Tumor mesenquimático fosfatúrico de pelvis: abordaje multidisciplinario / Phosphaturic mesenchymal tumor of the pelvis: A multidisciplinary approach

El tumor mesenquimático fosfatúrico es una entidad clinicopatológica sumamente infrecuente. Además de provocar dolor óseo insidioso y polimialgias, se acompaña de alteraciones del metabolismo fosfocálcico de difícil manejo clínico. El abordaje multidisciplinario resulta la clave del éxito en esta enfermedad. Presentamos una paciente de 52 años de edad con antecedente de tumor mesenquimático fosfatúrico en la hemipelvis derecha con extensión a la cadera homolateral de 10 años de evolución. Clínicamente presentaba osteomalacia oncogénica (hipofosfatemia e hiperfosfaturia) que no se corregía, pese a un agente de última generación, el burosumab, un inhibidor del factor de crecimiento fibroblástico 23, que aumenta la reabsorción tubular renal de fosfatos. En un comité multidisciplinario, se decidió la resección con márgenes oncológicos y se logró una mejoría clínica franca. Comunicamos este caso, debido a que es un cuadro infrecuente. Nivel de Evidencia: IV

Phosphaturic mesenchymal tumor (PMT) is an infrequent clinicopathological entity. It presents insidious bone pain and polymyalgia, accompanied by alterations in calcium and phosphorus metabolism that are difficult to resolve clinically. A multidisciplinary approach is a key to success in this pathology. We present the case of a 52-year-old female patient with a 10-year history of PMT in the right hemipelvis with ipsilateral hip extension. From the clinical point of view, she presented oncogenic osteomalacia (hypophosphatemia and hyperphosphaturia) that did not correct despite being administered the latest generation medication, burosumab, an FGF-23 inhibitor that increases renal tubular phosphate reabsorption. Resection with oncological margins was decided by a multidisciplinary committee resolving her clinical condition. Due to the rarity of this pathology, we decided to report the case. Level of Evidence: IV

Osteomalacia oncogénica secundaria a tumor mesenquimal fosfatúrico del pie / Oncogenic osteomalacia secondary to phosphaturic mesenchymal tumour of the foot

RESUMEN La osteomalacia oncogénica es un síndrome metabólico paraneoplásico caracterizado por hipofosfatemia debida a la pérdida renal de fosfato, con nivel bajo de vitamina D. Este trastorno está asociado con la liberación de factores fosfatúricos por células tumorales, especialmente el factor de crecimiento fibrolástico 23 (FGF23). Las neoplasias relacionadas con la osteomalacia oncogénica suelen ser tumores pequeños de linaje mesenquimatoso y pueden ser difíciles de localizar en algunos casos debido a su tamaño y ubicación poco accesible al examen físico. Presentamos a un paciente que desarrolló fracturas vertebrales y de cadera debido a osteomalacia oncogénica asociada con un tumor mesenquimatoso fosfatúrico del tejido graso profundo de la planta del pie, que finalmente se diagnosticó después de 3 años del inicio de los síntomas, cuando el tumor pudo ser localizado por el rastreo gammagráfico óseo con pentatreótido marcado con indio-111 y por las imágenes de resonancia magnética nuclear.

ABSTRACT Oncogenic osteomalacia is a paraneoplastic metabolic syndrome characterised by a low phosphates in the blood due to renal phosphate losses with inadequately normal or low vitamin D levels. This disorder is associated with the release of tumour cell-secreted phosphaturic factor, most notably fibroblast growth factor 23 (FGF-23). The neoplasms related to oncogenic osteomalacia are usually small tumours of mesenchymal lineage, and they may be difficult to locate in the physical examination in some cases, due to their size and inaccessible location. The case is presented of a patient who developed vertebral and hip fractures due to oncogenic osteomalacia associated with a phosphaturic mesenchymal tumour of the deep fat tissue in the sole of the foot. This was finally diagnosed after 3 years of the onset of symptoms after being located by bone scintigraphy with Indium-111 labelled pentetreotide and magnetic resonance imaging.

Osteomalacia. Diagnóstico y tratamiento / Osteomalacia. Diagnosis and treatment

Introducción: la osteomalacia se caracteriza por la falta de mineralización de la sustancia osteoide, que afecta al hueso cortical y al hueso esponjoso maduro. Es una enfermedad que se presenta en adultos y niños, aunque la causa es diferente en cada uno. Objetivo: exponer la generalidad de la osteomalacia por ser una enfermedad que produce serias afectaciones a la población que la padece, especialmente a los niños. Se enfatiza en el diagnóstico y su tratamiento. Desarrollo: a fin de resumir los elementos esenciales para establecer el diagnóstico de osteomalacia hay que plantear en primer lugar, la presencia de un trastorno de la mineralización ósea, de ahí que además de tener en cuenta las causas de la enfermedad, su curso clínico y la sintomatología. Conclusiones: una recomendación importante es no tener en cuenta la posibilidad de complicaciones en el curso de la enfermedad, como las fracturas, que, aunque sean parte del cuadro clínico, al producirse pueden ocasionar graves problemas, como el caso de las que aparecen en las costillas, que si se desplazan pueden interesar órganos vitales, de modo que en este tipo de pacientes no debe excluirse la posibilidad de emergencias o de urgencias reumatológicas tanto en los adultos como en los niños(AU)

