Normal Vitamin Research Articles

THU457 Variable Presentations Of Hypophosphatasia In Two Patients In The Outpatient Setting

Abstract Disclosure: A. Elmaaz: None. S. Batool: None. P. Dandona: None. Introduction: Hypophosphatasia is a rare disorder characterized by defective mineralization of bone and teeth which is caused by an autosomal inherited mutation in the tissue nonspecific alkaline phosphatase (ALP) encoding genes. Here we present two cases of multiple dental and bony defects secondary to low ALP enzyme activity due to hypophosphatasia. Case 1: A 27-year-old female with history of mitochondrial disease, gastroparesis, malabsorption syndrome, and autonomic dysfunction was referred to Endocrinology clinic because of persistently low serum ALP levels associated with recurrent muscle, joint, and bone pain since the age of 13. She had history of multiple tooth extractions because of dental developmental abnormalities and fractures. She also reported history of fractures of three of her fingers in both hands during her childhood and teenage years. The patient was adopted and was unaware of any biological family history. Physical examination was remarkable for short-statured female, 4'8". Notably, the middle phalanges in little fingers bilaterally were shorter than the other fingers. Workup showed vitamin D level of 21 (30-80) ng/ml, despite being on 50,000 IU twice a week for 6 months with normal PTH and ionized calcium levels. The repeated serum level of ALP was 24 (31-125) U/L with bone and liver isoenzymes levels of 42% and 58 % respectively. Vitamin B6 level was 13.2 (2.1-21.7) ng/ml. Bone mineral density was unremarkable. Case 2: A 53-year-old female with history of congenital left hip dysplasia, hypertension, and dyslipidemia was seen by Endocrinology service for evaluation of decreased ALP levels. She denied any history of falls or fractures. However, she reported chronic bone pain, especially in bilateral hip joints with history of multiple surgeries in her left hip joint. She had required teeth braces and multiple dental surgeries during her childhood due to dental maldevelopment. Her height was 4'8". Laboratory workup was remarkable for low serum ALP level of 30 U/L with bone isoenzyme of 24 %. Vitamin B6 level was 206.7 (2.1-21.7) ng/ml. She had elevated serum phosphorus levels with normal calcium, PTH, and vitamin D levels. Pyridoxal-5- Phosphate level was high. Bone mineral density revealed osteopenia. Conclusion: Hypophosphatasia is a rare disease, hence it could be easily missed due to high variability in clinical presentations and severity of symptoms. Low serum levels of ALP with history of bone pain, recurrent fractures, premature loss of deciduous teeth, or loss of adult dentition should raise the suspicion of hypophosphatasia. Resistance to vitamin D supplementation is another clue to the diagnosis. A multidisciplinary approach is required for appropriate management. Presentation: Thursday, June 15, 2023

FRI693 Pthrp Mediated Hypercalcemia In A Patient With Recurrent Hepatocellular Carcinoma

Abstract Disclosure: D. Bondarenko: None. M. Ahmad: None. M. Mack: None. P. Ucciferro: None. Background: Humoral hypercalcemia is seen in 30 percent of cancer patients, most commonly driven by parathyroid hormone related peptide (PTHrP) production, osteolytic cytokine production, and 1,25-OH vitamin D production. The most common malignancies associated with PTHrP mediated hypercalcemia are squamous cell carcinomas and breast cancer. Less often hepatocellular cancer presents with hypercalcemia. We describe the case of a patient presenting with hepatocellular carcinoma presenting with recurrent episodes of severe hypercalcemia due to excessive PTHrP production. Clinical Case: The patient was a 68-year-old male with a past medical history of recurrent hepatocellular carcinoma with liver transplant in the past and type 2 diabetes mellitus who presented to the emergency department (ED) for one day of altered mental status. The patient was noted to be extremely agitated and confused by his home health aide and EMS was called. In the ED the patient’s vital signs were as follows: blood pressure of 196/80 mmHg, heart rate of 82 beats per minute, respiratory rate of 18 breaths per minute and temperature of 36.6 degrees Celsius. Initial lab work showed: calcium 13.5 mg/dL, albumin 4.2 g/dL, ionized calcium of 1.63 mmol/L, creatinine 0.99 mg/dL (baseline 0.5 mg/dL), glucose of 438 mg/dL, bicarbonate 23 mmol/L, anion gap 19, and beta hydroxybutyrate 51 mg/dL. Hypercalcemia workup revealed a suppressed PTH of 5 pg/mL (normal 11-67 pg), normal 25-OH vitamin D 43.6 ng/ml (normal 30-100 ng/ml), normal 1,25-OH vitamin D 38 pg/ml (normal 18-72 pg/ml), and elevated PTHrp 36 pg/ml (normal 11-20 pg/ml). The patient was started on aggressive IV fluid resuscitation with normal saline, administered a one-time dose of zoledronic acid and administered a three-day course of calcitonin. For his significant hyperglycemia the patient was started on an insulin infusion and was eventually transitioned to his home basal bolus insulin regimen. On discharge, the patient was scheduled with his oncologist to begin denosumab as an outpatient; however, he chose a palliative approach due to the terminal nature of his disease and recurrent hospitalizations for hypercalcemia. Conclusion: Hypercalcemia of malignancy is common in many different carcinomas with squamous cell cancer, renal cell cancer, breast cancer and multiple myeloma being commonly associated with this phenomenon. Reports of hepatocellular carcinoma associated with hypercalcemia are less common and occur in only 4-8 % of cases. With this case report, we hope to highlight PTHrP as a potential mechanism of humoral hypercalcemia in patients with hepatocellular carcinoma and propose denosumab as a possible treatment for patients with refractory hypercalcemia of malignancy. Presentation: Friday, June 16, 2023

