RESUMEN
We report the case of a Caucasian patient with insulin autoimmune syndrome (IAS), defined as the association of hypoglycaemic attacks with insulin autoantibodies in individuals not previously treated with exogenous insulin. This rare syndrome (more than 200 published cases) has been reported mainly in Japan. Most affected patients present with other autoimmune disorders, most often Graves' disease. In most cases, insulin autoantibodies appear a few weeks after the beginning of treatment with a drug containing a sulphyldryl group. A significant increase in insulin and C-peptide plasma concentrations and the presence of other antiorgan antibodies are observed. The susceptibility haplotype is present in the Japanese population, which may account for the high frequency of IAS. Spontaneous remission is observed in 80% of cases, with cessation of hypoglycaemic attacks and disappearance of insulin autoantibodies some months after withdrawal of the drug. This rare cause of hypoglycaemia in Caucasian subjects should be considered in aetiologic investigation of spontaneous hypoglycaemia.
Asunto(s)
Antitiroideos/uso terapéutico , Autoanticuerpos/sangre , Enfermedades Autoinmunes/diagnóstico , Carbimazol/efectos adversos , Hipertiroidismo/tratamiento farmacológico , Hipoglucemia/inmunología , Insulina/inmunología , Propiltiouracilo/uso terapéutico , Antitiroideos/efectos adversos , Péptido C/sangre , Humanos , Hipoglucemia/etiología , Insulina/sangre , Japón , Masculino , Persona de Mediana Edad , Marruecos/etnología , Paris , Síndrome , Población BlancaAsunto(s)
Desamino Arginina Vasopresina/uso terapéutico , Diabetes Insípida/tratamiento farmacológico , Fármacos Renales/uso terapéutico , Desamino Arginina Vasopresina/administración & dosificación , Desamino Arginina Vasopresina/efectos adversos , Deshidratación/inducido químicamente , Humanos , Mutación/genética , Receptores de Vasopresinas/efectos de los fármacos , Receptores de Vasopresinas/genética , Fármacos Renales/administración & dosificación , Fármacos Renales/efectos adversos , Factores de Riesgo , Intoxicación por Agua/inducido químicamenteRESUMEN
UNLABELLED: Previous studies have failed to predict somatostatin analog response with somatostatin receptor scintigraphy in pituitary adenomas. In vitro studies have shown that the density of somatostatin receptors in pituitary tumors might be critical for octreotide response. METHODS: The density of somatostatin receptors was calculated in vivo combining the uptake index obtained from somatostatin receptor scintigraphy and the tumor volume obtained by MRI. The ratio of these two values, called density index (DI), was established in 32 of 37 consecutive patients with pituitary adenomas (11 had growth hormone-secreting adenomas, 4 thyroid-stimulating hormone-secreting and 17 nonfunctioning). It was compared with hormonal response, assessed in 15 secreting adenomas on growth hormone or thyroid stimulating hormone suppression (which was considered significant when it reached at least 50% of basal level), and with tumor shrinkage (which was considered significant when > or =20% of pretherapeutic value) in 12 secreting and 14 nonfunctioning adenomas. RESULTS: In agreement with previous reports, uptake index is not predictive of octreotide response. In contrast, DI predicts both hormonal suppression and tumor shrinkage (P = 0.009 and P = 0.0002, respectively) obtained with octreotide therapy. DI sensitivity, specificity and accuracy were 92% each, and a positive correlation was found between DI and the percentage of tumor shrinkage (r = 0.54, P = 0.004). CONCLUSION: The combination of scintigraphic and MRI data allows the computation of a DI for somatostatin receptors that points out patients who can profit from somatostatin analog treatment.