Introduction: osteomalacia is characterized by the lack of mineralization of the osteoid substance, which affects cortical bone and mature cancellous bone. It is a disease that occurs in adults and children, although the cause is different in each. Objective: to expose the generality of osteomalacia for being a disease that causes serious affectations to the population that suffers it, especially to children. Emphasis is placed on the diagnosis and its treatment. Development: in order to summarize the essential elements to establish the diagnosis of osteomalacia, we must first consider the presence of a bone mineralization disorder, hence, in addition to taking into account the causes of the disease, its clinical course and the symptomatology. Conclusions: an important recommendation is not to take into account the possibility of complications in the course of the disease, such as fractures, which, although they are part of the clinical picture, can cause serious problems when they occur, as in the case of those that appear in the ribs, which if they move may involve vital organs, so that in this type of patients should not exclude the possibility of emergencies or rheumatological emergencies in both adults and children(AU)

Uveítis anterior aguda asociada a raquitismo renal hipofosfatémico / Acute anterior uveítis associated to hypophosphatemic renal ricketts

Los raquitismos hipofosfatémicos hereditarios son un grupo de enfermedades caracterizadas por la pérdida renal de fosfatos. Cursan con hipocrecimiento disarmónico y deformidades óseas. La forma más común es el raquitismo hipofosfatémico ligado al cromosoma X, el cual es causado por mutaciones inactivantes en el gen PHEX. El objetivo de nuestro trabajo fue describir las alteraciones oculares encontradas y la evolución clínica en un paciente con raquitismo hipofosfatémico hereditario y uveítis anterior. Se presenta un niño de 9 años de edad con diagnóstico de raquitismo hipofosfatémico hereditario, valorado en el Servicio de Uveítis del Instituto Cubano de Oftalmología Ramón Pando Ferrer por presentar dolor ocular y molestias a la luz en el ojo derecho. En la exploración oftalmológica se constata una uveítis anterior con hipopión en el ojo derecho y depósitos de cristales en todo el espesor corneal y el iris en ambos ojos. Se indicaron esteroides tópicos con resolución del proceso inflamatorio. Los hallazgos en el segmento anterior del paciente son sugestivos de cistinosis, donde el acúmulo de cristales es la alteración corneal más típica de las manifestaciones oculares, con una incidencia del 90 por ciento en niños menores de un año, y los primeros órganos afectados son los riñones. Los raquitismos hipofosfatémicos hereditarios pueden cursar con depósitos de cristales corneales y procesos inflamatorios de la úvea anterior(AU)

Hereditary hypophosphatemic rickets are a group of diseases characterized by renal loss of phosphates. They appear with disharmonic hypogrowth and bone deformities. The most common form is the X-chromosome-linked hypophosphatemic rickets which is caused by inactivating mutations in PHEX gene. The objective of our work was to describe the ocular alterations and the clinical evolution in a patient with hereditary hypophosphatemic rickets and previous uveitis. Here is the case of a 9 years-old boy diagnosed with hereditary hypophosphatemic rickets, who was seen at the Uveitis Service of Ramon Pando Ferrer Cuban Institute of Ophthalmology. He presented with ocular pain and feeling of discomfort to light in his right eye. The ophthalmological exam yielded anterior uveitis with hypopyon in his right eye and crystal depots in the whole corneal thickness and the iris of both eyes. Topical steroids were prescribed to treat the inflammatory process. The findings in the anterior segment of the patients indicated the presence of cystinosis in which the accumulation of crystals is the most typical corneal alteration among the ocular manifestations. Its incidence reaches 90 percent in under one year-old children and the first affected organs are the kidneys. The hereditary hypophosphatemic rickets may appear with corneal crystal depots and inflammatory processes in the anterior uvea(AU)

Estudio Descriptivo: Niveles de 25 ­ Hidroxi Vitamina D en la Población que Acude al Servicio de Endocrinología del Instituto Ecuatoriano de Seguridad Social, Azogues ­ Ecuador, 2017 / Restrospective Research: Levels of 25 - Hydroxy Vitamin D in the population that goes to the Endocrinology Service of the Ecuadorian Institute of Social Security, Azogues - Ecuador, 2017

INTRODUCCIÓN: La Vitamina D es considerada una hormona, siendo químicamente liposoluble y se le relaciona con enfermedades inmunológicas, cardiometabólicas y cáncer. El objetivo es evaluar los niveles de 25 hidroxi vitamina D en los pacientes que acudieron al servicio de endocrinología. MÉTODOS: Se trata de un estudio retrospectivo, se tomaron 122 pacientes que acudieron al servicio de endocrinología del Instituto Ecuatoriano de Seguridad Social, durante el periodo durante el periodo de julio a septiembre del 2017. RESULTADOS: El promedio de vitamina D 23.99 ± 9.12 ng/ml, el 22 % presentaron vitamina D en rango normal (≥ 30 ng/ml) y el 78 % en insuficiencia/deficiencia (< 30 ng/ml). Los niveles de calcio y paratiroides no presentaron correlación con las disminuciones de vitamina D. CONCLUSIONES: Existe una importante disminución de la vitamina D en la población que acudió al servicio de Endocrinología durante el periodo estudiado, pese a la exposición solar directa que reciben los pobladores de la zona.

