Autoimmune hypophysitis
Encyclopedia
Autoimmune hypophysitis or Lymphocytic hypophysitis is defined as below normal production of one or more hormones
by the pituitary gland
due to autoimmunity
.
ACTH producing cells are effected resulting in adrenal insufficiency
. Lymphocytic Infundibuloneurohypophysitis (LINH) is when the posterior pituitary
is effected resulting in diabetes insipidus
and symptoms of an intracranial mass. Lymphocytic Infudibulopanhypophysitis (LIPH) is involvement of both the posterior pituitary and anterior pituitary involvement resulting in both diabestes insipidus and adrenal insufficiency.
or adrenal glands.
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 (i.e., use of blocking antibody
ipilimumab
) or idiopathic events that have presented symptoms which may disappear after relatively short term treatment (i.e., 1 year on corticoids or other immune suppressants).
gene which, coupled with other factors, may result in pan-autoimmunity primarily focusing on certain endocrine glands including the pituitary and thyroid.
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. 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.
, performed biopsies on hundreds of pituitary glands. The study indicated that perhaps as much as 5% of the population experiences some amount of autoimmune pituitary destruction. It is further hypothesized that perhaps half that many show, or may experience, clinical manifestations.
in 1962. The autopsy described destruction of the pituitary and thyroid consistent with autoimmune attack and included atrophy
of the adrenal glands. As Magnetic Resonance Imaging became more available diagnosis increased dramatically. At this time it is believed that the disease is far more prevalent than is diagnosed. Nevertheless, autoimmune hypophysitis is frequently referred to as a rare disease
and estimates as to its prevalence
vary.
Hypopituitarism
Hypopituitarism is the decreased secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain...
by the pituitary gland
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...
due to autoimmunity
Autoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...
.
Signs and symptoms
The symptoms depend on what part of the pituitary is effected. Lymphocytic adenohypophysitis (LAH) is when the anterior pituitaryAnterior pituitary
A major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...
ACTH producing cells are effected resulting in adrenal insufficiency
Adrenal insufficiency
Adrenal insufficiency is a condition in which the adrenal glands, located above the kidneys, do not produce adequate amounts of steroid hormones , primarily cortisol, but may also include impaired aldosterone production which regulates sodium, potassium and water retention...
. Lymphocytic Infundibuloneurohypophysitis (LINH) is when the posterior pituitary
Posterior pituitary
The posterior pituitary comprises the posterior lobe of the pituitary gland and is part of the endocrine system. Despite its name, the posterior pituitary gland is not a gland, per se; rather, it is largely a collection of axonal projections from the hypothalamus that terminate behind the anterior...
is effected resulting in diabetes insipidus
Diabetes insipidus
Diabetes insipidus is a condition characterized by excessive thirst and excretion of large amounts of severely diluted urine, with reduction of fluid intake having no effect on the concentration of the urine. There are several different types of DI, each with a different cause...
and symptoms of an intracranial mass. Lymphocytic Infudibulopanhypophysitis (LIPH) is involvement of both the posterior pituitary and anterior pituitary involvement resulting in both diabestes insipidus and adrenal insufficiency.
Pathophysiology
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 thyroidThyroid
The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
or adrenal glands.
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 (i.e., use of blocking antibody
Blocking antibody
A blocking antibody is an antibody that does not have a reaction when combined with an antigen, but prevents other antibodies from combining with that antigen.The term can also be used for inhibiting antibody, prozone phenomenon and, agglutination reaction....
ipilimumab
Ipilimumab
Ipilimumab , marketed as Yervoy, is a drug used for the treatment of melanoma, a type of skin cancer. It is a U.S...
) or idiopathic events that have presented symptoms which may disappear after relatively short term treatment (i.e., 1 year on corticoids or other immune suppressants).
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-4CTLA-4
CTLA4 also known as CD152 is a protein that plays an important regulatory role in the immune system...
gene which, coupled with other factors, may result in pan-autoimmunity primarily focusing on certain endocrine glands including the pituitary and thyroid.
Diagnosis
BiopsyBiopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
is the only means of accurate diagnosis
Diagnosis
Diagnosis is the identification of the nature and cause of anything. Diagnosis is used in many different disciplines with variations in the use of logics, analytics, and experience to determine the cause and effect relationships...
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
Chemical test
In chemistry, a chemical test is a qualitative or quantitative procedure designed to prove the existence of, or to quantify, a chemical compound or chemical group with the aid of a specific reagent...
does exist to detect antibodies to the pituitary without biopsy. 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.
Epidemiology
A large scale study on cadavers done in SwedenSweden
Sweden , officially the Kingdom of Sweden , is a Nordic country on the Scandinavian Peninsula in Northern Europe. Sweden borders with Norway and Finland and is connected to Denmark by a bridge-tunnel across the Öresund....
, performed biopsies on hundreds of pituitary glands. The study indicated that perhaps as much as 5% of the population experiences some amount of autoimmune pituitary destruction. It is further hypothesized that perhaps half that many show, or may experience, clinical manifestations.
History
Autoimmune attack of the pituitary gland resulting in reduced hormone production was first discovered as a result of an autopsyAutopsy
An autopsy—also known as a post-mortem examination, necropsy , autopsia cadaverum, or obduction—is a highly specialized surgical procedure that consists of a thorough examination of a corpse to determine the cause and manner of death and to evaluate any disease or injury that may be present...
in 1962. The autopsy described destruction of the pituitary and thyroid consistent with autoimmune attack and included atrophy
Atrophy
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations , poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply to the target organ, disuse or lack of exercise or disease intrinsic to the tissue itself...
of the adrenal glands. As Magnetic Resonance Imaging became more available diagnosis increased dramatically. At this time it is believed that the disease is far more prevalent than is diagnosed. Nevertheless, autoimmune hypophysitis is frequently referred to as a rare disease
Rare disease
A rare disease, also referred to as an orphan disease, is any disease that affects a small percentage of the population.Most rare diseases are genetic, and thus are present throughout the person's entire life, even if symptoms do not immediately appear...
and estimates as to its prevalence
Prevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...
vary.