Asunto(s)
Adenoma/diagnóstico por imagen , Octreótido/uso terapéutico , Neoplasias Hipofisarias/diagnóstico por imagen , Receptores de Somatostatina/análisis , Adenoma/metabolismo , Adulto , Anciano , Femenino , Hormona de Crecimiento Humana/metabolismo , Humanos , Radioisótopos de Indio , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/metabolismo , Cintigrafía , Radiofármacos , Tirotropina/metabolismo , Factores de TiempoRESUMEN
OBJECTIVE: Given the central role of the GnRH receptor (GnRHR) in the regulation of the gonadotrophin secretion, it might be implicated directly or indirectly in the pathogenesis of gonadotroph tumours. DESIGN: We determined if GnRHR mRNA was expressed in gonadotroph tumours using RT-PCR and analysed the GnRHR gene for the presence of mutations in its coding region, using direct sequencing of PCR products. Results were analysed according to the pattern of expression of alpha, beta-FSH and beta-LH subunit (SU) genes. SUBJECTS: RNA was extracted from 20 gonadotroph tumours identified by immunohistochemistry (> 10% of stained cells): 9 adenomas were functioning (high serum gonadotrophin levels), 3 were associated with high alpha-SU levels and 8 were nonfunctioning. Genomic DNA was extracted from 64 normal subjects. RESULTS: We found GnRHR mRNA in 12 tumours (60%): 8/9 functioning (88%), 1/3 alpha-secreting (33%) and 3/8 nonfunctioning (37.5%) gonadotroph adenomas. There was a significant association between GnRHR expression and immunostaining for beta-FSH (P = 0.014). The nucleotide sequence of the amplified products was identical to that of human pituitary except for the presence, in 3 functioning adenomas, of a silent C to T transition at nucleotide 453 encoding for the serine residue situated in the second intracellular loop at position 151. Heterozygosity provided evidence that both alleles were transcribed in these tumours. This substitution creates a Mae III restriction site. Genomic DNA from normal subjects were then tested for the presence of this new polymorphism. The frequency of the heterozygosity (18.7%) was not significantly different from that found in gonadotroph tumours (25%) and this new Mae III polymorphism site cannot be used as a tumoural marker. CONCLUSION: The GnRHR gene is preferentially expressed in functioning rather than in nonfunctioning gonadotroph adenomas, but no mutations altering the coding region of the gene were found to further substantiate its role in the pathogenesis of gonadotroph tumours.
Asunto(s)
Adenoma/genética , Adenoma/metabolismo , Gonadotropinas Hipofisarias/metabolismo , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/metabolismo , Receptores LHRH/genética , Adolescente , Adulto , Anciano , Secuencia de Bases , Femenino , Expresión Génica , Heterocigoto , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Polimorfismo GenéticoRESUMEN
Relationships between glycaemic control, hypertension, and development of microangiopathy have been well documented in Type 1 (insulin-dependent) but not in Type 2 (non-insulin-dependent) diabetes mellitus. Therefore, we have investigated these relationships in a cohort of 64 Type 2 patients free of retinopathy (by angiofluorography), who were regularly followed until development of retinopathy or for at least 7 years as outpatients. Glycaemic control was assessed by 1 to 4 HbA1 determinations per year. Retinal status was monitored by annual angiofluorography. Nonproliferative retinopathy developed in 14 patients (cumulative incidence at 13 years: 29.8%) after a mean diabetes duration of 14.3+/-8.9 years (range 2-27). In multivariate analysis (Cox model), mean HbA1 during follow-up (p < 0.001), and hypertension at first examination (p = 0.09) were associated with the development of retinopathy, but age, sex, BMI, diabetes duration, smoking, and fasting blood glucose were not. The relative risk for developing retinopathy (RR) was 7.2 (IC 95%: 1.61-32.4) in patients with a mean HbA1 during follow-up above the median value of the cohort (8.3%) compared with patients with HbA1 during follow-up below this value. RR was 2.5 (IC 0.8-8) in patients with HbA1 at first examination above compared to below the median value (8.4%). RR was 3.0 (IC 0.9-10) in patients treated for hypertension at baseline compared to those without treatment. A sixfold increase in retinopathy prevalence was observed between patients with mean HbA1 in the highest or lowest quartile of mean HbA1 distribution during follow-up. This longitudinal study indicates a strong association between long-term glycaemic control and the development of diabetic retinopathy in Type 2 diabetes.
