Food-dependent Cushing's syndrome: possible involvement of leptin in cortisol hypersecretion.

Stimulation ofcortisol secretion by food intake has been implicated in the pathogenesis of some cases of ACTH-independent Cushing's syndrome, via an aberrant response of the adrenal glands to gastric inhibitory polypeptide (GIP). We report here a novel case of food-dependent Cushing's syndrome in a patient with bilateral macronodular adrenal hyperplasia. In this patient we were able to confirm a paradoxical stimulation of cortisol secretion by GIP in vivo as well as in vitro on dispersed tumor adrenal cells obtained at surgery. In addition to GIP, in vitro stimulation of these cultured tumor adrenal cells with leptin, the secreted product of the adipocyte, induced cortisol secretion. By comparison, no such stimulation was observed in vitro in adrenal cells obtained from another patient with bilateral macronodular adrenal hyperplasia and Cushing's syndrome that did not depend on food intake, in tumor cells obtained from a solitary cortisol-secreting adrenal adenoma, and in normal human adrenocortical cells. These results demonstrate that as in previously described cases of food-dependent Cushing's syndrome, GIP stimulated cortisol secretion from the adrenals of the patient reported here. Therefore, they indicate that such a paradoxical response probably represents the hallmark of this rare condition. In addition, they suggest that leptin, which normally inhibits stimulated cortisol secretion in humans, participated in cortisol hypersecretion in this case. Further studies in other cases of food-dependent Cushing's syndrome, however, will be necessary to better ascertain the pathophysiological significance of this finding.

High risk for hyperlipidemia and the metabolic syndrome after an episode of hypertriglyceridemia during 13-cis retinoic acid therapy for acne: a pharmacogenetic study.

BACKGROUND: Administration of 13-cis retinoic acid (isotretinoin) for acne is occasionally accompanied by hyperlipidemia. It is not known why some persons develop this side effect. OBJECTIVE: To determine whether isotretinoin triggers a familial susceptibility to hyperlipidemia and the metabolic syndrome. DESIGN: Cross-sectional comparison. SETTING: University hospital in Lausanne, Switzerland. PARTICIPANTS: 102 persons in whom triglyceride levels increased at least 1.0 mmol/L (> or =89 mg/dL) (hyperresponders) and 100 persons in whom triglyceride levels changed 0.1 mmol/L (< or =9 mg/dL) or less (nonresponders) during isotretinoin therapy for acne. Parents of 71 hyperresponders and 60 nonresponders were also evaluated. MEASUREMENTS: Waist-to-hip ratio; fasting glucose, insulin, and lipid levels; and apoE genotype. RESULTS: Hyperresponders and nonresponders had similar pretreatment body weight and plasma lipid levels. When reevaluated approximately 4 years after completion of isotretinoin therapy, hyperresponders were more likely to have hypertriglyceridemia (triglyceride level > 2.0 mmol/L [>177 mg/dL]; odds ratio [OR], 4.8 [95% CI, 1.6 to 13.8]), hypercholesterolemia (cholesterol level > 6.5 mmol/L [>252 mg/dL]; OR, 9.1 [CI, 1.9 to 43]), truncal obesity (waist-to-hip ratio > 0.90 [OR, 11.0 (CI, 2.0 to 59]), and hyperinsulinemia (insulin-glucose ratio > 7.2; OR, 3.0 [CI, 1.6 to 5.7]). In addition, more hyperresponders had at least one parent with hypertriglyceridemia (OR, 2.6 [CI, 1.2 to 5.7]) or a ratio of total to high-density lipoprotein cholesterol that exceeded 4.0 (OR, 3.5 [CI, 1.5 to 8.0]). Lipid response to isotretinoin was closely associated with the apoE gene. CONCLUSION: Persons who develop hypertriglyceridemia during isotretinoin therapy for acne, as well as their parents, are at increased risk for future hyperlipidemia and the metabolic syndrome.

Low immunoglobulin levels in patients with cystic fibrosis: reduced inflammation or sign of common variable immunodeficiency syndrome?