THU455 Sclerostin Inhibitor Use In The Medical Management Of Osteogenesis Imperfecta Type III

Abstract Disclosure: M.D. Lundholm: None. A. Derkyi: None. S. Talvacchio: None. J.C. Marini: Other; Self; Ultragenyx, Amgen Inc. L.Z. Khan: None. Background: Osteogenesis imperfecta (OI) is a rare collagen-related hereditary skeletal disorder with an increased fracture risk from minimal trauma, short stature, and bone deformity. OI is associated with defects in collagen structure or synthesis, high bone turnover, and paradoxical bone hypermineralization. The optimal medical therapies for bone health in these patients are unknown. Clinical Case: A 27-year-old woman with OI presented to clinic for bone health. She was diagnosed with OI type III by phenotype, collagen biochemistry, and genetic analyses (heterozygous for a COL1A1 Gly187Ala substitution) following fractures at age 4 mos. She experienced dozens of fractures, has had orthopedic hardware in bilateral femora, left tibia, humerus, and radius, and right tibia, as well as spine fusion at age 7 yrs. She had not fractured in over 3 yrs which she attributed to the stability of her automatic wheelchair. She had no family history of OI and had been in studies at the NIH; from ages 6-9 yrs she received pamidronate (1 mg/kg/cycle q3m) with BMD improvement. Presently, her vitals were normal, with height of 3’6” (25-50th percentile for type III OI females) and weight of 64 lbs (BMI 25.5 kg/m2). On exam she had blue sclera, midface hypoplasia, dentinogenesis imperfecta, severe kyphosis and scoliosis, and a barrel chest. She had normal calcium, PTH, and 25-OH vitamin D levels. Skull CT showed 1 mm increase in basilar invagination (16 to 17 mm). DEXA demonstrated progressive decline in radial BMD from 0.671 g/cm2 to 0.625 g/cm2 over 3 yrs (z-score -0.4 to -1.1) into the osteopenic range. For worsening bone disease, she is starting romosozumab 210 mg monthly. Discussion: While several agents increase BMD in OI, there are no placebo-controlled studies to show an effect on fracture rate. Bisphosphonates including pamidronate are used most commonly, with increased areal BMD, decreased bone turnover, but also increased mineralization of already brittle bone. Overall, two Cochran reviews failed to support decreased fracture rates from bisphosphonates, and there is risk of adynamic bone with chronic use. There is even less evidence for use of denosumab which is additionally associated with a rebound effect upon discontinuation. Sclerostin inhibitors are the newest agents with both anabolic and antiresorptive effects and good results in OI mouse models. Phase 2 data with sestrusumab showed increased BMD and decreased bone turnover. Ongoing studies are looking at sclerostin inhibitor use in adults and adolescents. From a practical standpoint, romosozumab has a shorter effect with quicker offset than bisphosphonates if needed to stop for fracture healing. Conclusion: Sclerostin inhibitors are an option for the medical treatment of OI. Further investigation is needed to determine long-term safety, optimal duration, and use of sclerostin inhibitors in combination with antiresorptive agents in OI. Presentation: Thursday, June 15, 2023

THU143 A Novel Maternally Inherited GNAS Variant In A Family With Hyperphagia And Obesity

Abstract Disclosure: P. Purushothaman: None. A. Ramakrishnan: None. E.F. Gevers: None. Introduction: Heterozygous inactivating mutations in the maternal allele of the GNAS gene typically result in pseudohypoparathyroidism (PHP) characterized by developmental delay, short stature, obesity, hormone resistance and bone abnormalities. Recently, GNAS variants were also described in 1% of patients in the UK Genetics of Obesity cohort, resulting in reduced MC4R signalling. Here, we report another novel GNAS variant in family with hyperphagia and obesity and only mild features of PHP. Case: The proband presented at 6 years with hyperphagia and obesity from age 3 years. BMI was 30.4 (4.1 SDS) with height +1.9 SDS, and head circumference (HC) + 3.0 SDS. She had subtle brachydactyly, short toes and a café au lait patch. Developmental milestones and cognitive achievements were mildly delayed. Her 12-year-old brother [ height +2.1 SDS, weight +3.1 SDS, BMI 29.55 (2.9 SDS), HC +3.6 SDS] had been followed in an obesity clinic for a few years with hyperphagia, obesity, delayed developmental milestones and a recent diagnosis of autism. He also had subtle brachydactyly, as did the mother who was also obese (BMI 38.9) with a normal height but had normal cognition. Results: In the proband, initial investigations did not suggest hormone resistance. However, at 8.7 years, PTH was high [9.5 pmol/L (0.7-5.6)] with normal calcium and Vitamin D; TSH 6.6 mU/L (<6), FT4 11.8 pmol/L (10.8 - 19.0). She had hyperlipidaemia and fatty liver. X-ray hand showed generalised mild brachydactyly with a short right fifth metacarpal. In the brother, PTH tested for the first time at 12.9 years was 18.4 pmol/L (1.6-6.9), calcium and vitamin D were normal; TSH 4.04 mU/L (<4.2) and FT4 13.4 pmol/L. Next Generation Sequencing using the Cambridge Obesity gene panel detected a novel heterozygous (c.791A>C, p.(Asn264Thr) variant in exon 10 of GNAS in the proband and subsequently in the mother and brother confirming maternal inheritance. This variant has not been reported in control databases (1000 Genomes, ESP, ExAC and gnomAD, Human Gene Mutation Database and ClinVar). The variant is in a highly conserved region susceptible to missense mutations and has been classified as pathogenic using ACMG and ACGS guidelines. Discussion: In conclusion, we describe a novel heterozygous inactivating GNAS variant c.791A>C, p.Asn264Thr resulting in hyperphagia, obesity, developmental delay, macrocephaly, mild brachydactyly, tall stature and variable biochemical mild hormone resistance in 2 siblings and resulting in obesity, mild brachydactyly without cognitive impairment in the mother. These cases demonstrate the clinical heterogeneity of the monogenic disease. Clinical and biochemical screening for PHP and genetic screening for GNAS variants should be performed in patients presenting with obesity, even in the absence of classical signs of PHP, to reduce diagnostic delay. Presentation: Thursday, June 15, 2023

