bluuebunny/crossref_metadata_2025 huggingface dataset:
THU434 A Case Of An Atypical Femur Fracture Managed Medically With Teriparatide
Authors: Rupani Sawan V , Kotwal Anupam , Graeff-Armas Laura
Published: October 2023

Disclosure: S.V. Rupani: None. A. Kotwal: None. L. Graeff-Armas: None.

Atypical femur fractures (AFFs) are atraumatic or low-trauma femur fractures located in the sub-trochanteric region or femoral shaft. AFFs represent around 0.5% of all femur fractures. The increased use of bisphosphonates has led to a rise in the incidence of AFFs as it has emerged as a potential complication. While the mechanism of bisphosphonate-related AFFs has yet to be elucidated, one proposed mechanism is that bisphosphonates can cause over-suppression of bone turnover. If over-suppression is a contributing factor, then hypothetically, anabolic therapy can help heal existing fractures and prevent impending fractures by reversing over-suppression. Numerous animal models have demonstrated that parathyroid hormone and teriparatide enhance fracture healing. However, clinical trials and meta-analyses on the effects of teriparatide in fracture healing have been equivocal. There have been both retrospective and prospective studies, along with anecdotal reports demonstrating the benefits of teriparatide in healing in AFFs. However, there have been no randomized controlled trials assessing the efficacy of teriparatide in AFFs. Based on this limited evidence, the American Society for Bone and Mineral Research recommends considering teriparatide in patients who have failed conservative therapy. We present a case of an incomplete AFF in the setting of short-term bisphosphonate use that was managed with teriparatide in addition to conservative measures. Our patient presented with a complete right AFF treated surgically and an incomplete left AFF that we managed medically with teriparatide. Repeat left femur imaging six months after starting teriparatide therapy showed interval callus formation consistent with a healed fracture. Right femur imaging also showed a healing proximal femoral shaft fracture status post intramedullary fixation. She completed twenty-five months of teriparatide therapy and did not sustain any interval fractures. Repeat imaging one year after completion of teriparatide therapy continued to show a stable healed left AFF, along with a healed right AFF. She is currently more than two years post-completion of teriparatide and has remained fracture free. This case highlights the role that teriparatide may have as an option for medical management in incomplete AFFs and to accelerate healing in complete AFFs that have been managed surgically. Furthermore, with therapeutic options for osteoporosis management limited in the post-AFF setting, teriparatide helps increase bone mineral density and reduce future fracture risk. Randomized controlled trials are needed to draw definite conclusions on the efficacy of teriparatide in managing AFFs. However, this is difficult given the rare occurrence of AFFs. Therefore, case reports like ours offer insight into when teriparatide may be helpful in managing AFFs.

Presentation: Thursday, June 15, 2023
THU438 A Case Of Pregnancy Associated Osteoporosis
Authors: Maradana Sandhya , Iqbal Fizzah , Safran Marjorie
Published: October 2023

Disclosure: S. Maradana: None. F. Iqbal: None. M. Safran: None.

Background: Pregnancy associated osteoporosis (PAO) is a rare form of osteoporosis that is seen in late pregnancy and early post-partum period. Hip and vertebral body are most involved in PAO. Common clinical manifestation is back pain, and many patients suffer from vertebral fractures and kyphosis causing great physiologic burden and negative impact on quality of life. We report a case of PAO with good response to teriparatide. Clinical case: A 27-year-old female with no significant past medical history presented with severe acute back pain two months after delivery of her second child, whilst still breast feeding. Imaging studies demonstrated acute compression fractures of T12, L1, L2 and L3 vertebrae. She had regular monthly menstrual cycles prior to pregnancy with no previous history of fractures. Her pre pregnancy weight was 135 lbs and she had been physically active, while caring for her older son. Family history is notable for osteoporosis in multiple paternal aunts and maternal grandmother with no family history of fractures. There were no other identifiable risk factors. Evaluation for secondary causes of osteoporosis showed 25-OH vitamin D levels of 23 ng/mL (NL 30-100 ng/mL), TSH 1.72 uIU/mL (NL 0.28-3.8 uIU/mL), PTH 19 pg/mL (NL 14-64 pg/mL), calcium 9.7 mg/dL (NL 8.7-10.7 mg/dL), phosphorus 4 mg/dL (NL 2.5-4.5 mg/dL), tryptase 4 mcg/L (NL <11 mcg/L), alkaline phosphatase 111 U/L (NL 30-115 U/L) and 24-hour urine calcium 168 mg (NL 100-300 mg). Urine immune electrophoresis and serum immunofixation did not show any evidence of monoclonal gammopathy. DEXA scan showed low BMD with Z-score of −4.4 SD in lumbar spine -3.1 in femoral neck. She was diagnosed with PAO. She stopped breast feeding after the diagnosis. As the bone mineral density was very low, she was started on teriparatide along with calcium and vitamin D supplementation. One year after treatment initiation, her DEXA scan showed improved bone mineral density with Z-score of −3.5 in lumbar spine and −1.9 in femoral neck. Her osteoporosis is currently being managed with teriparatide with plan to continue for a total duration of 24 months. Conclusion: PAO is under-recognized and under-reported, with limited available evidence on the management. Spontaneous improvement in BMD is known to occur in 6-12 months after pregnancy and lactation have been completed, although, the addition of anti-resorptive treatment in this setting may result in superior BMD gain compared with calcium and vitamin D supplementation alone. Use of teriparatide has shown to have significant increase in BMD and help with pain relief in PAO. Teriparatide has helped with improving the BMD in our patient. Nevertheless, controlled trials are lacking, and the optimal timing of teriparatide use in these women remains uncertain.

