scholarly journals P41 Searching high and low for a cause of transient migratory bone oedema: fibroblast growth factor-23 secreting mesenchymal tumour

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Kerry Fisher ◽  
Sunil Melath ◽  
Sanjeev Patel
Keyword(s):  
Insufficiency Fractures ◽  
Foot And Ankle ◽  
Mesenchymal Tumour ◽  
Phosphate Reabsorption ◽  
Hydroxyvitamin D ◽  
Renal Phosphate Reabsorption ◽  
History Of ◽  
25 Hydroxyvitamin D ◽  
Fgf 23 ◽  
Bone Oedema

Abstract Background Fibroblast Ggrowth factor-23 (FGF-23) is a phosphate regulator primarily expressed by osteocytes. Excess FGF-23 leads to decreased hydroxylation of 25-hydroxyvitamin D and poor renal phosphate reabsorption. This leads to hypophosphataemia and represents a rare cause of osteomalacia, resulting in bone oedema and stress fractures. Methods A 57-year-old man with known skin psoriasis presented with a two-year history of left foot and ankle pain. On examination, he had chronic dactylitis of the left, big toe associated with skin psoriasis and nail pitting. Serum inflammatory markers were normal, and autoimmune screens for RF, anti-CCP and HLA-B27 were negative. Bilateral foot and ankle X-rays showed no bony abnormality. This was diagnosed as likely psoriatic arthritis and MRI showed talar bone oedema, felt to be related to the inflammatory arthritis. Symptoms settled well on non-steroidal anti-inflammatories. However, he presented two months later with focal distal tibial pain and swelling. There was no history of trauma. Repeat MRI showed proximal migration of bone oedema with stress fractures of the left posterior talus and distal tibial metaphysis. Results Blood tests showed low phosphate, elevated PTH, normal adjusted calcium, raised ALP and low 25-hydroxyvitamin D. DEXA scan confirmed osteoporosis of the hip. The patient was commenced on intravenous three-monthly pamidronate and colecalciferol (vitamin D3) supplements. Despite this, the patient continued to have migratory joint pain affecting the ankle, hip and sacroiliac joints. Methotrexate was prescribed to improve his psoriasis, but whilst his skin improved his legs remained painful. A repeat MRI showed new insufficiency fractures to the left talus and right neck of femur. Although taking colecalciferol supplementation, his serum phosphate remained low (0.5mmol/L). On further investigation, Myeloma screen and FDG PET were normal but he was noted to have an increased fractional urinary phosphate excretion indicating poor renal phosphate reabsorption. Serum FGF-23 assay was elevated at 131 mIU/L (normal <100mIU/L). The patient underwent 68-Gallium DOTATATE PET imaging, utilising a tracer specific for somatostatin receptors found on neuroendocrine tumours, which showed a T9 pedicle lesion. CT-guided biopsy confirmed a mesenchymal tumour as the cause of FGF-23 secretion, resulting in transient bone marrow oedema and insufficiency fractures. The patient has become asymptomatic on calcitriol (1,25-dihydroxyvitamin D) and phosphate supplementation, and is being considered for radiofrequency ablation therapy. Conclusion This case illustrates the need for thorough investigation of symptomatic, treatment-refractory hypophosphataemia. Although mild hypophosphatemia could indicate adult onset rickets, rarer causes such as FGF-23 secreting tumours should be considered. These tumours are notoriously difficult to locate; 68-Gallium DOTATATE PET may offer superior specificity to other imaging modalities, including FDG-PET, in detecting these mesenchymal tumours. FGF-23 decreases hydroxylation of vitamin D3 and renal phosphate reabsorption, and calcitriol alongside phosphate supplementation is advisable for symptomatic management until definitive treatment. Disclosures K. Fisher None. S. Melath None. S. Patel None.