FRI696 Endocrine Shades Of Silicone Fillers: A Case Of Calcitriol-mediated Hypercalcemia

Abstract Disclosure: M.S. Martinez Cruz: None. T.G. Lozovoy Madsen-Barbosa: None. C.J. Haas: None. Introduction: In rare cases, foreign body granuloma (FBG) reaction is so vast that it leads to severe systemic disease, including increased granuloma-mediated production of calcitriol. Case Description: A 42-year-old woman was referred to the ED due to elevated serum calcium and worsening GFR on routine blood work. She endorsed a two-week of generalized weakness, myalgias, polyuria, polydipsia, and intermittent constipation with prior episodes of such symptomatology. On her first presentation, severe hypercalcemia (13.8 mg/dL), acute-on-chronic renal disease, a normal TSH, an appropriately low PTH, elevated PTHrP, a low 25-hydroxy vitamin D, and a normal 1,25 dihydroxy-vitamin D were noted. She was treated with IV fluids and zoledronic acid 4mg IV one time with subsequent normalization of calcium levels. Six months later, she was re-admitted with similar complaints. Additional blood workup was unremarkable, including urine and serum protein electrophoresis and kappa/lambda ratio. She once again presented with similar complaints; additional workup revealed a normal 25-hydroxy vitamin D, mildly elevated serum angiotensin-converting enzyme, and a negative QuantiFERON-TB gold, but a marked elevation of 1,25 dihydroxy-vitamin D (138 pg/mL). She admitted to subcutaneous silicone filler injections in the lips, cheeks, and hips applied by a non-healthcare provider six years ago. She described that one year after the injections, she had noted intermittently indurated erythematous areas in the skin of the hips and upper lateral thighs that were notably tender to palpation. Diagnostic imaging included a whole-body PET-CT that demonstrated moderate FDG uptake within the subcutaneous adipose tissue of the lateral aspect of bilateral gluteal regions extending from the iliac crests to the upper thighs. She was diagnosed with silicone filler injection-induced hypercalcemia secondary to granulomatous inflammation and initiated on prednisone 20 mg PO daily with progressive normalization in her hypercalcemia (9.7 mg/dl) a month after initiation of treatment. Unique features/Teaching points: FBG reactions occur more commonly against permanent fillers like silicone, especially if injected in larger volumes and highly vasculature areas like hips or buttocks. These reactions may occur years after the initial injection. In rare cases, significant granulomatous immune response leads to the overactivity of 1-alpha-hydroxylase in activated macrophages, resulting in uncontrolled overproduction of calcitriol and, subsequently, hypercalcemia. FBG reactions may also cause increased levels of PTHrP, further contributing to hypercalcemia. Treatment focuses on general hypercalcemia management and FBG remission, most effectively achieved with anti-inflammatory corticosteroid doses. Further studies are needed to evaluate long-term treatment efficacy. Presentation: Friday, June 16, 2023

Unraveling the Connection: Visceral Adipose Tissue and Vitamin D Levels in Obesity.

Vitamin D deficiency and insufficiency are widespread on a global scale, with multiple factors playing a role in their development, such as limited exposure to sunlight, inadequate dietary consumption, as well as obesity and abdominal fat accumulation. Abdominal obesity, assessed with waist circumference (WC), is associated with metabolic syndrome and has been linked to low vitamin D levels. This study aimed to investigate the relationship between visceral adipose tissue (VAT) and vitamin D levels, particularly examining the potential threshold for vitamin D storage and sequestration using adipose tissue. The study was conducted between 2020 and 2022 with 58 patients from an internal medicine outpatient department. Patients with certain medical conditions and those taking medications affecting bone metabolism were excluded. Blood samples were collected at baseline and after 6 months of monthly cholecalciferol supplementation. Ultrasonography was used to evaluate adipose tissue measurements, including subcutaneous adipose tissue thickness, VAT, preperitoneal adipose tissue (PPAT), and prerenal adipose tissue (PRAT). Anthropometric measures such as the waist-to-hip ratio and waist-to-height ratio were also assessed. The results showed that all subjects had significant hypovitaminosis D at baseline. After 6 months of supplementation, the mean increase in vitamin D levels was 9.6 ng/mL, with 55.2% of subjects becoming deficient. The study revealed a significant correlation between follow-up vitamin D levels and waist circumference, hip circumference, and VAT. VAT exhibited a strong correlation not only with vitamin D levels but also with waist circumference. When analyzing gender differences, males showed a higher weight and waist-to-hip ratio, while females had higher body adiposity indexes and subcutaneous adipose tissue measurements. In conclusion, this study highlights the relationship between VAT and vitamin D levels, emphasizing the potential role of adipose tissue in vitamin D availability. Waist circumference was identified as a surrogate measure for VAT evaluation. Furthermore, the study showed variations in vitamin D response to supplementation between genders, with a higher percentage of males reaching normal vitamin D levels. Predictive factors for vitamin D levels differed between genders, with waist circumference being a significant predictor in males and body adiposity index in females.

