Pancreatitis aguda en el escenario de hipercalcemia por hiperparatiroidismo primario / Acute pancreatitis in the setting of hypercalcemia due to primary hyperparathyroidism

Introducción: describir el caso de un paciente con pancreatitis aguda secundaria a hipercalcemia por hiperparatiroidismo prImario. Esta es una causa poco frecuente de pancreatitis, asociada a morbimortalidad significativa en caso de no ser diagnosticada oportunamente Caso clínico: un hombre de 44 años, con antecedente de pancreatitis de presunto origen biliar que había requerido previamente colecistectomía, consultó por dolor abdominal y náuseas. Los estudios complementarios fueron compatibles con un nuevo episodio de pancreatitis aguda. Presentaba hipercalcemia y hormona paratiroidea (PTH) elevada, configurando hiperparatiroidismo primario. La gammagrafía informó hallazgos compatibles con adenoma paratiroideo. Se inició tratamiento con reanimación hídrica y analgesia con adecuada disminución de calcio sérico y resolución de dolor abdominal. Después de la paratiroidectomía se logró normalizar los niveles de calcio y PTH. Discusión: la pancreatitis aguda es una condición potencialmente fatal, por lo que la sospecha de causas poco frecuentes como la hipercalcemia debe tenerse en cuenta. El tratamiento de la hipercalcemia por adenoma paratiroideo se basa en reanimación hídrica adecuada y manejo quirúrgico del adenoma, con el fin de evitar recurrencia de pancreatitis y mortalidad. (AU)

Introduction: we describe the case of a patient with acute pancreatitis secondary to hypercalcemia due to primary hyperparathyroidism. This is a rare cause of pancreatitis associated with significant morbidity and mortality if not diagnosed in time. Clinical case: a 44-year-old man with a history of pancreatitis of presumed biliary origin, which had previously required cholecystectomy, consulted for abdominal pain and nausea. The laboratory findings were compatible with a new episode of acute pancreatitis. He presented hypercalcemia and an elevated parathyroid hormone (PTH), configuring primary hyperparathyroidism. Scintigraphy was performed, yielding findings compatible with parathyroid adenoma. Treatment with fluid resuscitation and analgesia was started, resulting in an adequate decrease in serum calcium and resolution of abdominal pain. After parathyroidectomy, calcium and PTH levels were normalized. Discussion: acute pancreatitis is a potentially fatal condition; therefore the suspicion of rare causes, such as hypercalcemia, should be considered. The treatment of hypercalcemia due to parathyroid adenoma is based on adequate fluid resuscitation and surgical management of the adenoma, to avoid recurrence of pancreatitis and death. (AU)

Crisis hipercalcémica, presentación inusual de adenoma paratiroideo: reporte de 2 casos / Hypercalcemic crisis, unusual presentation of parathyroid adenoma

La crisis hipercalcémica (CH) es una emergencia endocrina inusual, definida por la presencia de calcemia > 14 mg/dl asociada a disfunción renal, alteraciones cardiovasculares, gastrointestinales y del sensorio; también podría considerarse en pacientes con síntomas graves y calcemia menor. El hiperparatiroidismo primario (HPTP) y las neoplasias malignas son las etiologías más comunes de la hipercalcemia (90% de los casos); sin embargo, rara vez el primero se presenta como CH. Debido a la alta mortalidad asociada a esta entidad, es de gran importancia establecer diagnóstico y tratamiento precoces. Presentamos dos pacientes con crisis hipercalcémica como primera manifestación del HPTP, el 1.° con bloqueo auriculoventricular (AV) completo y el 2.° con pancreatitis aguda. La anatomía patológica (AP) reveló adenoma oxifílico en ambos casos, que es una variante histológica poco frecuente y puede manifestarse clínicamente de forma grave. Conclusiones: los adenomas paratiroideos son causa poco frecuente de CH. Consideramos el tipo histológico observado (adenoma oxifílico) como probable factor condicionante. La pancreatitis y especialmente el bloqueo AV son manifestaciones poco frecuentes de la CH. Resaltamos la importancia de la determinación de los niveles de calcio dentro de la evaluación inicial de todo paciente con bloqueo AV. (AU)

Hypercalcemic crisis (HC) is an unusual endocrine emergency, defined as the presence of serum calcium > 14 mg/dl related to kidney dysfunction, cardiovascular, gastrointestinal and sensory disturbances. It could also be considered in patients with severe symptoms and lower serum calcium levels. Primary hyperparathyroidism (PHPT) and malignant neoplasms are the most common hypercalcemia etiologies (90% of cases), nevertheless, the former hardly ever occurs as HC. Due to the high mortality associated with HC, it is crucial to establish early diagnosis and treatment.We report two patients with HC as the first manifestation of PHPT; the former with atrioventricular (AV) block and the latter with acute pancreatitis. Pathology revealed oxyphilic adenoma in both cases, which is an infrequent histological variant that can have a severe clinical manifestation. Conclusions: parathyroid adenomas are a rare cause of HC. We consider the histological type observed (oxyphilic adenoma) as a probable conditioning factor. Pancreatitis and especially AV block are rare manifestations of HC. We emphasize the importance of determining calcium levels in the initial evaluation of all patients with AV block. (AU)