P49 An unusual cause of transient migratory bone oedema: fibroblast growth factor-23 secreting a mesenchymal tumour

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Kerry Fisher ◽  
Sunil Melath ◽  
Sanjeev Patel
Keyword(s):  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Foot And Ankle ◽  
Mesenchymal Tumour ◽  
Hydroxyvitamin D ◽  
Renal Phosphate Reabsorption ◽  
History Of ◽  
25 Hydroxyvitamin D ◽  
Fgf 23 ◽  
Bone Oedema

Abstract Background Fibroblast growth factor-23 (FGF-23) is a phosphate regulator primarily expressed by osteocytes. Excess FGF-23 leads to decreased hydroxylation of 25-hydroxyvitamin D and poor renal phosphate reabsorption. This leads to hypophosphatemia and represents a rare cause of osteomalacia, resulting in bone oedema and stress fractures. Methods A 57-year-old man with known skin psoriasis presented with a two-year history of left foot and ankle pain. On examination, he had chronic dactylitis of the big toe and extra-articular features included skin psoriasis on the scalp, elbows, knees, and nail pitting. Serum inflammatory markers were normal, and autoimmune screens for RF, anti-CCP and HLA-B27 were negative. Bilateral foot and ankle X-rays showed no bony abnormality. This was diagnosed as likely psoriatic arthritis and MRI showed talar bone oedema, felt to be related to inflammatory arthritis. Symptoms settled well on non-steroidal anti-inflammatories. However, he presented with focal distal tibial swelling and pain, two months later. There was no history of trauma, Repeat MRI2 showed proximal migration of bone oedema with stress fractures of the left posterior talus and distal tibial metaphysis. Bloods tests showed low phosphate, elevated PTH, normal adjusted calcium, raised ALP and low 25-OH vitamin D. DEXA scan confirmed osteoporosis of the hip. The patient was commenced on bisphosphonate with 25-hydroxyvitamin D and phosphate supplementation. Despite this, the patient continued to have migratory joint pain affecting the ankle, hip and sacroiliac joints. Methotrexate was started for psoriasis and whilst his skin improved, his pain remained and further MRI showed left talar and right neck of femur insufficiency fractures. Results Although taking vitamin D3 supplementation, he remained hypophosphateamic 0.5mmol/L. Myeloma screen and PET FDG were normal. However, he was noted to have an increased fractional urinary phosphate excretion indicating poor renal phosphate reabsorption. One possible cause of this is elevated FGF-23, which was confirmed with FGF-23 assay (include levels and normal range). The patient underwent PET Ga-DOTATE imaging, utilising a tracer specific for somatostatin receptors found on neuroendocrine tumours. This showed a T9 pedicle lesion and a CT-guided biopsy confirmed a mesenchymal tumour as the cause of FGF-23 secretion, resulting in TBMO and insufficiency fractures. The patient has become asymptomatic on calcitriol and phosphate supplementation. He is now being considered for radiofrequency ablation therapy. Conclusion This case illustrates the need for a thorough investigation of symptomatic, treatment-refractory hypophosphataemia. Although mild hypophosphatemia could indicate adult-onset rickets, rarer causes such as FGF-23 secreting tumours should be considered. These tumours are notoriously difficult to locate; Ga-DOTATE PET is probably superior to other imaging modalities including FDG-PET in isolating mesenchymal tumours. Disclosures K. Fisher None. S. Melath None. S. Patel None.

scholarly journals TL 18206 - Foot and ankle insufficiency fractures among postmenopausal sedentary women

2019 ◽  
Vol 13 (Supl 1) ◽  
pp. 110S
Author(s):  
Miguel Viana Pereira Filho ◽  
Kelly Cristina Stéfani ◽  
Mônica Paschoal Nogueira
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Insufficiency Fractures ◽  
Foot And Ankle ◽  
Mineral Density ◽  
Hydroxyvitamin D ◽  
First Metatarsal ◽  
Metatarsal Bones ◽  
25 Hydroxyvitamin D ◽  
Metatarsus Adductus

