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Tumor-induced hypophosphatemia

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M Mulani
M Mulani
M Mulani
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K Somani
K Somani
K Somani
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Shrirang Bichu at Bombay Hospital & Medical Research Centre
Shrirang Bichu
Vanaja Ratna Kumari Billa at Andhra Medical College
Vanaja Ratna Kumari Billa
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Abstract and Figures

Significant hypophosphatemia is commonly due to Vitamin D deficiency. Any sporadic onset of hypophosphatemia in adults warrants workup to identify alternate causes. Hypophosphatemia may also be the only manifestation of an occult malignancy. A high index of clinical suspicion can help diagnose such conditions in early stages. Prompt treatment of the cause can correct this biochemical abnormality. We describe a case report of a woman presenting with severe hypophosphatemia and osteomalacia, leading eventually to the diagnosis of a phosphaturic mesenchymal tumor of the temporo-occipital bone. Surgical resection of tumor led to normalization of the biochemical parameters as well as a complete clinical recovery.
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66 © 2017 Indian Journal of Nephrology l Published by Wolters Kluwer - Medknow
in June 2013 with complaints of pain in both hip
joints for 2 months. The pain progressively worsened
over 2 months and led to a difficulty in standing up along
with severe difficulty in walking. On clinical examination,
there was marked proximal muscle weakness in the
lower limbs. X-rays revealed severe osteopenia in both
hip joints. The blood chemistry showed serum calcium
to be 9.0 mg/dl, serum phosphorus - 2.1 mg/dl, serum
alkaline phosphatase - 136 IU/ml, intact parathyroid
hormone - 61.5 pg/ml, Vitamin D - 19.3 nmol/L, and
serum thyroid-stimulating hormone - 10.3 mIU/L.
Her renal and liver functions tests were normal. She
was initially treated with oral calcitriol, oral calcium
supplements (calcium carbonate 500 mg BID) along
with parenteral cholecalciferol (6 lac IU) once a month,
and thyroxin was added for 6 months. However, there
was significant improvement neither in the proximal
motor weakness nor the degree of pain. Her rechecked
laboratories revealed high Vitamin D levels of 310 nmol/L
with a more severe hypophosphatemia (1.5 mg/dl).
These results prompted the primary care physician
to stop Vitamin D supplements and she was initiated
on teriparatide. She did not show significant clinical
improvement even with this over the next 6 months. She
Tumor‑induced hypophosphatemia
M. Mulani, K. Somani, S. Bichu, V. Billa
Department of Nephrology, Bombay Hospital and Medical Research Center, Mumbai, Maharashtra, India
ABSTRACT
Signicant hypophosphatemia is commonly due to Vitamin D deciency. Any sporadic onset of hypophosphatemia in adults
warrants workup to identify alternate causes. Hypophosphatemia may also be the only manifestation of an occult malignancy.
A high index of clinical suspicion can help diagnose such conditions in early stages. Prompt treatment of the cause can correct
this biochemical abnormality. We describe a case report of a woman presenting with severe hypophosphatemia and osteomalacia,
leading eventually to the diagnosis of a phosphaturic mesenchymal tumor of the temporo-occipital bone. Surgical resection of
tumor led to normalization of the biochemical parameters as well as a complete clinical recovery.
Key words: Hypophosphatemia, malignancy, osteomalacia
Introduction
Tumor-induced osteomalacia/hypophosphatemia (TIO)
is a rare acquired disorder. Patients typically present with
a history of chronic bone pain, fractures, and proximal
motor weakness. The tumors are often benign, small,
and difficult to detect. A recent report has suggested that
fibroblast growth factor 23 (FGF-23) is the most reliable
marker for the detection of these tumors.[1] We report a
case of TIO, the tumor being in the posterior cranial fossa.
The tumor was successfully resected by a left retromastoid
craniotomy approach. Serum phosphorus levels and
FGF-23 levels recovered to their normal range immediately
after the surgery. The diagnostic evaluation, etiology of
hypophosphatemia, and treatment are discussed.
Case Report
A 48-year-old woman consulted an orthopedic surgeon
How to cite this article: Mulani M, Somani K, Bichu S, Billa V.
Tumor‑induced hypophosphatemia. Indian J Nephrol 2017;27:66‑8.
