Brown tumors of the jaw: an atypical manifestation of primary hyperparathyroidism / Tumores pardos de mandíbula: una manifestación atípica de hiperparatiroidismo primario

Abstract Brown tumors represent the terminal stage of bone remodeling processes in primary hyperparathyroidism. Currently they are rare, and typically affect long bones, pelvis and ribs. Brown tumors may be not included in the initial differential diagnosis of bone disease, espe cially when they are present in atypical localizations. We reported two cases of oral brown tumors as the initial presentation of primary hyperparathyroidism. In the first case, a 44-year-old woman presented a painful and sessile lesion of 4x3 cm over the central body of the mandible which progressively increased in 4-month. The second case involved a 23-year-old woman who was referred with a 3-month history of a painful and ulcerated mass of 2 cm arising from left maxilla, episodes of gingival hemorrhage and difficulty of breathing. Both cases were solitary tumors with no evidence of palpable cervical lymphadenopathy. Incisional biopsy of oral tumors resul ted in giant cell and primary hyperparathyroidism was confirmed by laboratory tests. After parathyroidectomy, histology confirmed adenoma in both cases. Although this type of clinical presentation has almost disappeared in the recent decades, brown tumors should be consi dered in the differential diagnosis of bone oral masses.

Resumen Los tumores pardos son raros y, por lo general, afectan huesos largos, pelvis y costillas. Pueden no estar incluidos en el diagnóstico diferencial inicial como manifestación de enfermedad esquelética, es pecialmente cuando se presentan en localizaciones atípicas. Comunicamos dos casos de tumores pardos orales como presentación inicial de hiperparatiroidismo primario. En el primer caso, una mujer de 44 años presentó una lesión dolorosa y sésil de 4 × 3 cm sobre el cuerpo central de la mandíbula que aumentó de tamaño progresivamente en 4 meses. El segundo caso corresponde a una mujer de 23 años que acudió por presentar una masa dolorosa y ul cerada de 2 cm en maxilar izquierdo de 3 meses de evolución, episodios de hemorragia gingival y difi cultad para respirar. Todos fueron tumores solitarios sin evidencia de linfadenopatía cervical palpable. La biopsia incisional de los tumores orales resultó en células gigantes, y las pruebas de laboratorio confirmaron el hiperparatiroidismo primario. Tras la paratiroidectomía, la histología confirmó adenoma en ambos casos. Los tumores pardos representan la etapa terminal de los procesos de remodelación ósea en el hiperparatiroidismo primario. Aunque este tipo de presentación clínica casi ha desaparecido en las últimas décadas, los tumores pardos deben ser considerados en el diagnóstico diferencial de las masas óseas orales.

Brown tumors of the jaw: an atypical manifestation of primary hyperparathyroidism.

Brown tumors represent the terminal stage of bone remodeling processes in primary hyperparathyroidism. Currently they are rare, and typically affect long bones, pelvis and ribs. Brown tumors may be not included in the initial differential diagnosis of bone disease, especially when they are present in atypical localizations. We reported two cases of oral brown tumors as the initial presentation of primary hyperparathyroidism. In the first case, a 44-year-old woman presented a painful and sessile lesion of 4 × 3 cm over the central body of the mandible which progressively increased in 4-month. The second case involved a 23-year-old woman who was referred with a 3-month history of a painful and ulcerated mass of 2 cm arising from left maxilla, episodes of gingival hemorrhage and difficulty of breathing. Both cases were solitary tumors with no evidence of palpable cervical lymphadenopathy. Incisional biopsy of oral tumors resulted in giant cell and primary hyperparathyroidism was confirmed by laboratory tests. After parathyroidectomy, histology confirmed adenoma in both cases. Although this type of clinical presentation has almost disappeared in the recent decades, brown tumors should be considered in the differential diagnosis of bone oral masses.

