Pulmonary arterial hypertension (PAH) is a multi-factorial condition and the 
underlying pulmonary vascular disease is shaped by the combined action of 
genetic, epigenetic and immune-related factors. 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-proliferative 
action, can be permissive and drive angioproliferation. Signaling via the 
integrin αvβ3 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- 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.