This is an open access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows
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For reprints contact: reprints@medknow.com
Address for correspondence:
Dr. M. Mulani,
Room No. 206, 2nd Floor, New Wing, Bombay Hospital Institutes of
Medical Sciences, New Marine Lines, Mumbai ‑ 400 020,
Maharashtra, India.
E‑mail: mulani.mahendra@gmail.com
Access this article online
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Website:
www.indianjnephrol.org
DOI:
10.4103/0971-4065.179302
Case Report
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Mulani, et al.: Tumor induced hypophosphatemia
67
Indian Journal of Nephrology Jan 2017 / Vol 27 / Issue 1
needed support for walking and she stopped injection
teriparatide in September 2014.
Her hip and thigh pain worsened progressively and
she became bedridden. A magnetic resonance imaging
(MRI) done at this point was suggestive of a left
femoral neck insufficiency fracture, mild degenerative
changes in both hip joints, and stress edema of both
acetabulae. Twenty-four-hour urinary phosphorus was
901 mg (normal 500–1000 mg).
A few months later, in January 2015, she developed
new symptoms in the form of tinnitus and heaviness of
the left ear. An MRI brain and audiometry were done
which was normal. Coincidentally, around this time,
she was also started on oral phosphate supplements
and within a week, she showed marked improvement.
Her pain decreased and she was able to walk with
support. Blood chemistry showed improvement in serum
phosphorus level to 2.2 mg/dl within 2 weeks of starting
the supplement.
She was referred to our center for further evaluation
of all her problems in March 2015. On evaluating her
symptoms, persistent hypophosphatemia with no obvious
cause, and persistent new-onset auditory symptoms,
there was possibility of TIO. Somatostatin positron
emission tomography (PET) scintigraphy was done which
revealed a large lytic expansile lesion in left occipital
bone including the clivus and occipital condyles with
erosion of the mastoid and temporal bone [Figure 1].
Serum FGF-23 was tested, which was found to be very
high - 725 RU/ml (normal <180 RU/ml).
Another MRI brain with contrast confirmed a left
occipitotemporal bone space occupying lesion (SOL)
[Figure 2]. Angioembolization of the tumor was done on
March 30, 2015, with polyvinyl alcohol particles, and left
retromastoid craniotomy, and excision of the tumor was
done on the next day. Her phosphate supplements were
stopped perioperatively.
Histopathology of tumor was consistent with the
diagnosis of a phosphaturic mesenchymal tumor
[Figure 3]. Postsurgery, her serum phosphorus level
improved fairly quickly, over 4–5 days. Her hip pain
and weakness gradually improved. She started walking
without support. We stopped all her treatment. A repeat
FGF-23 done on the 10th day postsurgery showed a
significant drop to 155 RU/ml. Serum phosphorus also
improved to 2.6 mg/dl within 10 days and stayed at the
same level even after a month postsurgery without any
phosphate supplements.
Discussion
TIO is an uncommon condition. These tumors are usually
mesenchymal or mixed connective tissue arising from
either soft tissues or bone.[2] They are benign in nature.
Even in histologically malignant tumors, local recurrence
Figure 1: Positron emission tomography scintigraphy revealed large lytic
expansile lesion in left occipital bone including the clivus and occipital
condyles with erosion of the mastoid and temporal bone
Figure 2: Magnetic resonance imaging brain with contrast conrmed a large
left occipitotemporal bone tumor with lytic lesion
Figure 3: (a) Tumor histopathology shows grungy matrix with osteoclast-like
giant cells and mononuclear cell inltration suggestive of phosphaturic
mesenchymal tumor (b) tumor histopathology shows osteoclast-like
multinucleated giant cells and mononuclear cells inltration suggestive
of phosphaturic mesenchymal tumor
b
a
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Mulani, et al.: Tumor induced hypophosphatemia
68 Jan 2017 / Vol 27 / Issue 1 Indian Journal of Nephrology
or distant metastasis is extremely rare.[2] The most common
types of these tumors are hemangiopericytomas.[3] They
are located mostly in lower extremities, but arms, face,
skull, and neck are other potential sites. Gonzalez-Compta
et al.[4] reviewed 21 cases of osteomalacia induced by
head and neck tumors. The authors reported that 57% of
these tumors were located in the sinonasal area and that
the mean age at diagnosis was 45 years. Average time
from the onset of symptoms and diagnosis is usually more
than 2.5 years. Reasons for this delay in diagnosis are
the occult nature of the disease, nonspecific symptoms,
and the fact that serum phosphate levels are not part of
routine chemistry panel.[1] This slow-growing tumor can
occur in unusual sites in the body. Pirola et al.[5] reported
oncogenic osteomalacia of the thoracic spine. However,
oncogenic osteomalacia originating from the middle
cranial fossa is very rare.