Asunto(s)
Glucemia/análisis , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Retinopatía Diabética/epidemiología , Retinopatía Diabética/fisiopatología , Hemoglobina Glucada/análisis , Adulto , Anciano , Albuminuria , Análisis de Varianza , Presión Sanguínea , Distribución de Chi-Cuadrado , Creatinina/sangre , Angiopatías Diabéticas/epidemiología , Femenino , Humanos , Hipertensión/epidemiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Análisis de Supervivencia , Factores de TiempoRESUMEN
The mechanisms of chronic diarrhoea, a frequent symptom in diabetes mellitus, are multifactorial and complex, although small intestinal bacterial overgrowth and autonomic neuropathy seem to play a major role. This study evaluated the prevalence of small intestinal bacterial overgrowth and the effects of antibiotic treatment in a population of diabetic patients with chronic diarrhoea (defined as > 3 stools/24 h, weight > 200 g/24 h, duration > 3 weeks). Small intestinal bacterial overgrowth syndrome was diagnosed by glucose-hydrogen breath testing (sensitivity: 78%, specificity: 89%). The characteristics of diarrhoea (duration, number of stools per day, and gastrointestinal symptoms) were noted. Autonomic neuropathy was assessed by cardiac parasympathetic tests. A total of 35 patients were included, 15 with small intestinal bacterial overgrowth syndrome (43%, group 1) and 20 with no bacterial overgrowth (group 2). Age (52.9 +/- 13.5 vs. 53.9 +/- 11.8 years, NS), duration of diabetes (13.8 +/- 9.1 vs. 10.6 +/- 7.8 years, NS), and HbA1c level (10 +/- 2.9 vs. 10.9 +/- 2.4%, NS) were not different between the two groups. In group 1, duration of diarrhoea was longer (18.1 +/- 18.5 vs. 7.75 +/- 4.02 months, P = 0.05), the number of stools higher (7.1 +/- 5.7 vs. 4.6 +/- 2.6/24 h, P < 0.05), and gastrointestinal symptoms more frequent (13 vs. 10, P < 0.05). The prevalence of small intestinal bacterial overgrowth syndrome and gastrointestinal symptoms was not different in patients with and without autonomic neuropathy (9 vs. 8 and 12 vs. 11 respectively, NS). Eight patients with bacterial overgrowth received antibiotics (amoxicillin-clavulanic acid, 1.5 g/24 h for 10 days). Dramatic clinical improvement was observed in 6 out of 8 of these patients. It is concluded that small intestinal bacterial overgrowth should be considered in case of chronic diabetic diarrhoea because of its frequency (43%), facility of diagnosis, and often successful treatment with antibiotics.
Asunto(s)
Bacterias/aislamiento & purificación , Diarrea/epidemiología , Intestino Delgado/microbiología , Enfermedad Crónica , Femenino , Francia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , PrevalenciaRESUMEN
OBJECTIVE: The somatostatin analog octreotide has been demonstrated to improve optic tract compression caused by pituitary macroadenomas within hours of its administration and/or reduce tumor size in some patients. We report the results of a prospective multicenter study of the effects of octreotide on visual function and tumor size in patients with nonfunctioning pituitary adenomas or gonadotropin-secreting adenomas. METHODS: Twenty-four patients with visual defects caused by histologically confirmed macroadenomas were administered octreotide via continuous subcutaneous infusion, as follows: 100 micrograms the 1st day and, if necessary, 200 micrograms the 2nd and then 100 or 200 micrograms three times daily if visual function improved. Vision was assessed after 4 days, 1 month, and 2 months, including tumor size evaluation. Visual improvement was defined by a net gain of at least 2/10 in acuity and/or of more than 20% of the surface of one isopter (a reduction in tumor volume of > or = 20% of the initial measurement); opposite changes were defined as deterioration. RESULTS: Visual improvement was noted in 13 of 24 patients, 10 of 23 patients and 9 of 22 patients, and was not noted in 11 of 24 patients, 14 of 23 patients, and 13 of 22 patients after 4 days, 1 month, and 2 months, respectively. After 2 months, three adenomas had shrunk, three had not changed in size, and one had increased; visual function improved in the seven patients with these adenomas. Octreotide was discontinued in 13 patients for lack of efficacy. CONCLUSION: The incidence of visual improvement and tumor shrinkage noted in this study was higher than previously reported. Our data suggest that early onset of visual improvement might help in deciding which patients profit from octreotide. However, concomitant gain in visual acuity with deterioration in visual fields or visual improvement with an increase (moderate) in tumor size can occur.
