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Sulfonylureas (SU) continue to be a vital therapeutic category of oral hypoglycemic agents (OHAs) for the management of type 2 diabetes mellitus (T2DM). Physicians consider modern SU (gliclazide and glimepiride) as "safe and smart" choices for T2DM management. The presence of multiple international guidelines and scarcity of a national guideline may contribute to the challenges faced by few physicians in choosing the right therapeutic strategy. The role of SU in diabetes management is explicit, and the present consensus aims to emphasize the benefits and reposition SU in India. This pragmatic, practical approach aims to define expert recommendations for the physicians to improve caregivers' knowledge of the management of T2DM, leading to superior patient outcomes.
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INTRODUCTION: Gestational Diabetes Mellitus (GDM), diabetes diagnosed during pregnancy is associated with maternal (caesarean delivery, hypoglycaemia, hyperbilirubinaemia, shoulder dystocia, pre-term delivery and birth trauma) and fetal (Hyperbilirubinaemia in offspring, Neonatal hypoglycaemia, Macrosomia) complications. Despite, insulin being the standard treatment for GDM cases, there is no existing comprehensive consensus update on use of insulin in Indian patients with GDM. OBJECTIVE: To provide simple and easily implementable guidelines to healthcare physicians on use of insulin in GDM. METHODS: Each consensus based on indications, choice of insulin regimen , titration and insulin therapy during intrapartum and postpartum was presented based on established guidelines and published scientific literature. These evaluations were then factored into the national context based on the expert committee representatives' patient-physician experience in their clinical practice and common therapeutic practices followed in India for successful GDM management. RESULTS: Recommendations based on use of insulin in GDM has been developed. The key recommendations are:to monitor fasting plasma glucose (FPG) and 2-hour post prandial glucose PPG levels and the glycaemic targets are: FPG < 95 mg/dL and 2-hour PPG < 120 mg/dL, short-and intermediate acting human insulin are the first choice of insulin regimens, rapid-acting (Insulin Aspart or Lispro) may be considered, use basal/intermediate acting insulin at bedtime, if FPG>110 mg/dL. During intrapartum, start IV insulin infusion with hourly glucose monitoring. Those women who require insulin < 20 U over 24 hours prior to labor may not need interpartum use of insulin infusion and Insulin dosing is stopped after birth and capillary glucose monitoring for 24-48 hours. CONCLUSIONS: We hope that the consensus based recommendations mentioned in this paper will be a useful reference tool for healthcare practitioners to achieve glycaemic targets in GDM patients.
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Diabetes Gestacional/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Glucemia/metabolismo , Consenso , Diabetes Gestacional/sangre , Femenino , Humanos , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Periodo Periparto , Guías de Práctica Clínica como Asunto , EmbarazoRESUMEN
Hyperglycaemia occurs frequently in critically-ill patients. Not only does it occur among patients with pre-existing diabetes mellitus but elevated blood glucose values during an acute illness can also be seen in previously glucose-tolerant individuals (stress hyperglycaemia). Numerous observational studies have shown an increase in morbidity and mortality in critically ill patients with hyperglycaemia. Interestingly, outcomes in individuals with stress hyperglycaemia are worse than that in critically ill hyperglycaemic patients with pre-existing diabetes. Proper management of hyperglycaemia has been shown to result in improved clinical outcomes. Critically ill patients with hyperglycaemia should primarily be managed with intravenous insulin infusion to allow dynamic adjustment of treatment to suit the rapid changes in blood glucose values in these patients. Currently, there are in existence a fair number of published protocols to administer intensive intravenous insulin therapy that range from the relatively simple to the fairly complex. Different management strategies have been proposed depending upon whether the critically ill hyperglycaemic patient is stationed in the emergency department, the medical intensive care unit (ICU), the surgical ICU or the coronary care unit. Moreover, the ideal target blood glucose value to maintain in this group of patients remains controversial. Keeping these issues in mind, a group of leading experts in the fields of diabetes and critical care extensively reviewed the literature and framed recommendations with special attention to clinical practice in India. The aim was to formulate recommendations which are based on sound evidence and yet are simple and easy to understand and implement across the ICU throughout the country. In the current recommendations, intensive intravenous insulin therapy has been suggested as the preferred mode of managing hyperglycaemia in patients admitted to critical care settings. The current recommendations suggest using a simple and similar protocol for managing hyperglycaemia in critically-ill patients irrespective of their location among the various critical care units in a hospital. Recommendations have also been made for transition from intravenous to subcutaneous administration of insulin when the patient is transferred out of the critical care setting. It is hoped that the current recommendations shall form the basis for the management of hyperglycaemia in critically ill patients across the country.