Introduction: Insufficiency fractures occur in bones with decreased elastic strength. In contrast to fatigue or stress fractures, which affect normal bones and have been extensively studied in the literature, foot and ankle insufficiency fractures have been poorly researched to date. The objective of this study was to identify behavioral, biomechanical and metabolic factors associated with the development of foot and ankle insufficiency fractures. Methods: In total, 53 sedentary postmenopausal female patients who had foot and ankle insufficiency fractures and who were treated at the São Paulo State Civil Servant Hospital (Hospital do Servidor Público do Estado de São Paulo) were included in the treatment group, and 53 individuals were included in the control group. Data were collected on fracture site, body mass index (BMI), corticoid use, femoral and lumbar T-score measured by bone densitometry, and serum 25-hydroxyvitamin D level. The calcaneal angle, the angle between the first metatarsal and the talus and the metatarsus adductus angle were measured in radiographs. Results: The fractures affected the metatarsal bones in 47 patients. Other fracture sites included the lateral malleolus, lateral cuneiform bone, cuboid bone, tibia and calcaneus. All metatarsal bones were affected, most frequently the 5th. The most common fracture was a 5th metatarsal base fracture in zone II. There was no significant difference in mean BMI, serum 25-hydroxyvitamin D levels, alcohol consumption or smoking between the groups. The development of fractures was significantly associated with corticoid use (p<0.0001), low femur (p=0.028) and lumbar spine (p=0.002) bone mineral density and metatarsus adductus angle (p=0.02). When analyzed separately, 4th and 5th metatarsal fractures were associated with smaller angles between the talus and the first metatarsal (p=0.01). Conclusion: Foot and ankle insufficiency fractures among sedentary postmenopausal women are associated with corticoid use, low bone mineral density and biomechanical characteristics, such as pes cavus and metatarsus adductus. The presence of such fractures may be the first sign of bone fragility and should be used as criteria for initiating adequate treatment to prevent other fractures.

scholarly journals Relationship Between Level of Serum 25-Hydroxyvitamin D and Risk of Squamous Cell Carcinoma in an Iranian Population

2019 ◽  
pp. 278-282
Author(s):  
Mahboobeh-Sadat Hosseini ◽  
Fereshteh Salarvand ◽  
Amir Houshang Ehsani ◽  
Pedram Noormohammadpour ◽  
Shadi Azizzadeh ◽  
...  
Keyword(s):  
Vitamin D ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Outdoor Environment ◽  
Hydroxyvitamin D ◽  
Vitamin D Levels ◽  
History Of ◽  
25 Hydroxyvitamin D ◽  
The Relationship

Background: The relationship between vitamin D and skin squamous cell carcinoma (SCC) is not well defined. Objective: To investigate the relationship between vitamin D levels and the incidence of skin SCC for the first time in Iran. Methods and Study Design: In this case-control study, 126 subjects were enrolled (63 in each group) out of referents to Razi Skin Hospital in Tehran in 2014. The risk factors for cancer gathered by self-reported questionnaires and blood samples were obtained to measure the level of 25-hydroxyvitamin D. Multivariate logistic regression was used to neutralize the effect of confounding factors. Results: Cases of SCC were more likely to be in men, older than 49 years and working in an outdoor environment, and with longtime exposure to sunlight and a personal history of skin cancers. Family history of skin cancer and of cigarette smoking were not significantly related to SCC. In the SCC and control groups, 69.8% and 31.7%, respectively, had sufficient levels of vitamin D (P < 0.001). Mean level of 25-hydroxyvitamin D was 40.99 ng/mL in the SCC group and 26.34 ng/mL in the control group (P < 0.05). In the unadjusted model, the level of vitamin D as a continuous variable was positively related to SCC risk. In the adjusted model, vitamin D did not independently predict the likelihood of SCC. Conclusion: Vitamin D level and SCC risk are directly related, although not in an independent fashion. Indeed, this relation is severely confounded by exposure to sunlight, which was evidenced by an increased vitamin D level in the people working outside and the higher prevalence of SCC in the same population.

scholarly journals 25-Hydroxyvitamin D concentration and all-cause mortality: the Melbourne Collaborative Cohort Study

2016 ◽  
Vol 20 (10) ◽  
pp. 1775-1784 ◽  
Author(s):  
Alicia K Heath ◽  
Elizabeth J Williamson ◽  
David Kvaskoff ◽  
Allison M Hodge ◽  
Peter R Ebeling ◽  
...  
Keyword(s):  
Cohort Study ◽  
Cox Regression ◽  
Dried Blood Spots ◽  
Inverse Association ◽  
Blood Spots ◽  
Hydroxyvitamin D ◽  
Excellent Health ◽  
Melbourne Collaborative Cohort Study ◽  
History Of ◽  
25 Hydroxyvitamin D