Asunto(s)
Adenoma/tratamiento farmacológico , Antineoplásicos Hormonales/uso terapéutico , Gonadotropinas Hipofisarias/metabolismo , Síndromes de Compresión Nerviosa/tratamiento farmacológico , Octreótido/uso terapéutico , Enfermedades del Nervio Óptico/tratamiento farmacológico , Síndromes Paraneoplásicos Endocrinos/tratamiento farmacológico , Neoplasias Hipofisarias/tratamiento farmacológico , Trastornos de la Visión/tratamiento farmacológico , Adenoma/metabolismo , Adulto , Anciano , Antineoplásicos Hormonales/efectos adversos , Quimioterapia Adyuvante , Terapia Combinada , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Subcutáneas , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Síndromes de Compresión Nerviosa/diagnóstico , Octreótido/efectos adversos , Enfermedades del Nervio Óptico/diagnóstico , Síndromes Paraneoplásicos Endocrinos/diagnóstico , Neoplasias Hipofisarias/metabolismo , Estudios Prospectivos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Trastornos de la Visión/diagnóstico , Agudeza Visual/efectos de los fármacos , Campos Visuales/efectos de los fármacosRESUMEN
OBJECTIVE: A multicentre study was undertaken to determine the value of somatostatin receptor (sst) scintigraphy in predicting hormonal and visual responses to octreotide treatment in GH-secreting and non-functioning pituitary adenomas. SUBJECTS AND METHODS: Somatostatin receptor scintigraphy was performed in 48 patients (19 acromegaly, 29 non-functioning pituitary adenomas with ophthalmological defects). Results were expressed as an uptake index of the pituitary area. A threshold for positivity was determined in 23 subjects considered as controls. Thirty-five patients were treated for 1 month with octreotide (300 micrograms daily). The therapeutic response was assessed on GH and IGF-I suppression or evolution of the ophthalmological defects. The relationships between the somatostatin receptor scintigraphy result, the therapeutic effect of octreotide and in vitro studies performed in 12 tumours were studied. RESULTS: From the results of control subjects the uptake index threshold for positivity was 2. In patients, somatostatin receptor scintigraphy was positive in 64% and there was no relationship between uptake index and tumour size. In GH tumours, somatostatin receptor scintigraphy was positive in 68%; uptake index was related to octreotide-induced GH and IGF I suppression. The positive predictive value was 100% and the negative predictive value was 50%. In vitro studies showed detectable binding sites for somatostatin with sst2 and sst5 expression in the 4 GH tumours studied although somatostatin receptor scintigraphy was negative in 2 cases. In non-functioning pituitary adenomas somatostatin receptor scintigraphy was positive in 62%. Based on visual effects, the positive predictive value was 61% and the negative predictive value was 100%. A wide distribution of somatostatin binding sites was found in 8 non-functioning pituitary adenomas with expression of sst2 only. CONCLUSION: In the conditions of the study, in patients with acromegaly, positive somatostatin receptor scintigraphy predicts a hormonal response but the value of somatostatin receptor scintigraphy is limited by its low negative predictive value. In patients with non-functioning pituitary adenomas, negative somatostatin receptor scintigraphy predicts that there will be no visual improvement during octreotide treatment.
Asunto(s)
Adenoma/diagnóstico por imagen , Antineoplásicos/uso terapéutico , Hormona del Crecimiento/metabolismo , Octreótido/uso terapéutico , Neoplasias Hipofisarias/diagnóstico por imagen , Receptores de Somatostatina/análisis , Acromegalia/diagnóstico por imagen , Acromegalia/tratamiento farmacológico , Adenoma/tratamiento farmacológico , Adenoma/metabolismo , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/tratamiento farmacológico , Neoplasias Hipofisarias/metabolismo , Valor Predictivo de las Pruebas , Pronóstico , Cintigrafía , Estadísticas no Paramétricas , Resultado del Tratamiento , Campos Visuales/efectos de los fármacosAsunto(s)
Diabetes Mellitus Tipo 2/fisiopatología , Diarrea/tratamiento farmacológico , Octreótido/uso terapéutico , Adulto , Presión Sanguínea , Diabetes Mellitus Tipo 2/complicaciones , Diarrea/complicaciones , Frecuencia Cardíaca , Hormonas/sangre , Humanos , Ácido Hidroxiindolacético/sangre , Inmunoglobulinas/sangre , Masculino , Persona de Mediana Edad , Serotonina/sangre , Tirotropina/sangreRESUMEN
Patients with pituitary adenomas present with hypersecretion syndrome(s), and/or pituitary failure(s), and/or signs of mass effect, or incidentally. Pituitary function evaluation, visual acuity and field check-up, and MRI or at least CAT are compulsory for diagnosis, and for therapeutic approach; surgery for Cushing's disease, dopamine agonists for prolactinomas, somatostatin analogs or surgery for thyrotroph adenomas, surgery and/or somatostatin analogs and/or radiotherapy in acromegaly, surgery with additional irradiation in most adenomas of other types, or even expectation in some instances.