Los tumores pardos son raros y, por lo general, afectan huesos largos, pelvis y costillas. Pueden no estar incluidos en el diagnóstico diferencial inicial como manifestación de enfermedad esquelética, especialmente cuando se presentan en localizaciones atípicas. Comunicamos dos casos de tumores pardos orales como presentación inicial de hiperparatiroidismo primario. En el primer caso, una mujer de 44 años presentó una lesión dolorosa y sésil de 4 × 3 cm sobre el cuerpo central de la mandíbula que aumentó de tamaño progresivamente en 4 meses. El segundo caso corresponde a una mujer de 23 años que acudió por presentar una masa dolorosa y ulcerada de 2 cm en maxilar izquierdo de 3 meses de evolución, episodios de hemorragia gingival y dificultad para respirar. Todos fueron tumores solitarios sin evidencia de linfadenopatía cervical palpable. La biopsia incisional de los tumores orales resultó en células gigantes, y las pruebas de laboratorio confirmaron el hiperparatiroidismo primario. Tras la paratiroidectomía, la histología confirmó adenoma en ambos casos. Los tumores pardos representan la etapa terminal de los procesos de remodelación ósea en el hiperparatiroidismo primario. Aunque este tipo de presentación clínica casi ha desaparecido en las últimas décadas, los tumores pardos deben ser considerados en el diagnóstico diferencial de las masas óseas orales.

Hipopara-Red, Real Life Experience in 322 Patients With Hypoparathyroidism.

CONTEXT: Hypoparathyroidism is a rare disease and, as such, its natural history, long-term complications, and correct clinical management remain unclear. OBJECTIVE: To describe the natural history and clinical characteristics of the disease. DESIGN AND SETTING: To present a retrospective observational analysis from 7 specialized centers in Buenos Aires, Argentina. PATIENTS: Chronic hypoparathyroid patients followed-up between 1985 and December 2018. MAIN OUTCOME MEASURES: Data on demographics, etiology, clinical complications, biochemical parameters, dual-energy x-ray absorptiometry (DXA) values, and treatment doses were collected. RESULTS: A total of 322 subjects with chronic hypoparathyroidism were included; 85.7% were female, the mean age was 55.2 ±â€…16.8 years, and the mean age at diagnosis was 43.8 ±â€…16.8 years. Prevalence of surgical hypoparathyroidism was 90.7%, with the most common causes being thyroid carcinoma and benign thyroid disease. A history of hypocalcemia requiring hospitalization was present in 25.7% of the whole group and in 4.3% of patients who had a history of seizures. Overall, 40.9% of our patients had reported at least 1 neuromuscular symptom. Renal insufficiency was present in 22.4% of our patients and was significantly associated with age (P < 0.0001). Hyperphosphatemia was present in 42% of patients. A history of severe hypocalcemia, paresthesias, tetany, ganglia calcifications, seizures, and cataracts was significantly higher in nonsurgical patients. CONCLUSION: Although these patients were followed-up by experienced physicians, clinical management was heterogeneous and probably insufficient to assess all the potential complications of this chronic disease. Almost 70% of the study's group of patients met the experts' indications for considering the use of rhPTH 1-84. Being aware of this fact is the 1st step in improving our medical management of this disease in the future.

Disturbance Increases Microbial Community Diversity and Production in Marine Sediments.

Disturbance strongly impacts patterns of community diversity, yet the shape of the diversity-disturbance relationship remains a matter of debate. The topic has been of interest in theoretical ecology for decades as it has practical implications for the understanding of ecosystem services in nature. One of these processes is the remineralization of organic matter by microorganisms in coastal marine sediments, which are periodically impacted by disturbances across the sediment-water interface. Here we set up an experiment to test the hypothesis that disturbance impacts microbial diversity and function during the anaerobic degradation of organic matter in coastal sediments. We show that during the first 3 weeks of the experiment, disturbance increased both microbial production, derived from the increase in microbial abundance, and diversity of the active fraction of the community. Both community diversity and phylogenetic diversity increased, which suggests that disturbance promoted the cohabitation of ecologically different microorganisms. Metagenome analysis also showed that disturbance increased the relative abundance of genes diagnostic of metabolism associated with the sequential anaerobic degradation of organic matter. However, community composition was not impacted in a systematic way and changed over time. In nature, we can hypothesize that moderate storm disturbances, which impact coastal sediments, promote diverse, and productive communities. These events, rather than altering the decomposition of organic matter, may increase the substrate turnover and, ultimately, remineralization rates.