BACKGROUND: Vitamin D is considered a hormone, being chemically lipid soluble and is related to immunological, cardiometabolic and cancer diseases. This aim to evaluate the levels of 25 hydroxy vitamin D in the patients who attended the endocrinology service. METHODS: This was a retrospective study, taking 122 patients who attended the endocrinology service of the Ecuadorian Social Security Institute, during the period during the period from July to September 2017. RESULTS: The average of vitamin D was 23.99 ± 9.12 ng / ml, 22 % of vitamin D in normal range (≥ 30 ng / ml) and 78 % of insufficiency / deficiency (≥ 30 ng / ml). Calcium and parathyroid levels show no correlation with decreases in vitamin D. CONCLUSIONS: There is a significant decrease in the population in the population that went to the Endocrinology service during the period studied, to the direct solar incidence that the inhabitants of the area.

Displasia fibrosa ósea / Fibrous dysplasia of bone

La displasia fibrosa ósea es un trastorno no hereditario del desarrollo esquelético caracterizado por una proliferación anormal de fibroblastos y diferenciación deficiente de osteoblastos que conduce a un reemplazo del tejido óseo esponjoso por tejido conectivo fibroso. Es producida por una mutación somática activadora del gen GNAS1 que induce una activación y proliferación de células mesenquimales indiferenciadas con formación de tejido fibroso y trabéculas óseas anómalas. Existen formas monostóticas, poliostóticas y craneofaciales con diversos grados de dolor, deformidades y fracturas óseas, aunque muchos casos son asintomáticos. En ocasiones se producen quistes óseos aneurismáticos, hemorragias, compromisos neurológicos y raramente osteosarcomas. Algunos casos se asocian a síndrome de McCune-Albright, síndrome de Mazabraud y a osteomalacia por hipofosfatemia por pérdida tubular renal inducida por el FGF23 producido por el tejido displásico. Los hallazgos en las radiografías convencionales son característicos, aunque variables y de carácter evolutivo. La gammagrafía ósea es la técnica de imagen con mayor sensibilidad para determinar la extensión de la enfermedad. El diagnóstico diferencial incluye múltiples lesiones óseas de características similares y en raras ocasiones se requiere biopsia ósea o estudio genético para confirmarlo. No existe un consenso unánime acerca del abordaje terapéutico de estos pacientes, razón por la cual es necesario un enfoque multidisciplinario. La conducta puede ser expectante o quirúrgica según el tipo de lesiones y es importante el manejo del dolor y de las endocrinopatías asociadas. La mayor experiencia publicada se refiere al uso de bifosfonatos y, más recientemente, denosumab. Los tratamientos actuales son insuficientes para modificar el curso de la enfermedad y es necesario el desarrollo de nuevas moléculas que actúen específicamente en el gen GNAS1 o sobre las células mesenquimales afectadas. (AU)

Fibrous dysplasia of bone is a noninherited developmental anomaly of bone characterized by abnormal proliferation of fibroblasts and differentiation of osteoblasts that cause a replacement of trabeculous bone by fibrous connective tissue. It is caused by a somatic mutation in the GNAS1 gene, which induces an undifferentiated mesenquimal cells activation and proliferation with formation of fibrous tissue and abnormal osseous trabeculae. There are monostotic, polyostotic and craniofacial variants with different grades of bone pain, deformities and fractures, although many cases remain asymptomatic. Aneurysmal bone cysts, bleeding, neurological compromise and infrequently osteosarcoma are possible complications. Some cases are associated to McCune-Albright syndrome, Mazabraud syndrome or hypophosphatemia and osteomalacia due to to renal tubular loss induced by FGF23 produced by dysplastic tissue. The findings on conventional radiography are characteristic although variable and evlolve with time. Bone scintigraphy is the most sensitive technique to evaluate the extent of disease. Differential diagnosis include several osseous lesions of similar appearance and, in some cases, bone biopsy or genetic testing may be necessary. Today, there is no consensus regarding the therapeutic approach for these patients and it is necessary a multidisciplinary medical team. Watchful waiting or surgical interventions can be indicated, depending on the type of bone lesions. Bone pain and associated endocrinopathies management are very important. Most published experience refers to the use of bisphosphonates and, more recently, denosumab. Current treatments are insufficient to modify the natural curse of the disease and therefore, new molecules with specific action on GNAS1 gene or affected mesenchymal cells are necessary. (AU)

Phosphaturic mesenchymal tumor (PMT): exceptionally rare disease, yet crucial not to miss

