Résumé
Objective To investigate the value of chloride clearance test in differential diagnosis of Gitelman syndrome (GS). Methods For patients with hypokalemic metabolic alkalosis and highly suspected GS,clinical data were documented and SLC12A3 gene screening was performed as gold standard to diagnose GS. Hydrochlorothiazide (HCT) test and furosemide (FUR) test were performed according to the standard process. Baseline and maximal increasement of chloride excretion fraction (FECl,the net and relative increase measured as εFECl) were compared between patients and controls to evaluated the reaction to the corresponding diuretics. Receiver operating characteristic (ROC) curve was used to evaluate the sensitivity and specificity of HCT test in GS diagnosis. Results Totally 27 patients and 20 health controls received HCT test. Among those patients,23 were diagnosed with GS genetically. When using the net and relative εFECl to diagnose GS,the areas under the ROC curve were 0.987 (95% CI:0.963~1.000,P<0.001) and 0.984 (95%CI:0.950~1.000,P<0.001),respectively. When a reasonable cutoff value for εFECl was selected,the sensitivity and specificity were both higher than 95%. Eight patients received both HCT test and FUR test. Five of them showed decreased reaction to HCT(net εFECl≤2.86% or relative εFECl≤223%),while normal reaction to FUR.SLC12A3 mutations confirmed their GS. Three patients with blunt reaction to FUR showed normal reaction to HCT,finally they were diagnosed as BS clinically because no SLC12A3 gene mutation was detected. Conclusion Comprehensive application of HCT test and FUR test to evaluate the diuretic reaction can effectively differentiate GS and BS.
Sujets)
Humains , Études cas-témoins , Chlorures , Métabolisme , Diagnostic différentiel , Syndrome de Gitelman , Diagnostic , Hydrochlorothiazide , Cinétique , Mutation , Courbe ROC , Sensibilité et spécificité , Membre-3 de la famille-12 des transporteurs de solutés , Génétique , MétabolismeRésumé
THE causes of Cushing's syndrome are mainly divided into adrenocorticotropic hormone (ACTH) dependent and independent. ACTH dependent hypercortisolism represents excess ACTH se-creting by the pituitary or tumor outside the pituitary; and the latter one is also called as ectopic ACTH syndrome. Thorax is the most common location of causative lesions for ectopic ACTH syndrome, and the size of lesion is too small to be detected in some cases.1, 2 Cryptococcal pneumonia usually occurs in immunocompromised patients and excess cortisol production can theoretically produce a state of immunodeficiency. Development of cryptococcal pneumonia concomitant with Cushing syndrome (CS) was rare. Here, we report a case of pulmonary nodule in a patient with CS differentiated with ectopic ACTH-producing tumor. Cryptococcal pneumonia was diagnosed following lung resection.
Sujets)
Humains , Syndrome de sécrétion ectopique d'ACTH , Syndrome de Cushing , Tomographie par émission de positons , Nodule pulmonaire solitaire , TomodensitométrieRésumé
<p><b>BACKGROUND</b>Generalized glucocorticoid resistance syndrome is a rare familial or sporadic condition characterized by generalized, partial, target-tissue insensitivity to glucocorticoids. This syndrome is partially caused by mutations in the human glucocorticoid receptor (hGR) gene. The clinical spectrum of generalized glucocorticoid resistance is broad, ranging from fatigue or no symptoms to severe hypertension with hypokalemic alkalosis. The purpose of this study was to explore the genetic disorder of glucocorticoid resistance syndrome.</p><p><b>METHODS</b>We identified a 56-year-old male patient diagnosed with generalized glucocorticoid resistance syndrome accompanied with an adrenocortical adenoma. This asymptomatic patient referred to Peking Union Medical College Hospital for treatment of his adrenal incidentaloma. Endocrinological evaluation consistently revealed his elevated serum cortisol level. Total RNA was extracted from the patient's peripheral blood mononuclear leukocytes (PBMLs) and entire coding region of hGR alpha was amplified by reverse transcription (RT)-PCR. To confirm the possible mutation identified by sequencing RT-PCR products, genomic DNA sequence of hGR gene from the patient and 50 healthy controls was analyzed by PCR and directly sequencing.</p><p><b>RESULTS</b>A heterozygotic (C→T) substitution at nucleotide position of 1667 (exon 5) in GR alpha gene was found in this patient by sequencing of RT-PCR products of hGR gene. This substitution was also identified at genomic DNA level and it was absent in 100 chromosomes from 50 unrelated health controls. This substitution resulted in a threonine to isoleucine substitution (ACT→ATT) at amino acid 556 in the ligand-binding domain of GR alpha.</p><p><b>CONCLUSION</b>Generalized glucocorticoid resistance in this patient might be caused by a novel heterozygotic mutation in the ligand-binding domain of the GR alpha.</p>
Sujets)
Humains , Mâle , Adulte d'âge moyen , Adénome corticosurrénalien , Génétique , Résistance aux substances , Génétique , Maladies endocriniennes , Génétique , Glucocorticoïdes , Pharmacologie , Mutation ponctuelle , Récepteurs aux glucocorticoïdes , Génétique , RT-PCRRésumé
