Autoimmune hypophysitis
Autoimmune hypophysitis is defined as inflammation of the pituitary gland due to autoimmunity.
Signs and symptoms
Autoimmune hypophysitis can lead to deficiencies in one or more pituitary hormones, causing central diabetes insipidus if the posterior pituitary gland is affected as well as central adrenal insufficiency and central hypothyroidism if the anterior pituitary gland is affected. The symptoms depend on what part of the pituitary is affected. Lymphocytic adenohypophysitis occurs when the anterior pituitary cells are affected by autoimmune inflammation resulting in either no symptoms, adrenal insufficiency, hypothyroidism, or hypogonadism. In some cases, the presence of inflammation within the pituitary gland leads to interruption of dopamine flow from the hypothalamus into the pituitary causing high levels of the hormone prolactin and, often as a consequence, milk production from the breasts. Lymphocytic Infundibuloneurohypophysitis occurs when the posterior pituitary is affected resulting in diabetes insipidus. Both LAH and LINH may also lead to symptoms of an intracranial mass such as headache or disturbance of vision, i.e. bitemporal hemianopia. The pituitary produces multiple hormones relating to various metabolic functions. Sufficiently low production of certain pituitary hormones can be fatal resulting in the failure of the thyroid or adrenal glands.Common symptoms include nausea, vomiting, fatigue, loss of libido, amenorrhea, and dizziness. It is estimated that, typically, it takes from 12 to 40 years for autoimmune destruction to present symptoms. However, there have been cases of isolated attacks as a result of drug reactions or idiopathic events that have presented symptoms which may disappear after relatively short term treatment. However, more rapid development of the disorder is the rule when it occurs during, or shortly after, pregnancy. Indeed, autoimmune hypophysitis occurs more commonly during and shortly after pregnancy than at any other time.
Antibodies
80% of patients with pituitary antibodies also have antibodies to thyroid gland or its hormones. Likewise, 20% of autoimmune thyroid patients also have pituitary antibodies. It follows that a subset of thyroid patients may have a disease related to autoimmune hypophysitis. Recent research has focused on a defect at the CTLA-4 gene which, coupled with other factors, may result in autoimmunity primarily focusing on certain endocrine glands including the pituitary and thyroid.Cause
Most cases are autoimmune, some related to thyroid autoimmunity.Diagnosis
Lymphocytic hypophysitis continues to be a diagnosis of exclusion, and histopathology with tissue biopsy is needed for a definitive diagnosis. However, clinical, laboratory data, and imaging can all help with the diagnosis. First and foremost, patients present with symptoms of hypopituitarism and must undergo pituitary hormone function evaluation. Biopsy is the only means of accurate diagnosis as no autoantigen has been discovered. Biopsy of the pituitary gland is not easily performed with safety as it sits under the brain, however, a test does exist to detect antibodies to the pituitary without biopsy: autoantibodies to M 49,000 pituitary cytosolic protein may represent markers for an immunological process affecting the pituitary gland. Tests for normal pituitary gland hormone production tend to be expensive and in some cases difficult to administer. In addition, certain hormone levels vary largely throughout the day and in response to metabolic factors, making abnormal levels difficult to calibrate—further hampering diagnosis. Assessment for other autoimmune and inflammatory diseases should also be performed by obtaining complete blood count, complete metabolic panel, c-reactive protein, erythrocyte sedimentation rate, antinuclear antibody, and lupus antibodies at the very least. Gadolinium-enhanced MRI of the pituitary is the imaging of choice as well, and it is important to distinguish lymphocytic hypophysitis from a pituitary adenoma.Treatment
Inflammation typically resolves after several months of glucocorticoid treatment In patients unresponsive to, or have relapsing symptoms after corticosteroid treatment, immunosuppressive medications such as methotrexate, azathioprine, and cyclosporine are often prescribed. In particular, combined azathioprine/glucocorticoid therapy has been shown to successfully treat recurrent hypophysitis. Some cases of hyperprolactinemia due to pituitary inflammation have been treated with combined dopamine agonists - such as cabergoline/bromocriptine.Surgery is only an option for those suffering from visual problems/ophthalmoplegia, are suffering a mass-like effect from compression of nearby brain structures, or for the purposes of diagnostic histology.