Phosphaturic mesenchymal tumors (PMTs) are very rare tumors which are frequently associated with Tumor Induced Osteomalacia (TIO), a paraneoplastic syndrome that manifests as renal phosphate wasting. The tumor cells produce a peptide hormone-like substance known as fibroblast growth factor 23 (FGF23), a physiologic regulator of phosphate levels. FGF23 decreases proximal tubule reabsorption of phosphates and inhibits 1-α-hydroxylase, which reduces levels of 1-α, 25-dihydroxyvitamine D3. Thus, overexpression of FGF23 by the tumor cells leads to increased excretion of phosphate in the urine, mobilization of calcium and phosphate from bones, and the reduction of osteoblastic activity, ultimately resulting in widespread osteomalacia. Patients typically present with gradual muscular weakness and diffuse bone pain from pathologic fractures. The diagnosis is often delayed due to the non-specific nature of the symptoms and lack of clinical suspicion. While serum phosphorus and FGF23 testing can assist in making a clinical diagnosis of PMT, the responsible tumor is often difficult to locate. The pathologic diagnosis is often missed due to the rarity of PMTs and histologic overlap with other mesenchymal neoplasms. While patients can experience severe disabilities without treatment, excision is typically curative and results in a dramatic reversal of symptoms. Histologically, PMT has a variable appearance and can resemble other low grade mesenchymal tumors. Even though very few cases of PMT have been reported in the world literature, it is very important to consider this diagnosis in all patients with hypophosphatemic osteomalacia. Here we present a patient who suffered for almost 5 years without a diagnosis. Ultimately, the PMT was located on a 68Ga-DOTA TATE PET/CT scan and subsequently confirmed by histologic and immunohistologic study. Interestingly, strong positivity for FGFR1 by IHC might be related to the recently described FN1-FGFR1 fusion. Upon surgical removal, the patient's phosphate and FGF23 levels returned to normal and the patient's symptoms resolved.

Tumores indutores de osteomalácia: diagnóstico, caracterização tumoral e avaliação evolutiva em longo prazo de nove pacientes / Tumor-induced osteomalacia: diagnosis, tumor characterization, and clinical evaluation in nine patients over a long-term period

Tumores indutores de osteomalácia (TIOs) são raros, geralmente apresentam origem mesenquimal, têm produção excessiva de fosfatoninas sendo a mais comum o FGF23 (Fibroblast Growth Factor 23) que, em níveis elevados, provoca osteomalácia hipofosfatêmica. A cura dos TIOs envolve a remoção completa do tumor, o que torna essencial sua localização. OBJETIVOS: (1) caracterizar nove pacientes com TIO ao diagnóstico e avaliá-los evolutivamente em longo prazo; (2) avaliar a eficácia da cintilografia com Octreotida (Octreoscan®) e a da cintilografia de corpo inteiro com Mibi (MIBI) na detecção dos TIOs. MÉTODOS: O acompanhamento dos pacientes consistiu na avaliação clínica, na avaliação laboratorial com ênfase no metabolismo ósseo e na realização de exames de imagem para caracterização das deformidades esqueléticas. Para a localização dos TIOs, os pacientes foram submetidos a exames de Octreoscan®, MIBI, ressonância magnética (RM) e tomografia computadorizada (TC). RESULTADOS: O período de observação dos pacientes variou de dois a 25 anos. Ao diagnóstico, todos exibiam fraqueza muscular, dores ósseas e fraturas de fragilidade. Em relação à avaliação laboratorial, apresentavam: hipofosfatemia com taxa de reabsorção tubular de fosfato reduzida, fosfatase alcalina aumentada e níveis elevados de FGF23. O Octreoscan® permitiu a identificação dos TIOs nos nove pacientes e o MIBI possibilitou a localização dos TIOs em seis pacientes, sendo que ambos os exames foram concordantes entre si e com os exames topográficos (RM ou TC). Os achados histopatológicos das lesões dos nove pacientes confirmaram tratar-se de oito tumores mesenquimais fosfatúricos (PMTs) benignos e um PMT maligno. Após a primeira intervenção cirúrgica para a remoção dos TIOs, quatro pacientes encontram-se em remissão da doença e cinco evoluíram com persistência tumoral. Dos cinco, quatro foram reoperados e um aguarda nova cirurgia. Dos que foram reoperados, um paciente se mantém em remissão da...