Rapid response of hypercortisolism to vandetanib treatment in a patient with advanced medullary thyroid cancer and ectopic Cushing syndrome.

Medullary thyroid carcinoma (MTC) may rarely present with paraneoplastic syndromes. Among the most frequent ones are the appearance of diarrhea and ectopic Cushing syndrome (ECS). The ECS in the context of MTC is usually present in patients with distant metastatic disease. The use of drugs such as ketoconazole, metyrapone, somatostatin analogs and etomidate have been ineffective alternatives to control hypercortisolism in these patients. Bilateral adrenalectomy is often required to manage this situation. Recently, the use of tyrosine kinase inhibitors has been shown to be a useful tool to achieve eucortisolism in patients with metastatic MTC and ECS. We present a patient with sporadic advanced persistent and progressive MTC with lymph node and liver metastases, which after 16 years of follow-up developed an ECS. After one month of 300 mg/day vandetanib treatment, a biochemical and clinical response of the ECS was achieved but it did not result in significant reduction of tumor burden. However the patient reached criteria for stable disease according to response evaluation criteria in solid tumors (RECIST 1.1) after 8 months of follow-up.

Rapid response of hypercortisolism to vandetanib treatment in a patient with advanced medullary thyroid cancer and ectopic Cushing syndrome

Medullary thyroid carcinoma (MTC) may rarely present with paraneoplastic syndromes. Among the most frequent ones are the appearance of diarrhea and ectopic Cushing syndrome (ECS). The ECS in the context of MTC is usually present in patients with distant metastatic disease. The use of drugs such as ketoconazole, metyrapone, somatostatin analogs and etomidate have been ineffective alternatives to control hypercortisolism in these patients. Bilateral adrenalectomy is often required to manage this situation. Recently, the use of tyrosine kinase inhibitors has been shown to be a useful tool to achieve eucortisolism in patients with metastatic MTC and ECS. We present a patient with sporadic advanced persistent and progressive MTC with lymph node and liver metastases, which after 16 years of follow-up developed an ECS. After one month of 300 mg/day vandetanib treatment, a biochemical and clinical response of the ECS was achieved but it did not result in significant reduction of tumor burden. However the patient reached criteria for stable disease according to response evaluation criteria in solid tumors (RECIST 1.1) after 8 months of follow-up.

[Clinical experience in 37 cases of insulinoma]. / Experiencia clinica sobre 37 casos de insulinoma.

Insulinoma is the most frequent pancreatic islet cell tumor. Clinical manifestations include adrenergic and neuroglycopenic symptoms. Diagnosis is established through demonstration of inappropriately elevated insulin serum concentrations in the presence of hypoglycemia. The aim of this study is to show our experience in the management of insulinoma. Since 1988, 23 women (48 +/- 18 years) and 14 men (45 +/- 19 years) were studied. Seventy three percent of them suffered mainly from neuroglucopenic symptoms while 27% referred adrenergic signs. Mean duration of symptoms before diagnosis was 2.7 +/- 2 years. Mean fasting serum glucose was 32.4 +/- 8.7 mg/dl, insulin 38.2 +/- 39.7 microU/ml (RIA, n=11) or 23.8 +/- 18.1 microU/ml (chemoluminescence, n=26) and C-peptide 1.15 +/- 1.60 nmol/l (n=14). Twenty one patients developed clinical and/or biochemical hypoglycaemia within 9.0 +/- 5.2 hours of supervised fast. Preoperative localization was performed in 73% by imaging techniques, arterial calcium stimulation and/or intraoperative ultrasonography and palpation by the surgeon. Thirty six patients were operated on by conventional surgery in 25, or laparoscopic approach in 11 cases. In 22 patients, a solitary tumor was excised (61.1%). Six cases presented multiple insulinomas. Five patients had malignant insulinomas. In one case, a pattern of nesidioblastosis was found and 2 patients presented unspecific findings. In 3 patients another tumour (glucagonoma) was found (1 of them with MEN 1). One patient was treated with verapamil with good clinical response. Mean postoperative follow up was 60.4 +/- 59.9 months.