Biochemical analysis often detects abnormalities in serum
chemical concentrations. Generally, those patients who
have hypophosphatemia have normal calcium levels and
a low 1,25-dihydroxyvitamin D concentration. The most
reliable marker for the detection of TIO is FGF-23,[6]
which is a secreted peptide hormone overexpressed by
the tumor in patients with TIO. Fukumoto[7] reported that
FGF-23 suppresses phosphate reabsorption by decreasing
expression levels of the Type 2a and 2c sodium phosphate
cotransporter in the brush border membrane of proximal
tubules. At the same time, FGF-23 reduces serum
1,25-dihydroxyvitamin D levels in part by suppressing
1,25-dihydroxyvitamin D production. This process leads
to hypophosphatemia. Symptoms resolved once the tumor
is totally removed. Therefore, it is necessary to consider
the total excision of the tumor as a treatment strategy. To
locate these tumors, several imaging modalities have been
mentioned in literature, which are used. These include
computed tomography (CT), MRI, PET-CT, octreotide and
sestamibi scans, and even bone scintigraphy.[8]
Our patient initially underwent whole body MRI which
did not reveal any tumor. Later, somatostatin receptor
imaging was done which revealed a tumor near the
left posterior cranial fossa [Figure 1]. MRI brain with
contrast then showed a tumor in left occipital bone
including clivus and occipital condyle with temporal bone
erosion [Figure 2] which on biopsy revealed phosphaturic
mesenchymal tumor [Figure 3].
Conclusions
We treated a case of hypophosphatemia associated with
TIO. The tumor was successfully resected by using a
left retromasoid craniotomy approach. Phosphate levels
recovered to normal immediately after the surgery.
The pattern of abnormalities in serum Ca, P, Vitamin D,
alkaline phosphatase, and parathyroid hormone may
give a clue to the underlying cause of osteomalacia.
Osteomalacia of tumor origin should be suspected in the
relevant clinical context.
Financial support and sponsorship
Nil.
Conicts of interest
There are no conflicts of interest.
References
1. Jan de Beur SM. Tumor‑induced osteomalacia. JAMA
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4. Gonzalez‑Compta X, Mañós‑Pujol M, Foglia‑Fernandez M,
Peral E, Condom E, Claveguera T, et al. Oncogenic osteomalacia:
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Sganzerla EP. Oncogenic osteomalacia caused by a phosphaturic
mesenchymal tumor of the thoracic spine. J Neurosurg Spine
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6. Carpenter TO. Oncogenic osteomalacia – A complex dance of
factors. N Engl J Med 2003;348:1705‑8.
7. Fukumoto S. Fibroblast growth factor (FGF) 23 works as a
phosphate‑regulating hormone and is involved in the pathogenesis
of several disorders of phosphate metabolism. Rinsho Byori
2007;55:555‑9.
8. Gandhi GY, Shah AA, Wu KJ, Gupta V, Shoraka AR.
Tumor‑induced osteomalacia caused by primary broblast growth
factor 23 secreting neoplasm in axial skeleton: A case report. Case
Rep Endocrinol 2012;2012:185454.
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... We searched for all original and review articles in MED-LINE till December 2022. Individual search was carried out using the following terms: "oncogenic osteomalacia," "tumor induced osteomalacia," "FGF23," "skull base," and We were able to identify only other seven patients with TIO caused by a tumor located in the occipital bone [6][7][8][9][10][11][12]. ...
... Basal circulating FGF23 levels were reported in 6 out of 8 patients. C-terminal assay was used in all cases [8][9][10][11][12] except that reported here in which iFGF23 was measured. As in our case, the tumor was detected in other six patients by functional imaging [7][8][9][10][11][12]. ...