Denosumab can be used successfully as a bridge to surgery in patients with severe hypercalcemia due to primary hyperparathyroidism

SUMMARY Severe hypercalcemia is a medical emergency that requires immediate and aggressive management. Primary hyperparathyroidism (PHPT) often causes severe hypercalcemia. Volume resuscitation, parenteral salmon calcitonin, and administration of intravenous bisphosphonates are common measures used to stabilize patients. However, the use of these measures is inadequate in several patients and may even be contraindicated in individuals with renal insufficiency or severe systemic illness. This study demonstrated the efficacy and safety of denosumab in patients with severe hypercalcemia due to PHPT, when immediate surgery was not feasible. We present four patients with severe hypercalcemia due to PHPT. Immediate surgery was not feasible because the patients had severe systemic illness, such as seizures and altered sensorium (case 1); acute severe pancreatitis (cases 2 and 3); or coronavirus disease 2019 pneumonia (case 4). Intravenous normal saline and parenteral salmon calcitonin were inadequate for controlling hypercalcemia. Intravenous bisphosphonates were avoided because of severe systemic illness in all cases and impaired renal function in three cases. Denosumab was administered to control hypercalcemia and allow the stabilization of patients for definitive surgical management. Following denosumab administration, serum calcium levels normalized, and general condition improved in all patients. Three patients underwent parathyroidectomy after two weeks and another patient after eight weeks. The use of denosumab for the management of severe hypercalcemia due to PHPT is efficacious and safe in patients when immediate surgical management is not feasible due to severe systemic illness.

Tumor pardo del paladar, presentación atípica de hiperparatiroidismo primario en adolescente: buena evolución y normalización de la masa ósea tras paratiroidectomía / Brown tumor of the palate, atypical presentation of primary hyperparathyroidism in an adolescent: good evolution and bone mass normalization after parathyroidectomy

El hiperparatiroidismo primario (HPTP) es poco frecuente en niños y adolescentes. Hay escasos datos para el manejo de estos pacientes en pediatría. Las glándulas paratiroideas son glándulas endocrinas que secretan hormona paratiroidea (PTH) y regulan el metabolismo del calcio y del fósforo. La sobreexpresión de PTH se llama hiperparatiroidismo, que se clasifica en primario, secundario y terciario. En los adolescentes, 80 a 92% de los hiperparatiroidismos primarios se deben a adenoma paratiroideo. Presentamos el caso clínico de una adolescente con una primera manifestación atípica de HPTP, la presencia de un tumor pardo del paladar, presentación rara de adenoma paratiroideo, acompañado de hipercalcemia, marcada elevación de PTH y varias lesiones óseas. (AU)

Primary hyperparathyroidism (PHPT) in children and adolescents is uncommon. Guidelines for management in pediatric patients are limited. Parathyroid glands are endocrine glands that secrete parathyroid hormone (PTH) and regulate calciumphosphate metabolism. The overexpression of PTH is called hyperparathyroidism, and is classified as primary, secondary, and tertiary. In adolescents, 80 to 92% of PHPT cases are due to a parathyroid adenoma. We present here a case report of an adolescent with a brown tumor of the palate as the first manifestation of the disease, atypical and rare presentation of parathyroid adenoma in an adolescent. She had hypercalcemia, marked elevation of PTH and bone lesions. (AU)

Hiperparatiroidismo primario por carcinoma paratiroideo: caso problema y revisión / Primary hyperparathyroidism by parathyroid cancer: case report and review

El carcinoma paratiroideo (CP) es una neoplasia maligna con una incidencia de 0,015 cada 100.000 habitantes por año. Representa el 1% de los diagnósticos de hiperparatiroidismo primario y se manifiesta entre la 4.a y 5.a década de la vida, con una incidencia similar entre hombres y mujeres. La etiología del CP es incierta, ha sido asociada a formas esporádicas o familiares. Está caracterizado por altos niveles séricos de calcio y PTH y el desafío clínico-quirúrgico es el diagnóstico diferencial con otras entidades benignas como el adenoma o la hiperplasia de paratiroides. Aunque el diagnóstico de certeza es anatomopatológico, la sospecha clínica y el uso de métodos de baja complejidad (ecografía) con operadores avezados permite una correcta localización y abordaje pertinente del paciente para dirigir el tratamiento quirúrgico adecuado (resección en bloque) evitando persistencias y recurrencias de enfermedad. Se presenta el caso clínico de un paciente masculino que ingresa por síndrome de impregnación asociado a hipercalcemia, su abordaje diagnóstico, tratamiento y manejo interdisciplinario con discusión y revisión bibliográfica. (AU)

Parathyroid carcinoma (CP) is a malignant disease with an incidence of 0.015 per 100,000 inhabitants per year. It accounts for 1% of primary hyperparathyroidism diagnoses and occurs between the 4th and 5th decade of life, with a similar incidence between men and women. The etiology of CP is uncertain and has been associated with sporadic or family forms. CP is characterized by high serum calcium and PTH levels and the clinical-surgical challenge is the differential diagnosis with other benign entities such as parathyroid adenoma or hyperplasia. Although the diagnosis of certainty is achieved by pathological anatomy examination, the clinical suspicion and the use of low complexity methods (ultrasound) by experienced operators allows a correct localization and a patient-specific approach to direct the appropriate surgical treatment (block resection), avoiding persistence and recurrences of disease. The clinical case of a male patient admitted for severe hypercalcemia with multiple organ disfunction, the diagnostic approaches, treatment, and interdisciplinary management, together with review and discussion of the current literature are presented. (AU)

