Low Vitamin Research Articles

Vitamin D deficiency and intracranial aneurysms: Systematic Review

BackgroundLow vitamin D levels have been associated with an increased risk in patients with cerebrovascular diseases. However, solid evidence linking intracranial aneurysm (IA) to hypovitaminosis D is still lacking. This review aims to evaluate if there is a relationship between vitamin D deficiency and the incidence and rupture of IA. MethodsA systematic search of papers was performed in the following databases: MEDLINE, EMBASE, LILACS, and Web of Science. The selected papers covered data on vitamin D levels and the occurrence or rupture of IA and/or other complications of this condition. The risk of bias analysis was performed with tools developed by the National Heart, Lung, and Blood Institute. Tables were developed to synthesize the qualitative analysis of the data. ResultsSix studies from five different countries were included covering a total of 14,184 participants. A relationship between low vitamin D levels and IA incidence was detected in all studies. In terms of rupture and complications, there was a tendency of association with hypovitaminosis. DiscussionAmong the limitations of the papers, the following are noteworthy: sample size and selection, recording flaws inherent to retrospective designs, failure to consider confounding variables, and heterogeneity of data produced among the researches, making a quantitative analysis of the evidence unfeasible. From the results obtained, we can identify a higher incidence of hypovitaminosis D in patients with IA. Yet, further studies need to be conducted in investigating the relationships between low vitamin D levels and rupture or other complications (CRD42022363369).

12460 Bilateral Parietal Thinning: A Rare Condition Of Unclear Etiology

Abstract Disclosure: T.L. Madsen-Barbosa: None. M. Cheikh: None. I. Marcano: None. Background: Bilateral parietal bone thinning (BPT) is an infrequent and often underdiagnosed condition characterized by the external thinning of the skull's parietal bone. The pathophysiology is unclear, but some studies suggest a link to osteoporosis. We present a case of osteoporosis diagnosed on evaluation of BPT. Case Description: A 77-year-old woman with a history of chronic kidney disease (CKD stage IV) and type 2 diabetes was referred to the Bone Health Clinic for evaluation of low bone density. She initially presented to Neurosurgery clinic for evaluation of head indentations. A dual energy x-ray absorptiometry (DEXA) scan showed values in osteopenia range (left total hip bone mineral density (BMD) 0.678 and T-score of -2.2, left femoral neck BMD 0.272 and T-score of -1.6, and left 33% radius BMD 0.577 and T-score of -2.0), leading to the referral. The patient reported painless indentations in the parietal bones that had been progressing for four years, with no history of head trauma, inflammatory disease, or prolonged steroid use. A head computed tomography (CT) scan showed symmetric thinning of the skull’s parietal bones, with an average thickness of 2.34 mm (compared to 5.1 mm four years earlier). Review of prior images also revealed a T11 compression fracture on spine X-ray from 2019. Laboratory tests showed elevated parathyroid hormone (PTH) 155 pg/mL (reference range 15-65 pg/mL), low vitamin D 25-OH 10.6 ng/mL (reference range 30-100 ng/mL), elevated alkaline phosphatase 142 units/L (reference range 46-116 units/L), and high creatinine level 2.7 mg/dL (reference range 0.5-0.8 mg/dL), other laboratory tests were normal. After discussion with the patient and Nephrology, Denosumab therapy along with Calcium and Vitamin D supplementation were started in November 2023. The patient continues the treatment with antiresorptive medication every 6 months and head CT scan to monitor the skull thinning changes. Discussion: BPT is rare, with only approximately 150 cases reported. Crucial aspects such as its etiology, pathophysiology, treatment, and prognosis remain unknown. It can result from various conditions like trauma, systemic mastocytosis, diabetes mellitus, hereditary diseases, or idiopathic causes and mainly affects women of advanced age. Osteoporosis is suggested as a possible cause based on histological findings on prior studies that propose BPT may result from osteoporosis-induced decreased bone formation rather than increased bone destruction. The reason for excessive bone resorption in the skull of osteoporotic patients remains unclear. Our case highlights progressive and symmetric BPT possibly related to systemic conditions like osteoporosis, with a focus on treatment options. Conclusion: This case sheds light on the clinical presentation, imaging findings, pathogenesis, and treatment options for the rare condition of bilateral parietal bone thinning. Presentation: 6/3/2024