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Cuidados Críticos/métodos , Enfermedad Crítica/terapia , Diabetes Mellitus/tratamiento farmacológico , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Administración Intravenosa , Humanos , India , Inyecciones Subcutáneas , Guías de Práctica Clínica como AsuntoAsunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Hemoglobina Glucada/metabolismo , Automonitorización de la Glucosa Sanguínea , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/orina , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/orina , Glucosuria/orina , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Monitoreo AmbulatorioRESUMEN
BP control in diabetic patients is often poor. The contribution of secondary hypertension due to undiagnosed PA in hypertensive type 2 diabetic patients is not well studied. We prospectively screened 100 consecutive Asian type 2 diabetic patients with difficult-to-control or resistant hypertension for PA. PAC (pmol/L) to PRA (ng/mL/h) ratio was measured; those with PAC-to-PRA ratio >550 (corresponding PAC >415) underwent intravenous 0.9% SLT. Patients with PAC >/=140 following SLT had CT adrenals and bilateral AVS. Thirteen patients (13%) were confirmed to have PA, and all had resistant hypertension. Eight had a surgically correctable form of PA. Patients with PA had higher mean (SD) systolic [159.0 (10.6) vs. 146.0 (10.7) mmHg, p=0.001] and diastolic BP [94.6 (6.0) vs. 87.6 (5.9) mmHg, p=0.001], lower serum potassium [3.5 (0.6) vs. 4.3 (0.5) mmol/L, p=0.001], and higher PAC [679.3 (291.0) vs. 239.5 (169.4) pmol/L, p=0.001]. Identification and institution of definitive treatment for PA resulted in better BP control and in a reduction in the use of antihypertensive medications. Our findings demonstrate a high prevalence of PA in type 2 diabetic patients with resistant hypertension. Systematic screening for PA in this select group is recommended, as targeted treatment improves BP control.
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Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/etnología , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/etnología , Hipertensión Renal/diagnóstico , Hipertensión Renal/etnología , Anciano , Antihipertensivos/uso terapéutico , Pueblo Asiatico/estadística & datos numéricos , Comorbilidad , Resistencia a Medicamentos , Femenino , Humanos , Hipertensión Renal/tratamiento farmacológico , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Prevalencia , Factores de RiesgoRESUMEN
INTRODUCTION: Blockade of the renin-angiotensin-aldosterone system (RAAS) by either the angiotensin converting enzyme inhibitor (ACE-I) or the angiotensin II receptor blocker (ARB) has been shown to reduce albuminuria and delay the progression of diabetic nephropathy. This study evaluated the effect of dual blockade of the RAAS by adding an ACEI or an ARB to the administration of either drug alone on albuminuria in Asian type 2 diabetic patients with nephropathy. METHODS: 34 patients were randomly assigned to receive either enalapril 20 mg or losartan 100 mg once daily for eight weeks. Following this, all patients received a combination of enalapril 10 mg and losartan 50 mg daily for eight weeks, followed by enalapril 20 mg and losartan 100 mg daily for another eight weeks. The blood pressure and 24-hour urinary albumin excretion (UAE) were monitored. RESULTS: Following monotherapy with enalapril, there was a mean and standard error (SE) reduction in the UAE and mean arterial pressure (MAP) of 9.8 (SE 6.8) percent (p-value is 0.061) and 5.3 (SE 2.2) mmHg (p-value is 0.026), respectively; the reduction in UAE and MAP following monotherapy with losartan was by 10.9 (SE 14.1) percent (p-value is 0.053) and 4.5 (SE 1.9) mmHg (p-value is 0.034), respectively. Combination therapy with enalapril and losartan further reduced the UAE (11.2 [SE 8.7] percent, p-value is 0.009] despite there being no significant change in the MAP (-1.2 [SE 1.47] mmHg, p-value is 0.42). The adverse effects included dry cough (seven [19.4 percent] patients, resulting in the withdrawal of medication in two patients), and transient hyperkalaemia (two [six percent] patients). CONCLUSION: Dual blockade of the RAAS is safe and effective in reducing albuminuria in Asian type 2 diabetic patients with nephropathy.