Preeclampsia as an inaugural manifestation of primary hyperparathyroidism: A case report / Pré-eclâmpsia como manifestação inaugural de hiperparatiroidismo primário: Um caso clínico

Abstract Primary hyperparathyroidism is an endocrine disorder characterized by hypercalcemia and elevated or inappropriately normal levels of parathyroid hormone. The diagnosis is based on a biochemical evaluation, and a neck ultrasound is the first choice during pregnancy to access the parathyroid glands. Manifestations during pregnancy are rare and can be present with life-threatening complications, so the diagnosis is challenging. The conservative treatment is limited, and there is not enough data about its safety and efficacy during pregnancy. Surgery is the only curative treatment, and a parathyroidectomy performed during the second or third trimesters is considered safe. Recently, some authors suggested an association between primary hyperparathyroidism and preeclampsia. We describe a case of preeclampsia with severe features at 27 weeks of gestational age. The severity of the preeclampsiamotivated an early termination of the pregnancy by cesarean section. During the postpartum period, the patient presented life-threatening complications, such as severe hypercalcemia and acute pancreatitis. An ultrasound exam found two parathyroid nodules, suggestive of parathyroid adenomas. The patient recovered after the pharmacological correction of the calcemia levels.

Resumo O hiperparatiroidismo primário é umdistúrbio endócrino caraterizado pela elevação do cálcio sérico associada a níveis de paratormona elevados ou inapropriadamente normais. O diagnóstico é baseado em análises bioquímicas, e, na gravidez, o exame de imagem de primeira linha é a ecografia cervical. É uma doença rara na gravidez, e pode se apresentar com complicações ameaçadoras de vida, pelo que o seu diagnóstico é desafiante. O tratamento médico disponível é limitado, havendo poucos dados relativos à sua eficácia e segurança na gravidez. A cirurgia é o único tratamento curativo, e pode ser realizada no segundo ou terceiro trimestres. Tem sido descrita uma relação entre hiperparatiroidismo primário e pré-eclâmpsia. Apresenta-se um caso de uma grávida de 27 semanas com pré-eclâmpsia com critérios de gravidade, o que obrigou ao término da gravidez por cesariana. Verificou-se agravamento clínico no período pós-parto, com aparecimento de complicações graves, tais como hipercalcemia grave e pancreatite aguda. Ecograficamente, constataram-se duas massas paratiróideias sugestivas de adenomas da paratiroide. A doente recebeu tratamento médico, e teve melhora apenas após a correção dos níveis de cálcio sérico.

Hiperparatiroidismo primario por adenoma con gammagrafía negativa / Primary hyperparathyroidism due to negative scintigraphy adenoma

Introducción: El hiperparatiroidismo es una de las causas más frecuente de hipercalcemia. El 85 por ciento de los pacientes son mayores de treinta años, su frecuencia más alta se encuentra por encima de 60 años, a largo plazo puede producir una serie de complicaciones. Objetivo: Describir el caso clínico de hiperparatiroidismo primario que resultó negativa al estudio de gammagrafía con localización ectópica del adenoma. Caso Clínico: Paciente femenina de 20 años con antecedentes de litiasis renal y uretral de 7 años de evolución, la cual se sometió a 13 sesiones de litotricia y dos cirugías renales con recidivas, hace 6 meses se detectó cifras elevadas de calcio. Se realiza protocolo de estudio de hipercalcemia determinándose hiperparatiroidismo primario, ultrasonido y tomografía de cuello reportan lesión que podría corresponder a un adenoma paratiroideo paratraqueal; sin embargo, la gammagrafía con metoxi-isobutilisonitrilo y tecnecio 99 fue negativa. Se realizó cirugía de cuello convencional ya que la cirugía radioguiada no fue útil para la localización del adenoma paratiroideo intraoperatorio. Estudio histopatológico reportó adenoma paratiroideo. Conclusiones: En adenomas paratiroideo con gammagrafía negativa se puede hacer el diagnostico con estudios de imagen convencional. La localización ectópica del adenoma paratiroideo constituye una causa de gammagrafía negativa. La cirugía radioguiada no es útil en los adenomas paratiroides ectópicos con gammagrafía negativa(AU)

Introduction: Hyperparathyroidism is one of the most frequent causes of hypercalcemia. 85 percent of patients are older than thirty years, its highest frequency is over 60 years, in the long term it can produce a series of complications. Objective: To describe a clinical case of primary hyperparathyroidism that was negative in the scintigraphy study with ectopic location of the adenoma. Clinical case report: A 20-year-old female patient with a 7-year history of renal and urethral lithiasis, who had undergone 13 lithotripsy sessions and two recurrent kidney surgeries. Six months ago, elevated calcium levels were detected. A study protocol for hypercalcemia was carried out, determining primary hyperparathyroidism. Ultrasound and neck tomography report a lesion that could correspond to a paratracheal parathyroid adenoma; however, methoxy-isobutylisonitrile and technetium-99 scintigraphy was negative. Conventional neck surgery was performed since radioguided surgery was not useful for locating the intraoperative parathyroid adenoma. Histopathological study reported parathyroid adenoma. Conclusions: In parathyroid adenomas with negative scintigraphy, the diagnosis can be reached with conventional imaging studies. The ectopic location of the parathyroid adenoma is a cause of negative scintigraphy. Radioguided surgery is not helpful in scan-negative ectopic parathyroid adenomas(AU)

