This report describes an elderly patient evaluated for generalized fatigue, dyspnea, presyncopal episodes, and positional hypoxemia. Workup revealed posturally related oxygen desaturation, a patent foramen ovale (PFO), an atrial septal aneurysm, and primary adrenal insufficiency. Normal intracardiac pressures and a right-to-left PFO shunt were present only while the patient was in the upright position. Numerous etiologies of positional right-to-left shunting associated with platypnea-orthodeoxia have been described. Despite advancements in diagnostic and treatment modalities, the pathophysiology of right-to-left shunting with normal intracardiac pressure remains elusive. This report highlights the complexity of positional right-to-left shunting in hypoxemic patients with normal intracardiac pressures and multiple synergistic medical conditions.