What Is Autoimmune Hypophysitis?
Autoimmune hypophysitis, also known as lymphocytic hypophysitis, is a common chronic inflammatory condition that occurs due to autoimmunity and primarily affects the pituitary gland. It was originally called lymphocytic adenohypophysitis (LAH) since it was believed that the chronic inflammatory reaction was limited to the anterior hypophysis (anterior lobe of the pituitary gland). However, it was later discovered that the autoimmune inflammatory infiltrate could affect the infundibular stem and the posterior hypophysis (lobe) of the pituitary gland also. Therefore, the term lymphocytic infundibuloneurohypophysitis (LINH) was coined exclusively. Later on, it was identified that both the anterior lobe, the infundibular stem, and the posterior lobe of the pituitary gland could be involved in the inflammation, hence, the term lymphocytic pan hypophysitis was created.
What Is the Epidemiology of Autoimmune Hypophysitis?
The disease is more common in women than in men. It usually occurs at a younger age. It is most commonly seen in pregnant women and in postpartum females. It is a rare disorder with not more than five percent of the total population being affected by this disease. The incidence of all types of autoimmune pituitary hypophysitis is very low, with a total frequency of about one in nine million. However, it is believed that this frequency rate is underestimated due to the introduction of immune checkpoint pharmacological drug inhibitors that are being used for cancer treatments, which have dramatically affected the pituitary gland by causing endocrine side effects. The average age of occurrence for men is 45 years, and for women, it is 35 years.
What Is the Association Between Pregnancy and Autoimmune Hypophysitis?
The disorder has shown a striking association with pregnant women. The disease is either observed in the last trimester of pregnancy or in the initial two to three months of delivery. Autoimmune hypophysitis usually does not pose any complications for the fetus or the newborn baby. The condition is believed to conclude after post-vaginal delivery.
However, it is seen that the pituitary gland undergoes remarkable changes during pregnancy. The size of the gland increases (hypertrophy) because of the effect of increased estrogen activity. This increase in the size of the gland can cause pituitary antigens to release in large quantities. In addition, the pituitary blood flow pattern can also be altered. As a result, more blood is obtained from the systemic circulation in comparison to the hypothalamic-pituitary circulation. It is therefore hypothesized that the pituitary becomes more susceptible to the host’s immune system at the time of pregnancy.
What Are the Signs and Symptoms of Autoimmune Hypophysitis?
The symptoms of the disease are usually categorized into four main symptoms - sellar compression (sella is the bone-like compartment where the pituitary is located inside the skull), hypopituitarism, diabetes insipidus, and hyperprolactinemia (larger prolactin levels in the blood).
The clinical manifestations include:
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Headache.
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Optical disturbances.
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Hypogonadism (failure of the reproductive organs to develop properly).
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Postpartum lactation may be inhibited.
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Diabetes insipidus (increased urine output called polyuria and increased thirst called polydipsia).
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Higher levels of prolactin in the blood.
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Nausea and vomiting.
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Tiredness.
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Mental confusion.
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Absence of menstruation in females.
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Loss of libido.
What Are the Diagnostic Tests for Autoimmune Hypophysitis?
Autoimmune hypophysitis is a challenging disease to diagnose that depends on the diagnosis of exclusion. Therefore, a biopsy of the lesional tissue is required to confirm the diagnosis. However, along with the microscopic examination, clinical examination with a medical history, laboratory findings, and diagnostic imaging can aid with the diagnosis of the disorder.
Firstly, the patients that exhibit the signs and symptoms of hypopituitarism must undergo hormonal tests to evaluate the pituitary hormone function. A biopsy is the only definitive means to reach the correct diagnosis since to date no autoantigen has been identified. Tissue biopsy of the pituitary gland is not easy to perform since it is located within the brain.
However, there is a test that can be used to discover autoantibodies in the pituitary without performing a biopsy. These autoantibodies represent markers for an immune response that affects the pituitary gland. Tests that are performed to evaluate the hormone production in the normal pituitary gland are usually expensive and in a few cases, it is even difficult to implement these tests.
There are certain hormones whose levels largely depend on diurnal activity. The levels may also vary in response to metabolic factors thereby making it difficult to assess the abnormal hormonal levels which further hampers the diagnosis. The differential diagnosis for other autoimmune inflammatory disorders should also be carried out by performing a complete blood cell count, c-reactive protein test, blood test for erythrocyte sedimentation rate, antinuclear antibody test, and detection of lupus antibodies in particular. Gadolinium-enhanced magnetic resonance imaging of the pituitary gland is the diagnostic imaging test of choice. It is, however, crucial to differentiate between autoimmune hypophysitis and pituitary adenoma.
However, the microscopic diagnosis of this disease can be determined by surgery. An assumption of the diagnosis can be made through a combination of medical history and clinical manifestations. Pituitary biopsy is not always necessary.
What Is the Treatment of Autoimmune Hypophysitis?
The treatment of the disease is only symptomatic. The therapeutic approach for the disorder includes minimizing the size of the pituitary gland tissue. It may also involve replacing the abnormal endocrine function of the pituitary gland. Pituitary gland mass reduction is usually obtained by surgery of the pituitary gland, immunosuppressant drugs such as Azathioprine, Cyclosporine, or Methotrexate, and radiotherapy. Inflammation is usually suppressed after prolonged corticosteroid therapy. Therefore, surgery is the main treatment of choice for those patients who exhibit visual disturbances.
Conclusion
Autoimmune hypophysitis is a rare inflammatory disorder but is being recognized increasingly. The autoimmune disease should be considered in the differential diagnosis of other pituitary gland disorders and other autoimmune diseases. If surgery is not urgent as in the absence of any type of visual disturbances, medical management is usually the treatment of choice in such cases. Patient management will improve if the diagnosis is established quickly. The correlation between pregnancy and autoimmune hypophysitis should also be carefully evaluated since the symptoms can worsen during pregnancy.
