Tumor adrenal productor de corticotropina determinante de síndrome de Cushing / Cushing’s syndrome due to an ACTH-producing adrenal tumor

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Haploinsufficiency at GCK gene is not a frequent event in MODY2 patients.

OBJECTIVE: The aim of this study was to characterize glucokinase (GCK) alterations in maturity-onset diabetes of the young 2 (MODY2)-suspected patients and to investigate their clinical characteristics in relation to the parental origin of the mutation. PATIENTS AND METHODS: We studied a group of 57 unrelated Spanish patients presenting with MODY2 phenotype. Patients without mutation in the coding region of the GCK gene were screened for rearrangements by Multiplex Ligation-dependent Probe Amplification (MLPA). After classification according to the parental origin of the mutation, clinical characteristics were compared between the groups. RESULTS: We detected a point mutation or small deletion or insertion of the GCK gene in 47 patients (82.5%); 19 mutations were novel. In addition, we found a whole-gene deletion by MLPA. Patients carrying a GCK gene defect and those with MODY of unknown genetic origin shows similar phenotypes. Comparison of clinical parameters according to the origin of the mutation did not show any differences in the birth weight (BW) nor in age at diagnosis. Patients who inherited the mutation from the father had higher fasting glucose levels at diagnosis. CONCLUSION: Although the presence of haploinsufficiency of GCK is not a common cause of MODY2, gene dose analysis should be performed when no mutation is found. Strict maternal euglycaemia can contribute to intrauterine growth restriction and low BW when the foetus has inherited the GCK mutation from the mother. As foetal genotype in generally is not known, serial foetal abdominal scans may act as a surrogate for this.

Mutations in GCK and HNF-1alpha explain the majority of cases with clinical diagnosis of MODY in Spain.

OBJECTIVE: The aim of this study was to group patients with MODY (maturity-onset diabetes of the young) according to the genetic alterations underlying the disease and to investigate their clinical characteristics. PATIENTS AND METHODS: Molecular analysis of GCK (MODY2), HNF-1alpha (MODY3), HNF-4alpha (MODY1) and HNF-1beta (MODY5) genes was performed by DNA sequencing in 95 unrelated index probands (47M/48F; mean age 9.9 +/- 5.2 years) with clinical diagnosis of MODY. After classification into MODY subtypes according to the genetic alterations, clinical characteristics were compared between the groups. RESULTS: Seventy-six families were shown to carry mutations in GCK (34 of them previously unreported), eight families presented HNF-1alpha mutations, and a large genomic rearrangement in HNF-1beta was found in a family. No alteration was found in HNF-4alpha. Thus, relative frequencies in the group studied were 80% MODY2, 8.5% MODY3 and 1% MODY5. Comparison of clinical parameters according to genetic status showed significant differences between MODY2 and MODY3 patients in age at diagnosis (9.4 +/- 5.4 years vs. 12.7 +/- 4.6 years), diagnosis (impaired glucose tolerance vs. diabetes), diagnostic test used (OGTT vs. fasting glucose), treatment (diet and exercise vs. insulin/oral antidiabetic agents) and birth weight (2.96 +/- 0.44 kg vs. 3.40 +/- 0.67 kg). CONCLUSION: Almost 90% of the MODY cases in the group studied are explained by mutations in the major genes GCK (MODY2) and HNF-1alpha(MODY3), although differences in the relative prevalence of each form could be partly due to patient referral bias (paediatric vs. adult). In general, patients with MODY2 were diagnosed at an earlier age in life than MODY3 patients and had a milder form of diabetes. Moreover, the majority of patients with MODY2 mutations were treated with diet whereas half of MODY3 patients received pharmacological treatment.

Intraoperative monitoring of kinetic total serum calcium levels in primary hyperparathyroidism surgery.

BACKGROUND: In the setting of minimal approach Sestamibi-guided parathyroid surgery for primary hyperparathyroidism we evaluated if total serum calcium level monitoring is as valuable as intraoperative parathyroid hormone (iPTH) monitoring. STUDY DESIGN: Prospective open single-blinded efficacy trial of two intraoperative diagnostic monitoring methods (iPTH and total serum calcium level) on a cohort of surgical patients. All patients (n = 35) were undergoing parathyroid surgery at the Department of General Surgery at B Cruces' Hospital, Vizcaya, Spain, between October 1999 and March 2001. Kinetics of serum levels of Ca and iPTH during surgery and time of prediction of cure for each method (measured in the clinic, admission, and intraoperatively, such as induction of anesthesia, and every 5 minutes after removal of adenoma) were analyzed. RESULTS: Hypercalcemia and iPTH levels became corrected in 34 patients. Average serum calcium levels dropped from pathologic 11.07 +/- 0.41 mg/dL (mean +/- standard deviation) to normal values 9.7 +/- 0.82 mg/dL during the first intraoperative determination (minute 5), but mean iPTH decreased from pathologic (192 +/- 98 pg/mL) to normal values (39.93 +/- 25.12 pg/mL) during the third intraoperative determination (minute 15). Serum calcium level at 5 minutes after removal decreased by 100% in 34 patients, but iPTH only showed a similar drop during the third determination at 15 minutes. Frozen sections were conclusive for parathyroid tissue (20.56 +/- 10.3 minutes after removal). CONCLUSIONS: Intraoperative measurement of total calcium level might be an easier and less expensive method than iPTH measurement in the prediction of cure during surgery for primary hyperparathyroidism resulting from adenoma.