Asunto(s)
Adenoma/diagnóstico , Neoplasias Hipofisarias/diagnóstico , Adenoma/fisiopatología , Adenoma/terapia , Humanos , Imagen por Resonancia Magnética , Pruebas de Función Hipofisaria , Neoplasias Hipofisarias/fisiopatología , Neoplasias Hipofisarias/terapiaRESUMEN
The aim of this study was to find out whether the dysfunction of aldosterone pathway, previously proposed as a marker of secretory adrenal carcinoma, is also found in nonsecretory adrenal carcinomas, which pose even more difficult diagnostic problems even for patients with hypertension accompanied or not by hypokalemia. The exploration consisted of using the same method (RIA preceded by a chromatographic step) to determine the plasma levels of the following steroids in the mineral corticosteroid pathway: deoxycorticosterone (DOC), 18-hydroxydeoxycorticosterone (18-OHDOC), corticosterone (B), 18 hydroxycorticosterone (18 OH B), and aldosterone. The subjects included 16 adults, each presenting with an endocrinologically asymptomatic adrenal mass associated for some patients with hypokalemia and hypertension (8 with adrenal carcinoma, 2 with adrenal metastasis from other forms of cancer, and 6 adenomas). These results show that even in nonsecretory adrenal carcinoma, there is a dysfunction of the aldosterone pathway, which can be evaluated from the ratio between aldosterone and the substrate of 11 beta hydroxylase (DOC) and its derivative (18-OH DOC). This study suggests that exploration of mineralocorticosteroid pathway can be used as a hormonal marker of adrenal carcinoma for both secretory and non-secretory malignant masses.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/sangre , Neoplasias de las Glándulas Suprarrenales/patología , Aldosterona/sangre , Esteroides/sangre , Neoplasias de las Glándulas Suprarrenales/secundario , Adulto , Anciano , Biomarcadores de Tumor/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mineralocorticoides/sangre , Estudios RetrospectivosRESUMEN
Macrovascular disease represents a major cause of morbidity and mortality in patients with diabetes mellitus. Low-density lipoprotein (LDL) is involved in the pathogenesis of atherosclerotic lesions, through modifying processes such as oxidation. We examined the in vitro susceptibility to oxidation and the oxidizability of LDL isolated from the plasma of Type 1 and Type 2 diabetic patients. Two groups of diabetic patients (20 Type 1, 20 Type 2) were compared with sex- and age-matched non-diabetic control groups. In vitro oxidation of the purified LDL preparations was assessed by determination of the kinetics for the formation of conjugated dienes (lag phase duration, maximal rate and maximal dienes concentration) and by measurement of thiobarbituric acid-reacting substances (TBARS) in the presence of copper ions. LDL from both Type 1 and Type 2 diabetic patients exhibited a shorter lag phase duration for conjugated dienes formation (94 +/- 14 vs. 108 +/- 20 and 97 +/- 26 vs. 112 +/- 18 min for Type 1 and Type 2 diabetic groups vs. respective control groups, P < 0.05). We also observed an increase in maximal rate of conjugated dienes formation (2.21 +/- 0.55 vs. 1.52 +/- 0.31 and 2.02 +/- 0.55 vs. 1.52 +/- 0.31 nmol/mg LDL/min, P < 0.01) and of maximal production of TBARS (77.9 +/- 11.8 vs. 65.5 +/- 10.4 and 76.7 +/- 9.9 vs. 65.3 +/- 9.4 nmol/mg LDL protein, P < 0.05) in diabetic groups. Our results demonstrate both a higher susceptibility to oxidation and a higher oxidizability of LDL from diabetic patients, as much for Type 1 as Type 2 diabetic subjects with or without pre-existent vascular complications. This enhanced propensity of LDL oxidation in patients with diabetes mellitus could at least partly be attributable to quantitative and qualitative alterations in the chemical composition of LDL and to the glycoxidation process occurring on these lipoproteins.
Asunto(s)
Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Lipoproteínas LDL/sangre , Adulto , Cobre/química , Femenino , Humanos , Cinética , Peroxidación de Lípido/efectos de los fármacos , Lipoproteínas LDL/química , Masculino , Oxidación-Reducción , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Treatment with the somatostatin analog octreotide is associated with increased gallstone formation. The mechanism of formation of these stones is unclear. The purpose of this study was to examine the effect of a three-month treatment with octreotide on biliary lipid composition and the occurrence of cholesterol crystals in patients with acromegaly. Thirteen patients with active acromegaly, aged 24-76 years, received octreotide (100 micrograms three times daily) for three months. Fasting gallbladder bile was obtained during upper gastrointestinal endoscopy after ceruletide stimulation. Bile was studied before and at the end of the treatment period (N = 7), only before (N = 4), or only at the end of treatment (N = 2). Before treatment, all bile samples but one were supersaturated with cholesterol. However, none contained cholesterol crystals on microscopic examination. At the end of the treatment period, all but two samples were supersaturated with cholesterol. Three of nine samples contained cholesterol crystals, a proportion significantly higher than before treatment. The relative proportions of bile acids, cholesterol, and phospholipids, and the mean cholesterol saturation index were not different before and during treatment. Follow-up ultrasonography showed the occurrence of gallstones in four patients, including the three patients who had cholesterol crystals. We conclude that: (1) fasting gallbladder bile of patients with acromegaly is frequently supersaturated with cholesterol; (2) treatment with octreotide does not increase cholesterol saturation index, but may induce the occurrence of cholesterol crystals. The data are consistent with the view that gallstones induced by octreotide are cholesterol stones and suggest that the drug may impair gallbladder motility and/or decrease cholesterol nucleation time.