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Albuminuria/tratamiento farmacológico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/tratamiento farmacológico , Enalapril/uso terapéutico , Losartán/uso terapéutico , Anciano , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Pueblo Asiatico , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
When performed properly, bilateral inferior petrosal sinus sampling (BIPSS) for adrenocorticotropic hormone (ACTH) is rarely associated with complications. Major complications reported to date include thromboembolism, brain stem infarction, pontine haemorrhage, isolated sixth nerve palsy and venous subarachnoid haemorrhage. We describe a rare case where a predominant contrast extravasation into the subarachnoid space, admixed with a small quantity of venous blood, occurring during BIPSS in a 58-year-old woman with ACTH-dependent Cushing's syndrome, was misinterpreted as venous subarachnoid haemorrhage.
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Síndrome de Cushing/diagnóstico , Extravasación de Materiales Terapéuticos y Diagnósticos , Muestreo de Seno Petroso , Hemorragia Subaracnoidea/diagnóstico , Venas/patología , Hormona Adrenocorticotrópica/sangre , Tronco Encefálico/patología , Síndrome de Cushing/complicaciones , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , Tromboembolia/etiología , Tomografía Computarizada por Rayos X/métodosRESUMEN
A 45-year-old woman with poorly controlled hypertension and diabetes mellitus presented with left iliac fossa pain, constipation alternating with diarrhea, and weight loss. She had been diagnosed with idiopathic cardiomyopathy five years previously. Echocardiogram had shown a left ventricular ejection fraction (LVEF) of 35%; coronary angiogram was normal. Colonoscopy revealed sigmoid colitis with stenosis. Abdominal computed tomography revealed a 5 cm right adrenal tumor. Twenty-four hour urinary free catecholamines and fractionated metanephrine excretion values were elevated, confirming pheochromocytoma. Her colitis resolved after one month of adrenergic blockade. Repeat echocardiogram showed improvement of LVEF to 65%. After laparoscopic right adrenalectomy, the patient's hypertension resolved, and diabetic control improved. Timely management avoided further morbidity and potential mortality in our patient.
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Neoplasias de las Glándulas Suprarrenales/diagnóstico , Colitis Isquémica/etiología , Colon Sigmoide/irrigación sanguínea , Feocromocitoma/diagnóstico , Enfermedades del Sigmoide/etiología , Neoplasias de las Glándulas Suprarrenales/terapia , Adrenalectomía , Antagonistas Adrenérgicos alfa/uso terapéutico , Antagonistas Adrenérgicos beta/uso terapéutico , Cardiomiopatía Dilatada/complicaciones , Catecolaminas/análisis , Colitis Isquémica/terapia , Constricción Patológica/etiología , Constricción Patológica/terapia , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Persona de Mediana Edad , Fenoxibenzamina/uso terapéutico , Feocromocitoma/terapia , Propranolol/uso terapéutico , Enfermedades del Sigmoide/terapiaRESUMEN
A non-obese patient who was admitted initially with hypoglycemia had multiple episodes of cardiopulmonary arrests requiring resuscitations and a short period of mechanical ventilation. A subsequent sleep study confirmed the diagnosis of severe obstructive sleep apnea (OSA) and documented an episode of near-arrest with cerebral hypoxia during rapid eye movement sleep. We suggest that OSA coupled with impairment of arousal response and other apnea termination mechanisms had resulted in prolonged apnea, life-threatening hypoxemia, and cardiopulmonary arrest in this patient. We review the current understanding of the mechanisms of apnea termination in OSA and suggest that further studies are needed to investigate these mechanisms and their roles in sudden death during sleeping hours in patients with OSA.