FRI562 Not JUST Severe Hypothyroidism: Recognizing Autoimmune Polyglandular Syndrome

Abstract Disclosure: S.R. Jafarian-Kerman: None. A. Razzeto: None. G. Saini: None. M. Siddiqui: None. M. Islam: None. D. Behman: None. M. Carson: None. Background: Recognizing Autoimmune Polyglandular Syndrome (AIPS) in a patient who has chronic hypothyroidism, specifically with a non-classic presentation, is challenging. Clinical Case: A woman in her 50’s with hypothyroidism presented with one week of progressive dizziness and weakness. Medications include levothyroxine 125 μg weekly (per the patient, her PCP started this dose 8 months ago based on lab results). On physical examination: BP 101/74 mmHg; HR 56 bpm; T: 98.1 F (36.7 C); RR: 23/min; O2 Sat: 98%. Skin: vitiligo. Lab results demonstrated TSH: 839.6 μIU/mL (0.5-4.5) from 0.28 one year ago, free T4: 0.15 ng/dL (0.4-4.5), phosphorus: 2.3 mg/dL (2.7-4.5), vitamin D: 17.4 ng/dL (>30). She was started on daily levothyroxine 125 μg and intravenous fluids. On day 3 of admission, Rapid Response was called for blood pressure 54/39 mmHg. Myxedema coma was unlikely as she lacked altered mental status, hypothermia, hypoventilation, hyponatremia, or hypoglycemia; CT head was normal. On the same day, hydrocortisone 100 mcg q8h started due to high suspicion of adrenal insufficiency given low normal cortisol [7.1 ug/dL (6-20)] and hypotension. Due to the history of hypothyroidism, vitiligo, and the new diagnosis of adrenal insufficiency, we suspected AIPS. two days later, primary adrenal insufficiency was established by a positive Cosyntropin stimulation test (1 hour cortisol of 14.8 ug/dL; not reaching >18 μg/dL), elevated ACTH 72 pg/mL (6-50), Aldosterone <1 ng/dL (3-16), and low DHEA of 52 ng/dL (345-2030). Other labs were as follow: normal FSH 85.7 mIU/mL (23-116), elevated PTH 153 pg/mL (16-77) which decreased to 62 pg/mL with vitamin D supplementation, normal Vitamin B12, and negative renin and intrinsic factor antibodies. A diagnosis of AIPS was established and she was discharged on levothyroxine, fludrocortisone, and hydrocortisone. Conclusion: AIPS is typically idiopathic and may affect endocrine organ systems either simultaneously or sequentially. The 3 classic patterns are: Type 1 (most common): younger women, presents with candidiasis, hypoparathyroidism, and Addison’s disease. Type 2: middle-aged women, Addison’s disease, autoimmune thyroid disease and/or Type 1 diabetes. Type 3: Type 1 diabetes, pernicious anemia, vitiligo or alopecia, and normal adrenal cortical function. This patient is unique in that she has characteristics of both type 1 and 3 AIPS, but not diabetes. In this case, the combination of hypotension even in the setting of profoundly undertreated hypothyroidism, prompted the expanded evaluation. While isolated hypothyroidism is common among our internal medicine patients, those with additional symptoms, or in this case unexplained hypotension, should be evaluated for AIPS. Presentation: Friday, June 16, 2023

GNAQ/GNA11 Mosaicism Is Associated with Abnormal Serum Calcium Indices and Microvascular Neurocalcification

Mosaic mutations in genes GNAQ or GNA11 lead to a spectrum of diseases including Sturge-Weber syndrome and phakomatosis pigmentovascularis with dermal melanocytosis. The pathognomonic finding of localized "tramlining" on plain skull radiography, representing medium-sized neurovascular calcification and associated with postnatal neurological deterioration, led us to study calcium metabolism in a cohort of 42 children. In this study, we find that 74% of patients had at least one abnormal measurement of calcium metabolism, the commonest being moderately low serum ionized calcium (41%) or high parathyroid hormone (17%). Lower levels of ionized calcium even within the normal range were significantly associated with seizures, and with specific antiepileptics despite normal vitamin D levels. Successive measurements documented substantial intrapersonal fluctuation in indices over time, and DEXA scans were normal in patients with hypocalcemia. Neurohistology from epilepsy surgery in five patients revealed not only intravascular, but perivascular and intraparenchymal mineral deposition and intraparenchymal microvascular disease in addition to previously reported findings. Neuroradiology review clearly demonstrated progressive calcium deposition in individuals over time. These findings and those of the adjoining paper suggest that calcium deposition in the brain of patients with GNAQ/GNA11 mosaicism may not be a nonspecific sign of damage as was previously thought, but may instead reflect the central postnatal pathological process in this disease spectrum.

Vitamin B12 deficiency without anemia in Saudi Arabia: a single-center experience

Abstract Objectives The study aimed to estimate the prevalence of vitamin B12 deficiency in adult Saudi patients and anemia in those patients. Furthermore, the mean level of vitamin B12 in anemic and nonanemic participants was estimated. Methodology This retrospective study involved the evaluation of medical records from adult Saudi Arabian participants who underwent vitamin B12 level testing for nonspecific symptoms during 1 years (2022–2023) at a single center in the Al Qassim region of Saudi Arabia. The data for vitamin B12 level and anemia status among B12-deficient patients were estimated to calculate the prevalence of vitamin B12 deficiency and the prevalence of anemia in those patients. Results The prevalence of vitamin B12 deficiency was 11.46% among 8365 participants. The mean age among all vitamin B12-deficient patients was significantly lower compared with those with normal vitamin B12 levels. Female patients had a lower mean vitamin B12 level than male patients. The prevalence of anemia in the vitamin B12-deficient group was 23.46% among the total participants, with female patients having a significantly higher prevalence of anemia than males. The mean value for mean corpuscular volume (MCV) in anemic vitamin B12-deficient patients was normal, and the prevalence of macrocytosis was low (1.3%). The effect of gender on vitamin B12 deficiency and anemia status was significant. Conclusion The present study has provided additional evidence regarding the lack of a causal correlation between vitamin B12 deficiency and anemia. Moreover, the prevalence of vitamin B12 deficiency and anemia was higher in female patients than in males.

