3,070 research outputs found
PRKACA mutations in adrenal adenomas: Genotype/Phenotype correlations
No full textUntargeted, next generation sequencing approaches have provided deep insights into genetic events that result in unopposed steroidogenesis from the adrenal cortex. In particular, somatic mutations in the gene encoding the catalytic subunit α of protein kinase A (PKA) (PRKACA) were identified independently by several groups as the most frequently altered gene in cortisol-producing adenomas. Detailed functional studies could explore the molecular consequences of these hot-spot mutations and large international cohorts have provided the basis to explore the clinical characteristics associated with this mutation. Thereby, PRKACA mutations are highly specific for cortisol over-secretion, while they are absent or very rare in the context of other adrenal diseases. Patients carrying these somatic mutations are affected by a more severe phenotype and are identified at a younger age. Thus, these genotype/phenotype correlations provide further evidence for the importance of PKA-dependent pathways for adrenal physiology and disease
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Felix Almaraz, Author and Teacher, "The Tragic Calvalier."(photograph)
No full textPhotograph of Felix Almaraz, Author and Teacher, "The Tragic Calvalier."
The SPARTACUS Trial: Controversies and Unresolved Issues
Full text linkAdrenal vein sampling (AVS) is considered the gold standard for the differential diagnosis in patients with primary aldosteronism (PA). The distinction between unilateral and bilateral disease dictates the targeted therapeutic approach with surgery for aldosterone producing adenomas and medical therapy for patients with bilateral hyperplasia. Thereby, this diagnostic step is crucial in clinical care. As AVS is an invasive, not well standardized procedure that is restricted to few specialized centers, several attempts have been made to simplify diagnostic algorithms. In this clinical scenario, the recently published SPARTACUS trial aimed at answering the question whether AVS in fact is superior for differential diagnosis in comparison to imaging of the adrenal glands. In this multicenter study, patients were randomized to be treated according to AVS results or based on abdominal imaging only. Clinical outcome in both patient groups after one year was reported as not different. While the study results found broad interest, it also stirred considerable controversies. This review provides an overview on the different views regarding the outline of the SPARTACUS trial and the interpretation of its results
Camp signaling in cortisol-producing adrenal adenoma
No full textThe cAMP signaling pathway is one of the major players in the regulation of growth and hormonal secretion in adrenocortical cells. Although its role in the pathogenesis of adrenocortical hyperplasia associated with Cushing's syndrome has been clarified, a clear involvement of the cAMP signaling pathway and of one of its major downstream effectors, the protein kinase A (PKA), in sporadic adrenocortical adenomas remained elusive until recently. During the last year, a report by our group and three additional independent groups showed that somatic mutations of PRKACA, the gene coding for the catalytic subunit a of PKA, are a common genetic alteration in patients with Cushing's syndrome due to adrenal adenomas, occurring in 35-65% of the patients. In vitro studies revealed that those mutations are able to disrupt the association between catalytic and regulatory subunits of PKA, leading to a cAMP-independent activity of the enzyme. Despite somatic PRKACA mutations being a common finding in patients with clinically manifest Cushing's syndrome, the pathogenesis of adrenocortical adenomas associated with subclinical hypercortisolism seems to rely on a different molecular background. In this review, the role of cAMP/PKA signaling in the regulation of adrenocortical cell function and its alterations in cortisolproducing adrenocortical adenomas will be summarized, with particular focus on recent developments.</p
Adrenal function after adrenalectomy for subclinical hypercortisolism and Cushing's syndrome: A systematic review of the literature
No full textContext: The postoperative course of patients with subclinical hypercortisolism (SH) is yet to be clarified. The aims are to review the prevalence and predictive factors of postoperative adrenal insufficiency and the time to recover a normal adrenocortical function in patients with SH and Cushing's syndrome (CS). Evidence Acquisition: Using the PubMed database, we conducted a systematic review of the literature, selecting studies published from 1980 to 2013. Evidence Synthesis: Of the 1522 papers screened, 28 were selected (13 retrospective, 14 prospective, and one randomized controlled trial). The prevalence of postoperative adrenal insufficiency was 65.3% in 248 SH subjects and 99.7% in 377 CS patients. Patients with SH were reclassified according to the following diagnostic criteria: subjects defined by pathological dexamethasone test only (DEX), and those defined by the dexamethasone test with one (DEX-1) or two additional criteria (DEX+2);andtheywerecomparedwith CS patients. The prevalence of adrenal insufficiency was 51.4, 60.6, 91.3, and 99.7%, respectively, with no significant difference between the two latter groups. The test with the best compromise between sensitivity (64%) and specificity (81%) in predicting adrenal insufficiency was the midnight serum cortisol. The time to achieve eucortisolism was lower in SH patients than in CS patients (6.5 vs 11.2 mo; P < .001). Conclusions: Adrenal insufficiency occurs in about half of the patients with SH if defined only by the pathological dexamethasone test. However, prevalence of adrenal insufficiency and time to recovery are tightly related to the degree of hypercortisolism and diagnostic criteria to define SH, which might help to better define SH for future studies. Copyright © 2014 by the Endocrine Society
Human and Murine Cell Lines for Adrenocortical Carcinoma and Pheochromocytoma
Full text linkAdrenocortical carcinoma (ACC) and pheochromocytoma (PCC) are malignancies originating from distinct layers of the adrenal gland. ACCs arise from the adrenal cortex, are often detected at advanced stages and are associated with poor prognosis. PCCs are mostly benign, arise from the adrenal medulla and have a variable prognosis, with 10% of PCCs resulting in metastasis. Genetic background strongly influences metastasis of PCCs, and no reliable biomarkers that predict metastatic behavior exist to date. Current therapeutic strategies for both ACCs and PCCs are overall limited. Thus, novel preclinical models and drug screening approaches need to be established to aid in the identification of more promising drugs and treatment schemes. In this review, we summarize the currently available human and murine cell lines for both tumor entities
Parents’ assets and child marriage: are mother’s assets more protective than father’s assets?
