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We investigated the combined effect of fluoride exposure and Vitamin D deficiency in causing bone damage as a precursor to development of Fluorotoxic Metabolic Bone Disease. Thirty-six male Sprague-Dawley rats were divided into 6 groups of six; 3 groups received a Vitamin D deficient diet whereas the other 3 received a Vitamin D adequate diet. Serum total 25-hydroxyvitamin D (25OHD), calcium, phosphorus, creatinine, Alkaline phosphatase (ALP), albumin, Parathyroid hormone (PTH), Osteocalcin and C terminal telopeptide (CTx) were measured following exposure to varying levels of fluoride in drinking water (< 1.0, 15 and 50 ppm). Full body Dual-energy X-ray Absorptiometry (DXA) scans were used to examine changes in bone morphology pre and post exposure to fluoride. Renal tubular function was assessed using serum creatinine and urine Cystatin C. Histopathological examination of sections of bone and kidney tissues were also performed. Prior to fluoride exposure, DXA scans revealed a significant decrease in Bone Mineral Density (BMD) and Bone Mineral content (BMC) (p < 0.05) but a significant increase in fat mass (p < 0.05) and fat percentage (p < 0.01) among Vitamin D deficient rats, with no significant change in biochemical parameters. Following exposure to fluoride, BMD was significantly increased (p < 0.05) in both groups with a corresponding increase in serum ALP, bone fluoride content, Osteocalcin, CTx and urine fluoride with increasing levels of fluoride exposure. Serum creatinine calcium and phosphate and urinary cystatin C levels showed no significant changes. Light microscopy examination revealed mild thickening and increased osteoid in 80% of the Vitamin D deficient rats exposed to high levels of fluoride but renal tubular changes were found only in one experimental and one control animal. Fluoride deposited in rat bone affects both osteoblastic and osteoclastic activity. Also, these effects are accentuated in the presence of Vitamin D deficiency.
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We report herein a patient who developed diclofenac-induced acute rhabdomyolysis and hypovolemic shock. Timely recognition and management led to rapid recovery. Awareness of this potentially life-threatening side-effect is very important to encourage sparing and selective use of this drug in clinical practice.
Assuntos
Diclofenaco/efeitos adversos , Rabdomiólise/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Rabdomiólise/diagnósticoRESUMO
Determining the mutational status of susceptibility genes including RET, VHL, SDHx (SDHB, SDHC, SDHD) among patients with pheochromocytoma/paraganglioma (PCC/PGL) is gaining importance. These genes have not been systematically characterized among patients with PCC/PGL from India. The aim of the work was to screen the most frequently mutated genes among patients with PCC/PGL to determine the frequency and spectrum of mutations seen in this region. Fifty patients with PCC/PGL treated at our tertiary care hospital between January 2010 and June 2012 were screened for mutations in susceptibility genes using an algorithmic approach. Thirty-two percent (16/50) of patients were found to be positive for mutations including mutations among RET (n=4), VHL (n=6), SDHB (n=3), and SDHD (n=3) genes. None of these patients were positive for SDHC mutations. A significant association was found between young patients with bilateral tumors and VHL mutations (p=0.002). Two of the 3 patients with extra-adrenal SDHB associated tumors, had unique mutations, viz., c.436delT (exon 5) and c.788_857del (exon 8), one of which was malignant. High frequency of mutations seen among patients in this study emphasizes the need to consider mutational analysis among Indian patients with PCC/PGL.
Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Predisposição Genética para Doença , Mutação , Proteínas de Neoplasias/genética , Feocromocitoma/genética , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Centros de Atenção TerciáriaRESUMO
BACKGROUND: Medullary thyroid carcinoma (MTC) is a tumor arising from the para follicular (C) cells of the thyroid gland and can occur either sporadically or as part of an inherited syndrome. A proportion of these cases carry an autosomal dominant mutation in the RET (REarranged during Transfection) proto-oncogene. Screening for these mutations in the affected patients and the carriers "at risk" which includes the first-degree relatives is of utmost importance for early detection and prompt treatment including prophylactic thyroidectomy in cases that harbor these mutations. RESULTS: This report presents details of screening and subsequent follow-up of a large Indian family, where the index case was found to carry p. Cys634Ser mutation involving exon 11 of the RET gene. These data are of value considering the paucity of information within the region in context of screening large families affected by these mutations.