... C-terminal assay was used in all cases [8][9][10][11][12] except that reported here in which iFGF23 was measured. As in our case, the tumor was detected in other six patients by functional imaging [7][8][9][10][11][12]. The suspicious lesion was confirmed by MRI in our case and in other five patients [7][8][9][10] and by CT scan in another one [11]. ...
Occipital bone and tumor-induced osteomalacia: a rare tumor site for an uncommon paraneoplastic syndrome
Article
Full-text available
  • Jul 2023
Introduction: Tumor-induced osteomalacia (TIO) is an uncommon paraneoplastic syndrome due to the overproduction of fibroblast growth factor 23 (FGF23). It is predominantly caused by mesenchymal tumors and cured upon their complete removal. Non-surgical treatment is an alternative option but limited to specific clinical conditions. Methods: We report a challenging case of TIO caused by a tumor involving the occipital bone. We also performed a literature review of TIO caused by tumors localized at this site, focusing on clinical findings, treatment, and outcomes. Results: The patient, a 62-year-old male, presented with a long-lasting history of progressive weakness. Biochemical evaluation revealed severe hypophosphatemia due to low renal tubular reabsorption of phosphate with raised intact FGF23 values. A 68 Ga-DOTATATE PET/TC imaging showed a suspicious lesion located in the left occipital bone that MRI and selective venous catheterization confirmed to be the cause of TIO. Stereotactic gamma knife radiosurgery was carried out, but unfortunately, the patient died of acute respiratory failure. To date, only seven additional cases of TIO have been associated to tumors located in the occipital bone. Furthermore, the tumor involved the left side of the occipital bone in all these patients. Conclusion: The occipital region is a difficult area to access so a multidisciplinary approach for their treatment is required. If anatomical differences could be the basis for the predilection of the left side of the occipital bone, it remains to be clarified.
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... 2017). Our observation of hypo-phosphatemia in FD and FO in HCC category is consistent with literature findings that tumor reduces phosphate levels in occult neoplasms (Mulani et al. 2017) and treatment of the related cause might correct this biochemical abnormality. ...
Dietary modulations of folic acid affect the development of diethylnitrosamine induced hepatocellular carcinoma in a rat model
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  • J MOL HISTOL
The present study evaluated the role of dietary folate modulations in the development of hepatocellular carcinoma (HCC) in a rat model. Male Wistar rats were given diethylnitrosamine (DEN) carcinogen for a period of 18 weeks in addition to different folate modulations. Biochemical parameters were assayed and liver tissues were examined using various histopathological stains viz. Hematoxylin and eosin (H&E), Masson’s trichrome, Immunohistochemistry (IHC) staining for arginase-1 and α-smooth muscle actin (SMA). Serum folate and hepatic folate stores were decreased and increased in folate deficiency (FD) and folate oversupplemented (FO) group respectively. Analysis of serum liver function tests revealed deranged liver functioning in all the groups. H&E staining of rat liver demonstrated vague nodularity from 2nd to 8th week, fibrosis from 10th to 15th week, cirrhosis and HCC from 16th to 18th week. Combining the observations of H&E with IHC for arginase-1, 14 (50%), 11 (39.3%) and 17 (58.6%) rats showed HCC positivity in FN (folate normal), FD and FO diets respectively. IHC for α-SMA depicted increased staining with progression of the disease from fibrosis to cirrhosis in all the dietary groups. Collectively, findings of all the histopathological stains, revealed increase in the number of cirrhotic cases and decrease in the number of HCC cases in FD group, indicating delayed progression of HCC with FD. Moreover, FO led to more number of HCC and reduction in the number of cirrhotic cases, signifying early progression of HCC.
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... Then patients are often treated with calcium and phosphorus supplements. The lesion is not detected in the occipitocervical region until symptoms of nerve compression such as tinnitus[8] or a large mass occur. Our cases presented with a long-standing bone pain, headache and tongue de ection. ...