<p><b>OBJECTIVE</b>To construct mouse Zinc-alpha2-glycoprotein (mZAG) eucaryotic expression plasmid and identify its expression in 3T3-L1 preadipocytes.</p><p><b>METHODS</b>The total RNA from mouse liver tissue was extracted. The reverse-transcript(RT)-PCR method was used to amplify the complete domain sequence of mZAG, and the confirmed PCR products was inserted into expression plasmid by DNA ligation. The mZAG expression plasmids with various concentrations (0, 0.4, 0.8, and 1.6 microg) were transfected into 3T3-L1 preadipocytes, and ZAG expression in mRNA and protein level was determined by real-time fluorescence quantitative PCR and Western blot, respectively.</p><p><b>RESULTS</b>DNA sequencing confirmed the right sequence of mZAG expression plasmid pcDNA3.1(-)-mZAG. After the mZAG expression plasmid with different concentrations were transfected into 3T3-L1 preadipocytes, mZAG mRNA level significantly increased and reached 2.58 folds (P=0.002), 3.67 folds (P=0.000 and 5.19 folds (P=0.001) of that in the control group (no mZAG transfection). mZAG protein level also significantly increased and reached 2.75 folds of that in the control group (P=0.017). Treating 3T3-L1 cells with small interfering RNA (siRNA) sequence siRNA 1 and siRNA 4 resulted in a decrease of mZAG mRNA to 49% and 41% of those in the control group(no siRNA sequence transfection) (P=0.002P=0.000)and a decrease of mZAG protein to 55% and 62% of that in the control group (P=0.004,P=0.025).</p><p><b>CONCLUSIONS</b>mZAG expression plasmid pcDNA3.1(-)-mZAG was successfully established in this study. This plasmid can be well expressed in 3T3-L1 preadipocytes. siRNA 1 and siRNA 4 can effectively inhibit the expression of mZAG in these cells.</p>
Sujets)
Animaux , Souris , Cellules 3T3-L1 , Adipocytes , Métabolisme , Vecteurs génétiques , Plasmides , Génétique , Petit ARN interférent , Génétique , Protéines du plasma séminal , Génétique , Métabolisme , TransfectionRésumé
<p><b>OBJECTIVE</b>To investigate the feasibility of perioperative glycemic control with insulin glargine in type 2 diabetic patients.</p><p><b>METHODS</b>We retrospectively analyzed the clinical data of 16 type 2 diabetic inpatients treated with insulin glargine (research group) and 16 type 2 diabetic inpatients treated with the traditional intensified insulin therapy (control group) for perioperative glycemic control.</p><p><b>RESULTS</b>The fasting blood glucose values of the diabetic patients in the research group on the day of surgery and the first 3 postoperative days were (7.5 +/- 1.8), (8.2 +/- 1.8), (7.6 +/- 1.6), and (7.2 +/- 1.1) mmol/L, respectively, and were (9.0 +/- 2.8), (10.4 +/- 2.4), (8.8 +/- 2.7), (9.0 +/- 2.0) mmol/L in the control group, respectively. The fasting blood glucose values in the research group were significantly lower than the control group on the first and third postoperative day (P = 0.02 and 0.01, respectively). No hypoglycemic events were observed and all wounds were healed well in both groups.</p><p><b>CONCLUSION</b>With satisfied fasting blood glucose level and fewer episode of hypoglycemia, perioperative glycemic control by insulin glargine in type 2 diabetic patients is safe, effective, and convenient.</p>
Sujets)
Humains , Glycémie , Diabète de type 2 , Sang , Traitement médicamenteux , Hypoglycémiants , Utilisations thérapeutiques , Insuline , Utilisations thérapeutiques , Insuline glargine , Insuline à longue durée d'action , Soins périopératoires , Études rétrospectivesRésumé
<p><b>OBJECTIVE</b>To investigate the relationship between hypogonadism and insulin resistance in young male.</p><p><b>METHODS</b>Twenty-one hypogonadism young males aged 15 to 30 years were included in the clinical trial group, and 11 healthy young males of similar age and BMI in the control. Height, weight, serum FSH, LH, total testosterone (TT), nuclear type and bone age were measured for all the subjects. Serum glucose and insulin levels were taken through 3 h OGTT at 0, 30, 60, 120 and 180 min. And comparisons were made of the levels of fast glucose and insulin, areas under the curve of glucose and insulin and HOMA insulin resistance indexes (HOMA-IR) between the two groups.</p><p><b>RESULTS</b>(1) In the hypogonadism group the average value of TT was (0.9 +/- 0.6) nmol/L and 5 cases of Klinefelter syndrome had pubertal development with Tanner stage above P3, while the other 16 had no. (2) No significant differences were found in BMI, age, areas under the glucose and insulin secretory curve in OGTT between the two groups. (3) Three patients were diagnosed as IGT by OGTT in hypogonadism group, whose serum glucose levels at 120 min were 8.6, 7.9 and 8.2 mmol/L respectively. The maximal insulin excretion time was 30 min after glucose loading. No IGT or DM was found in the control group. (4) Significant difference was found in HOMA-IR and fast insulin level between the two groups.</p><p><b>CONCLUSION</b>(1) IGT incidence was higher in the hypogonadism group than in the control. (2) HOMA-IR and fast insulin levels were significantly higher in the hypogonadism group than in the control, which suggests that lower serum testosterone may cause insulin resistance in young male patients.</p>