No full textChild marriage places girls at an increased risk for dropping out of school early, sexually transmitted infections, teenage childbirth, and accompanying childbirth complications, including maternal mortality. The determinants of child marriage are not clearly understood, which hinders efforts to mount effective interventions. This study examined the link between economic resources and child marriage by investigating whether maternal and paternal asset ownership were longitudinally associated with daughters’ child marriage in Ethiopia. Drawing upon household bargaining theory, it was hypothesized that maternal assets would be more protective of daughters’ child marriage than paternal assets. Data for 4,293 girls from the nationally representative Ethiopia Socioeconomic Survey, fielded in 2011 and 2014, were employed. Logistic regression and instrumental variable analyses were used to examine the relationship between transition into child marriage during the study period and maternal and paternal assets, controlling for child-, family-, and community-level characteristics. Results show that a one standard deviation increase in mother’s assets was associated with 37–53% lower odds of daughter’s child marriage whereas a one standard deviation increase in paternal asset holdings was associated with 0–37% higher odds of daughter’s child marriage. Effects were strongest in regions where the dominant mode of marriage payments is bride price. These results suggest that the link between economic resources and child marriage depends on the gender of the parent who owns the resources. This study also highlights the interconnectedness of two targets of the gender equality Sustainable Development Goal—improvement of women’s ownership of assets and the elimination of child marriage—and suggests that the realization of one gender equality target could have implications for other targets.Peer reviewe
Disability among children of immigrants from India and China: is there excess disability among girls?
No full textWe investigate whether there is excess morbidity among daughters of Indian or Chinese immigrants in the US by studying the prevalence of disability among children. We use data from the 2012–14 American Community Surveys on approximately 20,000 US-born children of Indian and Chinese immigrants. Children of US natives are used as a comparison group to account for innate differences in disability between the sexes. Results indicate that there is excess disability among daughters compared with sons among children of Chinese immigrants and children of immigrants from northern or western Indian states; this excess disability declines with younger age at arrival or longer exposure to the host country. Analysis using children of Filipino immigrants as an alternative comparison group yields similar excess disability rates for females.Peer reviewe
Effect of Food Subsidies on Micronutrient Consumption
No full textIn this article, we study the effect of an exogenous increase in wheat and rice price subsidy to poor families resulting from a targeted food price subsidy program in India called the Targeted Public Distribution System (TPDS) on micronutrient intake in low-income families. Descriptive results show that wheat and rice have one of the lowest micronutrient density scores, suggesting that these are poor suppliers of micronutrients. Empirical analysis suggests that the increase in subsidy amount of Rs. 15-18 resulting from the TPDS expansion lowered calcium intake by 12-14 percent and had negligible to small (often negative) effects on the consumption of most micronutrients.Peer reviewe
Sex composition of children and spousal sexual violence in sub-Saharan Africa
No full textObjective
In societies with a cultural preference for sons over daughters, women who do not bear sons may be at increased risk for spousal violence. This study examined whether women with daughters only are at an elevated risk for spousal sexual violence compared to women with sons only in sub-Saharan Africa. The study tested the hypothesis that the association between sex composition of children and spousal sexual violence would be observed only in large families.
Methods
Data were from the most recent (as at February, 2016) Demographic and Health Surveys conducted in 22 sub-Saharan African countries for 37,915 women. Odds ratios comparing experience of spousal sexual violence of women with sons only to those with daughters only were estimated, separately for women with three or fewer children and those with four or more children, controlling for age, age at first cohabitation, age at first birth, educational attainment, urban residence, and household wealth.
Results
Having daughters only was associated with a greater likelihood of spousal sexual violence among women with many children (adjusted odds ratio [AOR] = 1.53; 95% CI = 1.02–2.30) but not among those with few children (AOR = 0.92; 95% CI = 0.82–1.04).
Conclusions for practice
A higher risk of sexual violence for women without sons suggests that son preference may have implications on women’s health and wellbeing. Efforts to further understand and address increased risk of sexual violence for women without sons should consider son preference and intra-couple conflict concerning fertility intentions.Peer reviewe
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