Pernicious anemia with false normal vitamin B12 levels caused by intrinsic factor antibodies interference: a case report

We present a case of a 48-year-old woman with a fortuitous discovery of macrocytic anemia and thrombocytopenia. Serum folate and vitamin B12 levels were normal. However, due to the presence of indirect signs of cobalamin deficiency, such as elevated homocysteine and methylmalonic acid, and signs of dyserythropoiesis on the bone marrow aspirate, pernicious anemia was suspected. Vitamin B12 dosage was repeated finding fluctuating but always normal results. Anti-intrinsic factor antibodies were present at a very high level, explaining the fluctuations and the interference found on the assay using competitive binding chemiluminescence (CBLA). Serum vitamin B12 dosage by electrochemiluminescence, a method described as not interfering with intrinsic factor antibodies, showed a collapsed vitamin B12 level. Measurement of vitamin B12 with CBLA after adsorption of immunoglobulins in the sample using protein G SepharoseTM, confirmed the interference of the cobalamin assay with autoantibodies. This case illustrates the difficulties regarding the analysis and standardization of the vitamin B12 assay for the diagnosis of pernicious anemia.

P05 Osteoporosis in thalassemia; a case with multifactorial aetiology

Abstract Introduction Thalassemia patients are prone to osteoporosis due to multifactorial reasons, including anaemia, bone marrow expansion, iron overload and hypogonadism. Case description A 41-year-old British Asian male with beta thalassemia major was referred to rheumatology in 2018 for osteoporosis. In 2008, aged 27 years, whilst playing football, he developed a distal radial fracture and ulnar styloid process fracture and a DEXA scan had revealed low bone mineral density (BMD) for age. Subsequently, he was started on Ibandronic acid by his haematologist for a total of 10 years. After he was referred to rheumatology in 2018, bisphosphonates were discontinued as he had 5% improvement in BMD, a decade of bisphosphonates and no further fractures. Further assessment revealed multiple contributory factors for his osteoporosis. • Consistency low vitamin D – 9.6 nmol/L in 2009, average value of 20 • He was diagnosed with hypogonadism, poor compliance with IM testosterone injections • He had diabetes which was not optimally controlled • Evidence of iron overload with average serum ferritin of 2000 ug/L with deferasirox While these factors were optimised, it was decided to adopt a watch and wait policy with regards to specific osteoporosis treatment. Review in 2023 revealed serum testosterone level of 20.1 nmol/L (6.9-23.2) with better compliance with testosterone injections. Fructosamine levels were 310 (normal range 200-285) but it has reduced from a peak of 370. Serum ferritin levels have reduced to 776 down from a high of 5600. Normal vitamin D levels were maintained. The DEXA scan in 2023 revealed a spine T score of −2.4 which showed 10.2% increase in bone mineral density. DEXA scan in 2020 revealed T score of −3.1 in spine and −1.9 in hips. The P1NP level was 56 (19-69) which has reduced from 100 in 2021. Improvements in BMD and bone turnover markers were achieved through optimising contributory factors without any specific osteoporosis treatment. He will be monitored with periodic BMD and bone turnover markers. Discussion Anaemia and subsequent bone marrow expansion is a recognised cause for osteoporosis in thalassemia patients. While regular blood transfusions inhibit bone marrow expansion, ineffective erythropoiesis is not fully supressed. This patient received 3 units of blood every 4 weeks. Bone marrow expansion occurs mostly in trabecular bone resulting in low BMD is areas which generally have increased amount of trabecular bone such as the spine. Our patient had a lower BMD in the spine compared to the femoral neck. Iron overload directly disrupts bone formation and can result in endocrinopathies which contributes to osteoporosis. Hypogonadism is another well-recognised cause and is primarily results from iron deposition in pituitary and at times in the gonads. Hormonal replacement therapy reduces bone loss. Studies have shown that hypogonadic patients have more severe osteoporosis and predominant involvement of the femoral neck. Iron overload can cause diabetes mellitus and impaired growth hormone/ insulin growth factor-1 (IGF-1) axis which can contribute to osteoporosis. Our patient did have diabetes but had normal IGF-1 levels when checked previously. Deferoxamine which is one of iron chelating agents have been shown to reduce collagen synthesis and increases osteoblast apoptosis which might contribute to the development of osteoporosis. Vitamin D levels are well known to be low in patients with thalassemia compared to the general population. While there are no RCT’s to show that bisphosphonates reduce fracture risk, surrogate markers such as increased BMD and reduction in bone turnover markers are known to occur. Therefore, current guidance (Standards for the Clinical Care of Children and Adults with Thalassaemia in the UK) recommends bisphosphonates to be considered in patients with a low BMD for age (Z-score < −2.0, T-score < −2.5 if post-menopausal or over 50), if there are fragility fractures or falling BMD despite adequate vitamin D levels, and hormone supplementation. Key learning points Learning point Important to assess for osteoporosis in thalassaemic patients. There are multiple factors contributing to the development of osteoporosis which needs to be addressed together with endocrinologist and haematologist. Bisphosphonates are recommended though further RCT evidence is required to support this