RESUMO
Hypokalaemic periodic paralysis (HPP) is a life-threatening condition. Our aim was to study the clinical profile and laboratory parameters of HPP patients and to develop an algorithm to determine the causes of HPP. 84 patients presented with HPP over a 3 year period. 58 (69.0%) were found to have renal tubular acidosis (RTA). The other causes were idiopathic HPP (8 (9.5%)), acute gastroenteritis (4 (4.8%)), suspected primary hyperaldosteronism and familial HPP (2 each (2.4%)) and suspected Gitelman/Bartter Syndrome and thyrotoxic periodic paralysis (1 each (1.2%)). The number of cases peaks in the hot season. Over a third of the patients (35.7%) had recurrent episodes. 80% had secondary HPP and therefore a biochemical evaluation is mandatory. A simple algorithm was developed. Both health professionals and patients need further education regarding this problem in order to improve diagnosis and treatment and to improve compliance.
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Acidose Tubular Renal/complicações , Paralisia Periódica Hipopotassêmica/diagnóstico , Paralisia Periódica Hipopotassêmica/etiologia , Administração Intravenosa , Adulto , Distribuição por Idade , Algoritmos , Diagnóstico Diferencial , Feminino , Humanos , Paralisia Periódica Hipopotassêmica/sangue , Paralisia Periódica Hipopotassêmica/tratamento farmacológico , Índia , Sulfato de Magnésio/administração & dosagem , Masculino , Pessoa de Meia-Idade , Cloreto de Potássio/administração & dosagem , Fatores de Risco , População Rural , Estações do Ano , Fatores Socioeconômicos , Resultado do TratamentoRESUMO
INTRODUCTION: We report a case of acute adrenal insufficiency (AAI) in a patient with antiphospholipid syndrome (APS). CASE REPORT: A 44-year-old female patient presented to us with acute abdominal pain associated with recurrent vomiting and giddiness. On examination, her blood pressure was 80/50 mm Hg. Systemic examination was normal. Further evaluation revealed hypocortisolemia with elevated plasma adrenocorticotropin hormone indicative of primary adrenal insufficiency. Her abdominal computed tomography scan showed features of evolving bilateral adrenal infarction. Etiological work-up revealed prolonged activated thromboplastin time, which didn't correct with normal plasma, her anti-cardiolipin antibody and lupus anticoagulant were also positive. She was diagnosed to have APS with adrenal insufficiency and she was started on intravenous steroids and heparin infusion. CONCLUSION: AAI due to the APS can present with acute abdominal pain followed by hypotension. A high index of suspicion is needed to make the correct diagnosis and to initiate appropriate treatment.
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The most common cause for menstrual abnormality and virilization in children and adolescents would be congenital adrenal hyperplasia. An elevated 17(OH) progesterone is invariably seen in this condition. Aromatase deficiency can also lead to a similar presentation but differs in several aspects. The age of onset of the clinical manifestations, the phenotype, biochemical abnormalities and karyotype help us to arrive at a definitive diagnosis. However sometimes the history is atypical, biochemical abnormalities may overlap between the different conditions and prior treatment may modify the clinical features. We report here a young adult with a late presentation of aromatase deficiency to highlight the differences between the two conditions. A 27 year old lady presented to us with history of primary amenorrhea and masculine voice. She lacked feminine secondary sexual characters, had eunuchoid body habitus and prominent clitoromegaly. Consanguinity in the parents, a neonatal sibling death and elevated basal 17(OH) progesterone in the patient suggested a possibility of congenital adrenal hyperplasia. But the eunuchoid body habitus raised FSH and lack of response to dexamethasone led to a diagnosis of aromatase deficiency. Variability in the degree of aromatase deficiency is known such that maternal virilization may not occur in pregnancy. Aromatase deficiency should be suspected when a patient presents with primary amenorrhea, absence of female secondary sexual characters, virilization and tall stature with eunuchoid body proportions, and biochemical features of ovarian failure. In our country one should be aware that late presentation and prior treatment may modify disease expression and contribute to the diagnostic challenge.