Introduction: In children with cystic fibrosis (CF), low immunoglobulin (IgG) levels have been reported to be associated with significantly less severe lung disease. However, decreased IgG can be a sign for common variable immunodeficiency (CVID) and affect clinical outcome. The aim of this study was to analyze clinical and serological data of patients having low IgG levels in routine blood tests at annual assessment, particularly their antibody response to polysaccharide antigens. Method: Retrospective chart review of demographic data of CF patients followed at the pediatric CF clinic throughout 2009. Clinical parameters (genotype, pancreas sufficiency, FEV1), presence of Pseudomonas aeruginosa (PA) and number of exacerbations per year were correlated with immunoglobulin and vaccination antibodies levels (antibodies to pneumococcal serotypes 14, 19, 23, 1, 5 and 7F measured by enzyme-linked immune-sorbent assay). Results: 4 out of 60 patients (6.7%) had lower IgG-levels for age. Ages ranged from 1 year 8 months to 11 years, 2 boys, 2 girls. Three patients were delF508 homozygotes, one heterozygote composite delF508/G542X. All were pancreatic insufficient. FEV1 ranged from 74 to 108%. One patient never had colonization by PA, 2 had intermittent PA colonization and one was chronically infected. After conjugated vaccination all patients had protective antibodies against serotypes 14, 19, 23F. For serotypes not included in the vaccine, only one patient had protective titers for 1 out of 3 serotypes. None of the patients had received unconjugated pneumococcal vaccine. There was no significant clinical difference in FEV1, PA colonization or number of exacerbations according to IgG and vaccination antibody levels. Conclusion: Cystic Fibrosis patients with low immunoglobulin levels have normal antibody response to protein antigens. However, despite recurrent infections, there seems to be delayed or deficient antibody response to polysaccharide antigens. Prospective studies are needed to evaluate the development of polysaccharide antibody responses in CF-patients to monitor for CVID. With early detection of CF by newborn screening program, long term follow up could be started early in childhood.

Oral findings in Midline Syndrome: a case report and literature review

We describe a female patient with a midline syndrome. The patient presents agenesis of the corpus callosum, encephalocele, iris coloboma, hypertelorism, submucosal cleft palate and dental anomalies. Despite being very characteristic, her phenotypical traits do not coincide exactly with those reported to date in the literature. The karyotype and the molecular cytogenetic study do not show mutations. We identify the presence of dental anomalies in the mother and other family members, not being identified MSX1 and PAX9 mutations that could the related with their etiology. Despite the fact that dental agenesis has been related to a large number of other malformation syndromes and congenital conditions, dental anomalies have only rarely been mentioned when reporting midline syndromes. These dental phenotypical traits, present in the patient and her family, could be considered part of the midline syndrome in carriers as well as in the patients.

Traducción médica comentada inglés-español: Polycystic Ovary Syndrome(Joyce King)

El trabajo se divide en tres partes: una traducción del ámbito médico inglés-español; un glosario de términos extraídos del texto con su equivalente en español, y un análisis de los principales problemas de traducción detectado y que son frecuentes en los textos biomédicos, con sus respectivas soluciones.

Positron Emission Tomography and Computer Tomography (PET/CT) in Prostate, Bladder, and Testicular Cancers.

Positron emission computed tomography (PET) is a functional, noninvasive method for imaging regional metabolic processes that is nowadays most often combined to morphological imaging with computed tomography (CT). Its use is based on the well-founded assumption that metabolic changes occur earlier in tumors than morphologic changes, adding another dimension to imaging. This article will review the established and investigational indications and radiopharmaceuticals for PET/CT imaging for prostate cancer, bladder cancer and testicular cancer, before presenting upcoming applications in radiation therapy.

Further delineation of the facial 13q14 deletion syndrome in 13 retinoblastoma patients.

Thirteen years ago, Motegi and colleagues (J Med Genet 1987;24:696-697) summarized the specific facial phenotype of six Japanese retinoblastoma patients with interstitial 13q14 deletions. Among a series of 228 propositi with retinoblastoma referred to the Lausanne Retinoblastoma Clinic for treatment and genetic counseling between 1986 and 1997, 13 (5.7%) were diagnosed with a cytogenetic de-novo 13q14 deletion. We confirm the presence of the reported facial phenotype in our population of Caucasian patients and describe additional clinical traits, thus extending the facial phenotype associated with the 13q14 deletion. Del(13q14) comprises, among others, cranial anomalies, frontal bossing, deeply grooved and long philtrum, depressed and broad nasal bridge, bulbous tip of the nose, thick lower lip, thin upper lip, broad cheeks, and large ears and lobules. Recognition of this particular facial appearance was instrumental in the genetic diagnosis of 13q deletions and in the presymptomatic diagnosis of retinoblastoma in a significant number of our cases. Identification of this phenotype in a retinoblastoma patient allows for efficient diagnosis of recurrence in his progeny and/or sibship, while its ignorance will compromise genetic counseling due to the possible difficulties in detecting large deletions by standard molecular mutation analysis. Recognition of this syndrome in newborns without known familial risk for retinoblastoma is even more important as it is a clear warning sign that indicates immediate ophthalmic examination.