Tumor-induced osteomalacia (TIO) is rare. The tumor usually has mesenchymal origin and produces excessive phosphatonins, most commonly FGF23 (Fibroblast Growth Factor 23), which at high levels causes hyphophostatemic osteomalacia. The cure for TIO is achieved through complete removal of the tumor. It is therefore essential identify its location. OBJECTIVES: (1) to characterize nine patients with TIO at diagnosis and to evaluate their follow-up over a long-term period; (2) to evaluate the efficacy of whole-body scintigraphy 111In-octreotide (Octreoscan®) and 99mTc-sestamibi (MIBI) in TIO detection. METHODS: Evaluations consisted of clinical and laboratory testing of bone metabolism and imaging to characterize skeletal deformities. To locate TIO, patients underwent Octreoscan®, MIBI, magnetic resonance (MRI), and computed tomography (TC). RESULTS: Patients were followed-up from two to 25 years. At diagnosis, all patients presented with muscle weakness, bone pain and fragility fractures. Laboratorial evaluation revealed hypophosphatemia with reduced tubular reabsorption of phosphate, increased alkaline phosphatase, and high levels of FGF23. TIO was identified in nine patients through Octreoscan® and in six patients through MIBI. Results of both types of scintigraphies matched one another as well with topographic examination (MR or CT). Histopathological findings of the lesions in the nine patients confirmed the existence of eight benign phosphaturic mesenchymal tumors (PMTs) and one malign PMT. After the first surgery for tumor resection, four patients were in remission, whereas five revealed tumoral persistence. Four of the latter five were re-operated, and one is still waiting for another surgery. Of those four patients, one became in remission, one died of clinical complications, one disclosed metastatic disease, and the last one had tumoral recurrence three years after the second surgery. Severe bone deformations were observed in patients whose...

Raquitismo e osteomalácia hipofosfatêmicos de origem genética mediados por FGF23: caracterização molecular, óssea e renal / FGF23-mediated inherited hypophosphatemic rickets: molecular characterization, bone analysis and renal evaluation

Introdução: raquitismo e osteomalácia hipofosfatêmicos de origem genética mediados por FGF23 (RQ/OM-FGF23) são caracterizados pelo aumento patológico dos níveis séricos de FGF23 com consequentes hiperfosfatúria e hipofosfatemia. A forma hereditária mais comum é a ligada ao X dominante (XLHR) ocasionada por mutações inativadoras no gene PHEX. Objetivos: identificar a etiologia molecular; avaliar a densidade mineral óssea (DMO) e a microarquitetura óssea e, determinar a prevalência de nefrocalcinose (NC), nefrolitíase (NL) e de alterações metabólicas urinárias em 47 pacientes com RQ/OM-FGF23 (16 crianças e 31 adultos). Métodos: as análises dos genes PHEX e FGF23 foram realizadas pelos métodos de Sanger e MLPA. A DMO areal (DMOa) foi avaliada por densitometria óssea (DXA), enquanto a DMO volumétrica (DMOv) e os parâmetros de microarquitetura óssea foram analisados por HR-pQCT. A NC foi classificada segundo uma escala de 0-3 (0 = ausência de NC; 3 = NC grave) pelas ultrassonografia (US) e tomografia computadorizada (TC) renais. A presença de NL foi analisada pela TC renal. Fatores de risco para NC e NL foram avaliados pela urina de 24 horas. Resultados: foram identificadas mutações no PHEX em 41 pacientes (87,2%). A avaliação óssea foi realizada em 38 pacientes com XLHR que foram comparados a controles saudáveis. Os pacientes tiveram maior DMOa em L1-L4 (p=0,03) e menor DMOa em 1/3 distal do rádio (p < 0,01). Em rádio distal, a DMOv total (Total.vBMD) e os componentes trabecular (Tb.vBMD) e cortical (Ct.vBMD) foram semelhantes entre os grupos. Na tíbia distal, os pacientes apresentaram menor Total.vBMD em relação aos controles devido ao déficit no Tb.vBMD (p < 0,01). Além do mais, ao separarmos por status metabólico, os pacientes descompensados tiveram menor Ct.vBMD em tíbia distal comparados aos controles (p=0,02). Quanto aos parâmetros estruturais, em rádio distal, os pacientes apresentaram menor número de trabéculas (Tb.N; p=0,01), maior espessura trabecular...

Background: FGF23-mediated hypophosphatemic rickets is a group of diseases characterized by a pathological increase of FGF23 serum levels, resulting in hyperphosphaturia and hypophosphatemia. In this group, the most common form of inheritance is the X-linked dominant (XLHR) caused by inactivating mutations in the PHEX gene. Aims: to identify the molecular basis; to evaluate the bone mineral density and bone microarchitecture; to determinate the prevalence of nephrocalcinosis (NC), nephrolithiasis (NL) and their related metabolic factors in 47 patients with FGF23-mediated hypophosphatemic rickets (16 children and 31 adults). Methods: PHEX and FGF23 were analyzed by conventional Sanger sequencing and MLPA. The areal BMD (aBMD) was evaluated by dual-energy x-ray absorptiometry (DXA), while the volumetric BMD (vBMD) and the bone microarchitecture were analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT). NC was investigated by renal ultrasonography (US) and computed tomography (CT) and classified using a 0-3 scale (0= no NC and 3= severe NC). The presence of NL was determined by renal CT. Risk factors for NC and NL were evaluated by 24-hour urinary samples. Results: 41 patients (87.2%) presented mutations in PHEX. The bone analysis was made in 38 XLHR patients compared to healthy controls. XLHR patients presented higher aBMD at L1-L4 (p=0.03) and lower aBMD at the distal third of the radius (p < 0.01). At the distal radius, HR-pQCT showed no differences in the vBMD neither in its trabecular (Tb.vBMD) and cortical (Ct.vBMD) components. At the distal tibia, the XLHR patients showed lower Total.vBMD (p < 0.01) compared to controls due to decreased Tb.vBMD (p < 0.01). Moreover, after XLHR patients were sorted by metabolic status, the noncompensated ones revealed lower Ct.vBMD at the distal tibia compared to their respective controls (p=0.02). Regarding to the microarchitectural parameters, at the distal radius, XLHR...