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Transtornos 46, XX do Desenvolvimento Sexual/complicações , Transtornos 46, XX do Desenvolvimento Sexual/diagnóstico , Amenorreia/etiologia , Aromatase/deficiência , Ginecomastia/complicações , Ginecomastia/diagnóstico , Infertilidade Masculina/complicações , Infertilidade Masculina/diagnóstico , Erros Inatos do Metabolismo/complicações , Erros Inatos do Metabolismo/diagnóstico , Virilismo/etiologia , Adulto , Feminino , HumanosRESUMO
BACKGROUND: Disseminated histoplasmosis is a chronic granulomatous disease caused by the dimorphic fungus, Histoplasma capsulatum. Clinical presentation can vary from the acute pulmonary to the chronic disseminated form. In India, disseminated histoplasmosis often presents with pyrexia of unknown origin with a presentation similar to 'disseminated tuberculosis' involving the adrenal glands and bone marrow. Due to rarity of the disease, data are lacking regarding its clinical presentation and outcome among immunocompromised and immunocompetent patients. METHODS: During January 2000 to December 2010, we identified 37 patients of disseminated histoplasmosis and attempted to characterize the differences between immuno- compromised and immunocompetent patients. Demographic characteristics, clinical presentation, risk factors, laboratory findings, diagnostic yield, treatment received and prognosis were noted and compared between the two groups. RESULTS: Eleven of 37 patients with disseminated histo- plasmosis were immunocompromised and 26 were immuno- competent. Comparison of their clinical features showed a higher frequency of skin lesions in the immunocompromised compared to the immunocompetent group (54.5% v. 11.5%). Pancytopenia and anaemia were more common among the immunocompromised (81.8%) compared to the immunocompetent (46.2%) group. In the immuno- compromised patients, the diagnosis was made most often by bone marrow aspirate and culture (72.7%) compared to the immunocompromised group where the diagnosis was most often obtained by adrenal gland biopsy and fungal cultures (57.7%). The cure rate was significantly higher in the immunocompetent group (73% v. 45%). CONCLUSION: The clinical presentation and outcome of patients with disseminated histoplasmosis differs among immunocompromised and immunocompetent patients.
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Glândulas Suprarrenais/patologia , Medula Óssea/patologia , Histoplasmose/complicações , Histoplasmose/diagnóstico , Imunocompetência , Hospedeiro Imunocomprometido , Adulto , Anemia/imunologia , Anemia/microbiologia , Antifúngicos/uso terapêutico , Biópsia , Feminino , Histoplasmose/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Pancitopenia/imunologia , Pancitopenia/microbiologia , Dermatopatias/imunologia , Dermatopatias/microbiologia , Resultado do TratamentoRESUMO
We present a case of prostatic calcification due to alkaptonuria with other clinical features.
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Calcinose/diagnóstico por imagem , Doenças Prostáticas/diagnóstico por imagem , Doenças da Coluna Vertebral/diagnóstico por imagem , Alcaptonúria/complicações , Humanos , Masculino , Pessoa de Meia-Idade , RadiografiaRESUMO
Phaeochromocytomas may be discovered incidentally when patients present with hypertensive crisis during general anaesthesia. A 49-year-old man underwent thyroidectomy 25 years ago and was diagnosed to have spindle cell carcinoma of the thyroid. He presented with recent onset of hoarseness of voice and was found to have a vocal cord nodule. He developed a hypertensive crisis during surgery. He was subsequently evaluated and found to have bilateral phaeochromocytoma. Further evaluation revealed a RET proto-oncogene mutation at codon 634 consistent with multiple endocrine neoplasia (MEN)-2A.