8732 Hypercalcemia: When It’s Not PTH, Why Not Blame Your Neighbor?

Abstract Disclosure: D. Misra: None. M.R. Brennan: None. L. Misra: None. A 60-year-old female with a history of recently diagnosed hyperthyroidism, hypertension, and seizure disorder presents with a four-month history of neck swelling and pain. The patient was diagnosed with hyperthyroidism four months prior to admission and was started on methimazole 10 mg three times a day for two months, then instructed to decreased to 10 mg daily. In addition to the four months of neck swelling and pain, the patient also endorsed difficulty swallowing, palpitations, constipation, and bilateral ankle edema. Vital signs were stable other than a heart rate in the low 100s. Physical exam revealed a fixed painful L sided neck mass with no signs of airway compromise and bilateral exophthalmos. Labs revealed TSH <0.01 uIU/mL, Free T4 2.1 ng/dL, TSI was elevated (>40) IU/L. potassium 3.2 mmol/L, hypomagnesemia 1.3 mg/dL, troponin of 55 ng/l and hemoglobin 9.3 g/dL. The patient had a calcium of 10.6 mg/dL and an ionized calcium of 5.73 mg/dL with a normal PTH (34 pg/mL) and a low Vitamin D (22 ng/mL). A CT of the neck was performed showing marked thyromegaly with innumerable subcentimeter hypodense nodules in both lobes and a dominant 1.1 nodule in right lobe. Initial therapy involved correction of the electrolytes, telemetry monitoring, and a consultation to the endocrine service. The endocrine team started the patient on methimazole 10mg/daily and ordered a thyroid scan. Scintigraphy was performed and was consistent with Graves’ disease. On Day #2 the patient’s vital signs had normalized and the patient was able to swallow and tolerate a regular diet, The scan showed an enlarged thyroid with diffuse nodular character and moderate hyperemia consistent with diffuse thyroiditis. The scan also described a multinodular goiter with the largest nodule measuring 2.2 cm. She was discharged on Day #3 on methimazole 10mg daily and asked to follow up with endocrinology. Graves’ disease is a common cause of hyperthyroidism and is caused by autoantibodies that increase the production of thyroid hormone. Along with classic symptoms of hyperthyroidism, our patient had hypercalcemia. This was non-PTH mediated and in the absence of other signs or symptoms of a malignancy or granulomatous process, the hypercalcemia is likely due to her hyperthyroid state. Hyperthyroidism-associated hypercalcemia is a rare complication in hyperthyroid patients but should not be forgotten when evaluating non-PTH mediated hypercalcemia as it can be corrected easily with appropriate medications or in this case with the correction of the hyperthyroidism. Consideration of this etiology may also reduce the number of extraneous labs and imaging when no other common etiology is found. Presentation: 6/2/2024

5043 Skeletal Microstructure in Men with Celiac Disease

Abstract Disclosure: A. Rubenstein: None. A. Kondapalli: None. S. Agarwal: None. M. Bucovsky: None. I. Colon: None. N. Kil: None. S. Lewis: None. B. Lebwohl: None. P. Green: None. M. Walker: Advisory Board Member; Self; Alexion Pharmaceuticals, Inc.. The pathophysiology of osteoporosis related to celiac disease (CD) remains incompletely understood. High resolution peripheral quantitative computed tomography (HRpQCT) has revealed microarchitectural deficits in women with CD, but no data exist in men. We prospectively studied bone health using DXA and HRpQCT in 17 men with duodenal biopsy-confirmed CD (mean age 43±16 years; 82% white, 6% Asian, 12% other) and 5 male controls (mean age 40±12 years; 80% white, 20% Asian). Compared to controls, men with CD had lower self-rated health scores (p<0.05), but age, BMI, alcohol use, physical activity, acid blocker use, and vitamin D intake did not differ. Among patients with CD, 23.5% had other autoimmune diseases (type 1 diabetes, hypothyroidism, vitiligo, systemic sclerosis). At CD diagnosis, mean age was 34.3 ± 14.8. CD patients had a mean CD and gluten-free diet duration of 8 years. 29% of patients (n=5/17) were enrolled within 13 months of CD diagnosis. Mean tissue transglutaminase IgA, serum calcium, PTH, Vitamin D, and alkaline phosphatase were normal, but vitamin D levels were < 30 ng/mL in 36% (n=5/14) and PTH was elevated in 11% (n=1/9). T- (-0.5±1.5 vs. 0.8±0.8, p=0.03) and Z-scores (-0.1±1.4 vs. 1.1±0.9, p=0.05) by DXA were normal at all sites but tended to be lower at the 1/3-radius only in CD compared to controls. By HRpQCT, there were no differences. Compared to a larger control group including HRpQCT data from an additional 14 normative database controls (n=19), CD had lower radial cortical (-4.7%, p=0.02) and tibial trabecular (-13.3%, p=0.04) vBMD and a trend toward lower cortical volumetric BMD (vBMD; -3.5%, p=0.06) at the tibia. Within the CD group, longer CD duration was associated with worse tibial cortical vBMD at (r=-0.55, p=0.02). Higher PTH (n=9) correlated with lower lumbar spine areal BMD (r=-0.75, p=0.02), tibial trabecular thickness (Tb.Th; r=-0.77, p=0.02) as well as radial cortical vBMD (r=-0.81, p<0.01), trabecular Tb.Th (r=-0.78, p=0.01), and cortical thickness (r=-0.75, p=0.02). Those with greater dietary vitamin D intake had higher total vBMD (r=0.50, p=0.04) and trabecular thickness at the tibia (r=0.51, p=0.04). Similarly, higher 25-hydroxy vitamin D levels were associated with higher total hip aBMD (r=0.58, p=0.03). In summary, CD in men is associated with lower areal BMD at the 1/3-radius by DXA and lower vBMD at the radius and tibia by HRpQCT. Low vitamin D levels and secondary hyperparathyroidism may contribute. Further work is needed to understand the extent and pathophysiology of skeletal disease in men with CD. Presentation: 6/3/2024

