A Large Benign Adrenocortical Adenoma Cosecreting Testosterone and Cortisol.

Most adrenal incidentalomas are benign neoplasms of the adrenal cortex. While the majority are nonfunctional, many secrete cortisol. Androgen- or estrogen-secreting adenomas are rare. A 44-year-old female, with history of hypertension and prediabetes, presented with worsening acne, hirsutism, secondary amenorrhea for 2 years, and a 40-pound weight gain. Laboratory evaluation showed high 24-hour urine free cortisol, suppressed adrenocorticotropic hormone (ACTH) level, indicative of ACTH independent Cushing syndrome, and elevated testosterone and androstenedione. Abdominal computed tomography (CT) revealed a 6.3 × 5.2 × 5.6 cm left adrenal mass. Patient underwent left open adrenalectomy. Pathology revealed benign adrenocortical adenoma. Postoperatively there was a significant improvement in her blood pressure and blood sugar levels, resumption of menses, and complete resolution of hyperandrogenism and hypercortisolism. We describe a patient with an adrenal adenoma cosecreting cortisol and androgen, leading to Cushing syndrome and significant virilization. Adrenal masses secreting androgens are less common and concerning for adrenocortical carcinoma (ACC). Patients with adrenal masses cosecreting multiple hormones should undergo workup expediently since ACC confers poor outcomes.

An Unlikely Source of Iodine Uptake: A Bronchogenic Cyst Masquerading as Metastatic Thyroid Cancer.

Radioactive iodine therapy and posttreatment scanning are essential components of differentiated thyroid carcinoma treatment and detection of metastatic disease. False-positive results can be seen on an I-131 scan and are important for clinicians to be aware of. Here, we present a case of a 33-year-old female with follicular thyroid carcinoma who was noted to have an area of moderate uptake in the chest on a whole-body scan following remnant ablation with 30 mCi of I-131 (1.11GBq) concerning for a metastatic hilar lymph node. This was determined to be a mediastinal bronchogenic cyst on surgical pathology. It has been previously proposed that the expression of sodium iodide symporters in some bronchogenic cysts could be the mechanism by which iodine uptake is seen within them. We were able to demonstrate positive immunohistochemical staining for both sodium iodide symporter and the associated paired box gene 8 transcription factor in the cyst sample, which supports the proposed theory.

Progress on Ras/MAPK Signaling Research and Targeting in Blood and Solid Cancers.

The mitogen-activated protein kinase (MAPK) pathway, consisting of the Ras-Raf-MEK-ERK signaling cascade, regulates genes that control cellular development, differentiation, proliferation, and apoptosis. Within the cascade, multiple isoforms of Ras and Raf each display differences in functionality, efficiency, and, critically, oncogenic potential. According to the NCI, over 30% of all human cancers are driven by Ras genes. This dysfunctional signaling is implicated in a wide variety of leukemias and solid tumors, both with and without viral etiology. Due to the strong evidence of Ras-Raf involvement in tumorigenesis, many have attempted to target the cascade to treat these malignancies. Decades of unsuccessful experimentation had deemed Ras undruggable, but recently, the approval of Sotorasib as the first ever KRas inhibitor represents a monumental breakthrough. This advancement is not without novel challenges. As a G12C mutant-specific drug, it also represents the issue of drug target specificity within Ras pathway; not only do many drugs only affect single mutational profiles, with few pan-inhibitor exceptions, tumor genetic heterogeneity may give rise to drug-resistant profiles. Furthermore, significant challenges in targeting downstream Raf, especially the BRaf isoform, lie in the paradoxical activation of wild-type BRaf by BRaf mutant inhibitors. This literature review will delineate the mechanisms of Ras signaling in the MAPK pathway and its possible oncogenic mutations, illustrate how specific mutations affect the pathogenesis of specific cancers, and compare available and in-development treatments targeting the Ras pathway.

A Mouse Primary Hepatocyte Culture Model for Studies of Circadian Oscillation.

Circadian rhythms regulate many aspects of behavior and physiological processes, and, through external signals, help an organism entrain to its environment. These rhythms are driven by circadian clocks in many cells and tissues within our bodies, and are synchronized by a central pacemaker in the brain, the suprachiasmatic nucleus. Peripheral oscillators include the liver, whose circadian clock controls persistent daily rhythms in gene expression and in liver-specific functions such as metabolic homeostasis and drug metabolism. Chronic circadian clock disruption, as in rotating shiftwork, has been linked to disorders including obesity, diabetes, and cardiovascular disease. The mouse primary hepatocyte culture model allows the examination of circadian rhythms in these cells. This article describes a transgenic mouse model that uses a bioluminescent reporter to examine the circadian properties of a core clock gene Period2. Hepatocytes are isolated using a modified collagenase perfusion technique and cultured in a sandwich configuration, then sealed in a buffered medium containing luciferin for detection of whole-culture or single-cell bioluminescence. After synchronization by a medium change, cultures demonstrate coherent circadian period and phase measures of bioluminescence from the PERIOD2::LUCIFERASE reporter.

Central type benzodiazepine receptors in Gulf War veterans with posttraumatic stress disorder.

BACKGROUND: A previous single photon emission computed tomography study showed decreased central type benzodiazepine receptors in the prefrontal cortex in Vietnam War veterans with posttraumatic stress disorder. To assess the generalizability of this finding to patients with more recent history, we studied central type benzodiazepine receptors in Gulf War veterans with posttraumatic stress disorder. METHODS: Nineteen Gulf War veterans with posttraumatic stress disorder and 19 age-matched, healthy, nondeployed veterans participated in a single photon emission computed tomography study using [(123)I]iomazenil. Regional total distribution volume (V(T)') was compared between two groups using Statistical Parametric Mapping 99 (Wellcome Department of Imaging Neuroscience, London, United Kingdom) and volumes of interest analysis. RESULTS: Benzodiazepine receptor levels did not show regional differences between the two groups, either with or without global normalization. Average difference in V(T)' was 2% across brain areas; however, by applying global normalization, V(T)' in the patient group showed significant negative correlation with childhood trauma scores in the right superior temporal gyrus. CONCLUSIONS: Less severe symptoms and shorter duration of the illness in the current group than the prior one may be the source of the difference in the results of the two studies.