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Paro Cardíaco/diagnóstico , Apnea Obstructiva del Sueño/diagnóstico , Adulto , Reanimación Cardiopulmonar , Presión de las Vías Aéreas Positiva Contínua/métodos , Diabetes Mellitus Tipo 2/complicaciones , Diagnóstico Diferencial , Trastornos de Somnolencia Excesiva/diagnóstico , Trastornos de Somnolencia Excesiva/etiología , Electrocardiografía , Paro Cardíaco/complicaciones , Paro Cardíaco/terapia , Humanos , Hipoglucemia/complicaciones , Hipoxia Encefálica/diagnóstico , Hipoxia Encefálica/etiología , Masculino , Neumonía por Aspiración/diagnóstico , Neumonía por Aspiración/etiología , Recurrencia , Respiración Artificial , Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/terapiaRESUMEN
INTRODUCTION: In a patient with hyperthyroidism, the detection of elevated thyroid hormone concentration with measurable thyroid-stimulating hormone (TSH) value poses considerable diagnostic difficulties. CLINICAL PICTURE: This 38-year-old lady presented with clinical features of thyrotoxicosis. Her serum free thyroxine concentrations were unequivocally elevated [45 to 82 pmol/L (reference interval, 10 to 20 pmol/L)] but the serum TSH values were persistently within the reference interval [0.49 to 2.48 mIU/L (reference interval, 0.45 to 4.5 mIU/L)]. TREATMENT: Investigations excluded a TSH-secreting pituitary adenoma and a thyroid hormone resistance state and confirmed false elevation in serum TSH concentration due to assay interference from heterophile antibodies. The patient was treated with carbimazole for 18 months. OUTCOME: The heterophile antibody-mediated assay interference disappeared 10 months following the initiation of treatment with carbimazole, but returned when the patient relapsed. It disappeared again 2 months after the initiation of treatment. CONCLUSIONS: Clinicians should be aware of the potential for interference in immunoassays, and suspect it whenever the test results seem inappropriate to the patient's clinical state. Misinterpretation of test values, arising as a result of assay interference, may lead to misdiagnosis, unnecessary and at times expensive investigations, delay in initiation of treatment and worst of all, the initiation of inappropriate treatment.
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Enfermedad de Graves/diagnóstico , Tirotoxicosis/diagnóstico , Tirotropina/sangre , Adenoma/diagnóstico , Adulto , Anticuerpos Heterófilos/análisis , Anticuerpos Heterófilos/inmunología , Errores Diagnósticos , Femenino , Humanos , Inmunoensayo , Neoplasias Hipofisarias/diagnóstico , Tirotoxicosis/sangre , Tirotoxicosis/inmunología , Tiroxina/sangreRESUMEN
Antineutrophil cytoplasmic antibody (ANCA)- associated vasculitis is a potentially life-threatening adverse effect of antithyroid medications. We present a 22-year-old woman with Graves' disease who developed recurrent episodes of arthritis while on treatment with propylthiouracil. A diagnosis of propylthiouracil-induced ANCA-associated vasculitis was established only after exhaustive rheumatological investigations failed to establish a cause for her arthritis. Anti-myeloperoxidase antibody (anti-MPO) titres were grossly elevated at 172.7 RU/mL (0-20). Her arthritis resolved promptly following the withdrawal of propylthiouracil and the anti-MPO titres declined over 16 months to 66.8 RU/mL. While she did not develop the life-threatening renal or respiratory tract complications, there was a delay in establishing the correct diagnosis with its attendant morbidity. This case highlights the need for greater awareness of this relatively rare adverse effect of antithyroid medications so as to allow its early detection, leading to the prompt cessation of the offending medication.
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Antitiroideos/efectos adversos , Artritis/inducido químicamente , Enfermedad de Graves/tratamiento farmacológico , Propiltiouracilo/efectos adversos , Vasculitis Leucocitoclástica Cutánea/inducido químicamente , Adulto , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Femenino , Enfermedad de Graves/complicaciones , HumanosRESUMEN
INTRODUCTION: At times, it may be difficult to differentiate early stage, low-grade adrenocortical carcinoma from benign adrenal adenoma. CLINICAL PICTURE: A 53-year-old lady underwent right adrenalectomy for a 4-cm adrenocortical tumour causing Cushing's syndrome. Histology revealed an adrenocortical adenoma. Sixteen years later, she presented with a 14-cm adrenal tumour, again on the right side. TREATMENT: She underwent surgical removal of the tumour. Histology confirmed adrenocortical carcinoma. OUTCOME: She died of metastatic disease 17 months later. CONCLUSIONS: This case highlights the importance of long-term, systematic follow-up of patients treated for benign adrenal adenomas, especially if the tumour size exceeds 4 cm.