AbstractObjectiveTo investigate relationships between mortality and circulating 25-hydroxyvitamin D (25(OH)D), 25-hydroxycholecalciferol (25(OH)D3) and 25-hydroxyergocalciferol (25(OH)D2).DesignCase–cohort study within the Melbourne Collaborative Cohort Study (MCCS). We measured 25(OH)D2and 25(OH)D3in archived dried blood spots by LC–MS/MS. Cox regression was used to estimate mortality hazard ratios (HR), with adjustment for confounders.SettingGeneral community.SubjectsThe MCCS included 29 206 participants, who at recruitment in 1990–1994 were aged 40–69 years, had dried blood spots collected and no history of cancer. For the present study we selected participants who died by 31 December 2007 (n2410) and a random sample (sub-cohort,n2996).ResultsThe HR per 25 nmol/l increment in concentration of 25(OH)D and 25(OH)D3were 0·86 (95 % CI 0·78, 0·96;P=0·007) and 0·85 (95 % CI 0·77, 0·95;P=0·003), respectively. Of 5108 participants, sixty-three (1·2 %) had detectable 25(OH)D2; their mean 25(OH)D concentration was 11·9 (95 % CI 7·3, 16·6) nmol/l higher (P<0·001). The HR for detectable 25(OH)D2was 1·80 (95 % CI 1·09, 2·97;P=0·023); for those with detectable 25(OH)D2, the HR per 25 nmol/l increment in 25(OH)D was 1·06 (95 % CI 0·87, 1·29;Pinteraction=0·02). HR were similar for participants who reported being in good, very good or excellent health four years after recruitment.ConclusionsTotal 25(OH)D and 25(OH)D3concentrations were inversely associated with mortality. The finding that the inverse association for 25(OH)D was restricted to those with no detectable 25(OH)D2requires confirmation in populations with higher exposure to ergocalciferol.

scholarly journals Paradoxical deterioration in seizure control due to anticonvulsant-induced hypocalcaemia

2019 ◽  
Vol 12 (12) ◽  
pp. e232429 ◽  
Author(s):  
Zachary Gauci ◽  
Christopher Rizzo ◽  
Simon Mifsud ◽  
Mario J Cachia
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Calcium Supplementation ◽  
Cytochrome P450 Enzyme ◽  
Hydroxyvitamin D ◽  
P450 Enzyme ◽  
History Of ◽  
25 Hydroxyvitamin D ◽  
History Of Epilepsy ◽  
Hepatic Cytochrome

Hepatic cytochrome P450 enzyme induction is associated with certain antiepileptic drugs (AEDs) and may result in hypocalcaemia secondary to vitamin D deficiency. We report a case of a 44-year-old man with a history of epilepsy, who presented with breakthrough seizures after having previously been seizure-free for 11 years. Investigations revealed severe hypocalcaemia with a corrected calcium of 1.7 mmol/L. His phenytoin dose was increased, and he was started on calcium supplementation. He was discharged with a corrected calcium level of 2.05 mmol/L but was readmitted 1 week later with further seizures and a corrected calcium of 1.89 mmol/L. 25-hydroxyvitamin D was low. AED-induced hypocalcaemia was suspected, which had been made paradoxically worse by the increase in phenytoin dose. Alfacalcidol was prescribed and he was switched from phenytoin to levetiracetam with resolution of hypocalcaemia and no further seizures. The authors recommend screening for calcium and vitamin D deficiency in patients on enzyme-inducing AEDs.

scholarly journals Normocalcemic Primary Hyperparathyroidism in Adults Without a History of Nephrolithiasis or Fractures: A Prospective Study

