RESUMEN
Common sites of lung cancer metastasis include the bone, brain, liver, and adrenal gland. Cancer metastasis to the pituitary gland or sellar region is a rare finding. Here, we present a case of pituitary gland metastasis from underlying lung cancer in a patient presenting with a predominance of pituitary symptoms over respiratory symptoms. A 48-year-old female was admitted to the hospital with progressive visual deficits, intractable headaches, constant nausea and vomiting, fatigue, polyuria, and polydipsia for about three months, all consistent with pituitary symptoms associated with secondary adrenal insufficiency, secondary hypothyroidism, and central diabetes insipidus. A brain MRI done two months earlier revealed a large mass in the pituitary gland and sella turcica area. Biochemical test abnormalities consistent with pituitary hormonal insufficiencies were noted, and subsequent imaging showed an enlarging pituitary mass and extensive metastases to the bones, brain, liver, adrenal gland, and lymph nodes. Bone biopsy was consistent with poorly differentiated adenocarcinoma of the lung as the primary site. The young age of this patient is uncommon compared to most patients with pituitary metastasis. Worsening pituitary symptoms with an enlarging pituitary mass and widespread metastases should alert consideration for pituitary metastasis and a search for a primary cancer site. Pituitary metastasis portrays a poor prognosis.
RESUMEN
Mitogen-activated protein kinases (MAPKs) signaling cascades regulate several cellular functions, including differentiation, proliferation, survival, and apoptosis. The duration and magnitude of phosphorylation of these MAPKs are decisive determinants of their physiological functions. Dual-specificity phosphatases exert kinetic control over these signaling cascades. Previously, we demonstrated that DUSP4-/- hearts sustain a larger infarct and have poor functional recovery, when isolated hearts were subjected to ischemia/reperfusion. Uncontrolled p38 activation and upregulation of Nox4 expression are the main effectors for this functional alteration. Here, dual-specificity phosphatase 4 (DUSP4) overexpression in endothelial cells was used to investigate the role of DUSP4 on the modulation of reactive oxygen species (ROS) generation and vascular function, when cells were subjected to hypoxia/reoxygenation (H/R) insult. Immunostaining with cleaved caspase-3 revealed that DUSP4 overexpression prevents caspase-3 activation and apoptosis after H/R. The beneficial effects occur via modulating p38 activity, increased NO bioavailability, and reduced oxidative stress. More importantly, DUSP4 overexpression upregulates eNOS protein expression (1.62 ± 0.33 versus 0.65 ± 0.16) during H/R-induced stress. NO is a critical small molecule involved in regulating vascular tone, vascular growth, platelet aggregation, and modulation of inflammation. The level of NO generation determined using DAF-2 fluorescence demonstrated that DUSP4 overexpression augments NO production and thus improves vascular function. The level of superoxide generated from cells after being subjected to H/R was determined using dihydroethidium-HPLC method. The results suggested that DUSP4 overexpression in cells decreases H/R-induced superoxide generation (1.56 ± 0.14 versus 1.19 ± 0.05) and thus reduces oxidant stress. This also correlates with the reduction in the total protein S-glutathionylation, an indicator of protein oxidation. These results further support our hypothesis that DUSP4 is an antioxidant gene and a key phosphatase in modulating MAPKs, especially p38, during oxidative stress, which regulates ROS generation and eNOS expression and thus protects against oxidant-induced injury or apoptosis. Overall, DUSP4 may serve as an excellent molecular target for the treatment of ischemic heart disease.