Presentation: Thursday, June 15, 2023
THU441 Teriparatide As Treatment For Severe Osteoporosis In Lung Transplant Recipients
Authors: Muir Christopher Alan , Raven Lisa Mary , Goodall Louise , Center Jacqueline R
Published: October 2023

Disclosure: C.A. Muir: None. L.M. Raven: None. L. Goodall: None. J.R. Center: None.

Background: Lung transplantation (LTx) is a life-saving treatment for end-stage pulmonary disease. With improvements in immunosuppression, LTx survival continues to improve with current 5-year survival rates of over 70%. Consequently, management of long-term transplant-related complications is increasingly important. Osteoporosis is one such complication, with the incidence of osteoporosis and osteoporotic fracture highest in LTx patients compared to other solid organ transplant recipients. Despite high fracture rates, including in patients treated with anti-resorptive medications, no data has been published using anabolic treatments for the management of osteoporosis in LTx recipients. Study design: Clinical case series. We present clinical, biochemical and bone mineral density data for four patients with severe osteoporosis post LTx treated with teriparatide. Results: Four LTx patients were treated with teriparatide 20 mcg daily for 18 months. Prednisone dose ranged between 5-10 mg daily throughout the treatment period. All patients had been previously treated for osteoporosis using zolendronate (last dose 12-24 months prior to teriparatide initiation). Bone turnover was monitored repeatedly during treatment in two patients. Following completion of teriparatide treatment, all patients received consolidation treatment with zolendronate (3 patients) or denosumab (1 patient). Bone density was measured prior and within 6-12 months after completion of teriparatide. All four patients experienced an increase in bone density at the spine (median 13%; range 2-14%) and total proximal femur (median 8%, range 6-10%) related to teriparatide treatment. No adverse effects were observed. Conclusion: Given that severe osteoporosis is highly prevalent in LTx patients and that fractures often continue to occur after treatment with anti-resorptive medication, teriparatide should be further studied as an alternative treatment in this clinical setting. Our experience in four patients suggest it is safe and effective.

Presentation: Thursday, June 15, 2023
THU453 Chronic Headaches As A Presentation For Monostotic Craniofacial Fibrous Dysplasia: A Case Study
Authors: Dyer Barbara , Bhattacharya Rajib Kumar
Published: October 2023

Disclosure: B. Dyer: None. R.K. Bhattacharya: None.

Background: Monostotic craniofacial fibrous dysplasia (CFFD) is often asymptomatic and is found incidentally on imaging. Previous reports described cases in which CFFD diagnosis was preceded by chronic headaches, but there remains a lack of clinical association between these diagnoses. Clinical Case: Patient is a 22-year-old female with a long history of chronic headaches who presented to the emergency department two days after a motor vehicle accident with complaints of headache, blurred vision, nausea, and dizziness. CT revealed an incidental sclerotic mass in the left frontal region measuring 7.9x7.3x3.7cm extending inferiorly into the left ethmoid sinus. At her primary care follow-up, she reported a pounding, left-sided headache in addition to balance issues, dizziness, nausea, and blurry vision. Workup was significant for vitamin D level of 11.2ng/mL (n = 30-100ng/mL), alkaline phosphate of 106U/L (n = 35-104U/L), and calcium of 9.1mg/dL (n = 8.6-10.3mg/dL). MRI was significant for a heterogeneous, hypointense expansile calvarial lesion within the left frontal and left sphenoid bones. The patient was diagnosed with CFFD based on radiologic findings. The patient was advised against surgical intervention due to her disease’s large, invasive nature. The patient was seen by neurology for recurrent headaches and was subsequently started on topiramate with partial symptom relief. Endocrinologist management included confirmation of monostotic CFFD by bone scan. Biopsy was deferred due to the low likelihood of malignant transformation, and bisphosphonate treatment was initiated. She was subsequently started on 5000 IU per day of vitamin D to normalize the vitamin D level before the initiation of bisphosphonate treatment for her pain. She received 5mg intravenous infusion of zoledronic treatment. At follow-up, the patient states she had significant improvement in all symptoms. Conclusion: Pain from FD can be debilitating and often increases in severity as the patient ages, though pain is not strongly correlated to presentation or disease burden. The mechanism by which CFFD produces pain is not fully elucidated. The unique innervation of bone and the creation of new sensory nerve fibers during inflammatory states may contribute. Additionally, excess IL-6 during inflammatory states may also play a role in pain production due to lesion expansion from osteoclast activation, cystic formation within the lesion, and hormonal reactivity of the lesion. Bisphosphonates are believed to inhibit IL-6 production, reducing osteoclastic activity and leading to symptomatic pain relief. In the case presented, the patient’s chronic headaches improved significantly following combination therapy with migraine abortive medication and bisphosphonate therapy. Early recognition and multidisciplinary treatment are key in the long-term management of CFFD pain.

Presentation: Thursday, June 15, 2023
THU463 Etiology Of Hypophosphatemia In A Patient With Co-existing Mesenchymal Tumor And Fibrous Dysplasia
Authors: Patil Madhuri , Wangsiricharoen Sintawat , Lazar Alexander , Guise Theresa Ann
Published: October 2023

Disclosure: M. Patil: None. S. Wangsiricharoen: None. A. Lazar: None. T.A. Guise: None.

