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Whether and how gender, obesity and the metabolic syndrome modify PAH and associated right heart failure is under intense investigation. Estrogens may enhance the process of pulmonary angioproliferation, but may also protect the right ventricle under pressure. Obesity may affect the pulmonary circulation via interactions with inflammatory cells and mediators, or via alterations in endocrine signaling. Obesity is a major risk factor for pulmonary hypertension in patients with elevated pulmonary venous pressure and preserved LV ejection fraction. Given the overlap between PAH and autoimmune diseases, hypothyroidism in patients with PAH is commonly considered a consequence of an autoimmune thyroiditis. In the clinical setting of hyperthyroidism, severe pulmonary hypertension may develop due to a hyperdynamic circulation, but a more complex situation presents itself when hyperthyroidism is associated with PAH. We recently showed in a relevant animal model of severe PAH that thyroid hormone, via its endothelial cell\u2010proliferative action, can be permissive and drive angioproliferation. Signaling via the integrin \u03b1v\u03b23 and FGF receptors may participate in the formation of the lung vascular lesions in this model of PAH. Whether thyroid hormones in euthyroid PAH patients play a pathobiologically important role is unknown\u2010 as we also do not know whether the commonly diagnosed hypothyroidism in patients with severe PAH is cardioprotective. This brief review highlights some recent insights into the role of metabolic and endocrine disorders in PAH.<\/jats:p>","DOI":"10.4103\/2045-8932.97592","type":"journal-article","created":{"date-parts":[[2012,6,22]],"date-time":"2012-06-22T17:20:50Z","timestamp":1340385650000},"page":"148-154","update-policy":"http:\/\/dx.doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":22,"title":["Severe Pulmonary Hypertension: The Role of Metabolic and Endocrine Disorders"],"prefix":"10.1002","volume":"2","author":[{"given":"Harm J.","family":"Bogaard","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine VU University Medical Center Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aysar Al","family":"Husseini","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Medicine Division and Victoria Johnson Laboratory for Lung Research Virginia Commonwealth University Richmond 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