Etiology

A variety of disorders may cause deficiencies of one or more pituitary hormones. These disorders may be genetic, congenital, traumatic (pituitary surgery, cranial irradiation, head injury), neoplastic (large pituitary adenoma, parasellar mass, craniopharyngioma, metastases, meningioma), infiltrative (hemochromatosis, lymphocytic hypophysitis, sarcoidosis, histiocytosis X), vascular (pituitary apoplexy, postpartum necrosis, sickle cell disease), or infectious (tuberculous, fungal, parasitic). Automimmune hypophysitis has been associated with checkpoint inhibitor cancer immunotherapy. The most common cause of hypopituitarism is neoplastic in origin (pituitary mass, or following hypophysectomy or radiation therapy). Pituitary hormone failure due to compression, destruction, or radiation therapy follows a sequential pattern, though this is highly variable: GH>FSH>LH>TSH>ACTH. Genetic causes of hypopituitarism may affect several hormones (e.g., pituitary dysplasia, PROP-1 and PIT-1 mutations) or be restricted to single pituitary hormones or axes (e.g., isolated GH deficiency, Kallmann syndrome, isolated ACTH deficiency). Hypopituitarism following cranial irradiation develops over 5–15 years. Varying degrees of partial to complete hormone deficiencies occur during evolution of hypothalamic and pituitary damage.