OVERVIEW

What is autoimmune hypophysitis?

Autoimmune hypophysitis (AH) is a rare disease caused by autoimmune-mediated inflammation affecting the pituitary gland and adjacent organs. It primarily manifests as hypopituitarism and compression symptoms on surrounding tissues due to pituitary enlargement, such as headaches, vision loss, and visual field defects. Some patients may experience spontaneous remission, but without timely treatment, others may die from pituitary apoplexy.

What is the pituitary gland?

The pituitary gland plays a crucial role in the endocrine system, acting as a bridge between the brain and peripheral organs. It receives commands from the superior brain and hypothalamus while regulating the "daily functions" of the body's peripheral organs.

Located at the base of the skull, the pituitary resembles a "light bulb" suspended in the sella turcica. The brain and hypothalamus connect to it via a thin "wire" (medically termed the pituitary stalk) to regulate its activity.

The pituitary is divided into anterior and posterior lobes, each with distinct functions.

• The anterior pituitary, or adenohypophysis, controls the secretion of hormones from major endocrine organs (e.g., thyroid, adrenal glands, and gonads). If the anterior pituitary malfunctions, these "subordinate" endocrine organs are affected, leading to related diseases.
• The posterior pituitary stores a hormone that regulates urine output (water excretion). If the posterior pituitary is damaged or the pituitary stalk is severed, this hormone cannot reach or be stored in the posterior pituitary, resulting in excessive urination. Some patients may need to urinate every 1–2 hours, requiring frequent nighttime drinking and urination, with daily urine output exceeding 10,000 milliliters.

Dysfunction of the anterior, posterior, or both lobes constitutes pituitary disease.

What is autoimmune disease?

There are many causes of pituitary disease. If it results from autoimmune inflammation, it is termed autoimmune hypophysitis.

The body maintains a "defense force" (the immune system) to protect its health. This "team" eliminates harmful external invaders (e.g., bacteria, viruses) and clears aged or dead tissues from the body.

Normally, this "army" distinguishes between "friend and foe," recognizing what benefits or harms the body. However, due to certain abnormalities (some reasons remain unexplained in medicine), the immune system "betrays" the body, attacking its own tissues and causing disease.

Well-known examples include rheumatoid arthritis and systemic lupus erythematosus, which are autoimmune diseases.

If the immune system attacks the pituitary and adjacent tissues, it is called autoimmune hypophysitis.

Is autoimmune hypophysitis common?

Autoimmune hypophysitis is uncommon, classified as a rare disease. Its estimated prevalence is about 0.2%–0.88%. Due to previous underdiagnosis and misdiagnosis, these figures likely underestimate its true incidence.

What are the types of autoimmune hypophysitis?

Autoimmune hypophysitis is divided into primary and secondary types:

• Primary autoimmune hypophysitis includes: primary lymphocytic hypophysitis (LYH), granulomatous hypophysitis, xanthomatous hypophysitis, necrotizing hypophysitis, IgG4 plasmacytic hypophysitis, and mixed hypophysitis.
• Secondary hypophysitis has identifiable causes, such as suprasellar diseases (lesions in the sella turcica or surrounding areas, e.g., Rathke’s cleft cyst, germinoma, or craniopharyngioma-related hypophysitis), systemic diseases (e.g., Wegener’s granulomatosis, sarcoidosis, tuberculosis, syphilis) affecting the pituitary, or rare cases induced by immunomodulatory drugs.

SYMPTOMS

What are the common manifestations of autoimmune hypophysitis?

Common manifestations of autoimmune hypophysitis include endocrine symptoms of hypopituitarism and compressive symptoms caused by pituitary enlargement (also known as sellar mass effects).

• Endocrine symptoms of hypopituitarism:
  • The most common is anterior pituitary hypofunction, leading to secondary adrenal insufficiency, hypothyroidism, and hypogonadism.
  • Posterior pituitary damage is also relatively common, primarily manifesting as diabetes insipidus.
  • Additionally, pregnant or postpartum patients with autoimmune hypophysitis may experience prolactin deficiency, resulting in postpartum lactation failure, while non-lactating patients may develop hyperprolactinemia.
  • Compressive symptoms caused by pituitary enlargement, such as headaches, vision loss, visual field defects, nausea, and vomiting.

What severe consequences can autoimmune hypophysitis cause?

Hypopituitarism caused by hypophysitis can affect multiple systems, severely impacting patients' quality of life.

More critically, the decline in adrenocorticotropic hormone (ACTH) secretion (clinically presenting as dizziness, nausea, vomiting, hypotension, loss of pubic and axillary hair, etc.) may progress to acute adrenal insufficiency when symptoms become severe or are compounded by stressors like infection. This can lead to hyponatremia, hypoglycemia, hypotensive shock, coma, or other severe consciousness impairments. It is a common endocrine emergency, and delayed treatment can be life-threatening.

CAUSES

What are the causes of autoimmune hypophysitis?

As mentioned earlier, this type of hypophysitis actually encompasses a broad category of diseases, with the common feature being autoimmune inflammation affecting the pituitary gland. The specific causes remain unclear in current medical understanding.

Who is more likely to develop autoimmune hypophysitis?