Asunto(s)
Acromegalia/tratamiento farmacológico , Bilis/química , Colesterol/análisis , Lípidos/análisis , Octreótido/uso terapéutico , Acromegalia/metabolismo , Adulto , Anciano , Ácidos y Sales Biliares/análisis , Cristalización , Femenino , Humanos , Masculino , Persona de Mediana Edad , Octreótido/efectos adversos , Fosfolípidos/análisis , Estudios ProspectivosRESUMEN
Fine-needle aspiration biopsy (FNAB) of thyroid nodules has been proposed as a preoperative screening method to reduce the number of patients with benign nodules referred for surgery. Only a few previously published studies have compared cytologic results with a systematic surgical control; furthermore, the role of ultrasound guidance for FNAB in obtaining representative material has been poorly evaluated. The authors tried to assess the diagnostic value of FNAB performed under ultrasonography in a series of patients with a cold nodule and a systematic surgical control. This prospective study included 132 consecutive patients, 19 men and 113 women, aged from 18 to 82 years. The rate of carcinomas was 13.8%. A very high rate of adequate material was obtained (96.2%). Sensitivity, specificity, and global accuracy were 95%, 87.7%, and 89%, respectively. These results, which are equivalent to those previously published but associated with a low level of insufficient material, emphasize the diagnostic value of thyroid FNAB.
Asunto(s)
Biopsia con Aguja , Nódulo Tiroideo/patología , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sensibilidad y Especificidad , Nódulo Tiroideo/diagnóstico por imagen , UltrasonografíaRESUMEN
OBJECTIVE: Free glycoprotein hormone alpha-subunit plasma levels have been reported to be increased in glycoprotein hormone-secreting adenomas and in acromegaly, but rarely in prolactinomas and in only two cases of Cushing's disease. The prevalence of elevated plasma alpha-subunit levels in patients with non-functioning adenomas is still unclear. In addition, no previous work has described plasma alpha-subunit levels in a comprehensive series of adenomas characterized by in-vivo secretion and/or immunocytochemistry. PATIENTS: Thirty-seven patients with definite prolactinomas and 48 with non-functioning tumours characterized by immunocytochemistry were studied, from a series of 145 consecutive patients including 33 acromegalics, 18 patients with glycoprotein hormone-secreting adenomas and 9 with Cushing's disease. MEASUREMENTS: Plasma free alpha-subunit was measured by radioimmunoassay in all patients and in a large sample of normal subjects to establish normal ranges according to sex, age and menstrual status. Tumour volume index was the product in cm3 of length, width and height of the adenoma as assessed by computerized tomography or magnetic resonance imaging. RESULTS: Twelve of the 37 (32%) patients with prolactinomas had increased plasma alpha-subunit levels; their tumours were significantly larger with significantly higher plasma PRL levels than those of patients without increased plasma alpha-subunit levels (P < 0.02). All prolactinomas above 50 cm3 were associated with alpha-subunit secretion, whereas only 6 of 29 smaller tumours were similarly associated. Twelve of the 48 'non-functioning' adenomas actually secreted alpha-subunit in vivo: 8 gonadotrophin-secreting, 2 'pure' alpha-secreting, one with negative immunocytochemistry and one necrotic adenoma. Their volumes were significantly higher than those of adenomas without increased plasma alpha-subunit levels (P < 0.04). Plasma alpha-subunit levels were increased in the 6 patients with TSH-secreting adenomas, 8 of 12 with FSH-secreting adenomas, 11 of 33 acromegalics and none of those with Cushing's disease. CONCLUSION: Plasma free alpha-subunit levels were increased in 49 of 145 patients (34%). For prolactinomas and 'non-functioning' adenomas, alpha-subunit hypersecretion was seen more often with larger tumours. Half of the cases with increased free alpha-subunit in this series were patients harbouring an adenoma which did not stain for an intact glycoprotein hormone.