Tumor induced osteomalacia (TIO) is a rare paraneoplastic phenomenon. Fibroblast growth factor-23 (FGF23) secretion from phosphaturic mesenchymal tumor (PMT) is implicated as the cause for hypophosphatemia and osteomalacia. Other rare conditions associated with dysregulated FGF23 production include fibrous dysplasia (FD). Coexistence of two unusual conditions which could increase FGF23 concentrations is rare. We report a case of PMT causing TIO in a patient with evidence of FD. A 79-year-old male was evaluated for worsening rib and right flank pain of more than one year duration. He also complained of generalized muscle weakness. His total alkaline phosphatase (ALP) levels were noted to be increased for many years. Computed tomography (CT) showed scattered sclerosis within ribs, and lytic lesions with cortical bone destruction in right iliac bone (4.3 x1.5 cm) and L4 vertebra. Biopsy of the right iliac lesion revealed findings compatible with PMT. Positron Emission Tomography (PET) showed fluorodeoxyglucose (FDG) avid lesion of the right anterior iliac wing, diffuse osteomalacia, insufficiency fractures of the ribs, as well as FDG avid lesions in left supra-acetabular area and in L4 vertebral body concerning for metastatic disease. Laboratory evaluation revealed ALP 306 (40-129 U/L), bone specific ALP 99 (0-20 mcg/L), phosphorus 1.5 (2.5-4.5 mg/dL), 25-(OH)-vitamin D 27 (30- 100 ng/mL), 24 hour urinary phosphorus 0.6 (0.4-1.3 g/24 hr), PTH 51.3 (15-65 pg/mL), FGF23 303 (<180 RU/mL), Calcium 10.3 (8.4-10.2 mg/dL), albumin 4.4 (3.5- 5.2 gm/dL), C-terminal telopeptide of type 1 collagen (CTX) 1611 (10-854 pg/mL). CT-guided cryoablation of the right iliac lesion was performed. Also, biopsy and cryoablation of the left supra-acetabular lesion was performed; pathology showed fibrous dysplasia (FD). Mutation analysis confirmed a mutation in exon 8 of GNAS gene. Post ablation, FGF23 dropped to 102 RU/mL and phosphorus increased to 3.0 mg/dL. The patient had significant improvement in bone pain and weakness. The patient with classic features of TIO improved with simultaneous cryoablation of both the PMT as well as the FD lesions. The unusual feature of the case is co-existence of PMT and FD. Malignant transformation of FD lesions is a rare complication. We confirmed that the PMT did not have GNAS mutation and is unlikely to arise from FD. And FGF23 in situ hybridization was strongly positive in the PMT and negative in the FD, ruling out FD as a contributor to patient’s hypophosphatemia. We plan to perform DOTATATE scan to differentiate PMT from FD in the L4 lesion. This is a unique case of coexistence of two separate conditions, both of which could secrete intact FGF23. Our studies suggest that PMT is the only etiology of hypophosphatemia and TIO.

Presentation: Thursday, June 15, 2023
THU470 Blood - Bone Connection? A Case Of A Young Woman With Bilateral Hip Osteonecrosis And Prothrombin Mutation
Authors: Sliwinska Aleksandra , Vanek Chaim
Published: October 2023

Disclosure: A. Sliwinska: None. C. Vanek: None.

Introduction: Osteonecrosis of the femoral head (ONFH) is a localized bone disease responsible for 10% of total hip replacements in the United States. Although the condition is a separate entity from osteoporosis, it may co-occur representing underlying systemic bone disease. Many risk factors (steroids, trauma, infections, thrombophilia, blood cell dyscrasias) can predispose to ONFH, therefore, diligent evaluation is required to reveal the underlying cause. There are no FDA approved therapies. Here, we present a case of young woman with bilateral osteonecrosis of femoral head who was found to have prothrombin gene mutation, severe osteoporosis, and was successfully treated with PTH analog therapy with abaloparatide. Case Description: 33-year-old Asian female with no past medical history presented to the Endocrinology clinic for a metabolic bone disease assessment. Two years prior, she developed progressive bilateral hip pain which prompted radiographic evaluation, discovering bilateral ONFH. She was managed non-surgically with a 6-month trial of oral alendronate. Worsening pain prompted left hip decompression surgery with stem cell transfer. Patient had no history of fragility fractures nor family history of bone disease. A bone density revealed Z scores of -3.9 and -3.5 in lumbar spine and total hip, respectively. She was taking 2000 IU vitamin D3 and 600 mg of elemental calcium daily. Her blood tests revealed normal basic metabolic panel, normal complete blood count and liver function tests. Calcium was 9.0 mg/dl (ref:8.6-10.2), albumin 4.6 mg/dl (3.5-4.7 mg/dl), phosphorus 4.0 mg/dl (2.4-4.7 mg/dl), PTH of 28 pg/ml (18-88 pg/ml), Vitamin D 25-hydroxy 41.3 ng/ml (30-80 ng/ml), and TSH was 1.66 mIU/L (0.39-4.17 mIU/L). Patient had an infectious, metabolic and rheumatological work-up that was negative. A thrombosis workup showed a heterozygous prothrombin gene (G20210A) mutation. Factor V Leiden mutation was negative. Repeat Hip MRI showed progression of her ONFH with marked bone marrow edema in femoral head bilaterally. Patient was then started on abaloparatide. After 6 months, hip MRI showed marked improvement with no bone marrow edema. Discussion: Osteonecrosis of the femoral head is a complex disease that can affect young individuals. Bilateral ONFH suggests systemic disease and a thorough work-up is necessary. Although the exact mechanism is unclear, it has been hypothesized that thrombin plays a role in bone homeostasis therefore hematologic disorders may predispose patients to both ONFH and osteoporosis. Medical treatment of ONFH, including bisphosphonates, statins, or anticoagulants, have been suggested. Recently the PTH analog, teriparatide, has shown promising results and found to be beneficial in treating osteonecrosis. Our case highlights importance of thorough work-up for patients with bilateral ONFH and successful use of anabolic agent in this population.

