Echographic characterization of extraocular muscles in pediatric patients with thyroid dysfunction.

PURPOSE: To characterize the size of extraocular muscles (EOMs) in a pediatric population with thyroid dysfunction using orbital echography. METHODS: Patients under age 18 with thyroid dysfunction who presented to an academic ophthalmology department from 2009 to 2020 and received orbital echography were included in this IRB-approved retrospective study. Data collected included age, clinical activity score (CAS), thyroid stimulating immunoglobulin (TSI), and extraocular recti muscle thickness on echography. Patients were organized into three age cohorts, after which statistical analysis compared recti measurements to previously reported normal ranges. RESULTS: Twenty patients with thyroid dysfunction were included. When comparing average recti muscle thicknesses of study patients to those of previously published normal children in similar age ranges, the levator-superior rectus complex was significantly increased in all age groups of children with thyroid dysfunction (p-values = <.004), and the levator-superior rectus complex was most frequently enlarged compared to published normal values (78% of eyes). CAS was not correlated with EOM size in the youngest group (5-10 years old, p-values >.315) but was significantly correlated in older groups (11-17 years old, p-values <.027). TSI was not correlated with EOM size in any group (p-values >.206). CONCLUSIONS: Echographic reference ranges for EOMs in children with thyroid dysfunction were established. There are increased rates of levator-superior rectus complex enlargement in children with TED compared to adults with TED, and EOM size is correlated with CAS in children older than 10 years. Though limited, these findings may serve as an additional tool for ophthalmologists to ascertain disease activity in pediatric patients with thyroid dysfunction.

Sonographic Evaluation of Pediatric Thyroid Nodules.

A thyroid nodule detected clinically or incidentally at medical imaging is a common indication for ultrasonography (US) in the adult population. This scenario is less frequently the case in pediatric patients, and the approach to evaluation of thyroid nodules deserves modification in these patients because of the increased probability of malignancy in children, compared with adults. Evaluating a thyroid nodule with US in a systematic way requires familiarity with a number of features that can be assessed and the terms that the radiologist uses in each category. The probability of malignancy is influenced by certain features, and several models have emerged to integrate these details into an overall risk assessment to guide management and biopsy of thyroid nodules. Clinical features of thyroid cancer differ between pediatric and adult patients, and risk factors and certain genetic syndromes portend earlier manifestation of thyroid malignancy. This article provides a review of (a) US features of thyroid nodules with an emphasis on the predictive capacity for malignancy, focused on the pediatric age group when the data exist, (b) clinical information, including risk factors and genetic syndromes pertinent to the pediatric population, and (c) the state of the current literature and controversies in diagnosing and managing pediatric thyroid cancer. ©RSNA, 2017.

Endothelin-1 impairs alveolar epithelial function via endothelial ETB receptor.

RATIONALE: Endothelin-1 (ET-1) is increased in patients with high-altitude pulmonary edema and acute respiratory distress syndrome, and these patients have decreased alveolar fluid reabsorption (AFR). OBJECTIVES: To determine whether ET-1 impairs AFR via activation of endothelial cells and nitric oxide (NO) generation. METHODS: Isolated perfused rat lung, transgenic rats deficient in ETB receptors, coincubation of lung human microvascular endothelial cells (HMVEC-L) with rat alveolar epithelial type II cells or A549 cells, ouabain-sensitive 86Rb+ uptake. MEASUREMENTS AND MAIN RESULTS: The ET-1-induced decrease in AFR was prevented by blocking the endothelin receptor ETB, but not ETA. Endothelial-epithelial cell interaction is required, as direct exposure of alveolar epithelial cells (AECs) to ET-1 did not affect Na,K-ATPase function or protein abundance at the plasma membrane, whereas coincubation of HMVEC-L and AECs with ET-1 decreased Na,K-ATPase activity and protein abundance at the plasma membrane. Exposing transgenic rats deficient in ETB receptors in the pulmonary vasculature (ET-B(-/-)) to ET-1 did not decrease AFR or Na,K-ATPase protein abundance at the plasma membrane of AECs. Exposing HMVEC-L to ET-1 led to increased NO, and the ET-1-induced down-regulation of Na,K-ATPase was prevented by the NO synthase inhibitor l-NAME, but not by a guanylate cyclase inhibitor. CONCLUSIONS: We provide the first evidence that ET-1, via an endothelial-epithelial interaction, leads to decreased AFR by a mechanism involving activation of endothelial ETB receptors and NO generation leading to alveolar epithelial Na,K-ATPase down-regulation in a cGMP-independent manner.

Hypoxia-mediated degradation of Na,K-ATPase via mitochondrial reactive oxygen species and the ubiquitin-conjugating system.

We set out to determine whether cellular hypoxia, via mitochondrial reactive oxygen species, promotes Na,K-ATPase degradation via the ubiquitin-conjugating system. Cells exposed to 1.5% O2 had a decrease in Na,K-ATPase activity and oxygen consumption. The total cell pool of alpha1 Na,K-ATPase protein decreased on exposure to 1.5% O2 for 30 hours, whereas the plasma membrane Na,K-ATPase was 50% degraded after 2 hours of hypoxia, which was prevented by lysosome and proteasome inhibitors. When Chinese hamster ovary cells that exhibit a temperature-sensitive defect in E1 ubiquitin conjugation enzyme were incubated at 40 degrees C and 1.5% O2, the degradation of the alpha1 Na,K-ATPase was prevented. Exogenous reactive oxygen species increased the plasma membrane Na,K-ATPase degradation, whereas, in mitochondrial DNA deficient rho(0) cells and in cells transfected with small interfering RNA against Rieske iron sulfur protein, the hypoxia-mediated Na,K-ATPase degradation was prevented. The catalase/superoxide dismutase (SOD) mimetic (EUK-134) and glutathione peroxidase overexpression prevented the hypoxia-mediated Na,K-ATPase degradation and overexpression of SOD1, but not SOD2, partially inhibited the Na+ pump degradation. Accordingly, we provide evidence that during hypoxia, mitochondrial reactive oxygen species are necessary to degrade the plasma membrane Na,K-ATPase via the ubiquitin-conjugating system.

Scorpion venom decreases lung liquid clearance in rats.

It has been reported that scorpion venom causes respiratory failure and pulmonary edema. However, the effects of this toxin on lung edema clearance have not been previously studied. We examined the effects of scorpion (Tityus serrulatus) venom on the ability of the lung to clear fluid and on alveolar epithelial Na,K-ATPase. The wet-to-dry lung weight ratio was increased in anesthetized rats injected intraperitonally with scorpion venom. Lung edema clearance decreased by up to approximately 60% in rats injected with the venom. Na,K-ATPase alpha1- and beta1-subunit protein abundance and activity decreased at the basolateral membranes of alveolar epithelial type II cells incubated with scorpion venom as compared with that of control animals. There was no difference in cell injury in alveolar epithelial type II cells incubated with scorpion venom for 60 minutes compared with that of control animals. We provide here the first evidence that scorpion venom decreases lung liquid clearance, probably by downregulating Na,K-ATPase in the alveolar epithelium.