Asunto(s)
Adenoma/metabolismo , Hormonas Glicoproteicas de Subunidad alfa/metabolismo , Neoplasias Hipofisarias/metabolismo , Prolactinoma/metabolismo , Adenoma/sangre , Adenoma/patología , Adolescente , Adulto , Anciano , Femenino , Hormonas Glicoproteicas de Subunidad alfa/sangre , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/sangre , Neoplasias Hipofisarias/patología , Prolactinoma/sangre , Prolactinoma/patologíaRESUMEN
Somatostatin receptor imaging (SRI) was performed in five patients with known non-functioning pituitary adenomas. To determine whether the pituitary uptake correlates with response to octreotide therapy, an uptake index (UI) was calculated. Pituitary adenomas were detected in all five patients. The UI was, respectively, 15.1, 3.7, 2.2, 2.2 and 2.2 (the UI calculated in 12 normal subjects was between 1 and 1.9). Only the patient with the highest UI (15.1) had a dramatic improvement in tumour volume and visual function in response to octreotide therapy. The UI might be a good predictive parameter of octreotide therapy efficacy in non-functioning adenomas.
Asunto(s)
Adenoma/diagnóstico por imagen , Octreótido/uso terapéutico , Neoplasias Hipofisarias/diagnóstico por imagen , Receptores de Somatostatina/análisis , Adenoma/tratamiento farmacológico , Adulto , Anciano , Femenino , Humanos , Radioisótopos de Indio , Persona de Mediana Edad , Hipófisis/química , Hipófisis/diagnóstico por imagen , Neoplasias Hipofisarias/tratamiento farmacológico , Cintigrafía , Somatostatina/análogos & derivadosRESUMEN
As they are clinically silent, gonadotroph cell pituitary adenomas are usually diagnosed only when pituitary enlargement causes visual impairment or hypopituitarism. In postmenopausal women presenting with pituitary tumors it can be difficult to determine whether gonadotropin hypersecretion is due to adenomatous or normal gonadotrophs prior to surgery. The usual GnRH dependency of gonadotropin secretion may be of diagnostic and therapeutic value. We therefore evaluated responses to the GnRH antagonist Nal-Glu-GnRH and to the long-acting GnRH agonist D-Trp6 (3.75 mg IM) in 9 and 4 patients with FSH- and/or alpha-subunit-secreting adenomas, respectively. Six of the 7 patients with FSH-secreting adenomas and one of the 2 patients with pure alpha subunit-secreting adenomas were studied postoperatively. In these patients postoperative FSH and/or alpha-subunit levels remained elevated and pituitary imaging by CT-scan and/or MRI disclosed tumoral residues. In the 2 remaining patients testing was performed preoperatively. A single administration of 5 mg Nal-Glu to the 7 patients with FSH-secreting adenomas produced a slight but significant fall in above-normal FSH levels from 24.4 +/- 15.4 IU/l to a nadir of 20.3 +/- 11.9 IU/l (-17%, p < 0.05) 20 h following the injection. LH levels fell markedly in the 6 patients with normal basal serum LH concentrations to those observed in hypophysectomized patients, while mean alpha-subunit levels were not modified. Alpha-subunit levels were not modified by Nal-Glu administration in the 2 patients with alpha-subunit-secreting adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Adenoma/sangre , Adenoma/patología , Hormona Liberadora de Gonadotropina/análogos & derivados , Hormona Liberadora de Gonadotropina/administración & dosificación , Neoplasias Hipofisarias/sangre , Neoplasias Hipofisarias/patología , Adenoma/química , Adulto , Anciano , Cápsulas , Femenino , Hormona Folículo Estimulante/análisis , Hormona Folículo Estimulante/sangre , Humanos , Inmunohistoquímica , Inyecciones Subcutáneas , Hormona Luteinizante/sangre , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/química , Testosterona/sangre , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
Among high density lipoprotein particles, LpAI particles which contain apolipoprotein A1 alone, appear to be involved in cholesterol transport from peripheral tissues to the liver. The aim of this cross-sectional study was to examine serum LpAI particle concentrations in Type 1 and Type 2 diabetic patients with renal lesions of differing grades, in comparison with normal controls and with nondiabetic patients presenting with chronic renal failure. LpAI concentrations and LpAI-to-apo A1 ratios were increased in Type 1 diabetic patients with normal albumin excretion. In Type 1 and in Type 2 diabetic patients with increased urinary albumin excretion, LpAI concentrations and LpAI-to-apo A1 ratios were found to be not different from those of normal controls. In diabetic and in nondiabetic patients with chronic renal failure, LpAI concentrations were decreased. These abnormalities may contribute to the development of macrovascular complications.
