Acquired hypopituitarism develops after birth from damage to the pituitary or the hypothalamus. The conditions that cause it differ in how they damage the gland: some compress it from around the sella (the bony hollow at the skull base that holds the pituitary), some interrupt its blood supply, some infiltrate or inflame it, some injure it directly, as trauma does, and some act through irradiation.
Neoplastic causes
A pituitary adenoma is the most common cause of adult-onset hypopituitarism, whether it secretes a hormone or not. Craniopharyngioma is the next most prevalent tumour in this group and is more common in children, with a peak age of 10-20 years. A Rathke’s cleft cyst is more often found in adults. Metastatic tumours and lymphoma are further neoplastic causes of hypothalamic-pituitary damage.
Vascular events
Pituitary apoplexy is the clinical consequence of haemorrhage or infarction in a pre-existing pituitary adenoma, and it can occur in several settings. It may follow a known adenoma, or it may be the first event; it can also occur after a postpartum event, which is known as Sheehan’s syndrome, and there the cause is the hyperplasia of the pituitary during pregnancy, which raises the risk of haemorrhage and infarction.
Predisposing factors include hypertension, which has been found in 26% of patients with apoplexy, diabetes, sickle cell anaemia and acute shock. Apoplexy is an endocrine emergency and manifests as a sudden and severe headache, visual disturbances or ophthalmoplegia from damage to cranial nerve III, IV or VI, severe hypoglycaemia, hypotension, shock and CNS haemorrhage.
An aneurysm near the sellar region can also compress the gland and cause hypopituitarism, most often an aneurysm of the suprasellar or infrasellar carotid arteries, or a suprasellar aneurysm of the anterior or posterior communicating arteries.
Inflammatory and infiltrative disease
Lymphocytic hypophysitis, an autoimmune inflammation of the gland, mostly occurs in postpartum women, and it is now thought that a significant number of patients previously diagnosed with Sheehan’s syndrome actually had this condition. It produces hyperprolactinaemia (a raised prolactin level), because the inflammatory process interrupts the dopamine inhibition of the lactotroph cells, and an MRI appearance of a prominent pituitary mass that resembles an adenoma. Hypopituitarism usually affects all the cell lineages, although in rare cases it is isolated, and mass compression adds visual disturbances and headache.
Infiltrative disease can involve both the hypothalamus and the pituitary, most often in sarcoidosis, amyloidosis and histiocytosis X. In more than half of these patients, diabetes insipidus is part of the picture. Growth retardation appears if the disorder occurs before puberty and interferes with GH release, and hyperprolactinaemia and hypogonadism are also common.
Checkpoint inhibitors and infection
Pituitary cells express CTLA-4 extensively, so the immune checkpoint inhibitors that block this molecule can produce hypophysitis, inflammation of the pituitary like that of the autoimmune form above. The involvement is heterogeneous and may extend to the adrenal gland, gonadal activity and the thyroid gland.
Infection of the region is uncommon but recognised: fungal infection after AIDS, bacterial infection with tuberculosis, and tertiary syphilis are the usual settings.
Traumatic brain injury
Trauma can damage the pituitary or its stalk, and studies show that in about 33% of traumatic brain injuries there is hypopituitarism 3 months after the trauma, with 22% still affected after 12 months of follow-up. Neurosurgical trauma to the region produces the same kind of injury.
Cranial irradiation
Cranial irradiation can damage the hypothalamus and pituitary, more so in children and adolescents. The degree of hormone deficiency depends mainly on the dose of irradiation and the time since it was completed: about two-thirds of patients who receive at least 50 Gy to the base of the skull will develop a hormone deficiency, usually 5-15 years after the radiotherapy. The usual order is GH deficiency first, then gonadotropin deficiency, thyroid deficiency and ACTH deficiency.
When post-traumatic, post-surgical or post-irradiation hypopituitarism is transient and short-lived, long-term follow-up is still indicated, because in about 25-40% of these patients the condition progresses to long-term hypothalamic or pituitary dysfunction.
Whatever the cause, the result is loss of particular hormones, and the next question is what that loss does to the patient.