2019 ◽  
Vol 51 (04) ◽  
pp. 243-247 ◽  
Author(s):  
Pedro Rosário ◽  
Maria Calsolari
Keyword(s):  
Primary Hyperparathyroidism ◽  
Prospective Study ◽  
Adult Population ◽  
Parathyroid Glands ◽  
Hydroxyvitamin D ◽  
Biochemical Diagnosis ◽  
History Of ◽  
25 Hydroxyvitamin D ◽  
The Impact ◽  
Diagnostic Criterion

AbstractThe prevalence and the diagnostic criterion of “normocalcemic” primary hyperparathyroidism (NPHPT) are still uncertain and there is no consensual definition. This prospective study evaluated the prevalence of NPHPT in 676 adults without a history of fractures or nephrolithiasis and who would be submitted to thyroidectomy, the impact of adopting different cut-off values for 25-hydroxyvitamin D and estimated glomerular filtration rate (eGFR), and the agreement between biochemical diagnosis and the surgical finding of altered parathyroid glands. NPHPT was diagnosed in patients with normal total and ionized calcium and elevated PTH (in 2 measurements) and without a known cause of secondary HPT, including eGFR<40 ml/min/1.73 m2 and 25-hydroxyvitamin D<20 ng/dl. The 4 parathyroid glands were fully explored in these patients. Forty-six patients (6.8%) had a laboratory diagnosis of NPHPT. Altered parathyroid glands were detected in only 4 patients, corresponding to 0.6% of all patients and to 8.7% of those with a biochemical diagnosis of NPHPT. The latter was confirmed in 0/174 men, 1/252 premenopausal women, and 3/250 postmenopausal women. Among the 42 patients with elevated PTH and without altered parathyroid glands, 25 had 25-hydroxyvitamin D between 20 and 30 ng/dl, 7 had eGFR between 40 and 60 ml/min/1.73 m2, and 9 had both. The prevalence of NPHPT was 0.74% in this adult population without a history of nephrolithiasis or fractures. The diagnostic criterion using eGFR>60 ml/min/1.73 m2 and 25-hydroxyvitamin D>30 ng/dl was more appropriate considering the agreement with the surgical finding of altered parathyroid glands.

scholarly journals Serum 25 hydroxyvitamin D levels and affecting factors among preconception fertile women

2020 ◽  
Author(s):  
Haiyan Fan ◽  
Lingyun Hui ◽  
Xiaoting Yan ◽  
Wei Hou ◽  
E Bai ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Reproductive History ◽  
Affecting Factors ◽  
Cross Sectional ◽  
Hydroxyvitamin D ◽  
Nulliparous Women ◽  
History Of ◽  
25 Hydroxyvitamin D ◽  
Fertile Women

Abstract Background: Recent study found that vitamin D before conception was considered as a potential additional determinant for achieving pregnancy and live births. The study aimed to evaluate the serum 25 hydroxyvitamin D (25(OH)D) levels and its affecting factors among preconception fertile women. Methods: This cross-sectional study enrolled 410 women aged 22-44 years who attended a preconception genetic counseling clinic from January 2018 to May 2019. Sociodemographic characteristics and reproductive history of women were collected, and height and weight were measured. Serum 25(OH)D concentration was assayed with chemiluminescence immunoassay. Descriptive statistics were used to examine serum 25(OH)D concentration, and socio-demographic characteristics and reproductive history among preconception women. Determinants of vitamin D deficiency and its affecting factors were assessed using χ2 test. Results: Findings showed 84.4% of women had serum 25(OH)D concentration below 20 ng/mL. Women working indoors as well as without a history of childbirth had significantly lower 25(OH)D levels compared with those non-working individuals and having delivered a previous child (both P <0.05). The 25(OH)D levels were the lowest in winter than in spring, summer, and autumn (all P <0.001). Women in winter have significantly elevated OR of 5.00 (95%CI 1.75–14.25) to develop vitamin D deficiency. Seasonal variation in serum 25(OH)D levels was not present in non-working individuals and women aged 31-44 years. Conclusions: Vitamin D deficiency is common among preconception women especially nulliparous women and working women, which propose to screen serum 25(OH)D on preconception evaluation and emphasize need vitamin D supplements and get sunshine exposure.