Phosphaturic mesenchymal tumor of the occipitocervical region: Report of two rare cases and literature review
Preprint
Full-text available
  • Aug 2020
Background Tumor-induced osteomalacia (TIO) is regarded as a rare paraneoplastic syndrome mainly caused by phosphaturic mesenchymal tumor (PMT). To our known, only 5 occipitocervical PMTs have been described in the world’s English literature. We reported two rare cases of occipitocervical PMT, and conducted a retrospective analysis of these 7 cases. The purpose of this study is to discuss the clinical characteristics and treatment of occipitocervical PMT.Case PresentationBoth patients were middle-aged females, and had a long-standing bone pain. In case 1, there were no abnormalities in biochemical indicators. The blood phosphorus was normal and alkaline phosphatase (ALP) was elevated in case 2. Magnetic resonance imaging (MRI) suggested that osteolytic bone destruction accompanied by a soft tissue mass in left C1-2 vertebra (case 1). In case 2, the bone destruction was located on the right C1-2 and the clivus. Then both patients underwent complete resection of tumor, and case 2 also received adjuvant radiotherapy, the histopathology revealed a PMT. Case 2 suffered recurrence during 5-year follow-up.Conclusions Occipitocervical PMT is quite rare, and only 5 cases have been reported in the literature. Currently, complete resection of the tumor is the best option. The surgery is difficult, and requires delicate operation due to the complex anatomy of the occipitocervical region. Postoperative radiotherapy has little effect on local control. And further research is needed to confirm the effectiveness of the newly-emerged therapies.
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Intracranial phosphaturic mesenchymal tumor: A rare case report and systematic review
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  • Feb 2025
  • MEDICINE
Rationale Phosphaturic mesenchymal tumors (PMTs) are rare soft-tissue and bone tumors that can occur intracranially. Low incidence, nonspecific symptoms, and diverse histomorphology of PMTs contribute to a high rate of misdiagnosis. Patient concerns This report presents a rare case of an intracranial PMT located in the posterior cranial fossa. In addition, a systematic review of previously reported intracranial PMT cases was conducted and summarized. Diagnoses Incorporating clinical symptoms, laboratory findings, and imaging features, the definitive diagnosis of PMT was based on pathological examination. Interventions The patient underwent consultations in endocrinology, orthopedics, and neurosurgery, and ultimately had a surgical procedure to remove the intracranial tumor. Outcomes After tumor resection, the patient’s laboratory values returned to normal, his symptoms improved, and he could walk again. Lessons Due to the rarity and high misdiagnosis rate of PMTs, no unified diagnosis and treatment standards have been established. Early identification, accurate diagnosis, and timely treatment are essential for optimal management. Surgical resection remains the preferred treatment for PMTs, with total tumor resection strongly recommended. In case of incomplete resection, tumor recurrence and persistent symptoms may necessitate adjunctive drug therapy and radiation therapy.
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Tumor-Induced Osteomalacia Caused by Primary Fibroblast Growth Factor 23 Secreting Neoplasm in Axial Skeleton: A Case Report
Article
Full-text available
  • Dec 2012
We report the case of a 66-year-old woman with tumor-induced osteomalacia (TIO) caused by fibroblast growth factor 23 (FGF-23) secreting mesenchymal tumor localized in a lumbar vertebra and review other cases localized to the axial skeleton. She presented with nontraumatic low back pain and spontaneous bilateral femur fractures. Laboratory testing was remarkable for low serum phosphorus, phosphaturia, and significantly elevated serum FGF-23 level. Magnetic resonance imaging (MRI) of the lumbar spine showed a focal lesion in the L-4 vertebra which was hypermetabolic on positron emission tomography (PET) scan. A computed tomography (CT) guided needle biopsy showed a low grade spindle cell neoplasm with positive FGF-23 mRNA expression by reverse transcriptase polymerase chain reaction (RT-PCR), confirming the diagnosis of a phosphaturic mesenchymal tumor mixed connective tissue variant (PMTMCT). The patient elected to have surgery involving anterior resection of L-4 vertebra with subsequent normalization of serum phosphorus. Including the present case, we identified 12 cases of neoplasms localized to spine causing TIO. To our knowledge, this paper represents the first documented case of lumbar vertebra PMT causing TIO. TIO is a rare metabolic bone disorder that carries a favorable prognosis. When a lesion is identifiable, surgical intervention is typically curative.