6539 Hungry Bone Syndrome & Osteoblastic Metastasis In The Setting Of Prostate Cancer : A Rare Cause Of Hypocalcemia

Abstract Disclosure: B. Sharma: None. M. Khan: None. A. Rao: None. P. Guido: None. Background: Hungry bone syndrome (HBS) is due to excessive calcium and phosphorus sequestration in the bone, manifesting as hypocalcemia and hypophosphatemia.It is most commonly seen as a postoperative complication of parathyroidectomy.Advanced prostate cancer with osseous metastasis has been previously described as is a rare cause of HBS. Clinical Case: A 65 year old male was admitted to the hospital with acute congestive heart failure and severe hypocalcemia.He exhibited symptoms of muscle spasms and perioral paraesthesias. Physical exam was positive for Trousseau's sign.Initial tests were consistent with severe hypocalcemia (corrected non-ionized calcium 6.8 [8.8-10.2] mg/dL), low ionized calcium (0.58 [1.10-1.30] mmol/L). Three weeks prior to admission, corrected non-ionized calcium was 9.8 mg/mL. Other labs showed normal magnesium, normal phosphorus, elevated alkaline phosphatase (1044 [45-117] U/L), low Vitamin D (12 [>30] ng/mL ), elevated iPTH (567 [19-88] pg/mL) and low PTH-rp (9 [11-20] pg/mL]. His electrocardiogram showed regular rate and rhythm with Qtc prolongation (497 ms).He had a significant oncological history of prostate cancer and multiple myeloma in remission.He was previously treated with zoledronic acid, discontinued 1 year prior to admission, for reducing skeletal complications while being treated for multiple myeloma. He had a recent workup with medical oncology for recurrence of prostate cancer due to elevated Prostate-specific antigen (380 [<4.00] ng/mL).Computed tomography imaging showed diffuse osteoblastic metastatic disease in the axial skeleton, pelvis and proximal femur. During hospital admission hypocalcemia was persistent, likely also due to concurrent furosemide use, necessitating the administration of intravenous calcium infusion and use of cholecalciferol and calcitriol.He was discharged on calcium carbonate 4500 mg twice a day, cholecalciferol 50 000 units weekly for 12 weeks and calcitriol 2 mcg twice a day. Conclusion: Hypocalcemia in the setting of prostate cancer is most commonly due to the use of bisphosphonates or Receptor activator of nuclear factor kappa-B ligand (RANK-L) inhibitors. Hypocalcemia in this case was due to sequestration of calcium in the bone by osteoblastic metastasis. This case illustrates the importance of recognising osteoblastic metastasis as a differential in protracted and severe hypocalcemia in malignancy.High doses of calcium, vitamin D, and calcitriol replacement are often needed as the hypocalcemia is usually severe and refractory with some cases requiring prolonged IV calcium infusion.Treatment of the underlying cancer and bone metastases with chemotherapy has been shown to improve hypocalcemia and reduce the requirement of calcium and vitamin D supplementation.There is limited data to suggest if bisphosphonates can be safely used in these cases for prevention of skeletal related events. Presentation: 6/1/2024

12372 A Rare Case Of Silicon Granulomatosis Induced Hypercalcemia In A Transgender Female

Abstract Disclosure: O.A. Aluko: None. I. Singh: None. Introduction: Hypercalcemia has been described in patients with most granulomatous disorders, of which sarcoidosis and tuberculosis are the most common. Granuloma formation is a rare, however well known complication of silicon implants and injections. We present a case of silicon granulomatosis induced hypercalcemia in a transgender female. Case Report 60-year-old transgender female, with past medical history of HIV on HAART was referred to Endocrinology for evaluation of hypercalcemia. She Bloodwork done a few weeks prior revealed elevated calcium 12.3 and low PTH of 9. Reported symptoms include worsening abdominal pain similar to prior gastritis flare, insomnia and significant weight loss. Denied any constipation, joint pain, mood changes, no history of bone fractures or kidney stones. Admitted to significant dairy intake - half a gallon of milk within 3 days and daily yogurt consumption. Endorsed inadequate daily fluid intake and she was not taking oral calcium or Vitamin D supplementation. Quit tobacco 9 years ago. Vitals were significant for tachycardia with HR 120/min, BP stable. Patient was referred to the ER for IV hydration and further evaluation with initial suspicion of malignancy. Repeat corrected calcium was 14.7, ionized calcium 6.8, PTHrP undetectable <2, borderline high 1,25 dihydroxyvitamin D 74.5, low vitamin D 17.9 and normal free T4 1.5. ACE, SPEP, UPEP levels within normal limits. Vitamin A low. CT chest/abdomen/pelvis revealed innumerable soft tissue foci in the subcutaneous adipose tissue of the flanks and lateral gluteal areas; nodular liver, suspected cirrhosis and portal hypertension. Imaging findings prompted further discussion regarding prior procedures. She endorsed history of silicone fillers in hips and breast implants 30 years ago. Images reviewed with radiology confirmed calcification around bilateral breast implants, with intracapsular rupture. Calcium improved with IV Fluids, bisphosphonates and steroids. The most probable cause of hypercalcemia was believed to be secondary to silicone granulomatosis. Innumerable granulomas were deemed irresectable, removal of the breast implants considered however not performed. She was later diagnosed with hepatitis B, cirrhosis and succumbed to sepsis and multiorgan failure. Conclusion Eliciting a detailed history, physical exam and correlating with imaging findings is imperative to establishing an uncommon diagnosis. PTHrP was low and there were no bony metastases making the possibility of malignancy related hypercalcemia less likely. FDG-PET if performed would reveal hypermetabolic nodules, often an initial indication to the underlying etiology. Presentation: 6/2/2024

7752 Navigating Hypercalcemia in Pregnancy: A Case Report

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

Vitamin D Deficiency as a Contributing Factor to Chronic Rhinitis in Middle-Aged and Older Adults: An Epidemiological Study.