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Hipertensão/complicações , Neoplasia Endócrina Múltipla Tipo 2a/diagnóstico , Neoplasias da Glândula Tireoide/complicações , Prega Vocal , Neoplasias das Glândulas Suprarrenais/complicações , Anestesia Geral , Carcinoma/cirurgia , Humanos , Doenças da Laringe/complicações , Masculino , Pessoa de Meia-Idade , Feocromocitoma/complicações , Proto-Oncogene Mas , Neoplasias da Glândula Tireoide/cirurgia , Tomografia Computadorizada por Raios XAssuntos
Análise Mutacional de DNA/métodos , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias da Glândula Tireoide/genética , Adulto , Carcinoma Neuroendócrino , Feminino , Predisposição Genética para Doença , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Proto-Oncogene Mas , Adulto JovemRESUMO
Pituitary adenomas are unique in several ways--they are rarely malignant and yet can be invasive of several compartments. Recurrences in tumors with bland histological features that have been radically excised are a reason for frustration faced by endocrinologists and neurosurgeons in treatment of pituitary adenomas. Several attempts have therefore been made to determine the growth potential of pituitary adenomas. The aim of the present study was to define the biological significance of the MIB-1 labelling index (MIB-1 LI) in pituitary adenomas. The study included 159 cases of surgically treated pituitary adenoma seen in a single institution. MIB-1 LI was not found to be related to age or gender. The mean MIB-1 LI for clinically functional adenomas was marginally higher than that for clinically non-functional adenomas. There was a significant difference in the MIB-1 LI for tumors with a maximum diameter of more than 4 cm at a MIB-1 LI of ≥2%, however this difference was not statistically significant at a higher MIB-1 LI cut off value of >3%. The mean MIB-1 LI was significantly higher in tumors causing hydrocephalus and in those with cavernous sinus invasion and not when invasion was defined as invasion by tumor in any direction. We conclude that large pituitary macroadenomas, tumors filling the third ventricle causing hydrocephalus and tumors with true cavernous sinus invasions are more likely to have a higher proliferation index. Close follow up of tumors showing these imaging features would be recommended.
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Antígeno Ki-67/metabolismo , Neoplasias Hipofisárias/diagnóstico , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/patologia , Fatores Sexuais , Adulto JovemRESUMO
BACKGROUND & OBJECTIVE: Western studies show that up to 65 per cent of patients with Crohn's disease have low serum 25-hydroxy vitamin D concentrations, and 45 per cent of these patients have metabolic bone disease. No data are available from India or from any country with comparable climatic conditions or ethnicity. We carried out this study to measure the serum 25 (OH) vitamin D levels of Crohn's disease patients and compare with matched controls and to assess the consequences of low 25 (OH) vitamin D levels on bone and mineral metabolism in these patients. METHODS: Adult patients with Crohn's disease were compared with age and sex matched patients diagnosed to have irritable bowel syndrome. Serum 25 (OH) vitamin D, the effect of disease characteristics, sunlight exposure and milk consumption on 25 (OH) vitamin D level, and the consequences of low 25 (OH) vitamin D level on bone and mineral metabolism were assessed. RESULTS: Thirty four patients with Crohn's disease (M:F, 24:10, age 39.2 +/- 12.9 yr) and 34 controls (M:F, 24:10, age 38.9 +/- 13.4 yr) were studied. 25 (OH) vitamin D levels were significantly lower in patients with Crohn's disease as compared to controls (Crohn's disease vs controls: 16.3 +/- 10.8 vs 22.8 +/- 11.9 ng/ml; P<0.05). The severity of disease activity as assessed by the Harvey Bradshaw score correlated negatively (Correlation coefficient -0.484, significance P<0.004), and the duration of sunlight exposure correlated positively (Correlation coefficient 0.327, significance P=0.007) with the serum 25 (OH) vitamin D level. INTERPRETATION & CONCLUSION: Serum 25 (OH) vitamin D levels were significantly lower among patients with Crohn's disease as compared to age and sex matched controls. Further, 25 (OH) vitamin D levels in patients with Crohn's disease were lower in those with severe disease activity and less sun exposure. Further studies need to be done to correlate low 25 (OH) vitamin D level with bone density and assess the effect of vitamin D supplementation in these patients.
