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JCEM Case Reports Jun 2024[This corrects the article DOI: 10.1210/jcemcr/luae044.].
[This corrects the article DOI: 10.1210/jcemcr/luae044.].
PubMed: 38827434
DOI: 10.1210/jcemcr/luae111 -
JCEM Case Reports Jun 2024Tumor-induced osteomalacia (TIO) is an exceedingly rare paraneoplastic condition characterized by hypophosphatemia, osteomalacia, fragility fractures, and fatigue. A...
Tumor-induced osteomalacia (TIO) is an exceedingly rare paraneoplastic condition characterized by hypophosphatemia, osteomalacia, fragility fractures, and fatigue. A 39-year-old man was assessed for hemoptysis, pathological rib fractures, and fatigue, and was found to have a chest mass with lung metastasis. Biopsy of the mass suggested high-grade epithelioid and spindle cell neoplasm. He was initially treated for soft tissue sarcoma with an ifosfamide-based regimen and developed Fanconi syndrome that resolved on cessation of ifosfamide. Serum phosphate remained low. A low tubular maximum reabsorption of phosphate to glomerular filtration rate ratio (TmP/GFR) indicated disproportionate phosphaturia, while a severely elevated fibroblast growth factor-23 (FGF23) level enabled a diagnosis of TIO. He was started on phosphate and calcitriol supplementation. Subsequent next-generation sequencing demonstrated a -fusion mutation, leading to reclassification of his malignancy to a sarcomatoid non-small cell lung carcinoma. He was switched to selpercatinib, a targeted -kinase inhibitor approved for locally advanced or metastatic -fusion-positive solid tumors. This induced tumor remission with subsequent normalization of his FGF23 levels and hypophosphatemia. Despite the presence of a confounding etiology like drug-induced Fanconi syndrome, persistence of hypophosphatemia should prompt a workup of TIO, especially in the presence of a tumor.
PubMed: 38817847
DOI: 10.1210/jcemcr/luae101 -
Cureus Apr 2024The synthesis and absorption of Vitamin D play crucial roles in numerous bodily functions, yet deficiencies persist due to factors like insufficient sunlight exposure... (Review)
Review
The synthesis and absorption of Vitamin D play crucial roles in numerous bodily functions, yet deficiencies persist due to factors like insufficient sunlight exposure and dietary inadequacy. Research underscores the significance of lifestyle elements such as diet, sun exposure, and physical activity in maintaining optimal Vitamin D levels. Strategies aimed at tackling deficiencies emphasize supplementation alongside lifestyle adjustments, especially in regions with abundant sunlight like the Middle East and North Africa (MENA). Despite the abundance of sunshine in the Arab world, there remains a prevalent issue of Vitamin D deficiency. This problem arises from various factors, including cultural practices such as traditional clothing covering most skin areas, which limit sun exposure, and environmental factors like air pollution that reduce UV penetration. Dietary habits and lifestyle choices also contribute to this deficiency. Dealing with the ongoing pandemic requires a focused effort to enhance awareness. While some individuals may recognize common diseases caused by Vitamin D deficiency, such as rickets and osteomalacia, many remain unaware of the broader health risks associated with the condition, including non-skeletal manifestations. Additionally, there is a lack of understanding regarding the numerous hidden benefits of this hormone. Therefore, prioritizing educational initiatives that delve into these aspects is essential to effectively combat the current health crisis. This literature review aims to report both skeletal and extraskeletal consequences of hypovitaminosis and briefly discuss the cause of paradoxical vitamin D deficiency in sunny regions like the MENA. This was done by reviewing pertinent articles published between January 2000 and January 2024, sourced from databases such as PubMed, UpToDate, Scopus, and CINAHL, focusing exclusively on English language literature and using keywords such as "Vitamin D deficiency" and "Extraskeletal manifestations."
PubMed: 38813297
DOI: 10.7759/cureus.59267 -
Bone Reports Jun 2024Tumor-induced osteomalacia (TIO), is a rare acquired paraneoplastic syndrome characterized by defective bone mineralization, caused by the overproduction of fibroblast... (Review)
Review
INTRODUCTION
Tumor-induced osteomalacia (TIO), is a rare acquired paraneoplastic syndrome characterized by defective bone mineralization, caused by the overproduction of fibroblast growth factor 23 (FGF23) by a tumor.
MATERIAL AND METHODS
We conducted a systematic review to identify all case reports of TIO, focusing on those associated with mesenchymal tumors. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) consensus, and we included patients with a diagnosis of TIO and histological confirmation of phosphaturic mesenchymal tumors or resolution of the condition after treatment of the tumor. Bibliographical searches were carried out until December 2023 in the Cochrane Library, Medline and Embase, as well as congress abstracts online.