Recent studies suggest a critical role for vitamin D in respiratory diseases, including asthma and allergic rhinitis. However, the relationship between vitamin D deficiency and chronic rhinitis, particularly in middle- and older-aged populations, remains underexplored. This study aimed to investigate the association between vitamin D deficiency and chronic rhinitis in middle- and older-aged adults while controlling for lifestyle and physical status factors. Data from 12,654 participants aged 40 years and older were analyzed from the fifth Korean National Health and Nutrition Examination Survey (2010-2012). The prevalence of chronic rhinitis and its association with serum vitamin D levels were assessed using multiple logistic regression models, adjusting for demographic, lifestyle, and physical characteristics. The prevalence of chronic rhinitis was 21.1%. Participants with chronic rhinitis had a higher prevalence of vitamin D deficiency (69.9% vs. 65.2%) and lower mean vitamin D levels (17.73 ng/mL vs. 18.19 ng/mL) compared to those without chronic rhinitis. After adjusting for confounding factors, vitamin D deficiency remained significantly associated with an increased likelihood of chronic rhinitis (OR = 1.21, 95% CI, 1.082-1.348, p = 0.001). This study identifies a significant association between vitamin D deficiency and chronic rhinitis in middle- and older-aged adults, suggesting that maintaining adequate vitamin D levels may be important in managing chronic rhinitis.

8157 Hypercalcemia To Hypocalcemia In Three Days: The Importance Of Asking The Questions

Abstract Disclosure: P. Kachhadia: None. K. Patel: None. S. Khan: None. A. Abu Limon: None. S. Aldasouqi: None. F. Akanbi: None. Z. Ul Abideen: None. Introduction: Severe hypercalcemia needing inpatient hospitalization requires very thorough history taking in order to determine etiology and treatment plan. Causes differ drastically, and misdiagnosis or mistreatment can be life threatening. Here, we present a case of symptomatic hypercalcemia secondary to milk-alkali syndrome that was treated promptly after admission with IV zoledronic acid, leading to severe symptomatic hypocalcemia and prolonged hospitalization. Case presentation: Patient is a 68 year old female with a PMH of breast cancer, osteoporosis and hiatal hernia who presented to the emergency department for fatigue, constipation and lightheadedness. On evaluation, she was found to have a creatinine of 1.54 (0.6-1.1 mg/dL), eGFR 36 (>90 mL/min/1.73 m²), Ca 18.48 (8.6-10.2 mg/dL), albumin 4.7 (3.4-5.4 g/dL), Mg1.4 (1.7-2.2 mg/dL), 25-OHD 18 (30-100), 1,25-Dihydroxy Vitamin D 7.4 (18-78 pg/mL), PTH 11.2 (15-65 pg/mL), phosphorus level 2.4 (2.5-4.5mg/dL), TSH 2.01 (0.4-4.0 mIU/L). SPEP and PTHrP were unremarkable. Due to history of prior breast cancer, imaging was done and CT showed new possible RUL pancoast tumor with RUL spiculated opacity. Patient was started on IV fluids and subsequently received IV zoledronic acid due to concern for severe hypercalcemia secondary to malignancy. By day 3 of treatment, patient's calcium decreased severely, down to a corrected calcium level of 6.4 (8.6-10.2 mg/dL). It was upon further investigation and discussion with the patient that we discovered the patient had received subcutaneous denosumab for her osteoporosis three weeks prior to admission. In addition, she was taking six tums daily (total 1 month duration) for symptoms of dyspepsia secondary her hiatal hernia. The patient’s severe hypocalcemia was treated with high dose oral calcium carbonate and vitamin D along with IV calcium gluconate. Magnesium was replaced daily. Through daily replacement, patient was kept in the hospital for a total of 10 days duration before her calcium levels were deemed safe for return home. Discussion: Hypercalcemia is a common cause of hospitalization worldwide. Testing should be comprehensive and history taking should be thorough to help navigate treatment plans. Bisphosphonates are indicated for hypercalcemia of malignancy, and its use otherwise may be the cause of severe hypocalcemia if not used in the right setting. In our case, the patient’s hypocalcemia was multifactorial from prior denosumab use and then subsequent zoledronic acid use. Additional risk factors included low vitamin D counts and disruption of high amounts of over the counter tums after being admitted to the hospital. Anchoring bias also led clinicians to believe that the hypercalcemia was secondary to malignancy. Consequently, this led to a prolonged 10 day hospitalization for persistently low calcium levels. Presentation: 6/1/2024

6812 A Rare Case of Polyglandular Autoimmune Syndrome Type 3B Presenting with Unsteady Gait Due to Subacute Combined Degeneration of the Spinal Cord Associated with Pernicious Anemia