Primary hyperparathyroidism in developing world: a systematic review on the changing clinical profile of the disease

ABSTRACT While the developed world is focusing on laying guidelines for selecting out cases of Asymptomatic primary hyperparathyroidism (PHPT) for surgical intervention and promoting minimal access surgery, the developing world is observing a change in disease spectrum from advanced symptomatic to lesser degree of symptomatic disease and not many with associated Vitamin D deficiency. Few studies from the developing countries of the world have focused on the changing clinical spectrum of PHPT. Objective of this study is to review the changing profile of PHPT in developing world. A systematic literature search was done in December 2017 focussing on publications from the developing world. All studies pertaining to the epidemiology of PHPT published after 1st January 2000 and published in English language were included for analysis. Most of the studies published from developing countries report a predominance of symptomatic disease (79.6% of all included patients) with musculoskeletal disease present in the majority of patients (52.9%). The combined mean serum total calcium (11.9 ± 1.4 mg/dL), serum PTH (668.6 ± 539 pg/mL), serum alkaline phoshpatase (619 ± 826.9 IU/L) and weight of excised parathyroid glands (4.4 ± 3.8 grams) are much higher than those reported from the western studies. Despite this, we found that there is a distinct trend towards a milder form of disease presentation and biochemical profile noticeable in more recent times. Although there is a striking difference in all aspects of PHPT disease epidemiology, clinical presentation and biochemical profile of developing and developed countries, there is a distinct trend towards a milder form of disease presentation and biochemical profile in more recent times.

Utilidad de la 18f-colina pet/tc en hiperparatiroidismo primario persistente o recurrente: experiencia inicial / Usefulness of 18f-choline pet / tc in persistent or recurrent primary hyperparathyroidism: initial experience

El hiperparatiroidismo persistente/recurrente representa un desafío en la localización del tejido paratiroideo hiperfuncionante. En esta subpoblación, los métodos convencionales ofrecen un menor rédito diagnóstico. La 18F-colina PET/TC podría ser una buena alternativa dada su mejor resolución espacial, capacidad de detectar glándulas ectópicas y la conjunción de la imagen molecular y anatómica. Sin embargo, la evidencia en este subgrupo de pacientes es escasa. Objetivo: evaluar la utilidad de la 18F-colina PET/TC como método de localización en el hiperparatiroidismo persistente o recurrente. Materiales y métodos: se analizaron los pacientes con 18F-colina PET/TC para hiperparatiroidismo entre diciembre de 2015 y enero de 2018 en un centro terciario de alto volumen. Se analizaron el número de lesiones, su localización, tamaño y el Standard Uptake Value máximo (SUV max) en las imágenes tempranas y tardías. Se compararon los resultados con los métodos convencionales. Resultados: 7 de 15 pacientes habían sido operados previamente (persistentes/recurrentes). La 18F-colina PET/TC detectó 6/7 casos (83,33%), la ecografía cervical 1/4 (25%) y el SPECT de paratiroides y la resonancia nuclear magnética 2/5 (40%). El SUV max obtenido fue variable, en la mitad de los casos a los 10 minutos y en los restantes a la hora; el tamaño promedio de las lesiones fue 8,61 mm (6-12 mm). Conclusiones: la 18F-colina PET/TC muestra una alta tasa de detección en los pacientes con hiperparatiroidismo persistente/recurrente. La combinación del comportamiento biológico del PET con los hallazgos morfológicos aportados por la TC con contraste endovenoso le ofrecería ventajas sobre otros estudios que podrían posicionarlo como método de primera línea en esta subpoblación. (AU)

Persistent or recurrent hyperparathyroidism represents a challenge regarding the localization of the hyper-functioning parathyroid tissue. In this subpopulation of hyperpharathyroid patients, conventional methods have a low diagnostic yield. The 18F-choline PET /CT could be a good alternative given its better spatial resolution, ability to detect ectopic glands, and the conjunction of the molecular and anatomical image. However, the evidence in this subgroup of patients is limited. Objective: to evaluate the utility of 18F-choline PET/ CT as a localization method in persistent or recurrent hyperparathyroidism. Materials and methods: patients with 18F-choline PET / CT for hyperparathyroidism between December 2015 and January 2018 in a high-volume tertiary center were included. The number of lesions, and their location, size, and maximum Standard Uptake Value (SUV) in the early and late images were analyzed. The results were compared to conventional methods. Results: 7 of 15 patients had been previously operated (persistent/recurrent). 18F-choline PET / CT detected 6/7 cases (83,33%), cervical ultrasound 1/4 (25%) and parathyroid SPECT and magnetic resonance 2/5 (40%). The maximum SUV was variable, one half at 10 minutes and the other half at 60 minutes; the average size of the lesions was 8.61 mm (6-12 mm). Conclusions: 18F-Choline PET / CT shows a high detection rate in patients with persistent / recurrent hyperparathyroidism. The combination of the biological behavior of PET with the morphological findings provided by CT with intravenous contrast would offer advantages over other studies that could position it as a first line method in this subpopulation. (AU)