Tumor-induced osteomalacia: the importance of early diagnosis / Osteomalácia induzida por tumor: a importância do diagnóstico precoce

Tumor-induced osteomalacia is a rare paraneoplasic syndromethat can be completely cured with the removal of the culprittumor. This study described the clinical history of a patientaffected by tumor-induced osteomalacia. The patient was a57-year-old female who sought hospital due to intense andprogressive pain in the lower limbs and muscle weakness, aswell diffuse osteoporosis and a variety of pathologic fracturesat radiographs. Laboratory tests revealed hypophosphatemiawith hyperphosphaturia and raised the hypothesis of tumorinducedosteomalacia. Whole-body technetium-99m octreotidescintigraphy revealed the presence of a focal area of radiotraceruptake in the medial region of the left tarsus. After tumorexcision, there was a rapid correction of serum phosphorus,reduction of musculoskeletal complaints and evidence of bonehealing. Despite the diagnosis and treatment, the patient hadan unfavorable clinical outcome; she developed sepsis frompulmonary focus, evolving into refractory septic shock anddeath. We stress the need for greater recognition of tumorinducedosteomalacia as a cause of clinical bone pain, fractures,osteopenia and muscle weakness, superimposed on thecharacteristic biochemical profile with hypophosphatemia andrelative hyperphosphaturia. Greater awareness of the disease willallow earlier diagnosis and ultimately a greater curative potentialfor patients afflicted with this syndrome.(AU)

Osteomalácia induzida por tumor é uma síndrome paraneoplásicarara que pode ser curada completamente com a ressecção dotumor causador. Este estudo descreveu a história clínica de umapaciente afetada pela osteomalácia induzida por tumor. Paciente,de 57 anos, deu entrada no hospital por dor em membros inferiores,e fraqueza muscular intensa e progressiva, assim comoosteoporose difusa e fraturas patológicas. Exames laboratoriaisevidenciaram hipofosfatemia com hiperfosfatúria e levantarama hipótese de osteomalácia induzida por tumor. Cintilografia detodo corpo com tecnécio-99m revelou a presença de área focalde captação do radiofármaco na região medial do tardo esquerdo.Após a ressecção do tumor, houve rápida correção do fósforosérico, redução das queixas musculoesqueléticas e evidência decalo ósseo. Apesar de diagnóstico e tratamento, a paciente apresentouum desfecho clínico desfavorável, desenvolvendo sepsede foco pulmonar, choque séptico e evoluindo a óbito. Nós enfatizamosa necessidade de maior reconhecimento da osteomaláciainduzida por tumor como causa de dor óssea, fraturas patológicas,osteopenia e fraqueza muscular, superpostos a um perfilbioquímico característico, com hipofosfatemia e hiperfosfatúriarelativa. Maior alerta sobre a doença permitirá um diagnósticomais precoce e maior potencial curativo aos pacientes afetadospor essa síndrome.(AU)

Fracturas en una mujer con mialgias difusas e hipocaliemias graves / Fractures in a woman with severe diffuse myalgias and hypokalemia

Resumen El déficit en la mineralización ósea caracteriza al raquitismo y a la osteomalacia, las cuales pueden ser secundarias a deficiencias de calcio o de vitamina D principalmente. La osteomalacia genera síntomas inespecíficos e insidiosos, usualmente minimizados, y puede confundirse con otras condiciones médicas. La densitometría ósea no diferencia entre osteoporosis y osteomalacia, por lo cual corresponde al clínico hacer una evaluación juiciosa de los síntomas, factores de riesgo, antecedentes, alteraciones de laboratorio y hallazgos radiológicos para tratar de descartar la presencia aislada o simultánea de osteomalacia. La exclusión de osteomalacia tiene importantes repercusiones terapéuticas y pronósticas. Presentamos el caso de una paciente con osteomalacia con varias fracturas espontáneas, pseudofracturas de Looser-Milkman, deformidades angulares en rodillas, mialgias difusas y antecedente de acidosis tubular renal, hipocaliemias graves y sordera neurosensorial, la cual venía rotulada y tratada erróneamente como osteoporosis. (Acta Med Colomb 2013; 38: 255-257).

Abstract The deficit in bone mineralization characterizes rickets and osteomalacia, which may be secondary to deficiencies of calcium or mainly of vitamin D. Osteomalacia generates unspecific and insidious symptoms, usually minimized , and can be confused with other medical conditions. Bone densitometry does not differentiate between osteoporosis and osteomalacia, so it is up to the clinician to make a wise assessment of symptoms, risk factors, history, laboratory abnormalities and radiographic findings to try to rule out the presence of isolated or simultaneous osteomalacia. The exclusion of osteomalacia has important therapeutic and prognostic implications. We report the case of a patient with osteomalacia with multiple spontaneous fractures, Looser-Milkman pseudo-fractures, angular deformities in knees, diffuse myalgias, and history of renal tubular acidosis, severe hipokalemias and sensorineural deafness, which had been wrongly labeled and treated as osteoporosis. (Acta Med Colomb 2013; 38: 255-257).