Experiencia clinica sobre 37 casos de insulinoma / Clinical experience in 37 cases of insulinoma

El insulinoma es el tumor neuroendocrino pancreático más frecuente. Se manifiesta por signos adrenérgicos y de neuroglucopenia. Su diagnóstico se confirma documentando la existencia de hipoglucemia junto a una inapropiada secreción de insulina. Desde 1988 fueron estudiados 23 mujeres (48 ± 18 años) y 14 varones (45 ± 19 años) con diagnóstico de insulinoma. La evolución de la enfermedad hasta el diagnósticofue de 2.8 ± 2.1 años. Veintisiete pacientes (73%) presentaron principalmente síntomas de neuroglucopenia, y el 27% refirió síntomas adrenérgicos. El laboratorio mostró glucemia en ayunas 32.4 ± 8.7 mg/dl, insulina (RIA) 38.2 ± 39.7 μU/ml (n=11), insulina (quimioluminiscencia) 23.8 ± 18.1 μU/ml (n=26), péptido C1.15 ± 1.6 nmol/l (n=14). El test de ayuno prolongado fue diagnóstico a las 9.0 ± 5.2 horas (n=21). La localizaciónpreoperatoria fue posible en el 73% por imágenes, arteriografía con estimulación de calcio y/o ecografía intraoperatoria. Once casos fueron operados por laparoscopia, y el resto por vía convencional. El diagnósticofue confirmado por histología e inmunohistoquímica. Veintidos pacientes (61.1%) presentaron insulinomas únicos(16 en cuerpo y cola, 6 en la cabeza y proceso uncinado), 6 eran portadores de insulinomas múltiples, 5 deinsulinomas malignos, 1 de nesidioblastosis del adulto y en 2 casos los hallazgos fueron incaracterísticos. En 3 pacientes se halló un glucagonoma asociado (1 de ellos con NEM1). Una paciente no fue operada recibiendotratamiento con verapamilo, con buena respuesta clínica. El seguimiento postquirúrgico fue de 60.4 ± 59.9 meses

Insulinoma is the most frequent pancreatic islet cell tumor. Clinical manifestations include adrenergic and neuroglycopenic symptoms. Diagnosis isestablished through demonstration of inappropriately elevated insulin serum concentrations in the presence ofhypoglycemia. The aim of this study is to show our experience in the management of insulinoma. Since 1988,23 women (48 ± 18 years) and 14 men (45 ± 19 years) were studied. Seventy three percent of them sufferedmainly from neuroglucopenic symptoms while 27% referred adrenergic signs. Mean duration of symptoms beforediagnosis was 2.7 ± 2 years. Mean fasting serum glucose was 32.4 ± 8.7 mg/dl, insulin 38.2 ± 39.7 μU/ml(RIA, n= 11) or 23.8 ± 18.1 μU/ml (chemoluminescence, n=26) and C-peptide 1.15 ± 1.60 nmol/l (n=14). Twenty one patients developed clinical and/or biochemical hypoglycaemia within 9.0 ± 5.2 hours of supervised fast. Preoperative localization was performed in 73% by imaging techniques, arterial calcium stimulation and/or intraoperative ultrasonography and palpation by the surgeon. Thirty six patients were operated on by conventional surgery in 25, or laparoscopic approach in 11 cases. In 22 patients, a solitary tumor was excised (61.1%). Six cases presented multiple insulinomas. Five patients had malignant insulinomas. In one case, a pattern of nesidioblastosis was found and 2 patients presented unspecific findings. In 3 patients another tumour(glucagonoma) was found (1 of them with MEN 1). One patient was treated with verapamil with good clinicalresponse. Mean postoperative follow up was 60.4 ± 59.9 months