Crisis hipercalcémica causada por adenoma paratiroideo: reporte de un caso clínico / Hypercalcemic crisis due to parathyroid adenoma: report of a clinical case

La hipercalcemia es un trastorno común que representa aproximadamente el 0,6% de todas las admisiones médicas agudas. El hiperparatiroidismo primario (HPTP) y las neoplasias malignas son las dos causas más comunes de elevación de los niveles séricos de calcio; constituyen, en conjunto, alrededor del 90% de todos los casos. La presentación sintomática clásica de la hipercalcemia se observa con relativa poca frecuencia en el mundo desarrollado; la presentación más común es la detección asintomática en las pruebas bioquímicas. Sin embargo, en casos raros, el HPTP puede desarrollar hipercalcemia aguda, grave y sintomática, llamada crisis hipercalcémica (CH). Esta condición se asocia a alteraciones profundas en el estado mental y las funciones cardíaca, renal y gastrointestinal en presencia de concentraciones marcadamente elevadas de calcio sérico y paratohormona (PTH). Mientras que algunas elevaciones en el calcio sérico pueden ser bien toleradas, los síntomas de la CH son severos. Si el tratamiento se retrasa, la CH puede provocar la muerte. Describimos el caso de un paciente masculino que ingresa en la unidad de cuidados críticos por una CH secundaria a un HPTP por adenoma paratiroideo. (AU)

Hypercalcaemia is a most common disorder, accounting for approximately 0,6% of all acute medical admissions. Primary hyperparathyroidism (PHPT) and malignancy are the two most common causes of increased serum calcium levels, together accounting for about 90% of all cases. The classical symptomatic presentation of hypercalcaemia is seen relatively rarely in the developed world, the most common presentation being asymptomatic and detected following on biochemical testing. However, in rare cases HPTP can result in acute, severe and symptomatic hypercalcemia, called hypercalcemic crisis (HC). This condition is associated with profound disturbances in mental status, and cardiac, renal, and gastrointestinal function in the presence of markedly increased serum calcium and parathyroid hormone (PTH) concentrations. While some elevations in serum calcium can be well tolerated, symptoms of HC are severe. If treatment is delayed, HC can result in death. We describe herein a case of a male patient who was admitted to the intensive care unit as a consequence of HC resulting from elevated PTH, secondary to a parathyroid adenoma. We describe the case of a male patient who was admitted to the critical care unit for a HC mediated by PTH secondary to a parathyroid adenoma. (AU)

Association of primary hyperparathyroidism and humoral hypercalcemia of malignancy in a patient with clear cell renal carcinoma

Hypercalcemia is found frequently in patients with cancer. Besides the etiology related to the malignancy, other causes should be considered in the differential diagnostic, as primary hyperparathyroidism, granulomatous diseases and the use of thiazide diuretics. We present a case report of a severe hypercalcemia due to a rare association and review the relevant literature. A female patient, 57 years old, sent to the Endocrinology Service of Hospital das Clínicas da Universidade do Paraná (SEMPR) in order to investigate severe hypercalcemia with frequent need of hospitalization. The patient was in chemotherapy treatment for recurrence of clear cell renal cancer. During the investigation she presented high level of parathyroid hormone (PTH) and parathyroid scintigraphy suggestive of hyperplasia/ adenoma of parathyroid, histopathological diagnosis was confirmed after parathyroidectomy. After surgery the patient presented undetectable levels of PTH. However, she continued with progressive increase of serum calcium, with no signs of bone metastases or change in vitamin D metabolism. The investigation showed high levels of PTH-related protein (PTHrP), leading us to the diagnosis of hypercalcemia of malignancy. The patient presented severe hypercalcemia due to the rare association of primary hyperparathyroidism and humoral hypercalcemia of malignancy due to secretion of PTHrP by tumor cells. The presence of isolated primary hyperparathyroidism, as a cause of hypercalcemia in cancer patients, has been described in approximately 5-10% of the patients. However, the association of primary hyperparathyroidism and humoral hypercalcemia of malignancy (which means with concomitant elevation of PTH and PTHrP) is rare, only three cases have been described in the literature. Arch Endocrinol Metab. 2015;59(1):84-8.

Brown Tumor of the Patella Caused by Primary Hyperparathyroidism: A Case Report

It has been reported that the common sites of brown tumors are the jaw, pelvis, ribs, femurs and clavicles. We report our experience in a case of brown tumor of the patella caused by primary hyperparathyroidism. An initial radiograph and CT showed an osteolytic lesion and MR images showed a mixed solid and multiloculated cystic tumor in the right patella. One month after the parathyroidectomy, rapid bone formation was observed on both radiographs and CT images.