Tumor mesenquimatoso fosfatúrico de fosa nasal con compromiso intracraneano: reporte de un caso y revisión de la literatura / Nasal fossa phosphaturic mesenchymal tumor with intracraneal compromise: case report and review of the literature

El tumor mesenquimatoso fosfatúrico (TMF) es una enfermedad extremadamente rara. Según evidencia reciente es causado por la sobreexpresión del factor de crecimiento fibroblástico 23 (FGF23), el cual genera hipofosfemia y osteomalacia. A continuación presentamos el caso de un paciente de 42 años con un tumor mesenquimatoso fosfatúrico de fosa nasal izquierda con extenso compromiso intracraneano. Cabe destacar que hasta la fecha hay 142 casos reportados de TMF en la literatura de los cuales solo 11 se ubican en fosa nasaly cavidades sinusales, y sólo dos de ellos ubicados en fosa nasal¹. El paciente tuvo una exitosa resolución quirúrgica con la consecuente normalización de parámetros analíticos (incluido el FGF23), mejoría sintomática y ausenia de recidiva hasta la fecha.

The phosphaturic mesenchymal tumor (PMT) is an extremely rare disease. According to recent evidence is caused by overexpression of fibroblast growth factor 23 (FGF23) which generates hypophosphatemia and osteomalacia. We report the case of a 42 year old patient with a left nasal fossa phosphaturic mesenchymal tumor with intracranial involvement. Should be noted that to date there are 142 reported cases of PMT in the literature of which only 11 are located in nasal fossa and sinus cavities, two of them located in nasal fossa¹. The patient had a successful surgical resolution with consequent normalization of analytical parameters (including FGF23), absence of symptoms and no recurrence to date.

Osteodistrofia hepática / Hepatic osteodystrophy

Osteodistrofia hepática é distúrbio de mineralização óssea associada à doença hepática crônica, sendo a osteoporose, e mais raramente a osteomalácia, sua forma de apresentação clínica. Apesar de pouco diagnosticada e com prevalência de grande variação na literatura, na maioria das vezes, apresenta-se de forma assintomática e, quando não identificada, aumenta consideravelmente o risco de fratura e sequelas permanentes. Seu diagnóstico, portanto, requer alta suspeição e faz-se, na prática clínica, por meio da avaliação da densitometria óssea. De fisiopatogenia multifatorial, envolve fatores genético, ambiental e do próprio estado clínico-nutricional do paciente. Uma atenção maior deve ser despendida a hepatopatas desnutridos, com cirrose hepática avançada, doença colestática crônica e transplantados pelo maior risco de desmineralização óssea. Nesta revisão, será discorrido sobre o metabolismo fisiológico da síntese óssea e a fisiopatologia do distúrbio de mineralização óssea, desde mecanismos fisiopatogênicos na doença hepática crônica, seu diagnóstico e revisão da terapêutica atual empregada.

Hepatic osteodystrophy is a disorder of bone mineralization associated to liver disease, clinically manifested by osteoporosis and more rarely osteomalacia. Although seldomly diagnosed and varying greatly in literature, most of the time, it presents asymptomatically and, when it is not recognized, it enhances considerably the risk of fracture and permanent sequelae. Indeed it requires a high grade of suspicion and it is confirmed by means of bone densitometry evaluation in clinical practice. Presenting with a multifactorial physiopathology, it involves factors, such as genetical, environmental, and patient clinical-nutritional status. A greater attention must be spent on patients with liver disease, especially those malnourished, with advanced cirrhosis, chronic cholestatic disease, and transplanted, because of a higher risk of bone demineralization. In this data, it will be reviewed the bone synthesis metabolism and the physiopathology of bone mineralization disorder ? since fisiopatogenic mechanisms in chronic liver disease, diagnosis and recent therapeutic review employed.

Osteodistrofia hepática / Hepatic osteodystrophy

Osteodistrofia hepática é distúrbio de mineralização óssea associada à doença hepática crônica, sendo a osteoporose, e mais raramente, a osteomalácia, sua forma de apresentação clínica. Apesar de pouco diagnosticada e prevalência com grande variação na literatura, na maioria das vezes, apresenta-se de forma assintomática e, quando não identificada, aumenta consideravelmente o risco de fratura e sequelas permanentes. Seu diagnóstico, portanto, requer alta suspeição e faz-se, na prática clínica, por meio da avaliação da densitometria óssea. De fisiopatogenia multifatorial, envolve fatores genético, ambiental e do próprio estado clínico-nutricional do paciente. Uma atenção maior deve ser despendida a hepatopatas desnutridos, com cirrose hepática avançada, doença colestática crônica e transplantados pelo maior risco de desmineralização óssea. Nesta revisão, será discorrido sobre o metabolismo fisiológico da síntese óssea e a fisiopatologia do distúrbio de mineralização óssea, desde mecanismos fisiopatogênicos na doença hepática crônica, seu diagnóstico e revisão da terapêutica atual empregada.