Experiencia clinica sobre 37 casos de insulinoma / Clinical experience in 37 cases of insulinoma

El insulinoma es el tumor neuroendocrino pancreático más frecuente. Se manifiesta por signos adrenérgicos y de neuroglucopenia. Su diagnóstico se confirma documentando la existencia de hipoglucemia junto a una inapropiada secreción de insulina. Desde 1988 fueron estudiados 23 mujeres (48 ± 18 años) y 14 varones (45 ± 19 años) con diagnóstico de insulinoma. La evolución de la enfermedad hasta el diagnósticofue de 2.8 ± 2.1 años. Veintisiete pacientes (73%) presentaron principalmente síntomas de neuroglucopenia, y el 27% refirió síntomas adrenérgicos. El laboratorio mostró glucemia en ayunas 32.4 ± 8.7 mg/dl, insulina (RIA) 38.2 ± 39.7 μU/ml (n=11), insulina (quimioluminiscencia) 23.8 ± 18.1 μU/ml (n=26), péptido C1.15 ± 1.6 nmol/l (n=14). El test de ayuno prolongado fue diagnóstico a las 9.0 ± 5.2 horas (n=21). La localizaciónpreoperatoria fue posible en el 73% por imágenes, arteriografía con estimulación de calcio y/o ecografía intraoperatoria. Once casos fueron operados por laparoscopia, y el resto por vía convencional. El diagnósticofue confirmado por histología e inmunohistoquímica. Veintidos pacientes (61.1%) presentaron insulinomas únicos(16 en cuerpo y cola, 6 en la cabeza y proceso uncinado), 6 eran portadores de insulinomas múltiples, 5 deinsulinomas malignos, 1 de nesidioblastosis del adulto y en 2 casos los hallazgos fueron incaracterísticos. En 3 pacientes se halló un glucagonoma asociado (1 de ellos con NEM1). Una paciente no fue operada recibiendotratamiento con verapamilo, con buena respuesta clínica. El seguimiento postquirúrgico fue de 60.4 ± 59.9 meses (AU)

Insulinoma is the most frequent pancreatic islet cell tumor. Clinical manifestations include adrenergic and neuroglycopenic symptoms. Diagnosis isestablished through demonstration of inappropriately elevated insulin serum concentrations in the presence ofhypoglycemia. The aim of this study is to show our experience in the management of insulinoma. Since 1988,23 women (48 ± 18 years) and 14 men (45 ± 19 years) were studied. Seventy three percent of them sufferedmainly from neuroglucopenic symptoms while 27% referred adrenergic signs. Mean duration of symptoms beforediagnosis was 2.7 ± 2 years. Mean fasting serum glucose was 32.4 ± 8.7 mg/dl, insulin 38.2 ± 39.7 μU/ml(RIA, n= 11) or 23.8 ± 18.1 μU/ml (chemoluminescence, n=26) and C-peptide 1.15 ± 1.60 nmol/l (n=14). Twenty one patients developed clinical and/or biochemical hypoglycaemia within 9.0 ± 5.2 hours of supervised fast. Preoperative localization was performed in 73% by imaging techniques, arterial calcium stimulation and/or intraoperative ultrasonography and palpation by the surgeon. Thirty six patients were operated on by conventional surgery in 25, or laparoscopic approach in 11 cases. In 22 patients, a solitary tumor was excised (61.1%). Six cases presented multiple insulinomas. Five patients had malignant insulinomas. In one case, a pattern of nesidioblastosis was found and 2 patients presented unspecific findings. In 3 patients another tumour(glucagonoma) was found (1 of them with MEN 1). One patient was treated with verapamil with good clinicalresponse. Mean postoperative follow up was 60.4 ± 59.9 months (AU)