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Doença de Crohn , Luz Solar , Vitamina D/sangue , Adulto , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/fisiopatologia , Osso e Ossos/metabolismo , Doença de Crohn/sangue , Doença de Crohn/complicações , Doença de Crohn/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Giant adenomas comprise a clinical/therapeutic subset of pituitary adenomas that pose a surgical challenge. The study population consisted of 28 patients who had giant pituitary adenomas, which are defined as tumors with a diameter greater than 5cm. Clinically, five tumors (18%) were endocrinologically functional and 23 (82%) were not. During surgery, one tumor was radically excised, four were subtotally excised, 12 were partially excised, and 11 were biopsied. All of the tumors showed typical histological features of pituitary adenoma. Of the 23 clinically non-functional adenomas, 18 were gonadotrophic tumors, four were null cell adenomas and one was a silent corticotroph adenoma. The MIB-1 labeling indices ranged from 0.1% to 2.0%. The mean topoisomerase labeling index was 0.75%. Microvessel density ranged from 0.42% to 5.55%, and there was moderately intense immunostaining for vascular endothelial growth factor. The present study found giant adenomas to be invasive but slow growing, histologically benign and often gonadotrophic in subtype.
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Adenoma/patologia , Adenoma/terapia , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/terapia , Adenoma/classificação , Adenoma/metabolismo , Adolescente , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Antígenos CD34/metabolismo , Feminino , Seguimentos , Humanos , Antígeno Ki-67/metabolismo , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Hipofisárias/metabolismo , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
The aim of this study was to describe the localization and management of patients with pancreatic insulinomas and determine the most effective localization and surgical techniques in the presence of significant financial constraints in the patient population. We retrospectively reviewed the case records of 18 patients with insulinomas treated at our institution over a period of 10 years. The medical records were reviewed for demographic data, clinical presentation, biochemistry, details of localization studies, intraoperative findings, postoperative outcome, and long-term follow-up. The sensitivities of the various localization procedures were calculated using the intraoperative findings as the gold standard. There were 10 men and 8 women in the study, with a median age of 43 years. All patients underwent a supervised 72-hour fast and developed symptomatic hypoglycemia within 48 hours. An average of 1.9 localization procedures was performed per patient. Computed tomography (CT) had a sensitivity of 62% and specificity of 100%. Magnetic resonance imaging and digital subtraction angiography had specificities of 85% and 100%, respectively, with a specificity of 66% and 50%, respectively. Fourteen patients underwent surgery. Intraoperatively the excised tumor was palpable in nine patients, and all patients had postoperative euglycemia. In five patients the tumor was not palpable during the time of surgery; three of these patients underwent blind distal pancreactomy, with two patients having persistent hypoglycemia during the postoperative period. Two patients had a negative exploratory laparotomy. Patients with a surgical cure were followed up for a mean period of 24 months. On the background of financial constraints in connection with patient care, CT scanning is a cost-effective option with good specificity. Intraoperative palpation of the tumor and enucleation is the most effective technique for surgical cure. Blind distal pancreactomy is not advocated for tumors that are not localized intraoperatively.