Abstract Disclosure: F. Mohammadrezaei: None. F. Sajid: None. C.A. Resta: None. J.G. Karam: None. A Rare Case of Polyglandular Autoimmune Syndrome Type 3B Presenting with Unsteady Gait due to Subacute Combined Degeneration of the Spinal Cord associated with Pernicious Anemia Background: The coexistence of Hashimoto's thyroiditis and pernicious anemia is well established and is recognized as Polyglandular Autoimmune Syndrome (PAS) Type 3B [1]. We describe a rare case of a patient presenting with subacute combined degeneration of the spinal cord leading to the diagnosis of PAS Type 3B. Case Presentation: A 37-year-old man with no known medical history presented to the Emergency Department after a fall in the subway station. On history, he complained of progressive bilateral lower extremity weakness of 10 months duration, necessitating assistance with ambulation, and significant weight gain, described as an increase in his pants size from 40 to 56. His physical examination was relevant for weight of 145kg, BMI of 46.5, normal motor strength and sensation of the upper extremities, decreased strength at 4 out of 5 of bilateral hip flexion and extension, and decreased vibration sensation of bilateral lower extremities. He could not fully stand or walk due to imbalance and weakness. Blood testing revealed a hemoglobin level of 11.4 gm/dl (14-18), MCV of 108.8 FL (80-94), a significantly low vitamin B12 at 89 pg/ml, and normal folate level. His TSH level was 9.26 MCIU/ML (0.39-4.08), with a free T4 of 0.74 ng/dl (0.8-1.8) and significantly elevated Thyroid Peroxidase Antibody titer at 4320 IU/ml (< 34.9). Intrinsic factor antibody and parietal cell antibody tests both came back elevated at 13.4 AU/mL (0.0-1.1) and 1.8 (<1.2), respectively. A head CT scan showed no acute pathology, but MRI spine with contrast revealed abnormal T2 hyperintensity, primarily affecting the lateral columns throughout the cervical and thoracic cord, likely indicative of subacute combined degeneration. The patient was diagnosed with autoimmune Hashimoto's thyroiditis, pernicious anemia, and subacute combined degeneration of the spinal cord due to vitamin B12 deficiency. He was treated with daily vitamin B12 1000mcg muscular injections, levothyroxine 75mcg orally daily (after ruling out adrenal insufficiency), and physical therapy. Conclusion: This case highlights the complexity of polyglandular autoimmune syndromes and the importance of recognizing atypical presentations early in the history of disease. Comprehensive evaluation and timely intervention are essential to mitigate the progression of these conditions and improve patients' quality of life. Reference: (1) Betterle C, Furmaniak J, Sabbadin C, Scaroni C, Presotto F. Type 3 autoimmune polyglandular syndrome (APS-3) or type 3 multiple autoimmune syndrome (MAS-3): an expanding galaxy. J Endocrinol Invest. 2023 Apr;46(4):643-665. Presentation: 6/1/2024

Taurine/chenodeoxycholic acid ratio as a potential serum biomarker for low vitamin B12 levels in humans.

Deficiency of vitamin B12 (B12 or cobalamin), an essential water-soluble vitamin, leads to neurological damage, which can be irreversible and anaemia, and is sometimes associated with chronic disorders such as osteoporosis and cardiovascular diseases. Clinical tests to detect B12 deficiency lack specificity and sensitivity. Delays in detecting B12 deficiency pose a major threat because the progressive decline in organ functions may go unnoticed until the damage is advanced or irreversible. Here, using targeted unbiased metabolomic profiling in the sera of subjects with low B12 levels v control individuals, we set out to identify biomarker(s) of B12 insufficiency. Metabolomic profiling identified seventy-seven metabolites, and partial least squares discriminant analysis and hierarchical clustering analysis showed a differential abundance of taurine, xanthine, hypoxanthine, chenodeoxycholic acid, neopterin and glycocholic acid in subjects with low B12 levels. Random forest multivariate analysis identified a taurine/chenodeoxycholic acid ratio, with an AUC score of 1, to be the best biomarker to predict low B12 levels. Mechanistic studies using a mouse model of B12 deficiency showed that B12 deficiency reshaped the transcriptomic and metabolomic landscape of the cell, identifying a downregulation of methionine, taurine, urea cycle and nucleotide metabolism and an upregulation of Krebs cycle. Thus, we propose taurine/chenodeoxycholic acid ratio in serum as a potential biomarker of low B12 levels in humans and elucidate using a mouse model of cellular metabolic pathways regulated by B12 deficiency.

Association between dietary vitamin B6 intake and endometriosis risk: evidence from the national health and nutrition examination survey.

Endometriosis is a multifaceted disorder with genetic, immune, inflammatory, and multifactorial origins. Vitamin B6 serves as a pivotal coenzyme in various metabolic pathways involving lipids, hemes, nucleic acids, proteins, and carbohydrates. Dysregulation or deficiency of vitamin B6 can perturb human physiology. However, the relationship between dietary vitamin B6 and endometriosis remains elusive. This study aims to explore how dietary intake of vitamin B6 is associated with the risk of endometriosis. Using cross-sectional data from the National Health and Nutrition Examination Survey, we analyzed information from American women aged 20-54 years between 1999 and 2006. After adjusting for relevant covariates, multivariable logistic regression analysis was employed to evaluate correlations. A total of 4,453 women were included in the study. The multiple linear regression model revealed a positive association between dietary vitamin B6 intake and the risk of endometriosis, even after controlling for confounding variables. Compared to individuals with lower vitamin B6 consumption (Q1: <0.94 mg/day), the adjusted odds ratio (OR) values for dietary vitamin B6 intake and endometriosis in Q2 (0.95-1.39 mg/day), Q3 (1.40-1.99 mg/day), and Q4 (>1.90 mg/day) were 1.22 (95% CI: 0.88-1.69, p = 0.23), 1.22 (95% CI: 0.86-1.73, p = 0. 279), and 1.51 (95% CI, 1.01-2. 24, p = 0.04), respectively. Our findings suggest a positive correlation between endometriosis and dietary vitamin B6 intake. Further investigations are imperative to establish a causal relationship between dietary vitamin B6 intake and endometriosis.

Vitamin D deficiency in non-scarring and scarring alopecias: a systematic review and meta-analysis.

