Causes of Hypopituitarism
There are a number of causes of hypopituitarism and these can generally be grouped into congenital, in which the defects are already present at birth, or acquired, in which the defects develop at some later date.
Congenital Causes
Most of the congenital defects are due to abnormal genes. These genes may involve the structures of the various hypothalamic releasing hormones that control the pituitary hormones, the place on the pituitary cells where these hypothalamic hormones attach (called the hormone receptors), the pituitary hormones themselves, or the place on the cells that the pituitary hormones bind to (receptors) in the various tissues of the body. As an example of these types of defects, defective growth causing short stature has been shown to arise because of defects in the GH releasing hormone receptor, in the GH molecule itself, and in the GH receptor. Most of these gene defects result in loss of a single hormone. Thus, a child could be born with defective activity of GH, causing short stature, TSH, causing underactive thyroid function, ACTH, causing underactive adrenal function, and LH and FSH, causing delayed or absent body development at puberty.
Other, more rare congenital pituitary disorders involve abnormal genes at earlier stages of development of the pituitary as the embryo develops. These disorders commonly involve multiple hormones. In rare cases with gene disorders that occur very early in development there may be other malformations of the head and brain that may be even more problematic.
Acquired Causes
Acquired hypopituitarism occurs when there is some destruction of the pituitary itself, the lower part of the hypothalamus that controls the pituitary, or the pituitary stalk. This destruction can occur at any age, but the age at which the destruction occurs will cause different types of clinical manifestations. Thus, destruction occurring during early childhood may manifest as failure to grow normally. Destruction occurring later in childhood may result in failure of normal pubertal development. Destruction during adult life may result in loss of the normal function of the pituitary hormones. Depending upon the disorder, there may also be varying degrees of hypopituitarism, ranging from partial loss of one hormone to complete loss of all hormones.
One of the most common causes of hypopituitarism is a tumor in the pituitary or hypothalamus. Simply because of their size, a large pituitary tumor may cause compression of the normal pituitary tissue, the pituitary stalk, or even the hypothalamus. These pituitary tumors themselves may secrete other hormones (and cause specific problems such as acromegaly or Cushing's disease) or may be nonfunctioning. Less commonly, tumors in the hypothalamus may cause problems; examples of these are craniopharyngiomas, Rathke's cleft cysts, meningiomas, gliomas, and hamartomas. Rarely, distant cancers may spread (metastasize) to the pituitary and present as a pituitary mass. Some uncommon diseases can invade or infiltrate the hypothalamus and pituitary, such as sarcoidosis and Langerhans' cell histiocytosis (histiocytosis X). One type of infiltrative disease of the pituitary occurs primarily in pregnant women (lymphocytic hypophysitis). Ballooning out of one of the large blood vessels adjacent to the pituitary, called an aneurysm, can press against the pituitary as well. Sometimes, the blood vessels to the pituitary undergo spasm during an obstetric hemorrhage, causing poor blood supply and death of the pituitary tissue (Sheehan's syndrome). Irradiation to the pituitary area either from direct irradiation for a pituitary tumor or more indirect irradiation given to other head and neck tumors can also cause hypopituitarism. Finally, trauma to the pituitary can cause hypopituitarism; this may occur from neurosurgery in the area or after blunt head trauma as from an automobile accident.
There tends to be an order in which pituitary hormones are lost with expanding mass lesions in the pituitary as follows: GH, then LH and FSH, then ACTH, and then TSH. However, in any single individual the pattern of loss may be different from this.
