Primary empty sella: Why and when to investigate hypothalamic-pituitary function.

Empty sella (ES) is defined as an herniation of the subarachnoid space into the sella turcica, which is associated with stretching of the pituitary stalk and flattening of pituitary gland against the sellar floor. The term “empty sella” was first used by Sheehan and Summer in 1949 to describe the empty appearance of the sella turcica at autopsy due to contraction of the pituitary following postpartum pituitary necrosis; subsequently autoptic series of subjects with ES but without any evidence of pituitary disease have been described (1, 2). ES has been classified as either primary or secondary. Secondary ES may be caused either by pituitary adenomas undergoing spontaneous necrosis, infective, vascular, autoimmune, and traumatic causes or by surgery and radiotherapy. Conversely, “primary ES” (PES) is not related to the previously mentioned conditions; the pathogenesis of PES would include congenital incomplete formation of the sellar diaphragm, and supra-sellar causes such as stable or intermittent increase in intracranial pressure. Clearly, the widespread use of computed tomography and magnetic resonance imaging techniques, has made PES a frequent “incidental” finding. Data from autoptic and neuroradiological studies report ES in a percentage ranging from 5.5% to 35% of subjects, being more frequent in women (female/male:4/1) and in obese subjects (3-6). PES may be an asymptomatic radiological finding or associated with variable clinical conditions ranging from obesity, hypertension, menstrual disturbances, and endocrine dysfunction to signs of intracranial hypertension and/or spontaneous cerebrospinal fluid (CSF) rhinorrhea. Early studies suggested that endocrine disturbances in PES were uncommon. More recent studies have indicated a high prevalence of pituitary dysfunction such as some degree of hypopituitarism and/or hyperprolactinemia; however, there is still no consensus on their clinical relevance. Moreover, neurological and/or ophthalmological signs and symptoms could be dissociated from the endocrine picture (3). Therefore, the present Opinion Document is aimed at clarifying why and when to investigate hypothalamic-pituitary function in patients with PES.