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Neoplasias de la Corteza Suprarrenal/patología , Carcinoma Corticosuprarrenal/patología , Síndrome de Cushing/etiología , Recurrencia Local de Neoplasia/patología , Neoplasias de la Corteza Suprarrenal/complicaciones , Neoplasias de la Corteza Suprarrenal/cirugía , Adenoma Corticosuprarrenal/patología , Carcinoma Corticosuprarrenal/complicaciones , Carcinoma Corticosuprarrenal/secundario , Carcinoma Corticosuprarrenal/cirugía , Diagnóstico Diferencial , Resultado Fatal , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Presentation of anaplastic thyroid carcinoma with thyrotoxicosis is extremely rare and its occurrence in a patient with Wegener's granulomatosis has not been reported previously. We describe an elderly lady with Wegener's granulomatosis who developed a rapidly growing anaplastic thyroid carcinoma in a preexisting multinodular goiter and discuss the mechanism of thyrotoxicosis in this patient.
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Carcinoma/complicaciones , Bocio Nodular/complicaciones , Neoplasias de la Tiroides/complicaciones , Tirotoxicosis/etiología , Anciano , Carcinoma/patología , Resultado Fatal , Femenino , Granulomatosis con Poliangitis/complicaciones , HumanosRESUMEN
Aging is associated with a gradual decline in the function of a number of endocrine glands. While there are phenotypic similarities seen in the changes of aging with some endocrine hormone deficiency states, the relationship between the decline in growth hormone (GH) secretion, and the decrease in serum insulin-like growth factor-I (IGF-I), with these body composition changes is far from clear. The decline in serum IGF-I, unlike that of thyroxine and estradiol, is not accompanied by an increase in pituitary GH secretion. The recent enthusiastic recommendation for GH 'replacement' in the aging population with low serum IGF-I remains highly controversial. The evidence is still unclear on any significant beneficial effect of such replacement in healthy fit elderly men and women. There is some early evidence of beneficial effects of such replacement in the frail elderly. There are no studies that have investigated the effect of GH on longevity in humans, but results from animal studies on caloric restriction and longevity do not suggest that GH administration will increase life span. There is still insufficient evidence that treatment with exogenous GH in the healthy elderly that attains serum IGF-I levels similar to that of young adults is beneficial or safe.
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Envejecimiento/fisiología , Hormona de Crecimiento Humana/fisiología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Envejecimiento/sangre , Envejecimiento/efectos de los fármacos , Hormona de Crecimiento Humana/efectos adversos , Hormona de Crecimiento Humana/sangre , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Longevidad , Valores de Referencia , Factores de RiesgoRESUMEN
OBJECTIVE: To audit our practice of performing ovarian and adrenal venous catheterization and sampling in hyperandrogenic women who fail to suppress their elevated androgen levels following a 48-h low-dose dexamethasone suppression test (LDDST). We considered the technical success rate of catheterization, the extra information obtained in addition to the standard biochemical tests and imaging findings, and the impact of sampling on management decisions. DESIGN: A retrospective analysis of the results of all ovarian and adrenal venous catheterizations performed at St Bartholomew's Hospital, London, in the years 1980-1996. PATIENTS AND METHODS: Baseline ovarian and adrenal androgens were measured in all women presenting with symptoms and signs of hyperandrogenism. Those patients who failed to suppress their elevated testosterone (T), androstenedione (A4) and/or dehydroepiandrosterone-sulphate (DHEAS) levels following a LDDST to within the normal range or to less than 50% of the baseline value were investigated further with adrenal computed tomography (CT), ovarian ultrasound, and ovarian and adrenal venous catheterization and sampling. RESULTS: Results were available in 38 patients. The overall catheterization success rate was: all four veins in 27%, three veins in 65%, two veins in 87%. The success rate for each individual vein was: right adrenal vein (RAV) 50%, right ovarian vein (ROV) 42%, left adrenal vein (LAV) 87% and left ovarian vein (LOV) 73%. Eight patients were found to have tumours by means of imaging (adrenal CT and ovarian ultrasound), three adrenal and five ovarian, seven