RESULTS
We identified 769 articles with 1979 cases reported. Most patients were adults, with a higher incidence on men. Disease duration before diagnosis is a mean of 4.8 years. Most tumors were histologically classified as PMT. Lower limbs were the predominant location. Hypophosphatemia was present in 99.8 % of patients. The FGF23 was elevated at diagnosis in 95.5 %. Resection of the tumor was the treatment of choice in most of patients. After resection, there was a clinical improvement in 97.6 % of cases, and serum phosphorus and FGF23 levels returned to normal ranges in 91.5 % and 81.4 % of the patients, respectively.
CONCLUSION
TIO is usually misdiagnosed with rheumatological or musculoskeletal disorders. The diagnosis should be suspected in patients with hypophosphatemic osteomalacia, and the measurement of serum FGF23 can be useful for diagnosis and management.
PubMed: 38774264
DOI: 10.1016/j.bonr.2024.101772 -
Clinical Case Reports May 2024Tumor-induced osteomalacia is a rare but potentially serious disease with nonspecific misguiding manifestations that can result in a wrong diagnosis and being treated...
KEY CLINICAL MESSAGE
Tumor-induced osteomalacia is a rare but potentially serious disease with nonspecific misguiding manifestations that can result in a wrong diagnosis and being treated for rheumatologic or other similar diseases. In patients with unexpected fractures, resistant musculoskeletal pains, and hypophosphatemia, this diagnosis should be considered by the physicians and approached through a complete history taking, physical exam laboratory, and radiologic evaluation to give the opportunity of on-time treatment to the patient.
ABSTRACT
Tumor-induced osteomalacia (TIO) is an uncommon mesenchymal tumor that results in disproportionate phosphorus excretion, primarily leading to bone-related symptoms. Laboratory, imaging, and histopathological evaluation can confirm this pathologic condition. In this case, we present the history and subsequent clinical parts of a 50-year-old woman who presented with an unusual presentation of generalized musculoskeletal pains and a right ankle mass. Her disease was diagnosed with multidisciplinary evaluation and was approached by a surgical treatment. The patient was treated with total resection of the tumor, which led to complete resolution of musculoskeletal and metabolic abnormalities, which were resolved following total tumor resection. TIO is a paraneoplastic disease that results in abnormal secretion of phosphatonins, particularly fibroblast growth factor 23 (FGF23). This can cause hypophosphatemia, hyperparathyroidism, lower bone density, and increased risk of pathologic fractures. These tumors are mostly cured by surgical ± radiotherapy. The present study aims to provide insight into the fact that a TIO diagnosis is not always straightforward. However, in suspicious cases such as unexplained hypophosphatemia, it should be considered to prevent delayed diagnosis of the progressive pathology. The earlier treatment can prevent several complications and reduce the risk of mortality.
PubMed: 38770413
DOI: 10.1002/ccr3.8885 -
Asian Journal of Surgery May 2024
PubMed: 38760218
DOI: 10.1016/j.asjsur.2024.04.158 -
International Journal of Molecular... Apr 2024Wilson disease is a genetic disorder of the liver characterized by excess accumulation of copper, which is found ubiquitously on earth and normally enters the human body... (Review)
Review
Wilson disease is a genetic disorder of the liver characterized by excess accumulation of copper, which is found ubiquitously on earth and normally enters the human body in small amounts via the food chain. Many interesting disease details were published on the mechanistic steps, such as the generation of reactive oxygen species (ROS) and cuproptosis causing a copper dependent cell death. In the liver of patients with Wilson disease, also, increased iron deposits were found that may lead to iron-related ferroptosis responsible for phospholipid peroxidation within membranes of subcellular organelles. All topics are covered in this review article, in addition to the diagnostic and therapeutic issues of Wilson disease. Excess Cu primarily leads to the generation of reactive oxygen species (ROS), as evidenced by early experimental studies exemplified with the detection of hydroxyl radical formation using the electron spin resonance (ESR) spin-trapping method. The generation of ROS products follows the principles of the Haber-Weiss reaction and the subsequent Fenton reaction leading to copper-related cuproptosis, and is thereby closely connected with ROS. Copper accumulation in the liver is due to impaired biliary excretion of copper caused by the inheritable malfunctioning or missing ATP7B protein. As a result, disturbed cellular homeostasis of copper prevails within the liver. Released from the liver cells due to limited storage capacity, the toxic copper enters the circulation and arrives at other organs, causing local accumulation and cell injury. This explains why copper injures not only the liver, but also the brain, kidneys, eyes, heart, muscles, and bones, explaining the multifaceted clinical features of Wilson disease. Among these are depression, psychosis, dysarthria, ataxia, writing problems, dysphagia, renal tubular dysfunction, Kayser-Fleischer corneal rings, cardiomyopathy, cardiac arrhythmias, rhabdomyolysis, osteoporosis, osteomalacia, arthritis, and arthralgia. In addition, Coombs-negative hemolytic anemia is a key feature of Wilson disease with undetectable serum haptoglobin. The modified Leipzig Scoring System helps diagnose Wilson disease. Patients with Wilson disease are well-treated first-line with copper chelators like D-penicillamine that facilitate the removal of circulating copper bound to albumin and increase in urinary copper excretion. Early chelation therapy improves prognosis. Liver transplantation is an option viewed as ultima ratio in end-stage liver disease with untreatable complications or acute liver failure. Liver transplantation finally may thus be a life-saving approach and curative treatment of the disease by replacing the hepatic gene mutation. In conclusion, Wilson disease is a multifaceted genetic disease representing a molecular and clinical challenge.
