Publisher Summary This chapter discusses the causes of hypopituitarism. Hypopituitarism can result from metastatic spread either to the pituitary itself or it may be secondary to failure of release of hypothalamic factors. The hormonal abnormality reflects the exact anatomical site of tumor spread. Primary carcinoma of the pituitary gland is exceedingly rare. Diabetes insipidus has been observed to be the most common clinical manifestation of pituitary metastatic involvement. Patients with hypopituitarism can experience mild to moderate normocytic normochromic anemia, reflecting reduced bone marrow function. Hyponatremia, if present, is because of relative water intoxication rather than sodium loss, as aldosterone secretion by the adrenal glands is maintained. Partial hypopituitarism is more common than total loss of all pituitary secretions. Luteinizing hormone secretion is affected first, followed by growth hormone, follicle stimulating hormone, adrenocorticotropic hormone, and thyroid stimulating hormone secretion. The pattern of pituitary hormone loss can also be affected by the position of the metastasis within the gland as well as by generalized pressure effects. These can be accompanied by hyperprolactinemia if normal dopaminergic inhibitory control has been damaged.