Autoimmune hypophysitis is more common in women, with incidence rates 2–5 times higher than in men across different etiologies. In women, the onset is often associated with pregnancy (nearly half occur during late pregnancy or within 2 years postpartum). The average age of onset is also younger in women compared to men.

Is autoimmune hypophysitis contagious?

Autoimmune hypophysitis is not contagious.

Is autoimmune hypophysitis hereditary?

The exact causes of autoimmune hypophysitis remain unknown, and there is currently insufficient data to determine whether it is hereditary.

DIAGNOSIS

How is autoimmune hypophysitis diagnosed?

A definitive diagnosis of autoimmune hypophysitis requires a pituitary biopsy and histopathological examination, which is the gold standard. However, doctors can also make a comprehensive judgment based on the patient's condition. If three or more of the following criteria are met, the diagnosis of autoimmune hypophysitis can be confirmed:

• Young age of onset (especially under 30 years old);
• Anterior pituitary involvement, sequentially presenting with adrenal insufficiency, hypothyroidism, hypogonadism, etc.;
• Acute onset of headache, ophthalmoplegia, vision loss and/or visual field defects, nausea, vomiting, etc.;
• Central diabetes insipidus;
• Concurrent positive autoimmune antibodies or other autoimmune diseases;
• Imaging shows diffuse, symmetric intrasellar masses and/or suprasellar extension, with loss of the posterior pituitary bright spot on T1-weighted images; intact sellar floor without collapse or destruction; possible dural tail sign.

What tests are needed for the diagnosis of autoimmune hypophysitis?

Generally, pituitary function tests, immune-related antibody tests, cerebrospinal fluid analysis, imaging studies, and ophthalmologic examinations are required. A pituitary biopsy and histopathological examination may be performed if necessary.

• Pituitary function tests: Primarily used to evaluate anterior and posterior pituitary function.
• Anterior pituitary function is assessed by measuring baseline hormone levels, including adrenocorticotropic hormone (ACTH), cortisol, thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), growth hormone (GH), insulin-like growth factor-1 (IGF-1), prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and estradiol. Stimulation tests may be performed for further evaluation if needed.
• Posterior pituitary function is assessed via 24-hour urine output, blood and urine osmolality, and water deprivation/vasopressin tests.
• Immune-related antibody tests: Used to assist in diagnosis. Tests include antineutrophil cytoplasmic antibodies (ANCA), anti-adrenal antibodies, anti-thyroid peroxidase antibodies (TPOAb), thyroid receptor antibodies (TRAb), thyroglobulin antibodies (TgAb), Sjögren's syndrome antibodies, antinuclear antibodies (ANA), islet cell antibodies, and glutamic acid decarboxylase antibodies (GADAb). Currently, anti-pituitary antibody testing is not available in China.
• Cerebrospinal fluid analysis: Requires lumbar puncture for cerebrospinal fluid sampling. Tests include routine analysis (total cell count, white blood cell count, lymphocyte ratio, etc.), biochemistry (glucose, chloride, protein, etc.), and tumor markers (alpha-fetoprotein, human chorionic gonadotropin, carcinoembryonic antigen).
• Imaging studies: Such as sellar MRI to evaluate the pituitary and surrounding structures.
• Ophthalmologic examinations: Including visual field and visual acuity tests to assess symptoms of pituitary enlargement compressing adjacent tissues.
• Pituitary biopsy and histopathological examination: Performed when the diagnosis is unclear to confirm the condition.

TREATMENT

Which department should I visit for autoimmune hypophysitis?

Endocrinology.

How is autoimmune hypophysitis treated?

The treatment principles for autoimmune hypophysitis include early diagnosis, eliminating factors that may worsen the condition, and appropriate hormone replacement therapy.

The primary goal of treatment is symptom relief, including reducing the size of sellar lesions and providing hormone replacement therapy for pituitary dysfunction:

• Treatments to shrink sellar lesions mainly include glucocorticoids, immunosuppressants, surgery, and radiotherapy.
• For pituitary insufficiency, hormone replacement follows the principle of "replacing what is missing and how much is missing." In special cases, the replacement dose should be appropriately increased. The order of hormone replacement should prioritize adrenal corticosteroids, followed by (or simultaneously with) thyroid hormones to prevent pituitary crisis.

Can autoimmune hypophysitis be cured?

In some cases, such as during pregnancy or postpartum, autoimmune hypophysitis may resolve spontaneously, meaning complete recovery is possible. However, many patients cannot be cured.

DIET & LIFESTYLE

Does autoimmune hypophysitis require follow-up? How to follow up?

Autoimmune hypophysitis requires follow-up. This mainly includes improvement of symptoms, pituitary function (such as rechecking relevant hormones), imaging (such as sellar MRI), and improvement of headaches, vision, and visual field disturbances.

PREVENTION

Can Autoimmune Hypophysitis Be Prevented?

The pathogenesis of autoimmune hypophysitis is still unclear, and there are currently no effective measures for prevention.

How Can Patients with Autoimmune Hypophysitis Prevent Other Diseases?

Early diagnosis, actively eliminating factors that may worsen the condition, and appropriate hormone replacement therapy are key to preventing complications.