Presentation: Thursday, June 15, 2023
OR03-05 Cinacalcet Acts As A Spatially Biased Allosteric Modulator To Enhance CaSR Signaling From Endosomal Membranes
Authors: Wyatt Rachael , Gorvin Caroline M
Published: October 2023

Disclosure: R. Wyatt: None. C.M. Gorvin: None.

The calcium-sensing receptor (CaSR) is a G protein-coupled receptor that plays a fundamental role in extracellular calcium homeostasis by activating Gαq/11 and Gαi/o signaling to regulate parathyroid hormone (PTH) release. CaSR can also continue signaling once internalised (known as sustained signaling) to elicit responses that are distinct from those at the plasma membrane. Loss-of-function mutations of CaSR cause familial hypocalciuric hypercalcemia type 1 (FHH1), while Arg15 mutations in the adaptor protein-2 σ-subunit (AP2σ) cause FHH3, by impairing CaSR internalisation and disrupting sustained signaling. However, the sustained signaling pathway has been incompletely defined and the effects of allosteric modulators on the process are unknown. Here we examined CaSR membrane trafficking and G protein activation in different endomembrane compartments using bystander BRET and HILO advanced imaging in HEK293 cells. This showed that internalised CaSR is targeted to Rab5-positive early endosomes and Rab4-positive early-to-recycling membranes, and not to degradation pathways as previously hypothesised. CaSR exclusively recruits active Gq/11 to early endosome membranes to drive sustained signals that produce distinct transcriptional profiles than those from plasma membranes. We next mutated a C-terminal region within CaSR predicted to form a dileucine endocytic motif that interacts with AP2σ. NanoBiT assays confirmed that the CaSR-dileucine mutant disrupted interactions between CaSR and AP2σ to the same magnitude as AP2σ-Arg15 mutations. Moreover, this CaSR-dileucine mutant impaired CaSR internalisation and reduced Gq/11 sustained signals from Rab5 and Rab4 endosomes to similar levels to those observed in cells expressing the FHH3-associated AP2σ-Arg15 mutant. Gi/o and G12/13 responses from plasma membranes were not affected by the CaSR-dileucine mutant. Finally, we assessed whether the CaSR positive allosteric modulator, cinacalcet, affects sustained signalling. When exposed to cinacalcet CaSR significantly increased the recruitment of active Gq/11 to early endosomes, resulting in a significant increase in signaling, while signals from the plasma membrane were not different to vehicle-treated cells. In summary, we have demonstrated that CaSR is targeted to an early-to-recycling endosomal pathway, which could explain how CaSR responds rapidly to fluctutations in serum calcium to maintain calcium homeostasis. Moreover, we have defined the endocytic motif within the CaSR required for sustained signaling and shown that cinacalcet is a spatially-biased allosteric modulator of the CaSR that preferentially enhances signaling from endosomal membranes. Thus, FHH3-associated AP2σ mutations, CaSR dileucine mutants and cinacalcet can be used as tools to better understand CaSR spatiotemporal signaling and define its physiological significance.

Presentation: Thursday, June 15, 2023
SAT177 Molecular Analysis Of AMBRA1 As A Candidate Tumor Suppressor In Sporadic Parathyroid Adenomas
Authors: Chinwo Stephanie , Costa Jessica , Arnold Andrew , Bellizzi Justin
Published: October 2023

Disclosure: S. Chinwo: None. J. Costa: None. A. Arnold: None. J. Bellizzi: None.

Primary hyperparathyroidism is a common endocrine disorder that is most often caused by a sporadic single-gland parathyroid adenoma. Currently, the only known and experimentally validated oncoprotein for parathyroid adenomas is cyclin D1. The overexpression of cyclin D1 protein has been reported in 20-40% of cases and about 8 percent of cases harbor a DNA rearrangement involving the cyclin D1 (CCND1) locus. Otherwise, the molecular mechanisms underlying this cyclin D1 overexpression have yet to be identified. Here, we explored a potential parathyroid tumorigenic mechanism that could increase cyclin D1 stability through a defect in the AMBRA1 E3 ligase adaptor, a molecule responsible for its degradation. Evidence that AMBRA1 may be a tumor suppressor gene includes the accumulation of cyclin D with hyperproliferation in AMBRA1-deficient cells, the context-dependent growth of tumors in Ambra1-deficient mice, and the finding that low levels of AMBRA1 correlated with poor clinical outcomes in The Cancer Genome Atlas. Therefore, we proceeded to examine AMBRA1 for evidence of tumor suppressor-type inactivation within a cohort of 98 typical parathyroid adenomas. Genomic DNA samples from these tumors were subjected to PCR-amplification of all 18 coding exons of AMBRA1, followed by Sanger sequencing. Sequences were analyzed by comparison to the normal reference sequence: ENST00000683756.1, seeking to assess any observed intragenic or splice-site variants as potential or likely loss-of-function mutations. Thus far, with 97 percent of the coding region for this 1298-amino acid protein fully sequenced, we have identified an inactivating mutation in 1 of the 98 tumors (1%): c.126G>A in exon 2, resulting in an early stop codon p.Trp42*. Sequencing the patient’s matched germline DNA confirmed the mutation was somatic and showed loss of heterozygosity. We also identified likely-nonpathogenic variants in 5 parathyroid adenomas: missense variant c.3385G>T (p.Ala1129Ser), 3’ UTR variants c.*576A>T and c.*491T>C and synonymous variants c.579C>T and c.2776C>T, each in a single tumor. 4 of 5 were found as germline variants in the normal population and the one missense scored benign by in silico criteria. To conclude, our observations suggest that AMBRA1 may function as a classical tumor suppressor gene in sporadic parathyroid adenomas at very low frequency. Further study may include protein expression analysis of AMBRA1 to investigate influences on gene expression. To further elucidate the mechanisms behind cyclin D1 overexpression in parathyroid adenomas, other molecules that participate in its degradation should be explored as potential tumor suppressors.