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Insulinoma/cirurgia , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Angiografia Digital , Feminino , Hospitais Rurais , Humanos , Hipoglicemia/etiologia , Índia , Insulinoma/diagnóstico por imagem , Insulinoma/patologia , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Complicações Pós-Operatórias/etiologia , Encaminhamento e Consulta , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
The syndrome of hyperostosis and hyperphosphataemia (HHS) is very rare. It can mimic bone infections and tumours. A nine-year-old girl presented with pain in her left lower leg. Radiographs showed patchy sclerosis in the tibial diaphysis. Investigations were normal except for hyperphosphataemia. Open biopsy showed chronic inflammation. Bacterial cultures were negative. Four months later, she had pain in the other leg. On evaluation for hyperphosphataemia, there was increased renal reabsorption of phosphates. She responded to analgesics. In patients between six and 16 years of age, HHS must be considered when there is painful diaphyseal swelling of long bones associated with isolated hyperphosphataemia. The painful episodes can recur. Surgical decompression can be considered if conservative treatment methods are ineffective.
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Hiperostose/diagnóstico , Hiperfosfatemia/diagnóstico , Tíbia , Criança , Diagnóstico Diferencial , Feminino , Humanos , Hiperostose/diagnóstico por imagem , Hiperfosfatemia/diagnóstico por imagem , Radiografia , Síndrome , Tíbia/diagnóstico por imagemRESUMO
BACKGROUND AND OBJECTIVES: Glycated hemoglobin (HbA1c) provides an accurate and reliable method to assess the glycemic control in patients with Diabetes. Its measurement is limited by the inconvenience of sample collection that requires venipuncture, sample handling and storage factors. The aim of this study was to assess the feasibility of using a dried capillary blood spot on a filter paper to estimate HbA1c, to check its stability at room temperature and to compare these values with the venous sample HbA1c by Turbidimetric Inhibition Immunoassay (TINA, Tina-quant HbA1c II). METHODS: Venous blood samples of seventy eight patients with Type 1 or type 2 diabetes, were collected in EDTA containing vacutainers. Stability of HbA1c was studied in capillary blood samples blotted on to Whatman number 1 filter paper and stored at room temperature, for the first 20 patients enrolled in the study. After establishing the stability over a ten day period, HbA1c values obtained on the capillary blood spots were compared with those obtained from the venous blood samples of the remaining 58 patients. RESULTS: Glycated hemoglobin is found to be stable in dried capillary blood spots on filter paper till the 10th day, stored at room temperature. It however, shows an inherent variability of +/- 15%, which falls within the permissible variability (18%) of the quality control material. Seventy nine percent of the capillary HbA1c values were found to fall within this range. With linear regression, we derived the relationship between filter paper and venous HbA1c values. The regression equation was as follows: Cap.HbA1c = 0.95 (Ven.HbA1c) + 1.4. The filter paper results were highly correlated with the venous sample values (r = 0.889, p < 0.01). CONCLUSION: Measurement of glycated hemoglobin in dried blood spots on filter paper gives reliable and reproducible results. In our study, the mean capillary sample HbA1c value was 12% higher compared to the venous sample HbA1c values. Therefore a higher normal range may have to be used for interpreting the dried blood spot capillary blood HbA1c values.
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Capilares , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Filtração/instrumentação , Hemoglobinas Glicadas/análise , Humanos , Monitorização Fisiológica , Valores de Referência , Reprodutibilidade dos TestesRESUMO
Tumoral calcinosis is a rare calcifying disorder that is associated with deposition of calcium crystals in the periarticular tissues. The mass is most often around the hips, elbows, shoulders, and feet but may be occasionally found elsewhere. We report a case of multiple sporadic tumoral calcinoses in an adult male over the scalp. The scalp as a site of tumoral calcinosis has not been previously reported in adults. Previous surgical excisions done on two occasions had resulted in recurrence of the tumors. This report highlights the need to include tumoral calcinosis in the differential diagnosis of tumors of the scalp.