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Oncogenic osteomalacia: Case report and review of head and neck associated tumours
Article
Full-text available
  • May 1998
Oncogenic osteomalacia is an uncommon syndrome characterized by mineral metabolism abnormalities that disappear after the resection of an associated tumour. Head and neck is the second most frequent location of these tumours. We describe a case with an ethmoido-frontal phosphaturic mesenchymal tumour and review oncogenic osteomalacia-associated tumours. Among 21 cases found, 57 per cent affected the sinonasal area and 20 per cent the mandible. The diagnosis of the tumour lasted a mean of 4.7 years from the onset of osteomalacia, and most of them showed a significant vascular component. An aggressive surgical approach is recommended.
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Tumor-Induced Osteomalacia
Article
  • Dec 2008
Tumor-induced osteomalacia (TIO) is a rare, paraneoplastic disease that can be difficult to distinguish from genetic forms of hypophosphatemia and severe osteomalacia. The hallmark of TIO, and its genetic phenocopies, is renal phosphate wasting and abnormal vitamin D metabolism; specifically, lack of compensatory increase in 1,25-dihydroxyvitamin D (1,25(OH)2D3) in response to hypophosphatemia. Ultimately, unchecked renal phosphorus excretion and relative 1,25(OH)3 deficiency leads to osteomalacia, a metabolic bone disease characterized by a failure of mineralization and resultant weak, painful bones. Physical examination often reveals bone pain, especially with palpation of the anterior tibia and sternum. In children, long bone deformity, lower extremity bowing, and chest wall deformity is observed. If TIO is suspected, an extensive examination for masses or nodules is warranted, concentrating on soft tissues adjacent to long bones, distal extremities, the oral cavity and jaw, and the groin. Hypophosphatemia secondary to renal phosphate wasting has a wide differential diagnosis. These disorders can result from primary renal defects, overproduction of the phosphaturic hormone, FGF23, from normal or dysplastic bone and ectopic production of FGF23 or other phosphaturic proteins from tumors. Most tumors responsible for TIO are of mesenchymal origin, and are found in bone or soft tissue. The most common sites are in the long bones and extremities, but nasopharynx, sinuses, and groin are other locations. TIO is only definitively treated by identification and resection of the causative tumor. In addition, recently, the calcium-sensing receptor agonist, cinacalcet, has been shown to be an effective adjuvant in the treatment of TIO.
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Oncogenic osteomalacia caused by a phosphaturic mesenchymal tumor of the thoracic spine: Case report
Article
  • May 2009
Phosphaturic mesenchymal tumors that cause the paraneoplastic syndrome known as oncogenic osteomalacia are rare. The authors report on the case of a 57-year-old man with a history of osteomalacia and in whom was diagnosed a thoracic spine tumor at the T-4 level. Complete tumor resection was accomplished. The histological diagnosis was phosphaturic mesenchymal tumor (mixed connective tissue variant). After lesion removal, the paraneoplastic syndrome resolved. At the 24-month follow-up, no recurrence of the disease was observed. The clinical presentation, surgical technique, and follow-up in this case were reviewed in detail.
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Oncogenic osteomalacia associated with a meningeal phosphaturic mesenchymal tumor: Case report
Article
  • Mar 1996
  • J NEUROSURG
A 60-year-old woman suffered from hypophosphatemic osteomalacia secondary to a frontal intracranial tumor. Oral administration of phosphate and 1-alpha-hydroxyvitamin D3 provided only temporary symptomatic relief. A computerized tomography (CT) scan of the patient's head revealed a large subfrontal tumor attached to the dura. Following removal of the tumor, the patient's hypophosphatemia subsided; her level of 1,25-dihydroxyvitamin D3, which was undetectable preoperatively, returned to normal, and she had symptomatic improvement. Three years later, decreasing levels of phosphate and 1,25-dihydroxyvitamin D3 indicated tumor recurrence, before it was detected by CT scan. Histological examination of the tumor provided the diagnosis of "mixed connective tissue variant of phosphaturic mesenchymal tumor." The characteristic histological features of this relatively rare entity are discussed. This is the first report of a surgically treated intracranial phosphaturic mesenchymal tumor that caused oncogenic osteomalacia.