Numerous studies have linked vitamin D deficiency (VDD) to the pathogenesis of various alopecia disorders. This study aimed to investigate whether patients with alopecia are more likely to have VDD or lower vitamin D levels than controls, and the prevalence of VDD among patients with certain alopecia disorders. Electronic searches were conducted using PubMed, Embase, Scopus, and Cochrane Library databases from the dates of their inception until September 2024. Studies that reported data allowing for the calculation of odds ratios, mean differences, or correlation coefficients related to vitamin D levels and alopecia were included, while studies without a confirmed diagnosis of alopecia or those involving patients taking vitamin D supplements were excluded. It was found that 51.94% of patients with alopecia areata (AA), 50.38% of patients with female pattern hair loss (FPHL), 47.38% of patients with male androgenic alopecia (MAGA), 53.51% of patients with telogen effluvium (TE), and 38.85% of patients with primary scarring alopecia had VDD. Compared to controls, AA patients had a pooled odds ratio (OR) of VDD of 2.84 (95% confidence interval: 1.89-4.26, I2 = 84.29%, p < 0.01) and a pooled unstandardized mean difference (UMD) of vitamin D levels of -8.20 (-10.28 - -6.12, I2 = 74.25%, p < 0.01) ng/mL. For FPHL patients, a pooled OR of VDD of 5.24 (1.50-18.33, I2 = 81.65%, p < 0.01) and a pooled UMD of vitamin D levels of -15.67 (-24.55 - -6.79, I2 = 91.60%, p < 0.01) ng/mL were found. However, for MAGA, a pooled VDD OR of 4.42 (0.53-36.61, I2 = 88.40%, p < 0.01), and a pooled UMD of vitamin D levels of -2.19 ng/mL (-4.07 - -0.31 ng/mL, I2 = 7.64%, p = 0.37) were found. For TE patients, pooled UMD of vitamin D levels of -5.71 (-10.10 - -1.32) ng/mL were found. People with alopecia frequently have VDD; however, only in patients with AA or FPHL was the association of VDD and decreased vitamin D levels statistically significant compared to control. The findings indicate screening for vitamin D could benefit patients with AA or FPHL, potentially addressing vitamin D deficiency. Further study on vitamin D supplementation as a treatment for alopecia is recommended.

Low Serum Vitamin E Levels Positively Correlate with the Severity of Acne Vulgaris

ABSTRACT Acne vulgaris (AV) is a common disorder of the pilosebaceous, especially prevalent in adolescents. Acne vulgaris ranks among the top ten most prevalent diseases globally. Although AV may resolve spontaneously, sequelae such as scar formation can persist, causing aesthetic and psychological disturbances. There is an antioxidant to counteract acne-causing oxidative stress, vitamin E, which is an important antioxidant in the human body. Therefore, vitamin E in the skin can reduce the formation of squalene peroxide and prevent the occurrence of AV. This is an analytical observational study using a cross-sectional design. The investigation was conducted at the Dermatology and Venereology Clinic of Prof. Dr. I.G.N.G. Ngoerah Denpasar Hospital and the laboratory of the Faculty of Medicine, Udayana University, from February 2024 until the sample size was fulfilled. The sample consisted of patients aged 12-45 years with acne vulgaris who visited the clinic and were then selected through consecutive sampling according to the inclusion and exclusion criteria. In the non-AV group, the mean serum vitamin E level was 19.3 ± 0.99 µg/ml, whereas in the AV group, it was 4.49 ± 19.1 µg/ml, indicating a significant variance. There was a positive correlation between low vitamin E levels and the severity of AV. The linearity graph shows the direction of the relationship between serum vitamin E levels and the severity of AV, which leads to the lower right, indicating that the higher the severity of AV, the lower the serum vitamin E levels. The mean levels differed significantly between the non-AV and AV groups. A favorable association was found between low vitamin E levels and the severity of AV. Keywords: Acne Vulgaris, Severity, Serum Vitamin E, Reactive Oxygen Species (ROS)

Association Between Body Mass Index (BMI), Vitamin D, and Testosterone Levels.

Introduction Obesity is measured scientifically by calculating body mass index (BMI). Body mass index in men is linked to various hormonal imbalances. This study aims to observe the relationships between BMI, vitamin D, and testosterone levels in patients attending the outpatient clinic at Hayatabad Medical Complex, Peshawar, Pakistan. Methods This observational cross-sectional study involved 272 patients, presenting to the medical outpatient department from January 1st, 2023, to December 31st, 2023. Body mass index, serum vitamin D, and testosterone levels were measured for each participant. Body mass index was categorized into normal, overweight, and obese. Statistical analysis was calculated, including descriptive statistics, logistic regression, and correlation analysis to evaluate associations between these variables. Results The mean BMI of the participants was 25.82 ± 7.88 kg/m². A significant inverse correlation was observed between BMI and vitamin D levels (r = -0.79, p < 0.001) and between BMI and testosterone levels (r = -0.87, p < 0.001). A positive correlation was found between vitamin D and testosterone levels (r = 0.87, p < 0.001). Logistic regression analysis revealed that higher BMI in the range of overweight or above was associated with a 2.5-fold increase in the likelihood of vitamin D deficiency (odds ratio (OR) = 2.50, 95% CI = 1.8-3.5, p < 0.001) and a 3.1-fold increase in the likelihood of low testosterone levels (OR = 3.10, 95% CI = 2.2-4.3, p < 0.001). Conclusion In this study, higher BMI is significantly associated with lower vitamin D and testosterone levels. These findings suggest that addressing obesity could help mitigate hormonal imbalances, such as vitamin D deficiency and low testosterone, which are linked to metabolic health risks. It can also be hypothesized that obesity can be a risk factor for vitamin D and testosterone deficiency.