P06 Think of hypophosphatasia if atypical fracture with persistent low ALP levels

Abstract Introduction Hypophosphatasia (HPP), a rare, underdiagnosed metabolic genetic bone disease caused by diminished or absent expression of the tissue non-specific alkaline phosphatase (TNSALP) enzyme. The mutation of alkaline phosphatase (ALPL) gene leads to wide-ranging clinical manifestations, broadly classified into six different types based on age of onset and severity of the disease. Fragility fractures are predominant characteristics of adult onset HPP and are often misdiagnosed as osteoporosis, stipulating antiresorptive treatment. However, bisphosphonates (BP) make HPP more susceptible to atypical fractures and thus are contraindicated. A recent study shows 1:4 atypical femoral fracture cases are linked with monogenic bone diseases including HPP. Case description A 63-year-old Caucasian female was referred to our osteoporosis clinic, at the age of 57 following an atypical right femur fracture while on bisphosphonate and steroids. Her past medical history includes multiple right thigh sarcoma at the age of 39, 45 and 49 years requiring multiple surgeries and localised radiotherapy. She was also diagnosed with ocular myasthenia gravis two years before the atypical fracture, requiring long term high dose steroids. Her other co-morbidities include type 2 diabetes and hypertension. Due to long term steroids, her primary care physician initiated weekly 70 mg oral alendronic acid. However, three months later she had a spontaneous right mid shaft femur fracture. The patient experienced one year of right thigh pain prior to fracture which was not brought to medical attention. She underwent intramedullary nailing and successful rehabilitation. A thorough assessment in fracture liaison service spotted the history of primary tooth loss with roots intact in childhood, and chronic dental problems crowning in adult life requiring many caps and crowns. Her mother has a history of “childhood onset rickets”, bowing of legs and complete loss of all her permanent teeth at the age of 30 years. A review of blood tests revealed normal calcium, vitamin D and parathyroid levels, multiple low alkaline phosphatase levels between 16 – 23 U/L(normal range 30-130 U/L) prior to bisphosphonates, vitamin B6 fasting blood test had shown raised result at 140 (normal range 40-100). Xray of the left femur was normal. The dual energy X-ray absorptiometry (DEXA) scan yielded normal T score. The genetic test confirmed heterozygous gene mutation in ALPL gene, confirming a diagnosis of hypophosphatasia. She recovered well from her fracture and manages to walk more than one mile unaided. She is currently under regular follow-up in our hypophosphatasia clinic and has stopped bisphosphonates indefinitely. Discussion The underlying cause for atypical femoral fracture (AFF) in this case is multifactorial; long-term steroids, radiotherapy, HPP and bisphosphonate usage. Regardless, there is a relationship between hypophosphatasia and AFF. Some studies have proved that more than 90% of the patients with AFF used long term BPs. The defective ALPL gene in HPP affects bone mineralisation, resulting in accumulation of inorganic pyrophosphate (PPi), which impairs hydroxyapatite crystal formation causing recurrent fractures, osteopenia, delayed wound healing, dental problems, atypical and pseudo fractures. Bisphosphonates are chemical derivates of PPi, and thus inversely affect bone mineralisation especially in cases of TNSALP mutations and thus are contraindicated in HPP. The atypical fractures often may remain undiagnosed for a long time despite often prolonged prodromal pain occurring before the actual fracture. Careful clinical evaluation and plain X-ray will help to make the diagnosis. Hypophosphatasia related fractures mostly occur laterally in the subtrochanteric diaphysis. AFF cases often require surgical repair with intramedullary nailing. If an imminent atypical fracture is diagnosed early, prophylactic surgery is sometimes recommended. After three months of alendronic acid, bone turnover markers are usually suppressed, therefore despite the short time of alendronate exposure, this is likely to have contributed to the atypical femur fracture. Also, genetic test revealed inherited autosomal dominant trait of HPP in this case, enabled family screening and prevention of potential use of future bisphosphonates in affected family members. Key learning points HPP presenting in adulthood may be more common than previously though with a recent study estimating prevalence of the mild HPP genotype to be 1:508, although not all cases will be symptomatic. A persistent low alkaline phosphatase together with a fragility or atypical fracture raises suspicion of hypophosphatasia. A thorough clinical evaluation, fasting vitamin B6 levels, urine phosphoethanol amine levels and ALPL genetic test will aid the diagnosis. Severe cases of hypophosphatasia are treated with asfotase alfa, enzyme replacement therapy, to prevent debilitating complications, while most mild and moderate cases are offered supportive management. Bisphosphonate treatment is contraindicated in hypophosphatasia. It is worth reviewing ALP levels prior to antiresorptive therapy in suspected cases, as bisphosphonates often reduce ALP levels, masking the diagnosis. High risk Osteoporosis cases should be discussed in a multidisciplinary setting with careful risk-benefit evaluation. Cases like this highlight the importance of early HPP diagnosis to avoid contraindicating treatments and their consequences.