of which underwent operation. In six of these patients the clinical presentation was suggestive of the presence of a tumour; in addition, the combination of imaging findings allowed the detection of suspicious adrenal and ovarian masses in all eight cases. The five patients with ovarian tumours had serum testosterone levels > 4.5 nmol/l. In a further eight patients, laparotomy was performed based on a combination of diagnostic and therapeutic indications; in two of these patients the catheterization results were suggestive of an ovarian tumour. All these eight patients were shown histologically to have polycystic ovarian syndrome (PCOS), and no occult ovarian tumour was identified. None of the patients with nontumourous hyperandrogenism had a baseline testosterone level in excess of 7 nmol/l (median 4.4 nmol/l, range 2.5-7 nmol/l). CONCLUSIONS: Our results suggest that ovarian and adrenal venous catheterization and sampling should not be performed routinely in women presenting with symptoms and signs of hyperandrogenism, even if they fail to suppress their elevated androgen levels to a formal 48-h LDDST. All patients presenting with symptoms and signs of hyperandrogenism and elevated androgen levels, and where the suspicion of an androgen-secreting tumour is high, should have adrenal CT and ovarian ultrasound imaging to detect such a tumour. Venous catheterization and sampling should be reserved for patients in whom uncertainty remains, as the presence of a small ovarian tumour cannot be excluded on biochemical and imaging studies used in this series alone. Its use should be restricted to units with expertise in this area.
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Glándulas Suprarrenales/irrigación sanguínea , Recolección de Muestras de Sangre/métodos , Cateterismo/estadística & datos numéricos , Hiperandrogenismo/etiología , Auditoría Médica , Ovario/irrigación sanguínea , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Glándulas Suprarrenales/diagnóstico por imagen , Adulto , Androstenodiona/sangre , Sulfato de Deshidroepiandrosterona/sangre , Dexametasona , Femenino , Glucocorticoides , Humanos , Hiperandrogenismo/sangre , Persona de Mediana Edad , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/diagnóstico por imagen , Ovario/diagnóstico por imagen , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/diagnóstico por imagen , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y Especificidad , Testosterona/sangre , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
OBJECTIVE: Combination chemotherapy with the two agents streptozotocin (SZT), which is a nitrosurea, and 5-fluorouracil (5-FU), an alkylating agent, has a long-established role in the treatment of neuroendocrine tumours; however, it is often accompanied by considerable toxicity, and it has not been assessed in a comparative manner with other current chemotherapy regimens. In order to assess the therapeutic response and adverse effects using an alternative nitrosurea, lomustine (CCNU), which has a different side-effect profile, in combination with 5-FU, we have reviewed all patients with neuroendocrine tumours who received this form of treatment in our department. DESIGN: Retrospective analysis of the case notes of patients with metastatic neuroendocrine tumours who received treatment with the combination of CCNU and 5-FU, and who were followed up according to a defined protocol in a given time frame. PATIENTS: Thirty-one patients with metastatic neuroendocrine tumours (18 with carcinoid tumours, five islet-cell tumours, five chromaffin-cell tumours and three medullary carcinoma of the thyroid) treated with the combination of CCNU and 5-FU, and when necessary additional therapy, over a 22-year period, were included in this analysis. MEASUREMENTS: The symptomatic, hormonal and tumoural responses before and after chemotherapy with the combination of CCNU and 5-FU over a median follow-up duration of 25 months (range 9-348 months) were recorded. Of the 31 patients (16 males; median age 52 years, range 20-86 years), eight (four males; median age 61 years, range 30-74 years) were treated with the combination of CCNU and 5-FU alone (Group 1), whereas the other 23 patients (12 males; median age 47 years, range 20-86 years) received additional therapy with other chemotherapeutic regimens, somatostatin analogues, alpha-interferon or radiolabelled meta-iodobenzylguanidine (131I-MIBG) therapy (Group 2). RESULTS: A total of 121 therapeutic cycles was administered (mean 3.9, range 1-14 cycles). None of the patients obtained a complete tumour