Risk Factors Associated with Advanced Colorectal Neoplasia in Adults Younger than Age 45.

Colorectal cancer (CRC) is rising in young adults between ages 20 to 49 years. CRC screening is endorsed for average-risk individuals beginning at ages 45 to 49 years. Targeting screening for individuals <45 years may be warranted if risk factors for advanced neoplasia can be identified. To identify factors associated with advanced colorectal neoplasia in adults aged <45 years. Individuals ages 18 to 44 years who underwent colonoscopy at Cleveland Clinic between 2011 and 2021 with ≥1 advanced neoplasm (AN) were included. Patients with inflammatory bowel disease or inherited CRC syndromes were excluded. Demographics, comorbidities, family history of CRC, and colonoscopy indication were obtained. Patients with a normal colonoscopy constituted the control group. A multivariable logistic regression model was used to investigate the relationship between clinical variables and the presence of advanced colorectal neoplasia. In all, 13,006 patients were included, of which 651 (5%) patients had AN: 404 (62%) with tubular adenoma ≥10mm, 29 (4.5%) tubular adenoma with high-grade dysplasia, 210 (32%) tubulovillous adenomas, 27 (4%) traditional serrated adenomas, 82 (13%) sessile serrated lesions ≥10mm, 7(2%) sessile serrated lesions with dysplasia, and 29 (4.4%) patients had a CRC. Factors associated with AN were older age (means 38.5 vs. 36.6y), history of smoking, diabetes, non-White race, higher body mass index (29.9 vs. 28.5kg/m 2 ), and lower vitamin D (27.6 vs. 32.2 ng/dl), all P <0.001. In the reduced multivariable model, factors associated with AN included tobacco use (OR 2.026 (current vs. never, P <0.0001), age (OR increase by 1.06 per year, P <0.0001), male gender (OR 1.476, P <0.0001), family history of CRC (OR 3.91, P <0.0001), aspirin use (1.31, P =0.035), and diabetes (OR 2.106, P 0.001). Increasing age, male gender, exposure to tobacco, family history of CRC, diabetes, and aspirin use were independently associated with advanced neoplasia in adults younger than 45. Targeted early screening to young adults with these risk factors may be justified. Large collaborative prospective studies are needed to validate our findings.

Metabolic Syndrome, Inflammation, Oxidative Stress, and Vitamin D Levels in Children and Adolescents with Obesity.

Metabolic syndrome (MetS) is associated with systemic inflammation, oxidative stress, and hypovitaminosis D. Our aim was to determine whether vitamin D mediates inflammation and oxidative stress, assessed through selected biomarkers, in children with obesity and/or MetS. Eighty children with normal weight, overweight, or obesity were analyzed for serum vitamin D, C-reactive protein, leukocytes, adiponectin, monocyte chemoattractant protein-1, myeloperoxidase, interferon-inducible T-cell alpha chemoattractant (I-TAC/CXCL11), superoxide dismutase-1, fasting lipid and glucose levels, ultrasound-measured abdominal fat thickness, waist circumference, body mass index and blood pressure. Children with obesity or overweight had lower vitamin D levels, increased blood pressure, visceral and subcutaneous fat thickness, and higher leukocytes, C-reactive protein, and myeloperoxidase levels. Those with MetS also had lower adiponectin levels. Vitamin D levels are negatively correlated with body mass index, waist circumference, and visceral and subcutaneous fat thickness. Correlation, mediation, and regression analyses showed no link between vitamin D and inflammatory/oxidative stress variables. The novel biomarker I-TAC did not correlate with obesity or vitamin D status. Our results indicate that vitamin D does not significantly mediate inflammation or oxidative stress in children and adolescents with obesity and/or MetS. Selected inflammation/oxidative stress biomarkers appear to be altered primarily due to obesity rather than vitamin D status.

Impact of vitamin D deficiency on ischemic stroke severity: Insights from a prospective study

Background. Ischemic stroke, characterized by the obstruction of blood flow to the brain, is a major cause of morbidity and mortality globally. The severity of ischemic stroke is typically assessed using the National Institutes of Health Stroke Scale (NIHSS), which predicts patient outcomes. Recent research suggests a potential link between low vitamin D levels and an increased risk of cerebrovascular events, including ischemic stroke. However, the specific relationship between vitamin D deficiency and stroke severity remains underexplored. Objective. This study aimed to investigate the correlation between serum vitamin D levels and NIHSS scores in patients with ischemic stroke to determine if vitamin D deficiency contributes to the severity of neurological deficits observed in these patients. Materials and methods. This prospective observational study was conducted at Saveetha Medical College, Chennai, involving 86 patients presenting with acute ischemic stroke. Inclusion criteria included age ≥ 18 years, confirmed diagnosis of acute ischemic stroke by neuroimaging, and presentation within 24 hours of symptom onset. Exclusion criteria included hemorrhagic stroke, conditions affecting vitamin D metabolism, and vitamin D supplementation. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured using chemiluminescence immunoassay (CLIA), and NIHSS scores were assessed within 24 hours of admission. Statistical analyses included Pearson’s correlation and multivariate linear regression to adjust for confounders. Results. The study found a significant negative correlation between serum 25(OH)D levels and NIHSS scores at admission (Pearson correlation coefficient r = -0.4081, p &lt;0.001). Multivariate regression analysis confirmed this association (β = -0.3994, p &lt;0.001) after adjusting for age, sex, and comorbidities. Age (β = 0.1123, p = 0.009) and comorbid conditions (β= 0.9565, p = 0.008) were also significantly associated with higher NIHSS scores. Conclusion. The study demonstrates a significant negative correlation between serum 25-hydroxyvitamin D levels and ischemic stroke severity, suggesting that higher vitamin D levels may be associated with less severe strokes. Further research is needed to explore the mechanistic pathways and therapeutic potential of vitamin D in stroke management, emphasizing the importance of maintaining adequate vitamin D levels to potentially reduce stroke severity and improve patient outcomes.