scholarly journals Effects of Vitamin D Supplementation on Renin and Aldosterone Concentrations in Patients with Advanced Heart Failure: The EVITA Trial

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Armin Zittermann ◽  
Jana B. Ernst ◽  
Sylvana Prokop ◽  
Uwe Fuchs ◽  
Jens Dreier ◽  
...  
Keyword(s):  
Heart Failure ◽  
Vitamin D ◽  
Placebo Group ◽  
Vitamin D Supplementation ◽  
Advanced Heart Failure ◽  
Study Cohort ◽  
Entire Study ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Fgf 23

Objective. 1,25-Dihydroxyvitamin D (1,25([OH]2D) is considered to be a negative endogenous regulator of the renin-angiotensin-aldosterone system (RAAS), but the effect of vitamin D supplementation on the RAAS is inconclusive. Design. In this prespecified secondary analysis of a randomized controlled trial, we assessed in 165 patients with heart failure (vitamin D group: n=83; placebo group: n=82) the effect of three years of vitamin D supplementation with 4000 IU daily on parameters of the RAAS (renin and aldosterone) and on circulating 1,25(OH)2D, plasma phosphate, and fibroblast growth factor (FGF)-23. We assessed age- and baseline-adjusted between-group differences at study termination. Results. Almost all patients were under treatment with beta-blockers, inhibitors of the RAAS, and diuretics. Initially, the frequency of concentrations above the laboratory-specific reference range (renin: >23.9 mIU/L; aldosterone: >232 ng/L) in the vitamin D and placebo group was 87.7% and 92.7%, respectively (renin), and 24.1% and 32.5%, respectively (aldosterone). Vitamin D increased adjusted 1,25(OH)2D concentrations significantly (mean treatment effect and 95% CI: 18.3 pmol/L,7.3 to 29.3 pmol/L; P<0.001) but had no significant effects on phosphate (0.18 mmol/L, −0.00 to 0.35 mmol/L; P=0.051), FGF-23 (685 RU/mL, −213 to 1585 RU/mL; P=0.134), renin (312 mIU/L, −279 to 902 ng/L; P=0.298), or aldosterone (−0.19 ng/L, −5.09 to 4.70 ng/L; P=0.938). Vitamin D supplementation was, however, associated with an increase in renin concentrations in the subgroup with baseline 25-hydroxyvitamin D below 30 nmol/L (n=67; 1365 mIU/, 343 to 2386 mIU/L; P=0.010). Conclusions. In patients with advanced heart failure treated according to evidence-based guidelines, vitamin D supplementation did not significantly influence parameters of the RAAS in the entire study cohort but was associated with an increase in plasma renin concentrations in the subgroup with low baseline 25-hydroxyvitamin D concentrations.

scholarly journals Hypercalcaemia, adrenal insufficiency and bilateral adrenal histoplasmosis in a middle-aged man: a diagnostic dilemma

2019 ◽  
Vol 12 (8) ◽  
pp. e231142 ◽  
Author(s):  
Sweety Agrawal ◽  
Alpesh Goyal ◽  
Shipra Agarwal ◽  
Rajesh Khadgawat
Keyword(s):  
Adrenal Insufficiency ◽  
Intermittent Fever ◽  
Diagnostic Dilemma ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
History Of ◽  
25 Hydroxyvitamin D ◽  
Bony Metastases ◽  
Involuntary Weight Loss

A 45-year-old man presented with a 3-month history of involuntary weight loss, anorexia, postural dizziness and intermittent fever. On investigation, he was found to have parathyroid hormone (PTH)-independent hypercalcaemia, with negative workup for 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D excess, thyrotoxicosis, multiple myeloma and bony metastases. On further evaluation, he was detected to have primary hypoadrenalism with bilateral adrenal enlargement, secondary to adrenal histoplasmosis. Hypercalcaemia improved with hydration and physiological steroid replacement even before initiation of antifungal therapy, confirming adrenal insufficiency as the cause for hypercalcaemia. Hypercalcaemia resulting from hypoadrenalism secondary to adrenal histoplasmosis is rare and should be suspected whenever evaluating a patient with PTH-independent hypercalcaemia.

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