Tumor pardo multifocal como manifestación del hiperparatiroidismo primario por adenoma paratiroideo asociado a carcinoma papilar de tiroides / Brown tumor of the pelvis associated with hyperparathyroidism

Background: Brown tumors of bones are an uncommon manifestation of hyperparathyroidism. Case report: We report a 35 years old male presenting with pain and paresis of the left superior limb. Part of his humerus was excised due to a diagnosis of a giant cell tumor. He was admitted again to the hospital due to pelvic pain, malaise and constipation. A right cervical nodule was found. Laboratory evaluation confirmed the presence of a hyperparathyroidism. The biopsy of the pelvic lesion disclosed a brown tumor. The patient was subjected to a parathyroidectomy and the pathological study of the surgical piece showed a right parathyroid adenoma and a right thyroid papillary micro carcinoma. In the postoperative period the patient had a hungry bone syndrome, which was adequately treated.

Introducción: La paratohormona es una hormona encargada de la homeostasis del calcio, el hiperparatiroidismo es una patología con manifestaciones renales y óseas, el Tumor Pardo es una rara presentación de esta enfermedad. Caso clínico: Hombre de 35 años con dolor y paresia en extremidad superior izquierda, fue resecado parte del húmero por un diagnóstico de Tumor de Células Gigantes; reingresa con dolor pélvico derecho, malestar general, astenia y estreñimiento. Se descubre un nódulo cervical derecho e hipersensibilidad en la pelvis derecha. Los exámenes de laboratorio muestran hiperparatiroidismo; la biopsia de la lesión pélvica es diagnóstica de Tumor Pardo, encontrándose además una hipercaptación paratiroidea derecha. Operado, el diagnóstico histopatológico fue: Adenoma paratiroideo derecho y un micro carcinoma papilar tiroideo; en el post-operatorio desarrolló un Síndrome de Bone Hunger, el cual fue superado y dado de alta. Discusión y conclusiones: El Tumor Pardo no es una verdadera neoplasia; producido por intensa actividad osteoclástica, tiene características histológicas y radiológicas inespecíficas y su diagnóstico se realiza por datos clínicos y bioquímicos. El hiperparatiroidismo puede llevar a la formación de Tumores Pardos; se sugiere realizar estudios de la glándula tiroides en pacientes con hiperparatiroidismo.

Brown tumors of the femur and pelvis secondary to a parathyroid carcinoma: Report of one case / Tumores pardos de fémur y pelvis secundarios a carcinoma de paratiroides: Informe de un caso

Brown tumors result from excess osteoclast activity and consist of collections of osteoclasts intermixed with fibrous tissue and poorly mineralized woven bone. They are secondary to hyperparathyroidism (HPT). Their incidence is higher in primary than in secondary hyperparathyroidism. We report a 69 years-old male, admitted in a state of confusion, lethargy and bedridden, with a pathological fracture of the femur caused by a brown tumor. The laboratory examination revealed a hypercalcemia (8.85 mEq/L), with high levels of ionized Ca (5.48mEq/L), serum alkaline phosphatases (416 U/L) and serum parathormone (120 pg/mL). Ultrasound examination of the neck showed a large parathyroid tumor, probably corresponding to a carcinoma. A primary HPT was diagnosed. The patient was hydrated and high doses of diuretics and bisphosphonates were administered. After correction of serum calcium and neurologic symptoms, the patient was operated, performing an extensive resection of the tumor. The pathology report confirmed the diagnosis of parathyroid carcinoma.

Los tumores pardos son una consecuencia de una actividad osteoclástica excesiva y consisten en osteoclastos mezclados con tejido fibroso y tejido óseo mal mineralizado. Son secundarios a hiperparatiroidismo y más comunes en hiperparatiroidismo primario. Informamos de un hombre de 69 años que ingresa confuso y letárgico con una fractura patológica del fémur causada por un tumor pardo. El laboratorio mostró hipercalcemia de 8,85 mEq/L, fosfatasas alcalinas de 416 U/L y parathormona de 120 pg/mL. La ecografía del cuello mostró un tumor paratiroideo sospechoso de carcinoma. Se diagnosticó un hiperparatiroidismo primario. El paciente se hidrató y estabilizó con diuréticos y bifosfonatos. Una vez estabilizado, se operó efectuando una extensa resección del tumor. El estudio anatomopatológico confirmó el diagnóstico de cáncer de paratiroides.

Bone disease in primary hyperparathyroidism / Doença óssea no hiperparatiroidismo primário

Bone disease in severe primary hyperparathyroidism (PHPT) is described classically as osteitis fibrosa cystica (OFC). Bone pain, skeletal deformities and pathological fractures are features of OFC. Bone mineral density is usually extremely low in OFC, but it is reversible after surgical cure. The signs and symptoms of severe bone disease include bone pain, pathologic fractures, proximal muscle weakness with hyperreflexia. Bone involvement is typically characterized as salt-and-pepper appearance in the skull, bone erosions and bone resorption of the phalanges, brown tumors and cysts. In the radiography, diffuse demineralization is observed, along with pathological fractures, particularly in the long bones of the extremities. In severe, symptomatic PHPT, marked elevation of the serum calcium and PTH concentrations are seen and renal involvement is manifested by nephrolithiasis and nephrocalcinosis. A new technology, recently approved for clinical use in the United States and Europe, is likely to become more widely available because it is an adaptation of the lumbar spine DXA image. Trabecular bone score (TBS) is a gray-level textural analysis that provides an indirect index of trabecular microarchitecture. Newer technologies, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), have provided further understanding of the microstructural skeletal features in PHPT.