Asunto(s)
Apolipoproteína A-I/metabolismo , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Neuropatías Diabéticas/sangre , Lipoproteína(a)/análogos & derivados , Adulto , Albuminuria , Apolipoproteína A-I/análisis , Apolipoproteínas/análisis , Apolipoproteínas/metabolismo , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Diabetes Mellitus Tipo 1/orina , Diabetes Mellitus Tipo 2/orina , Neuropatías Diabéticas/orina , Femenino , Hemoglobina Glucada/análisis , Humanos , Fallo Renal Crónico/sangre , Lipoproteína(a)/sangre , Masculino , Persona de Mediana Edad , Valores de Referencia , Triglicéridos/sangreRESUMEN
OBJECTIVE: Gonadotroph adenomas are generally revealed by symptoms of mass effect at the stage of macroadenoma. Most of them hypersecrete FSH and/or gonadotrophin subunits. Rarely they hypersecrete LH, which could induce endocrinological symptoms. As the glycoprotein inhibin is secreted by the gonads under FSH control, we have evaluated whether high immunoreactive inhibin (iINH) levels correlated with FSH hypersecretion and whether iINH and FSH levels were related to tumour volume in subjects with gonadotroph adenomas. PATIENTS: Forty-five patients (30 men, 15 women) were retrospectively selected on the basis of immunostaining technique using specific antibodies raised against FSH-beta, LH-beta and glycoprotein alpha-subunit. MEASUREMENTS: Immunoreactive inhibin (iINH) was measured by radioimmunoassay using antiserum 1989 raised to bovine inhibin. Tumour volume index was the product in cm3 of length, width and height of the adenoma as assessed by computerized tomography. RESULTS: In men (age 21-61 years), iINH levels were positively correlated with FSH levels (Spearman's r = 0.67, P < 0.001), and both iINH and FSH levels were significantly correlated with tumour volume index (Spearman's r = 0.38, P < 0.05 and r = 0.39, P < 0.05 respectively). In the subgroup of men with normal FSH levels (n = 17), the correlation of FSH with tumour volume index was high: Spearman's r = 0.56, P < 0.05. In the post-menopausal women (n = 8, age > 55 years), iINH levels were undetectable or below the follicular phase range regardless of FSH values. In the premenopausal women (n = 7, age 22-49 years, follicular phase or amenorrhoea) iINH levels were above follicular phase range in three women including one who had very high FSH levels. CONCLUSIONS: These data show that in men with gonadotroph adenoma FSH levels are related to tumour mass and suggest that a significant part of circulating FSH in patients with normal FSH levels arises from the tumour. The significant correlation between iINH and FSH levels demonstrates that tumoral FSH is bioactive and that high iINH levels do not exert any feedback control on tumoral FSH secretion. Therefore the coexistence of high FSH levels with high iINH levels is strongly suggestive of a gonadotroph adenoma. Gonadotroph adenomas seem to represent a unique model of long-term FSH stimulation of inhibin-producing cells, in some way analogous to that created by repetitive administration of exogenous FSH.
Asunto(s)
Adenoma/química , Hormona Folículo Estimulante/análisis , Inhibinas/análisis , Neoplasias Hipofisarias/química , Adenoma/metabolismo , Adenoma/patología , Adulto , Anciano , Femenino , Hormona Folículo Estimulante/metabolismo , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/metabolismo , Neoplasias Hipofisarias/patología , Estudios RetrospectivosRESUMEN
We report on eight patients with diabetic thoracoabdominal neuropathy in whom careful evaluation of peripheral and autonomic nervous system function was performed. All patients had non insulin-dependent diabetes mellitus of 10.5 +/- 6.7 years mean (+/- SD) known duration with poor glycemic control. Thoracic (n = 7) or abdominal (n = 1) pain of sudden onset involved several adjacent dermatomal segments and was bilateral and asymmetrical in 7/8 patients. Four patients had hypoesthesia in the painful zone and six presented with significant weight loss (6.2 +/- 4.3 kg) which reversed after the relief of pain. Truncal electromyogram was abnormal in 7/7 patients. Nerve damage was not limited to thoracic nerves since electrophysiological studies evidenced distal polyneuropathy in all patients. The autonomic nervous system was also involved. Sympathetic skin response was abnormal in 7/7 patients and autonomic cardiovascular function tests demonstrated cardiac denervation in 5/5 patients. In 4/4 patients a marked relief of pain was noted within one week with amitriptyline treatment. This report confirms the characteristic clinical presentation of diabetic thoracoabdominal neuropathy. Moreover, it suggests that this neuropathy is part of a diffuse damage that also involves peripheral nerves of the limbs and autonomic nervous system.