Topics: Humans; Hepatolenticular Degeneration; Copper; Iron; Ferroptosis; Reactive Oxygen Species; Liver; Animals
PubMed: 38731973
DOI: 10.3390/ijms25094753 -
International Journal of Molecular... Apr 2024To maintain an optimal body content of phosphorus throughout postnatal life, variable phosphate absorption from food must be finely matched with urinary excretion. This... (Review)
Review
To maintain an optimal body content of phosphorus throughout postnatal life, variable phosphate absorption from food must be finely matched with urinary excretion. This amazing feat is accomplished through synchronised phosphate transport by myriads of ciliated cells lining the renal proximal tubules. These respond in real time to changes in phosphate and composition of the renal filtrate and to hormonal instructions. How they do this has stimulated decades of research. New analytical techniques, coupled with incredible advances in computer technology, have opened new avenues for investigation at a sub-cellular level. There has been a surge of research into different aspects of the process. These have verified long-held beliefs and are also dramatically extending our vision of the intense, integrated, intracellular activity which mediates phosphate absorption. Already, some have indicated new approaches for pharmacological intervention to regulate phosphate in common conditions, including chronic renal failure and osteoporosis, as well as rare inherited biochemical disorders. It is a rapidly evolving field. The aim here is to provide an overview of our current knowledge, to show where it is leading, and where there are uncertainties. Hopefully, this will raise questions and stimulate new ideas for further research.
Topics: Humans; Phosphates; Animals; Renal Reabsorption; Kidney; Kidney Tubules, Proximal
PubMed: 38731904
DOI: 10.3390/ijms25094684 -
Saudi Journal of Kidney Diseases and... Nov 2023Tumor-induced osteomalacia (TIO) is a disorder in which the clinical signs and symptoms of osteomalacia and the biochemical abnormalities of hypophosphatemia,...
Tumor-induced osteomalacia (TIO) is a disorder in which the clinical signs and symptoms of osteomalacia and the biochemical abnormalities of hypophosphatemia, phosphaturia, and low serum levels of 1,25(OH)2 Vitamin D3 are secondary to a neoplasm. A 33-year-old woman presented with musculoskeletal pain and proximal myopathy with a duration of 2.5 years which was treated with Vitamin D supplements. On the basis of the biochemical tests and histopathology, she was reevaluated and found to have TIO secondary to a phosphaturic mesenchymal tumor. The tumor was resected (limb salvage with endoprosthesis), and she had no pain or weakness at followup. The case reminds the readers to consider the possibility of TIO when evaluating patients with isolated hypophosphatemia, which may lead to long-term disability and prolonged morbidity if untreated. Early recognition and diagnosis of TIO is crucial since resection of the tumor usually reverses its manifestations.
Topics: Humans; Female; Adult; Osteomalacia; Paraneoplastic Syndromes; Hypophosphatemia; Muscular Diseases; Mesenchymoma; Treatment Outcome; Limb Salvage; Biopsy; Neoplasms, Connective Tissue
PubMed: 38725216
DOI: 10.4103/sjkdt.sjkdt_250_23 -
Internal Medicine (Tokyo, Japan) May 2024In this report, we describe a unique case of an 80-year-old woman who developed chronic bromine poisoning due to the prolonged ingestion of over-the-counter (OTC)...
In this report, we describe a unique case of an 80-year-old woman who developed chronic bromine poisoning due to the prolonged ingestion of over-the-counter (OTC) medication containing bromovalerylurea (BVU), thus leading to the onset of drug-induced partial Fanconi syndrome and resultant osteomalacia. The patient's condition improved following the cessation of bromide intake. This case highlights the potential risks of chronic BVU exposure and the importance of caution regarding the use of OTC medications containing BVU.
PubMed: 38692916
DOI: 10.2169/internalmedicine.3128-23