response. A partial tumour response (not a complete but a 50% or greater reduction of all measurable tumour) was seen in six out of the 29 patients (21%) (four out of eight in Group 1 and two out of 21 in Group 2, respectively). There was no tumour progression in eight out of the 29 patients (27.5%) (one out of eight in Group 1 and seven out of 21 in Group 2, respectively). The median survival over the period of the study was 48 months (95% confidence interval, CI, 22-74 months). The overall 5-year survival rate was 42% (95% CI, 17-67%) for all patients and 50% (95% CI, 18-83%) for the carcinoid group alone, according to Kaplan-Meier analysis. A complete or partial symptomatic response was obtained in 12 out of 27 (44%) patients who presented with symptoms (four out of eight in Group 1 and eight out 19 in Group 2, respectively) and a complete or partial hormonal response in eight out of 19 patients (42.1%) who presented with hormonally active disease (two out of four in Group 1 and six out of 15 in Group 2, respectively). Nine out of the 15 (60%) patients with carcinoid tumours who presented with symptoms obtained a symptomatic response, five out of 10 patients (50%) a hormonal response, and four out of 16 (25%) patients a partial tumoural response, respectively. The combination of CCNU and 5-FU was safe and well tolerated. Serious side-effects necessitating the termination of CCNU and 5-FU were seen only in two patients, and mainly consisted of reversible bone marrow suppression. No chemotherapy-related death was recorded. CONCLUSIONS: Chemotherapy with CCNU and 5-FU, either alone or in combination with other therapeutic modalities, produces considerable symptomatic and hormonal improvement and moderate tumour regression/stabilization according to currently accepted WHO criteria, particularly in patients with metastatic gastroenteropancreatic neuroendocrine tumours with minimal adverse effects. However, long-term survival was still relatively poor. It may therefore be a valuable additional therapl was still relatively poor. It may therefore be a valuable additional therapeutic option, particularly for well-differentiated carcinoid and islet-cell tumours, but mainly reserved for when there is no response or progression of the disease after currently available first-line treatment with somatostatin analogues or radiopharmaceuticals.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Tumores Neuroendocrinos/tratamiento farmacológico , Tumores Neuroendocrinos/secundario , Adulto , Anciano , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Lomustina/administración & dosificación , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/mortalidad , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
INTRODUCTION: Several studies have assessed the impact of the 1997 American Diabetes Association (ADA) recommendation, of using fasting plasma glucose (FPG) concentration, to diagnose diabetes mellitus in population-based cohorts. However, data concerning the impact of this recommendation in the hospital setting are limited. As the performance characteristics of diagnostic tests vary depending on the prevalence of diabetes in the population studied, we have examined the clinical impact of adopting the ADA recommendations in comparison to the traditional 2-hour post-load glucose (2HPG) concentration used by the World Health Organisation (WHO) in diagnosing diabetes and other categories of glucose intolerance in Singaporean hospital patients. MATERIALS AND METHODS: We analysed the results of the standard 75 g oral glucose tolerance test (OGTT) performed on 625 patients in our hospital from 1994 to 1999. RESULTS: The prevalence of diabetes amongst these 625 patients was 36.8% (230) based on the ADA recommendation of using FPG, 42.8% (263) on using the 2HPG and 52.0% (325) on using the full 1998 WHO criteria. The degree of agreement (kappa) in establishing the diagnosis of diabetes between the FPG and 2HPG cut-offs was 0.48. Ninety-five (15.2%) individuals had diabetes based on the 2HPG alone, 62 (9.9%) based on the FPG alone and 168 (26.9%) based on both the FPG and 2HPG. Eighty-six (13.8%) individuals had impaired fasting glucose (IFG) and 123 (19.7%) had impaired glucose tolerance (IGT). The kappa-value between IFG and IGT was 0.08. CONCLUSION: Fasting plasma glucose concentration was an inadequate parameter in diagnosing diabetes and intermediate categories of glucose intolerance in our cohort of subjects. Our findings suggest that the OGTT remains an important diagnostic tool for classifying glucose tolerance in our hospital patients.