A doença óssea no hiperparatiroidismo primário grave é representada pela osteíte fibrosa cística (OFC). Dor óssea, deformidades esqueléticas e fraturas patológicas são achados comuns na OFC. A densidade mineral óssea está, usualmente, extremamente diminuída na OFC, mas é reversível após a cura cirúrgica. Os sinais e sintomas da doença óssea grave incluem dor óssea, fraturas patológicas e fraqueza muscular proximal com hiper-reflexia. O comprometimento ósseo é tipicamente caracterizado pela aparência em “sal-e-pimenta” nos ossos do crânio, erosões ósseas e reabsorção das falanges, tumores marrons e cistos. Na radiografia, observam-se desmineralização difusa e fraturas patológicas especialmente nos ossos longos das extremidades. No hiperparatiroidismo primário (HPTP) sintomático grave, as concentrações séricas de cálcio e PTH estão usualmente bem elevadas e o comprometimento renal se caracteriza pela presença de urolitíase e nefrocalcinose. Uma nova tecnologia, recentemente aprovada para uso clínico nos Estados Unidos e na Europa, torna-se provável se difundir rapidamente, pois utiliza as imagens geradas pela densitometria DXA. O escore trabecular ósseo (TBS), obtido por meio da análise do nível da textura cinza das imagens dos corpos vertebrais, fornece informações indiretas sobre a microarquitetura trabecular. Novos métodos, como a tomografia de alta resolução quantitativa periférica computadorizada (HRpqCT), têm proporcionado conhecimentos adicionais sobre os achados da microarquitetura esquelética no HPTP.

Normocalcemic primary hyperparathyroidism: long-term follow-up associated with multiple adenomas / Hiperparatireoidismo primário normocalcêmico associado a múltiplos adenomas

Normocalcemic primary hyperparathyroidism (NPHPT) is a condition characterized by elevation of the parathyroid hormone (PTH) in the presence of normal serum calcium and the absence of secondary causes. The case described illustrates the long-term follow-up of a postmenopausal woman with NPHPT patient who progressed with multiple adenomas. This case reports a 77-year-old female who has chronic generalized pain and osteoporosis. Her initial serum PTH was 105 pg/mL, with total serum calcium of 9.6 mg/dL, albumin 4.79 g/dL, phosphorus 2.8 mg/dL, and 25OHD after supplementation was 34.6 ng/mL. The bone densitometry (BMD) results were as follows: lumbar spine: T-score -3.0, femoral neck: T-score -2.6 and distal radius: -4.2. Other causes of secondary hyperparathyroidism were ruled out and cervical ultrasound and Tc-99-Sestamibi scan were negative. She used oral alendronate and three infusions of zoledronic acid for treatment of osteoporosis. In the 10th year of follow-up, after successive negative cervical imaging, ultrasound showed a nodule suggestive of an enlarged right inferior parathyroid gland. PTH levels in fluid which was obtained during fine-needle aspiration (FNA) were over 5,000 pg/mL and a Sestamibi scan was negative. The patient underwent parathyroidectomy, and a histological examination confirmed parathyroid adenoma. Post-operatively serum PTH remained elevated in the presence of normal serum calcium levels. A follow-up cervical ultrasound showed a new solid nodule suggestive of an enlarged right superior parathyroid gland. PTH levels in the aspiration fluid were remarkably high. A second parathyroidectomy was performed, with the excision of a histologically confirmed parathyroid adenoma. In conclusion, this is an unusual presentation of NPHPT and highlights the long-term complications.

Hiperparatiroidismo primário normocalcêmico (NPHPT) caracteriza-se pela elevação do hormônio da paratiroide (PTH), na ausência da elevação dos níveis séricos de cálcio e exclusão de causas secundárias. O caso descrito ilustra o seguimento de uma mulher na pós-menopausa com NPHPT que evoluiu com múltiplos adenomas. Este caso relata uma paciente de 77 anos de idade que tem dor generalizada crônica e osteoporose. O PTH inicial foi elevado com níveis séricos de cálcio, albumina, fósforo e 25OH vitamina D normais. A densitometria óssea (DMO) evidenciou um T-SCORE da coluna lombar: -3.0, colo do fêmur: -2.6 e rádio distal: -4.2. Outras causas de hiperparatireoidismo secundário foram descartadas e a ultrassonografia cervical e varredura com Sestamibi foram negativos. Fez uso de alendronato e três infusões de ácido zoledrônico para o tratamento da osteoporose. No décimo ano de seguimento, depois de sucessivas imagens negativas, a ultrassonografia evidenciou um nódulo sugestivo de adenoma de paratireoide inferior direita. A paciente foi submetida à paratireoidectomia, e um exame histológico confirmou a hipótese. A elevação dos níveis séricos de PTH no pós-operatório se manteve com níveis normais de cálcio. A nova ultrassonografia cervical evidenciou outro nódulo sugestivo de adenoma de paratireoide superior direita. Uma segunda paratireoidectomia foi realizada, cujo histológico confirmou outro adenoma de paratireoide. Conclui-se que essa é uma apresentação incomum de NPHPT e destaca as complicações a longo prazo.