Hepatic osteodystrophy is a disorder of bone mineralization associated to liver disease, clinically manifested by osteoporosis and more rarely osteomalacia. Although seldomly diagnosed and varying greatly in literature, most of the time, it presents asymptomatically and, when it is not recognized, it enhances considerably the risk of fracture and permanent sequelae. Indeed it requires a high grade of suspicion and it is confirmed by means of bone densitometry evaluation in clinical practice. Presenting with a multifactorial physiopathology, it involves factors, such as genetical, environmental, and patient clinical-nutritional status. A greater attention must be spent on patients with liver disease, especially those malnourished, with advanced cirrhosis, chronic cholestatic disease, and transplanted, because of a higher risk of bone demineralization. In this data, it will be reviewed the bone synthesis metabolism and the physiopathology of bone mineralization disorder - since fisiopatogenic mechanisms in chronic liver disease, diagnosis and recent therapeutic review employed.

Osteomalacia inducida por tumor / Tumor-induced osteomalacia

La osteomalacia inducida por tumor es un síndrome paraneoplásico secundario en la mayoría de los casos a tumores de origen mesenquimal. Se caracteriza por pérdida aumentada de fosfato a nivel urinario por el efecto inhibidor que ejerce el factor de crecimiento fibroblástico 23 sobre el transporte de fósforo en el túbulo renal proximal. Debe sospecharse en un paciente con debilidad y dolor osteomuscular generalizado que se presente con hipofosfatemia, normocalcemia, fosfatasa alcalina elevada y niveles de 25 hidroxivitamina D y PTH normales. El tratamiento definitivo de la enfermedad es la resección quirúrgica del tumor. Cuando se desconozca la neoplasia primaria o no sea posible el tratamiento quirúrgico debe iniciarse reposición de fósforo y calcitriol. En este artículo se presenta el primer caso de una paciente con osteomalacia inducida por tumor asociada a un carcinoma lobulillar infiltrante de seno.

The tumor-induced osteomalacia is a paraneoplastic syndrome secondary in most cases to tumors of mesenchymal origin. It is characterized by increased lost of urinary phosphate by the inhibitory effect exerted by the fibroblast growth factor 23 on phosphorus transport in the proximal renal tubule. Should be suspected in a patient with weakness and generalized muscle in addition to hypophosphatemia, normocalcemia, elevated alkaline phosphatase and normal serum 25-hydroxyvitamin D and PTH. The definitive treatment of the disease is surgical resection of the tumor. When the primary tumor is unknown or is not possible the surgical treatment should be initiated replacement of phosphorus and calcitriol. This paper presents the first case of a patient with tumor-induced osteomalacia associated with lobular breast cancer.

Efectos de la cirugía bariátrica sobre el metabolismo óseo / Effects of bariatric surgery on bone health

There is concern about the long term complications of bariatric surgery and among these, the derangements in bone metabolism that could increase the risk of osteopororosis. Most studies show an elevated bone turnover in operated patients with loss of bone mass, that are partially explained by the development of a secondary hyperparathyroidism. We have shown that, among postmenopausal women, bone resorption remains elevated, even five years after the operation, although not associated to loss of bone mass. The pathophysiology of these alterations is complex and includes an reduction in mechanical load and calcium absorption and postoperative changes in signaling hormones that have an effect on bone, coming from adipose tissue (estrogens, leptin and adiponectin), liver (insulin like growth factor-1), pancreas (insulin and amylin) or the bowel (ghrelin, glucagon-like peptide 2, peptide YY, gastric inhibitory polypeptide). Available evidence suggest that bariatric surgery should be considered a risk factor for osteoporosis. We recommend the incorporation of bone health in pre operative evaluation. We also give suggestions to prevent the adverse effects of bariatric surgery on bone health.

Osteomalacia hipofosfatémica secundaria a sarcoma de muslo: caso clínico / Hypophosphatemic osteomalacia secondary to a sarcoma: report of one case

Tumor induced osteomalacia is uncommon and is characterized by an isolated and not PTH dependent reduction in tubular phosphate reabsorption. This alteration is produced by phosphaturic factors, such as fibroblast growth factor-23 (FGF-23) that are secreted by tumors. We report a 41 years old female presenting with joint pain and progressive loss of muscle strength in the lower limbs. Initial laboratory assessment showed hypophosphatemia, elevated alkaline phosphatases, normal intact parathormone levels, low levels of 25 hydroxy vitamin D and an elevated 24 h phosphaturia. Bone mineral density showed spine and femoral neck osteopenia. A positron emission tomography (PET) revealed a right thigh tumor with lung metastases. Its biopsy disclosed a fibrosarcoma. FGF-23 levels, measured by ELISA were markedly elevated. The patient was discharged with palliative measures.