Asunto(s)
Glucemia/análisis , Diabetes Mellitus/diagnóstico , Intolerancia a la Glucosa/diagnóstico , Prueba de Tolerancia a la Glucosa , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Prueba de Tolerancia a la Glucosa/normas , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , SingapurRESUMEN
INTRODUCTION: Hypoglycaemic episodes in patients with diabetes mellitus are mostly due to excess doses of exogenous insulin or oral hypoglycaemic agents, coupled with poor caloric intake and excessive unplanned physical exertion. Hypoglycaemia as a result of endogenous hyperinsulinaemia due to an insulinoma is extremely rare in such patients. CLINICAL PICTURE: This patient with type 2 diabetes mellitus presented with episodes of syncope. Investigations confirmed recurrent hypoglycaemia from endogenous hyperinsulinaemia, with localisation of a tumour in the tail of the pancreas. TREATMENT: Distal pancreatectomy and splenectomy. Histology confirmed an insulinoma. OUTCOME: No further hypoglycaemic episodes were noted. The patient returned to his diabetic state with rather poor glycaemic control. CONCLUSIONS: Repeated hypoglycaemic episodes in a patient with diabetes mellitus despite complete withdrawal of hypoglycaemic agents should lead one to consider other causes of hypoglycaemia.
Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Hipoglucemia/etiología , Insulinoma/complicaciones , Neoplasias Pancreáticas/complicaciones , Síncope/etiología , Humanos , Insulinoma/cirugía , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/cirugíaRESUMEN
OBJECTIVE: Meta-iodo-benzyl-guanidine labelled with 131-iodine [(131)I-mIBG] has been used extensively for imaging tumours originating from the neural crest but experience with its therapeutic use is limited, particularly for non-catecholamine secreting tumours. In order to assess the therapeutic response and potential adverse effects of the therapeutic administration of (131)I-mIBG, we have reviewed all patients who had received this form of treatment in our department. DESIGN: Retrospective analysis of the case notes of patients with neuroendocrine tumours who received treatment with (131)I-mIBG and were followed-up according to a defined protocol in a given time frame. PATIENTS: Thirty-seven patients (18 with metastatic carcinoid tumours, 8 metastatic phaeochromocytoma, 7 metastatic paraganglioma and 4 metastatic medullary carcinoma of the thyroid) treated with (131)I-mIBG over a 15-year period were included in this analysis. MEASUREMENTS: The symptomatic, hormonal and tumoural responses before and after (131)I-mIBG therapy over a median follow-up duration of 32 months (range 5-180 months) were recorded. Of the 37 patients (22 males; median age 51 years, range 18-81 years), 15 were treated with (131)I-mIBG alone whereas the other 22 received additional therapy. RESULTS: A total of 116 therapeutic (131)I-mIBG doses were administered [mean cumulative dose 592 mCi (21.9 GBq); range 200-1592 mCi (7.4-58.9 GBq)]. None of the patients showed a complete tumour response. However, 82% of patients treated with (131)I-mIBG alone and 84% who received additional therapy showed stable disease over the period of follow-up. Overall survival during the period of the study was 71%. The overall 5-year survival rate was 85% (95% confidence interval, 72-99%) for all patients and 78% (95% confidence interval, 55-100%) for the carcinoid group alone, according to Kaplan-Meier analysis. Symptomatic control was achieved in all the patients treated with (131)I-mIBG alone, and in 72% of those receiving additional therapy. Hormonal control was noted in 50% and 57% of patients, respectively. (131)I-mIBG therapy was safe and well tolerated. Serious side-effects necessitating the termination of (131)I-mIBG therapy were seen in only 2 of our patients. CONCLUSIONS: (131)I-mIBG therapy produces symptomatic and hormonal improvement and moderate tumour regression/stabilization in patients with metastatic neuroendocrine tumours with minimal adverse effects. It may be a valuable alternative or additional therapeutic option to the currently available conventional treatment modalities.