfer her home calcitriol and phosphorus replacement regimen was not administered leading to treatment interruption of 7 days. On postoperative day 1 she became hypotensive, tachycardic with non-specific ST-T changes and encephalopathic requiring ICU care. At the time of endocrinology consultation, she was non-verbal, not following simple commands, had severe hypophosphatemia, transaminitis, hyperbilirubinemia, elevated LDH, anemia and elevated troponin. She required aggressive phosphate and calcitriol replacement reaching 4 doses of 20mEq IV Na- Phos daily, Na-KPhos Q6H and Calcitriol IV 0.5mcg Q8H over the course of 72 hours. After 4 days in the ICU, once phosphorous levels normalized, she had dramatic improvement in mental status and gradual resolution of laboratory abnormalities.

Discussion: To our knowledge, this is the first report of a patient with TIO associated with NF-1 presenting with severe symptomatic hypophosphatemia causing metabolic encephalopathy and multiple organ dysfunction following surgery. It underscores the fact that abrupt interruption of calcitriol and phosphorus supplementation in such cases can cause acute hypophosphatemia carrying high morbidity. High phosphate replacement requirements are indicative of severity of phosphate depletion. This case illustrates importance of recognition of presence of urinary phosphate wasting syndrome in hospitalized patients in order to minimize risk of preventable complications and morbidity.

<![CDATA[MON-346 Secondary Hyperparathyroidism and Other Complications in a Post-Roux-En-Y Patient: A Case Report]]> Roux-en-y Gastric Bypass is a very common surgical procedure in managing morbid obesity. Approximately 303,890 roux-en-y surgeries were performed in the United States in between the years of 2012 to 2017, and the number is steadily increasing as more Americans are diagnosed with obesity.i

This featured case report describes a 52-year-old female presenting with complications seven years following Roux-en-y gastric bypass. Four years post-operatively, she presented to the ER with a pelvis fracture. It was incidentally found that she had osteoporosis with a t-score of -2.9. It was also found that her bone mineral density (BMD) for women for her age was low with a z-score of -3.5 and her 10-year probability of getting fractures was high with a Fracture Risk Assessment Tool (FRAX) score of 6.2%. Seven years following Roux-en-y gastric bypass, she presented to our primary care office with Vitamin B12 deficiency and secondary hyperparathyroidism due to Vitamin D deficiency. We attempted to correct the deficiencies with high dose of Vitamin D, Vitamin B12, and calcium citrate. Eight months later, the B12 levels was normalized, but the secondary hyperparathyroidism and Vitamin D deficiency were not corrected. This case illustrates the complications that can occur following a Roux-en-y Gastric Bypass, importance of supplement compliance, and proper follow-up with Roux-en-y patients.


i American Society for Metabolic and Bariatric Surgery. (2018). Estimate of Bariatric Surgery Numbers, 2011-2017 | American Society for Metabolic and Bariatric Surgery. [online] Available at: [Accessed 31 Oct. 2019].