Presentation: Saturday, June 17, 2023
SAT195 A Curious Case Of Severe Reversible PTH-mediated Hypercalcemia Of Pregnancy
Authors: Albanese Isabella , Nicolas Nathalie , Sipen Wing Simon , Mitmaker Elliot , Vautour Line
Published: October 2023

Disclosure: I. Albanese: None. N. Nicolas: None. S.S. Wing: Grant Recipient; Self; Pfizer Global R&D. Other; Self; Almac Discovery (Independent Contractor). E. Mitmaker: None. L. Vautour: None.

Background: Primary hyperparathyroidism is rarely diagnosed in pregnancy as symptoms may overlap with those of pregnancy and biochemical diagnosis may be masked by physiologic changes in calcium homeostasis. Hyperparathyroidism in pregnancy is associated with increased maternal and fetal complications. While mild disease is treated conservatively, moderate to severe disease is generally treated surgically in the second trimester. Safe pharmacotherapy options are limited in pregnancy. Case: A 35-year-old woman G3P1 at 10 weeks presented to our institution with polyuria, bone pain and weakness with labs demonstrating severe hypercalcemia (Calcium total: 3.82mmol/L (normal: 2.12-2.62); PTHi: 12pmol/L (normal: 1.5-9.3)). PTHrP was suppressed. She had a prior history of PTH-mediated hypercalcemia in her first pregnancy. She previously underwent three exploratory surgeries in which only three parathyroid glands were found and removed. The hyperparathyroidism and hypercalcemia persisted post-operatively thus she also required intravenous fluids, calcitonin and cinacalcet. The pregnancy was otherwise uncomplicated. Post-partum, she developed hypoparathyroidism and hypocalcemia. Throughout this current pregnancy, multiple imaging modalities were used (ultrasound, MRI and parathyroid sestamibi), none of which were unable to localize any hyperfunctioning parathyroid tissue. Thus, management was limited to medical therapy. Despite aggressive hydration, calcitonin and cinacalcet, total calcium and PTH levels consistently rose reaching peaks of 4.06mmol/L and 45.4pmol/L, respectively. Given hypercalcemia severity and associated neurological symptoms, she was also given bisphosphonates (pamidronate 60mg and zoledronic acid 4mg). She underwent C-section at 25+3 weeks due to fetal decelerations and placental insufficiency. She again developed hypoparathyroidism and hypocalcemia 1-week post-partum. Genetic testing was negative for any causes of hyperparathyroidism. Discussion: This is a unique case of severe PTH-mediated hypercalcemia in that the exact mechanism is unknown but appears to be pregnancy-mediated and reversible such that it only occurs in pregnancy with subsequent hypoparathyroidism post-partum. Investigations to better elucidate the mechanism of this are ongoing.

Presentation: Saturday, June 17, 2023
SAT216 Multiple Reasons Of Secondary Hyperthyroidism And Unexpected Results
Authors: Dzherieva Irina , Volkova Natalia , Brovkina Snezhana , Reshetnikov Igor , Gritsenko Lyubov , Mamedova Tuntul , Ismailov Unus
Published: October 2023

Disclosure: I. Dzherieva: None. N. Volkova: None. S. Brovkina: None. I. Reshetnikov: None. L. Gritsenko: None. T. Mamedova: None. U. Ismailov: None.

Background: Revealing the cause of secondary hyperparathyroidism might be a difficult problem especially if a patient has a few diseases to lead to this condition. Clinical Case: A 52-year-old-man was referred to our service for revealing the cause of weakness which started after COVID 19. When the patient was treated by rivaroxaban there was an unusual feature such as a hemoptysis, so the medicine was canceled. In medical history only the Achilles tendovaginitis was performed. The patient plays football twice a weak regularly, does not smoke, does not use drags. The physical examination showed nothing special. An arterial blood pleasure was 120/80 mm Hg, Body Mass Index was 25,4 kg/m2. Laboratory workup showed high erythrocyte sedimentation rate (ESR)(33mm/hr), leukocytosis (11000mm3) and a normocytic anemia(Hb 115 g/l),hematuria (16650 RBCsper hpf). Creatinine was 163µmol/L, glomerular filtration rate (GFR) was 43 ml/min/1.73m 2 , total serum calcium corrected for the patient's albumin concentration was 2.47 mM/L (2.15-2.50 mM/L), parathyroid hormone (PTH-intact) was 130 pg/mL (10-65 pg/mL),the level of 25-hydroxyvitamin D was 14.4 ng/mL(30.0-100.0 ng/mL). Chest radiograph findings were as follows: bilateral irregular, nodular, and patchy opacities. After vitamin D deficiency correction level of PTH-intact became normal (65 ng/mL). Serological tests : antinuclear antibody [ANA] and double-stranded DNA [dsDNA], ANCA were performed. Antineutrophil cytoplasmic antibody (ANCA) test result revealed perinuclear ANCA related to myeloperoxidase with the level more than 80 IgG. According to this finding Microscopic polyangiitis was diagnosed. Conclusion: This case has shown that sometimes there are two reasons for development of secondary hyperthyroidism and only successive actions help to choose right way for diagnosis.

