Daniel Soares Freire

Combined expression of BUB1B, DLGAP5, and PINK1 as predictors of poor outcome in adrenocortical tumors: validation in a Brazilian cohort of adult and pediatric patients

BACKGROUND A recent microarray study identified a set of genes whose combined expression patterns were predictive of poor outcome in a cohort of adult adrenocortical tumors (ACTs). The difference between the expression values measured by qRT-PCR of DLGAP5 and PINK1 genes was the best molecular predictor of recurrence and malignancy. Among the adrenocortical carcinomas, the combined expression of BUB1B and PINK1 genes was the most reliable predictor of overall survival. The prognostic and molecular heterogeneity of ACTs raises the need to study the applicability of these molecular markers in other cohorts. OBJECTIVE To validate the combined expression of BUB1B, DLGAP5, and PINK1 as outcome predictor in ACTs from a Brazilian cohort of adult and pediatric patients. PATIENTS AND METHODS BUB1B, DLGAP5, and PINK1 expression was assessed by quantitative PCR in 53 ACTs from 52 patients - 24 pediatric and 28 adults (one pediatric patient presented a bilateral asynchronous ACT). RESULTS DLGAP5-PINK1 and BUB1B-PINK1 were strong predictors of disease-free survival and overall survival, respectively, among adult patients with ACT. In the pediatric cohort, these molecular predictors were only marginally associated with disease-free survival but not with overall survival. CONCLUSION This study confirms the prognostic value of the combined expression of BUB1B, DLGAP5, and PINK1 genes in a Brazilian group of adult ACTs. Among pediatric ACTs, other molecular predictors of outcome are required.

Expression of LIN28 and its regulatory microRNAs in adult adrenocortical cancer

LIN28 control cells reprogramming and pluripotency mainly through miRNA regulation and has been overexpressed in many advanced cancers. In this study, we evaluated the prognostic role of LIN28 and its regulatory miRNAs in a large cohort of adrenocortical tumours (ACTs).

Development and internal validation of an adrenal cortical carcinoma prognostic score for predicting the risk of metastasis and local recurrence

To develop and internally validate a prognostic score to predict the risk of metastases or recurrence in patients with adrenal cortical carcinomas (ACC).

A premenopausal woman with virilization secondary to an ovarian Leydig cell tumor

Background. A 33-year-old woman presented to an endocrinology clinic with a 5-year history of secondary amenorrhea. 2 years before presentation, she had noticed progressively worsening signs of virilization.Investigations. Measurement of levels of serum free and total testosterone, androstenedione, dehydroepiandrosterone sulfate and gonadotropins; transvaginal ultrasonography, abdominal and pelvic MRI and 18F-fluorodeoxyglucose PET imaging.Diagnosis. Virilization secondary to an ovarian Leydig cell tumor.Management. The patient underwent a left salpingo-oophorectomy that confirmed the diagnosis of a unilateral Leydig cell tumor. Complete normalization of androgens and gonadotropin levels was achieved after surgery.

Hyperinsulinism/hyperammonemia (HI/HA) syndrome due to a mutation in the glutamate dehydrogenase gene

The hyperinsulinism/hyperammonemia (HI/HA) syndrome is a rare autosomal dominant disease manifested by hypoglycemic symptoms triggered by fasting or high-protein meals, and by elevated serum ammonia. HI/HA is the second most common cause of hyperinsulinemic hypoglycemia of infancy, and it is caused by activating mutations in GLUD1, the gene that encodes mitochondrial enzyme glutamate dehydrogenase (GDH). Biochemical evaluation, as well as direct sequencing of exons and exon-intron boundary regions of the GLUD1 gene, were performed in a 6-year old female patient presenting fasting hypoglycemia and hyperammonemia. The patient was found to be heterozygous for one de novo missense mutation (c.1491A>G; p.Il497Met) previously reported in a Japanese patient. Treatment with diazoxide 100 mg/day promoted complete resolution of the hypoglycemic episodes.

Síndrome de Nelson: relato de caso

The aim of this article is to present and discuss several aspects of the pathogenesis, the clinical, hormonal, and imaging diagnosis, and the treatment of Nelsons syndrome, based on a typical patients report, in whom several therapeutic approaches were shown to be ineffective.

Hiperaldosteronismo primário causado por aldosteronoma: problemas no diagnóstico etiológico

Primary aldosteronism (PA) represents an important cause of secondary hypertension, potentially curable, and it has been receiving particular attention due to its increasing prevalence, after the beginning of the use of plasma aldosterone concentration to plasma renin activity ratio as a screening method. We present a case of PA caused by an aldosteronoma associated with a contralateral nonfunctioning adrenal adenoma, which resulted in difficulties in the final diagnosis. We discuss the most appropriated tests to screen, confirm the diagnosis of PA and define the etiology of the disorder, especially the adrenal veins sampling to distinguish the aldosteronoma and idiopathic hyperaldosteronism and to guide successful treatment.