Experiencia clinica sobre 37 casos de insulinoma / Clinical experience in 37 cases of insulinoma

El insulinoma es el tumor neuroendocrino pancreático más frecuente. Se manifiesta por signos adrenérgicos y de neuroglucopenia. Su diagnóstico se confirma documentando la existencia de hipoglucemia junto a una inapropiada secreción de insulina. Desde 1988 fueron estudiados 23 mujeres (48 ± 18 años) y 14 varones (45 ± 19 años) con diagnóstico de insulinoma. La evolución de la enfermedad hasta el diagnósticofue de 2.8 ± 2.1 años. Veintisiete pacientes (73%) presentaron principalmente síntomas de neuroglucopenia, y el 27% refirió síntomas adrenérgicos. El laboratorio mostró glucemia en ayunas 32.4 ± 8.7 mg/dl, insulina (RIA) 38.2 ± 39.7 μU/ml (n=11), insulina (quimioluminiscencia) 23.8 ± 18.1 μU/ml (n=26), péptido C1.15 ± 1.6 nmol/l (n=14). El test de ayuno prolongado fue diagnóstico a las 9.0 ± 5.2 horas (n=21). La localizaciónpreoperatoria fue posible en el 73% por imágenes, arteriografía con estimulación de calcio y/o ecografía intraoperatoria. Once casos fueron operados por laparoscopia, y el resto por vía convencional. El diagnósticofue confirmado por histología e inmunohistoquímica. Veintidos pacientes (61.1%) presentaron insulinomas únicos(16 en cuerpo y cola, 6 en la cabeza y proceso uncinado), 6 eran portadores de insulinomas múltiples, 5 deinsulinomas malignos, 1 de nesidioblastosis del adulto y en 2 casos los hallazgos fueron incaracterísticos. En 3 pacientes se halló un glucagonoma asociado (1 de ellos con NEM1). Una paciente no fue operada recibiendotratamiento con verapamilo, con buena respuesta clínica. El seguimiento postquirúrgico fue de 60.4 ± 59.9 meses (AU)

Insulinoma is the most frequent pancreatic islet cell tumor. Clinical manifestations include adrenergic and neuroglycopenic symptoms. Diagnosis isestablished through demonstration of inappropriately elevated insulin serum concentrations in the presence ofhypoglycemia. The aim of this study is to show our experience in the management of insulinoma. Since 1988,23 women (48 ± 18 years) and 14 men (45 ± 19 years) were studied. Seventy three percent of them sufferedmainly from neuroglucopenic symptoms while 27% referred adrenergic signs. Mean duration of symptoms beforediagnosis was 2.7 ± 2 years. Mean fasting serum glucose was 32.4 ± 8.7 mg/dl, insulin 38.2 ± 39.7 μU/ml(RIA, n= 11) or 23.8 ± 18.1 μU/ml (chemoluminescence, n=26) and C-peptide 1.15 ± 1.60 nmol/l (n=14). Twenty one patients developed clinical and/or biochemical hypoglycaemia within 9.0 ± 5.2 hours of supervised fast. Preoperative localization was performed in 73% by imaging techniques, arterial calcium stimulation and/or intraoperative ultrasonography and palpation by the surgeon. Thirty six patients were operated on by conventional surgery in 25, or laparoscopic approach in 11 cases. In 22 patients, a solitary tumor was excised (61.1%). Six cases presented multiple insulinomas. Five patients had malignant insulinomas. In one case, a pattern of nesidioblastosis was found and 2 patients presented unspecific findings. In 3 patients another tumour(glucagonoma) was found (1 of them with MEN 1). One patient was treated with verapamil with good clinicalresponse. Mean postoperative follow up was 60.4 ± 59.9 months (AU)