Presentation: Saturday, June 17, 2023
SAT222 More Than Skin Deep: A Case Of Psoriasis Associated With Hypoparathyroidism
Authors: Sheth Grishma , Alsayed Mahmoud
Published: October 2023

Disclosure: G. Sheth: None. M. Alsayed: None.

Introduction: Primary hypoparathyroidism is commonly encountered post-surgically, however isolated cases are rarely seen without clear risk factors. Severely low calcium levels have been shown to correlate with flare ups and worsening of psoriasis. Treatment of hypocalcemia has been thought to improve and prevent the progression of this skin rash. This case highlights an interesting presentation of psoriasis in which the severity was likely related to hypocalcemia. Clinical Case: 25 y/o F with no prior past medical history presented to the emergency room with diffusely worsening skin rash and fever. She had bilateral erythematous plaques on her anterior legs for a few months that was progressively worsening. A few days prior, she started noticing erythema and scaling on her upper body and back. Her on arrival labs were remarkable for a calcium level of 4.5 mg/dL (8.8-10.4). Patient declined any symptoms at the time but did state she had noticed tingling in her face and hand/foot cramps occurring on and off over the last 6 months. Her EKG was remarkable for a mildly prolonged QT interval. She was treated with IV calcium gluconate 4 grams without improvement in her calcium. She ultimately was placed on a calcium gluconate drip and oral calcium carbonate 2 grams every 2 hours. Meanwhile, her work up revealed a PTH of <6 pg/mL, phosphate of 7 mg/dL, magnesium of 1.7 mg/dL, and vitamin D of 23 ng/mL. To elucidate the cause of her newly diagnosed primary hypoparathyroidism, iron studies were ordered to rule out hemochromatosis and ceruloplasmin to rule out Wilson’s disease, both of which returned negative. She had no history of radiation therapy or prior blood transfusions. She denied any family history of calcium disorders. Therefore, PTH antibody testing was sent to a send out lab and is currently pending. Patient was ultimately weaned off of the calcium drip with low normal calcium values around 7.5-8.5 mg/dL. She was placed on calcium carbonate 2 grams every 6 hours with plans for close outpatient labs and follow up. She was seen by dermatology in the hospital and was diagnosed with erythrodermic psoriasis. She was given an IL-17 inhibitor, Taltz, with significant improvement in her rash over her 2 day hospital stay. Conclusions: This case brings to light the importance of a thorough investigation of primary hypoparathyroidism and to recognize the rare genetic or autoimmune etiology as a possibility. Additionally, this case identifies the association of psoriasis with hypocalcemia. Studies have recognized a correlation of severity of psoriasis in patients with low calcium as was seen in this patient. Moreover, treatment with calcium supplementation may have a role in improving skin manifestations.

Presentation: Saturday, June 17, 2023
SAT225 An Unexpected Case Of Hypocalcemia
Authors: Nogueira Cordeiro Monica Fabiola , Jason Epstein Eric
Published: October 2023

Disclosure: M. Nogueira Cordeiro: None.

Calcitriol and oral calcium supplementation remains the standard of care in the management of hypoparathyroidism. The targeted serum calcium level for this condition is quite narrow, typically at the lower end of the reference range to avoid hypercalciuria, but above the calcium level from which a patient may develop symptoms. Pharmacokinetic and pharmacodynamic properties vary among different over-the-counter (OTC) calcium salt preparations, therefore it is important for the provider and patient to understand the differences in calcium formulations to meet therapy goals. We present a case of symptomatic hypocalcemia related to a patient unknowingly switching from calcium carbonate to tricalcium phosphate supplementation. A 71 year-old woman with a history of thyroid cancer status post total thyroidectomy complicated by permanent hypoparathyroidism, CKD stage III, nephrolithiasis and hypercalciuria presented for a follow up visit complaining of perioral numbness for approximately one month. Laboratory evaluation revealed hypocalcemia, hyperphosphatemia, hypomagnesemia and a normal 25-OH-vitamin D level: Ca 7.3 mg/dL (8.5-10.5 mg/dL), Phos 5.6 mg/dL (2.5-4.5 mg/dL), Mg 1.1 mg/dL (1.7-2.8 mg/dL), 25-OH-vit D 45 ng/mL (30-60 ng/mL). Prior to this, her serum calcium had been well controlled, avoiding symptomatic hypocalcemia and hypercalciuria, for years. She had remained on her usual dose of calcitriol, but had changed her calcium supplement to 500 mg of tricalcium phosphate three times per day from calcium carbonate 650 mg three times a day. Rather than adjust her calcitriol, she was recommended to stop tricalcium phosphate and restart the previous regimen of calcium carbonate; serum calcium and phosphorus improved within 72 hours (Ca 7.7 mg/dL, Phos 3.8 mg/dL) and two weeks later her calcium level was back at goal (8.2 mg/dL), phosphate level had normalized (4.5 mg/dL) and she was no longer symptomatic. Tricalcium phosphate is not generally recommended for patients with hypoparathyroidism given they are less available and not as well tested. Previous studies have shown conflicting outcomes for serum calcium elevation after an oral load of tricalcium phosphate when compared with calcium carbonate. Elderly individuals might also experience an elevation in phosphate levels after a tricalcium phosphate load. Additionally, the elemental calcium in OTC tricalcium formulations is often less than what is available in similar appearing calcium carbonate or citrate supplements. Although calcium carbonate and citrate are the most commonly prescribed calcium supplements, other preparations are available OTC and it is difficult to tell these apart. Given the narrow goal of serum calcium for patients with hypoparathyroidism, providers should confirm the calcium formulation at each visit and counsel the patient to notify them if any changes are made in their oral calcium supplementation.