Regional features of vitamin D content in the body of newborns and children of the first year of life

Objective. To assess the vitamin D availability of newborn babies, nursing mothers and children of the first year of life living in various regions of Belarus.Materials and methods. 114 children were examined. Group I included 31 newborns from Gomel, group II — 40 newborns living in Minsk, group III — 43 children — were infants (1–12 months) from Gomel. Mothers of group I children (31 women) were also additionally examined. To assess vitamin D availability, we determined the level of 25 (OH) D - the main metabolite of vitamin D.Results. In newborns of group I a low vitamin D content was found. Normal vitamin D content was not detected in any child. The average content level is 25(OH)D in the blood serum of mothers of newborns was significantly higher than in their children. The absolute majority of mothers had vitamin D insufficiency or deficiency, regardless of taking preventive doses of vitamin D. In newborn children of group II, the average content level is 25(OH)D was higher than in group I. In children of group II, 25(OH)D deficiency was statistically more common. In group III, the normal vitamin D content was detected only in 62,8 % of children.Conclusion. A high prevalence of vitamin D deficiency has been established in newborn children and their mothers both in Gomel and Minsk. The administration of vitamin D in the first year of a child’s life in a preventive dose does not allow in 37.2% of cases to ensure its optimal level in the blood serum. Taking vitamin D by pregnant women for prophylactic purposes does not allow to ensure an optimal level of 25 (OH)D more than 30 ng/ml in a newborn baby. It is necessary to carry out comprehensive diagnostic, preventive and corrective measures to eliminate vitamin D insufficiency and deficiency.

The Relationship between the Severity of Lumbar Spinal Stenosis and Levels of Vitamin D and Parathyroid Hormone

Background: It is known that parathyroid hormone (PTH) and vitamin D have a wide variety of effects on bone metabolism. However, the levels of PTH and vitamin D in patients with lumbar spinal stenosis (LSS) have not been adequately investigated in the literature. Objective: The objective of this study was to investigate the relationship between PTH and vitamin D levels and the severity of stenosis in patients with LSS. Materials and Methods: This retrospective observational study included consecutive patients who presented to the Neurosurgery outpatient clinic with chronic leg pain and low back pain and were diagnosed with LSS between January 2019 and July 2022. Patients were categorized into three groups based on their vitamin D and parathyroid hormone status. Group 1: High parathyroid hormone and Low vitamin D levels; Group 2: Normal parathyroid hormone and low vitamin D levels; Group 3: Normal parathyroid hormone and vitamin D levels. There were 17 (37%), 10(22%), and 19(41%) subjects in groups I, II, and III, respectively. Results: The mean age of the groups with a total of 46 patients I, II and III were 62.2±11, 58.3±6, and 63.2±6.4 years, respectively (p=0.553). Sex of the study groups was not statistically different, either (p=0.079). Spinal canal AP diameter (p=0.002) and ligamentous interfacet distance (p=0.008) were significantly different in study groups. Vitamin D positively correlated with Spinal canal AP diameter (r=0.56, p<0.001) and ligamentous interfacet distance (r=0.51, p=0.003), while PTH was inversely correlated with them (r=-0.33, p=0.020), ( r=-0.47, p=0.007) . Conclusion: Vitamin D is significantly correlated with the diameters of spinal canal AP and ligamentous interfacet distance. PTH is negatively correlated with the diameters of spinal canal AP and ligamentous interfacet distance. Keywords: Lumbar spinal stenosis, Vitamin D, Parathyroid hormone, Neurogenic claudication, Low back pain, Ligamentous interfacet distance.

ISCHEMIC STROKE(CVA) AND VITAMIN-D LEVEL

Vitamin D(25-hydroxyvitaminD), a neuroprotective prohormone, is associated with neurological disorders in particular ischemic stroke. In ischemic stroke patients lower than normal vitamin D level is more prevalent and number of male patients had low vitamin D as compared to number of female patients. Statistically significant, vitamin D in low level range was found in ischemic stroke with diabetes mellitus than patients with normal blood glucose level. Elevated CRP level was also found in those patients who had low vitamin D level. Compared to normotensive stroke patients, decreased value than normal vitamin D range were found in patients having hypertension. Ischemic stroke with associated dyslipidemia patients had low levels of vitamin D as compared to patients with normal lipid. Deficient levels of vitamin D were found mostly in age group more than 60 years.

Feasibility of an implantable bioreactor for renal cell therapy using silicon nanopore membranes

The definitive treatment for end-stage renal disease is kidney transplantation, which remains limited by organ availability and post-transplant complications. Alternatively, an implantable bioartificial kidney could address both problems while enhancing the quality and length of patient life. An implantable bioartificial kidney requires a bioreactor containing renal cells to replicate key native cell functions, such as water and solute reabsorption, and metabolic and endocrinologic functions. Here, we report a proof-of-concept implantable bioreactor containing silicon nanopore membranes to offer a level of immunoprotection to human renal epithelial cells. After implantation into pigs without systemic anticoagulation or immunosuppression therapy for 7 days, we show that cells maintain >90% viability and functionality, with normal or elevated transporter gene expression and vitamin D activation. Despite implantation into a xenograft model, we find that cells exhibit minimal damage, and recipient cytokine levels are not suggestive of hyperacute rejection. These initial data confirm the potential feasibility of an implantable bioreactor for renal cell therapy utilizing silicon nanopore membranes.