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Tumor-induced osteomalacia and the regulation of phosphate homeostasis
Article
  • Oct 2000
  • BONE
Tumor-induced osteomalacia (TIO) is a rare and unique syndrome characterized by hypophosphatemia, excessive urinary phosphate excretion, reduced 1,25-dihydroxyvitamin D concentrations, and osteomalacia. Removal of the tumor is associated with a cure of the lesion. Several laboratories have now shown that conditioned medium derived from cultures of such tumors contain a small, heat-sensitive substance ("phosphatonin") of <25,000 daltons that specifically inhibits sodium-dependent phosphate transport in cultured renal proximal tubular epithelia. This substance does not increase cyclic adenosine monophosphate (cAMP) formation in tubular epithelial cells and does not increase cAMP excretion in urine. A substance with similar properties is present in the circulation of patients on hemodialysis. A syndrome with a remarkably similar biochemical phenotype, namely, X-linked hypophosphatemic rickets (XLH), also has a circulating factor with properties similar, if not identical, to those of the tumor-derived factor, "phosphatonin." The molecular defect in XLH has been shown to be due to a mutant endopeptidase, PHEX, whose substrate might be "phosphatonin." Hypophosphatemia and other biochemical abnormalities in TIO are due to excessive production of "phosphatonin" with normal PHEX function, whereas the biochemical abnormalities in XLH are caused by a mutant PHEX enzyme that fails to process "phosphatonin."
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Oncogenic Osteomalacia — A Complex Dance of Factors
Article
  • May 2003
  • NEW ENGL J MED
This article has no abstract; the first 100 words appear below. Oncogenic osteomalacia has fascinated physiology-minded physicians for decades. The traditional name for this peculiar disorder connotes its classification as a paraneoplastic phenomenon. Such a characterization is a bit off the mark, however, in that the involved “neoplasm” is often (but not always) of limited clinical significance apart from its causal role in the musculoskeletal disease. Tumors responsible for oncogenic osteomalacia are usually benign rather than invasive, whereas generalized, debilitating osteomalacia and rickets are the important clinical problems for the patient. The assay for the measurement of circulating levels of fibroblast growth factor 23 (FGF-23), the development of which is described . . . Dr. Carpenter reports having received consulting fees from Merck and Genzyme and a grant from CuraGen. Source Information From the Section of Pediatric Endocrinology, Yale University School of Medicine, New Haven, Conn.
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Tumor-Induced Osteomalacia
Article
  • Oct 2005
  • J Am Med Assoc
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic form of renal phosphate wasting that results in severe hypophosphatemia, a defect in vitamin D metabolism, and osteomalacia. This debilitating disorder is illustrated by the clinical presentation of a 55-year-old woman with progressive fatigue, weakness, and muscle and bone pain with fractures. After a protracted clinical course and extensive laboratory evaluation, tumor-induced osteomalacia was identified as the basis of her clinical presentation. In this article, the distinctive clinical characteristics of this syndrome, the advances in diagnosis of TIO, and new insights into the pathophysiology of this disorder are discussed.
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[Fibroblast growth factor (FGF) 23 works as a phosphate-regulating hormone and is involved in the pathogenesis of several disorders of phosphate metabolism]
Article
  • Jul 2007
  • Rinsho Byori Jpn J Clin Pathol
Fibroblast growth factor (FGF) 23 was identified as the latest member of the FGF family. Subsequent studies showed that FGF23 reduces the serum phosphate level by suppressing proximal tubular phosphate reabsorption. This phosphaturic action of FGF23 derives from the suppressive effect of FGF23 on the expression of type 2a and 2c sodium-phosphate cotransporter in the brush border membrane of proximal tubules. At the same time, FGF23 reduces the serum level of 1,25-dihydroxyvitamin D [1,25(OH)2D] which results in suppressed intestinal phosphate absorption. Establishment of an enzyme-linked immunosorbent assay for FGF23 indicated that excess actions of FGF23 result in hypophosphatemic rickets/osteomalacia such as X-linked, autosomal dominant, autosomal recessive hypophosphatemic rickets/osteomalacia, and tumor-induced rickets/osteomalacia. In contrast, deficiency of FGF23 action causes hyperphosphatemic tumoral calcinosis. These results indicate that FGF23 is a hormone regulating serum phosphate and 1,25(OH)2D levels.
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