Presentation: Saturday, June 17, 2023
SAT227 A 17-year old Teenager With Recurrent Syncopes In The Setting of Hypocalcemia
Authors: Chartoumpekis Dionysios V , Bountouris Panagiotis , Dimitropoulos Konstantinos , Habeos Ioannis G
Published: October 2023

Disclosure: D.V. Chartoumpekis: None. P. Bountouris: None. K. Dimitropoulos: None. I.G. Habeos: None.

Background: One of the main reasons of syncope is the long QT syndrome. The exercise-induced hypocalcemia in a background of primary hypoparathyroidism is sometimes overlooked in the differential diagnosis. Clinical Case: A 17-year old female was transferred to the emergency room of the University Hospital of Patras after having experienced a syncope while swimming. She described in the past 6 months similar episodes during exercise (running, cycling). A basic investigation with full blood count, sodium, potassium, cortisol and TSH levels along with a brain MRI and an ECG were performed at her primary care physician. Due to a discovered long QT she was addressed to a cardiology private office for further investigation. However, before the planned appointment she had this episode while swimming and she was admitted to the cardiology department. During her hospitalization a serum calcium of 4.7 mg/dl and a serum P of 9.4 mg/dl were discovered with a non-detectable PTH. The endocrinology division was called for further evaluation. Chvostek and Trousseau’s signs were positive. The patient was administered a calcium gluconate drip and in parallel a treatment with calcium carbonate and alphacalcidol was initiated. The possibility of an autoimmune polyendocrine syndrome was excluded as the patient did not present candidiasis, adrenal insufficiency, autoimmune thyroid disease or diabetes. After her exit from the hospital she was followed up at the outpatient endocrinology clinic and her daily doses of calcium carbonate and alphacalcidol was modified several times as the [CaxP] was always higher than 55 mg2/dl2 and when the dose of calcium carbonate was lowered she developed symptomatic hypocalcemia. During the first month of her follow-up a cataract in the right eye was discovered and a brain MRI unveiled basal ganglia calcifications. No signs of renal stones or nephrocalcinosis were seen in the ultrasound. As the calcium and phosphate levels, after almost 9 months of changes in the treatment schemes, were not optimal, a treatment with recombinant PTH was initiated. This treatment aided the patient to reach low normal levels of calcium and [CaxP] lower than 55 mg2/dl2. The patient is followed up every six months in the endocrinology outpatient clinic. Conclusion: This is an interesting case of primary hypoparathyroidism possibly of autoimmune origin. The presence of syncopes during exercise could be due to a further drop of calcium levels due to transient respiratory alkalosis. This case can be useful in the teaching of differential diagnosis of long QT syndrome, the management and evaluation of an hypocalcemia and the rule out of autoimmune polyendocrine syndromes in the context of a primary hypoparathyroidism.

Presentation: Saturday, June 17, 2023
SAT229 Symptomatic Hypocalcemia In The Setting Of Crohn’s Disease With Severe Hypomagnesemia
Authors: Cuan Katherine , Reisman Tamar
Published: October 2023

Disclosure: K. Cuan: None. T. Reisman: None.

Introduction: People with Crohn’s Disease (CD) are at risk for various nutritional deficiencies due to decreased oral intake, malabsorption, and increased intestinal losses. CD often causes a negative calcium balance, which does not usually cause hypocalcemia because the bones serve as a reservoir for calcium. However, symptomatic hypocalcemia may occur if a concurrent severe hypomagnesemic state is present. The factors resulting in hypocalcemia in patients with magnesium deficiency are impaired PTH secretion, PTH resistance, and vitamin D deficiency. Clinical Case: A 33-year-old man with CD and rheumatoid arthritis presented following a seizure with additional symptoms of hand cramping and facial twitching. He had previously undergone three small bowel resections and had a history of hypocalcemia due to malabsorption. Although this patient had previously been admitted due to a hypocalcemic seizure, he did not start oral calcium supplements at that time. No issues with magnesium were identified previously. On this encounter, he was found to have a corrected calcium (cCa) of 5.3 mg/dL, undetectably low magnesium at <0.7 mg/dL, normal phosphorus, 25-hydroxyvitamin D at 3.5 ng/mL, and an elevated intact PTH (iPTH) at 169 pg/mL. Aggressive intravenous calcium and magnesium repletion improved cCa to 7.4 mg/dL and magnesium to 2 mg/dL with no further seizure activity. He was discharged on calcium carbonate, calcitriol, and ergocalciferol. A month later, he presented to our endocrinology clinic asymptomatic but with a cCa of 6 mg/dL and magnesium at <0.7 mg/dL. Further biochemical workup revealed normal phosphorus, 25-hydroxyvitamin D at 7.9 ng/mL, and an inappropriately normal iPTH at 49 pg/mL. He was readmitted to the hospital where intravenous repletion improved cCa to 8.1 mg/dL and magnesium to 1.9 mg/dL. His recurrent hypomagnesemia was attributed to malabsorption. An increased dose of calcitriol and oral magnesium were added to his discharge medication regimen, in addition to his ergocalciferol and calcium carbonate. Three days later, he had a cCa level of 7.1 mg/dL as an outpatient. Conclusion: Patients with CD often have nutrient deficiencies, especially if they have had surgical resection within the intestinal tract. Our patient initially developed hypocalcemia from malabsorption, which was then exacerbated by the severely hypomagnesemic state. During his initial hospital encounter, the elevated iPTH level indicated PTH resistance. On his second encounter, the normal iPTH level suggested hypoparathyroidism. Given the relationship between magnesium and calcium homeostasis, addressing the hypomagnesemia eventually aided in achieving stabilization of serum calcium levels. Thus, in patients who are at risk for malabsorption and have recurrent symptomatic hypocalcemia, it is prudent to check magnesium levels as it can affect long term management of hypocalcemia.