Relation between Vitamin D Deficiency and Dry Eye

Background Tears are very important to the overall health of the eye and vision. The tear film is mechanically distributed over the ocular surface through a neuronally controlled blinking mechanism. Normal blink reflex, contact between the external ocular surface and the eye lids, and normal corneal epithelium are three factors required for effective resurfacing of the tear film (tear stability). (1) Objective To demonstrate the relation between vitamin D deficiency and dry eye disease searching for finding a correlation between dry eye parameters with vitamin D deficiency. Patients and Methods Cross sectional study. A total 50 patients attending the ophthalmology outpatient clinic of General Ain Shams Hospital, from February 2019 to October 2019 were enrolled in the study after the approval of the research ethical committee in the Faculty of Medicine, Ain Shams University. They were divided randomly into 2 groups. Group 1: consisted of 35 patients who were vitamin D deficient. Group 2: consisted of 15 patients who had normal vitamin D levels (control group). Results The study showed that there was statistically significant increase in symptoms of dry eye in female patients than male patients and there was statistically significant decrease in the level of tear film break up time, Shirmer test and serum 25 (OH) vitamin D in cases with dry eye than those without. It was found that there was statistically significant decrease in vitamin D level in female cases than male cases. Also, there was statistically significant decrease in vitamin D level in cases with symptoms of dry eye and conjunctival hyperemia than cases without. There was also statistically significant positive correlation between serum 25 (OH) vitamin D and tear film break up time and Shirmer test. Conclusion The present study suggests that patients with vitamin D deficiency may suffer from dry eye. Investigations to confirm and quantify a clinical diagnosis of dry eye should include serum 25 (OH) vitamin D when suspecting vitamin D deficiency especially in patients prone to this type of vitamin deficiency.

Correlation of Vitamin D status with TSH levels in postmenopausal women; A pilot study

Vitamin D (VitD) insufficiency is present in over half of population worldwide. Over a billion people worldwide are vitamin D deficient or insufficient. It has been long known that VitD insufficiency contributes to development of osteopenia and osteoporosis. We performed a retrospective review of data of 60 patients in postmenopausal age group (45-75 years) during their routine blood investigation for the first time at Government Medical College and Guru Nanak Dev Hospital Amritsar over a period of 3 months (February 2023 to April 2023). Vitamin D levels were insufficient (10-30 ng/mL) in 35% of the patients, deficient (10 ng/mL) in 18.5%, and normal in the remaining 35%. TSH levels were low (less than 0.3 mIU/L) in 5%, high (more than 4.5 mIU/L) in 18.3%, and normal (0.3-4.5 mIU/L) in the remaining 76.6%. 54% (n-11) of individuals with elevated TSH had vitamin D deficiency, while 18% had insufficient vitamin D. 100%(n-3) patients with low TSH had normal vitamin D levels. TSH and vitamin D levels were normal in 22 individuals. High TSH levels was associated with low vitamin D levels, low TSH levels was associated with normal serum vitamin D level. Hence association was linear between TSH and vitamin D in post-menopausal women.

A Case Report of Nitrous Oxide-induced Myelopathy: An Unusual Cause of Weakness in an Emergency Department.

Weakness is a common symptom that within itself does not indicate a specific diagnosis. Recreational inhalant use such as nitrous oxide (NO) may not often be disclosed. Additionally, professional or occupational history, such as being a dentist or dental assistant, should be determined because of higher reported rates of NO misuse. Nitrous oxide can cause vitamin B12 deficiency and resulting neuropathy. Nitrous oxide toxicity can have a wide variation of presentations with or without laboratory abnormalities or remarkable imaging findings, which can further complicate a diagnosis of weakness secondary to NO use. A 33-year-old female presented to the emergency department with progressive bilateral leg numbness and objective weakness after repeated recreational NO use. After an extensive workup, she was found to have vitamin B12 deficiency and an electromyography study consistent with myeloneuropathy, despite normal imaging. She was prescribed high-dose vitamin B12 therapy and stopped using NO. One year after diagnosis, our patient maintained NO sobriety and had near-complete resolution of prior neurologic deficits. The use of recreational inhalant and the patient's occupation should be considered when a patient presents with weakness. Obtaining vitamin B12 and methylmalonic acid levels should be considered for diagnosis. However, NO-induced neuropathy can be seen in patients with normal vitamin B12 and methylmalonic levels and patients do not always have abnormal imaging findings. The healthcare team should consider the varied presentations and findings of substance-induced conditions such as NO toxicity.

Association of vitamin D levels with severity and outcome of COVID-19 infection among inward patients at a tertiary care unit in Sri Lanka

Introduction: A link between vitamin D and COVID-19 infection has been expressed by many experts. In this study, we aim to investigate the association of the prevalence of vitamin D deficiency with the severity and outcome of COVID-19 infection in patients who are admitted to Teaching Hospital Batticaloa, Sri Lanka. Methods: A retrospective cross-sectional study was conducted among COVID-19 patients over a period of one month in May 2021. All patients who tested positive for COVID-19 were included. Patients with chronic kidney disease, known vitamin D deficiency, and patients on vitamin D supplements were excluded from the study. The vitamin D deficiency was defined according to the Oxford Academic Endocrine Society guidelines. The severity of the COVID-19 was defined according to the Provisional Clinical Practice Guidelines on COVID-19 suspected and confirmed patients. Primary endpoints of this study were 'recovered from COVID-19' or 'death'. Data was analysed to report the proportion of patients with different vitamin D levels and disease severity. Chi-squared and Fisher's exact tests were used to analyse the results. A p-value of <0.05 was considered as statistically significant. Results: Out of 141, 58% were males. Mild, moderate, and severe COVID-19 were observed in 29.8%, 48.2%, and 22.0% of patients respectively. Only 30.5% of the population had normal vitamin D levels while the rest had some degree of vitamin D insufficiency. None of the patient population had severe vitamin D deficiency status. A 52.9% in the moderate category of COVID-19 severity had insufficient levels of vitamin D levels. Those that recovered from COVID-19 were 93.6%. No significant association was observed between the severity of COVID-19 and vitamin D deficiency (p=.1041 ). Interestingly hypoxia was significantly prevalent among those with normal vitamin D levels (p=.0005). vitamin D deficiency does not impact the mortality rate among COVID-19 patients (p=.6559). Conclusions: The association of vitamin D levels with COVID-19 severity and mortality was not statistically significant.