Associação entre gamopatia monoclonal de significado indeterminado e hiperparatireoidismo primário no diagnóstico diferencial das hipercalcemias - Relato de caso / Unknown significance monoclonal gammopathy (USMG) and primary hyperparathyroidism (PH) on diferential diagnosis of hypercalcemia - Case report

A gamopatia monoclonal de significado indeterminado (GMSI) é uma doença pré-maligna rara assintomática, definida por uma concentração de imunoglobulina monoclonal no soro menor que 3 g/dL e uma proporção de células plasmocitárias na medula óssea menor que 10%, na ausência de lesões líticas ósseas, anemia, hipercalcemia e insuficiência renal relacionadas com a proliferação de células plasmáticas monoclonais. O hiperparatireoidismo primário (HP) é uma doença relativamente frequente, afetando aproximadamente um em cada 1000 indivíduos. Alguns trabalhos sugerem que a frequência de HP está aumentada em neoplasias, ampliando o espectro da etiologia da hipercalcemia nesses pacientes. Relata-se, aqui, um caso de paciente de 63 anos admitido para investigação de anemia, parestesias e dores em membros inferiores, além de insuficiência renal. Durante investigação, verificou-se hipercalcemia, pico monoclonal sérico de IgA/lambda, sem critérios para mieloma múltiplo, e adenoma de paratireoide. O mesmo foi submetido à paratireoidectomia, cujo anatomopatológico revelou adenoma de paratireoide. Após a cirurgia, houve retorno dos níveis de cálcio e de função renal ao normal.

The monoclonal gammopathy of undetermined significance (USMG) is a pre-malignant rare asymptomatic disease, defined by a concentration of immunoglobulin in serum monoclonal more than 3 g/dL and a proportion of plasma cells in bone marrow more than 10% in the absence of lytic bone lesions, anemia, hypercalcemia and renal failure related to monoclonal cell proliferation. Primary hyperparathyroidism (PH) is a relatively frequent disease, affecting approximately one in 1,000 individuals. Some studies suggest that the frequency of PH is increased in cancer, broadening the spectrum of etiology of hypercalcemia in these patients. We report here a case of a 63 years-old patient admitted for investigation of anemia, paresthesias, pain in the lower limbs and kidney failure. During investigation, there was hypercalcemia, serum monoclonal peak of IgA/lambda without criteria for multiple myeloma and with parathyroid adenoma. Patient was submitted to parathyroidectomy, which anatomicopathological revealed parathyroid adenoma. After surgery, levels of calcium and kidney function returned to normal.

Oro-mandibular manifestations of primary hyperparathyroidism.

Aims and Objective : To determine the effects of Primary Hyperparathyroidism on oral cavity in a symptomatic contemporary Indian population by taking note of the following parameters: (1) Radiological alteration of lamina dura, (2) mandibular cortical width, (3) prevalence of brown tumor, and (4) mandibular tori. Study Design : Twenty-six patients of Primary Hyperparathyroidism were examined clinically and radiologically for extra- and intraoral abnormalities. Loss of lamina dura, mandibular cortical width, presence of mandibular tori, and brown tumors were assessed and correlated with serum Calcium, Phosphate, Parathormone, and Alkaline phosphatase. The results were compared with twenty-six age- and gender-matched control subjects. The data was expressed as mean ± SD, and a probability (p) value of < 0.05 was considered significant. Pearson's statistical method was used to assess the significant correlation between radiological measurements and biochemical values. Results : Generalized absence of the lamina dura was the most consistent finding and there was a significant correlation between its loss and altered parathormone, alkaline phosphatase, and inorganic phosphate, but not with serum calcium or the duration of the disease. Mean values (in mm) for the cortical indices were significantly lower in the patients compared to the controls and correlated significantly with parathormone and alkaline phosphatase. None of the patients had mandibular tori and only one patient had a brown tumor. Conclusion : Loss of lamina dura, ground glass appearance, and mandibular cortical width reduction are common findings in primary hyperparathyroidism and these are significantly correlated with elevated parathormone and alkaline phosphatase. However, the presence of brown tumors and oral tori are less commonly encountered features.

Preoperative Predictive Factors for Parathyroid Carcinoma in Patients with Primary Hyperparathyroidism

This study was conducted to review the clinical characteristics of parathyroid carcinoma (PC) and to evaluate potential preoperative predictive factors for PC in patients with primary hyperparathyroidism (PHPT). We performed a retrospective review of electronic medical records of 194 patients with pathologically confirmed PHPT in affiliated teaching hospitals of Seoul National University from January 2000 to March 2011. Adenoma was diagnosed in 171 patients, hyperplasia in 12, and carcinoma in 11. Several biochemical measurements were higher in patients with PC than in patients with benign disease, including serum total calcium (P < 0.001), intact parathyroid hormone (P = 0.003), and alkaline phosphatase (ALP) (P < 0.001). Tumors were larger in PC than in benign disease (P < 0.001). Multivariate analysis revealed that serum ALP level (P < 0.001) and tumor size were associated with PC (P = 0.03). Tumor size and serum ALP level were evaluated as preoperative predictive factors for PC using ROC analyses: a tumor size of 3.0 cm (sensitivity 90.9%, specificity 92.1%) and serum ALP level of 285 IU/L (83.3%, 97.0%) had predictive value for the diagnosis of PC in patients with PHPT. In conclusion, elevated serum ALP and a large parathyroid mass at the time of diagnosis can be helpful to predict PC in patients with PHPT.