Presentation: Saturday, June 17, 2023
SAT234 Variations In Clinical Practice Patterns For Hypoparathyroidism
Authors: Deering Kathleen L , Harshaw Qing , Mitchell Deborah M , Larsen Niccole J , Weiss Blandine , Loustau Patrick , Allas Soraya
Published: October 2023

Disclosure: K.L. Deering: None. Q. Harshaw: None. D.M. Mitchell: None. N.J. Larsen: None. B. Weiss: None. P. Loustau: None. S. Allas: None.

Objectives: Emerging evidence regarding optimal treatment for patients with chronic hypoparathyroidism (cHP) has led to the development of updated evaluation and management guidelines. The goal of this study was to determine how current practice patterns for individuals with cHP compare with these guidelines. Methods: We extracted data from a large US claims database (130 million patients) from Oct 2014 to Dec 2019. cHP was defined as an HP diagnosis claim ≥6 months following neck surgery or ≥2 claims ≥6 months apart. Patient data were extracted from 1 year prior to surgery (if applicable) and up to 2 years following their qualifying HP claim. Additionally, a panel comprised of 103 endocrinologists and nephrologists (US=40, UK=21, France=21, Germany=21) was assembled and conducted chart reviews with each participant contributing data for 5 patients with cHP in their practice. Results: 5,302 patients met criteria for cHP from the claims database, while the physician panel chart review included 515 cHP patients. In the claims database, 33.0% saw an endocrinologist and 9.4% or less saw a nephrologist during the 1-year follow-up. Panel physicians reported being the decision maker for 93% of their cHP patients and 90% of the patients were seen at least twice per year. Guidelines recommend all new and established cHP patients be monitored for key laboratory values every 3-12 months. Overall, while neither study found monitoring practices consistent with guidelines, there was less laboratory monitoring in the database study than in the physician panel: serum magnesium (36.6%; 57%), serum phosphorous (36.8%; 90%), urine calcium (10.0%; 57%), and renal imaging (20.9%; 34%). Additionally, patients were monitored for bone health in the database study and physician panel (bone mineral density: 10.7%; 44%; bone markers: 5.2%; 25%). Conclusion: Real-world practice patterns vary from guideline recommendations; however, the practice patterns from the physician panel study align more closely with recommendations than the claims database study. This discrepancy may be due to patients less frequently utilizing physicians specialized in cHP in the database study. Our data underscore challenges with optimizing care for patients with this rare disorder. In addition, they suggest that ongoing efforts to educate both patients and physicians about management guidelines may improve care and ultimately enhance health and quality of life in cHP.

Presentation: Saturday, June 17, 2023
THU596 Heteromerization Of The Angiotensin II Type 1 Receptor And The Bradykinin Type 2 Receptor
Authors: Johnstone Elizabeth K M , Pfleger Kevin D G
Published: October 2023

Disclosure: E.K. Johnstone: Grant Recipient; Self; Australian Research Council. K.D. Pfleger: Grant Recipient; Self; Australian Research Council. Stock Owner; Self; Dimerix Bioscience Pty Ltd.

Background: Receptor heteromerization is the phenomenon whereby two different receptors form a functional complex that attains unique pharmacological properties. Consequently, receptor heteromers can be considered novel drug targets, with the potential to achieve greater therapeutic selectivity and specificity. In a landmark study, the first receptor heteromer to be associated with a disease was the heteromer that forms between the angiotensin II type 1 (AT1) receptor and the bradykinin type 2 (B2) receptor (1). The AT1-B2 heteromer reportedly led to increased angiotensin II signalling, which was implicated in the angiotensin II hypersensitivity involved in pre-eclampsia. However, the validity of this study was questioned by a collaboration of several groups who were unable to find any evidence for a physical or a function interaction between the two receptors (2). As a consequence of these conflicting studies, the existence of the AT1-B2 receptor heteromer has remained controversial. Aim: Investigation of evidence for heteromerization of the AT1 receptor and the B2 receptor. Methods: AT1 receptor and B2 receptor pharmacology and potential heteromerization was investigated in HEK293FT cells using various bioluminescence resonance energy transfer (BRET)-proximity based assays, as well as Dimerix’s Receptor-Heteromer Investigation Technology (Receptor-HIT) (3). Receptor-HIT enables the investigation of receptor heteromers through their specific ligand-induced proximity to interacting proteins. BRET assays, including in the Receptor-HIT configuration, allow real time, live cell monitoring of proximity between biomolecules of interest. Results: Using the Receptor-HIT assay, we confirmed the existence of the AT1-B2 receptor heteromer in HEK293FT cells. We found that the heteromer was able to recruit various GPCR interacting proteins, such as G proteins and arrestin in a bradykinin-dependent manner. Additionally, the heteromer also internalised and trafficked through the cell upon treatment with bradykinin. The close proximity of the two receptors was confirmed using a variation of the Receptor-HIT assay, which monitors receptor-ligand binding rather than protein-protein interactions. Discussion: Our study supports the existence of the AT1-B2 receptor heteromer and identifies various pharmacological properties of the complex. Further studies are required to relate these molecular properties to physiological consequences of heteromerization. (1)AbdAlla et al. Nat Med2001, 7 (9), 1003 1009.(2)Hansen et al. J Biol Chem2009;284(3):1831 1839.(3)Johnstone et al. Biochem Soc T. 2021;49:1555–65.

Presentation: Thursday, June 15, 2023