Vitamin B12 responsive developmental and epileptic encephalopathy due to a novel mutation in the FUT2 gene: a case report

BackgroundVitamin B12 deficiency is a recognised cause of neurological manifestations, including peripheral neuropathy, behavioural changes, and seizures. However, developmental and epileptic encephalopathy due to vitamin B12 deficiency is very rare. Here, we report an infant with vitamin B12-responsive developmental and epileptic encephalopathy due to a novel mutation in the fucosyltransferase 2 (FUT2) gene responsible for vitamin B12 absorption.Case presentationAn 11-month-old girl of non-consanguineous parents presented with recurrent episodes of seizures since four months. Her seizures started as flexor epileptic spasms occurring in clusters resembling infantile epileptic spasms syndrome with hypsarrhythmia in the electroencephalogram. She was treated with multiple drugs, including high-dose prednisolone, vigabatrin, sodium valproate, levetiracetam and clobazam, without any response, and she continued to have seizures at 11 months. She had an early developmental delay with maximally achieving partial head control and responsive smile at four months. Her development regressed with the onset of seizure; at 11 months, her developmental age was below six weeks. On examination, she was pale and had generalised hypotonia with normal muscle power and reflexes.Her full blood count and blood picture revealed macrocytic anaemia with oval and round macrocytes. Bone marrow aspiration showed hypercellular marrow erythropoiesis with normoblastic and megaloblastic maturation. Due to the unusual association of refractory epilepsy and megaloblastic anaemia, a rare genetic disease of the vitamin B12 or folate pathways was suspected. The whole exome sequencing revealed a homozygous missense variant in exon 2 of the FUT2 gene associated with reduced vitamin B12 absorption and low plasma vitamin B12 levels, confirming the diagnosis of vitamin B12 deficiency related developmental and epileptic encephalopathy. She was started on intramuscular hydroxocobalamin, for which she showed a marked response with reduced seizure frequency.ConclusionWe report a novel variant in the FUT2 gene associated with vitamin B12-responsive developmental and epileptic encephalopathy and megaloblastic anaemia. This case report highlights the importance of timely genetic testing in children with refractory developmental and epileptic encephalopathy to identify treatable causes.

Association between Serum Vitamin D Level and Parkinson’s Disease: Case Control Study in a Tertiary Level Hospital, Bangladesh

Background: Parkinson's disease is a neurodegenerative disorder that is frequently observed in individuals who are 50 years of age or older. The etiology of this disease is still unknown, but research has shown the influence of factors like vitamin D acting as a hormone in Parkinson's disease. The current study aimed to explore the association between serum vitamin D levels and Parkinson's disease. Methods: In 2019 to 2020, the current researchers conducted this case control study on 50 patients with Parkinson’s disease and 50 healthy subjects as the control group in the department of Neurology of Sir Salimullah Medical College &amp; Mitford Hospital, Dhaka, Bangladesh. Demographic information (age, gender, and education), serum levels of vitamin D in the two groups, disease duration, disease severity, and cardinal features of the disease in the patient group were investigated. Data were analyzed using the SPSS 23 software with the t-test, Kruskal Wallis, Mann-Whitney, and adjusted logistic regression. Results: The mean age of cases was 72.30 ±454 and the control group had a mean age of 60.08±8.305. Regarding the symptoms of the cases tremor 30 (60%), rigidity 5 (10%), bradykinesia 12 (24%) and postural instability 3 (6%) and regarding disease duration (y) &lt;5 years-26 (52%), 5 to 10 years-17 (34%), &gt;10years 7 (14%) and disease severity 1 to 2.5 – 26 (52%) , 2.5-to-3 -18 (36%) and &gt;3 – 6 (12%) Serum vitamin D levels of males were 17.70±6.06 ng/mL in patients and 30.31±5.59ng/mL in control groups, respectively which is clinically significant. Serum vitamin D levels of females were 20.03±5.75ng/mL in patients and 28.53±6.31ng/mL in control groups, respectively, which is clinically significant (P = 0.001). For the participants under 60 years of age, the mean serum vitamin D levels were 27.70±0.00 ng/mL and 30.78±5.44 ng/mL in patient and control groups, respectively. In participants aged 60 and older, the mean serum vitamin D levels were 18.40±5.91 ng/mL and 28.13±6.26 ng/mL in patient and control groups, respectively. These differences were statistically significant (P=0.001).Logistic regression analysis with adjusted demographic variables showed that the observed lower levels of serum vitamin D in cases compared with the control group was statistically significant(OR=4.17;95% CI:1.37,12.71;P=0.012). Conclusion: There was a significant relationship between low serum vitamin D and Parkinson’s disease. Bangladesh J Medicine 2024; 35: 180-186