The pituitary gland sits at the base of the brain and regulates many vital functions by releasing hormones. Lymphocytic hypophysitis (LH) is a rare inflammatory disorder affecting this gland. It is an autoimmune condition where the immune system targets the pituitary tissue, causing inflammation and swelling. LH is one of the most frequent types of primary hypophysitis and can significantly reduce hormone production.
Defining Lymphocytic Hypophysitis
Lymphocytic hypophysitis is an autoimmune disease where immune cells, specifically T and B lymphocytes, infiltrate the pituitary gland. This infiltration causes inflammation (hypophysitis), leading to the enlargement and dysfunction of the gland. LH is an inflammatory mass, not a tumor, although its appearance on imaging can mimic one. The resulting inflammation damages hormone-producing cells, leading to various degrees of pituitary hormone deficiency.
The condition is classified as primary when the inflammation is isolated to the pituitary gland, or secondary when it is associated with other systemic diseases, particularly other autoimmune disorders. Between 20% and 50% of patients diagnosed with LH also have other autoimmune conditions, such as Hashimoto thyroiditis or Graves’ disease. The disorder shows a strong predilection for women (up to a 9:1 ratio) and frequently manifests during late pregnancy or the postpartum period. This may be due to the physiological enlargement of the pituitary during pregnancy, which triggers the autoimmune response.
Recognizing the Clinical Presentation
The symptoms of lymphocytic hypophysitis depend on the size of the inflamed gland and the extent of hormone deficiency. The first category involves mass effect symptoms caused by the physical swelling of the pituitary pressing on nearby structures. Persistent, severe headaches are common, as is impaired vision due to pressure on the optic chiasm. This pressure can lead to visual field defects, specifically the loss of peripheral vision.
The second category of symptoms stems from hormonal deficiencies (hypopituitarism) as the immune attack destroys hormone-producing cells. Adrenocorticotropic hormone (ACTH) deficiency is often the earliest and most frequent impairment, leading to central adrenal insufficiency. Symptoms of adrenal insufficiency include profound fatigue, low blood pressure, nausea, and vomiting, which requires quick attention.
If thyroid-stimulating hormone (TSH) is affected, patients develop central hypothyroidism, resulting in cold intolerance, weight changes, and sluggishness. Deficiencies in gonadotropins (luteinizing hormone and follicle-stimulating hormone) lead to menstrual irregularities in women and loss of libido in both sexes. If the inflammation affects the posterior pituitary or the stalk connecting it to the brain, it can cause central diabetes insipidus, characterized by excessive thirst and frequent urination.
Diagnostic Confirmation
Diagnosing lymphocytic hypophysitis is challenging because its clinical and radiological features overlap significantly with those of pituitary tumors. The diagnostic workup relies on laboratory tests and advanced imaging to differentiate LH from other sellar masses. Laboratory testing involves evaluating pituitary hormone function to identify specific deficiencies.
Blood tests measure levels of hormones like ACTH, TSH, prolactin, and sex hormones to determine the extent of hypopituitarism. Identifying adrenal insufficiency is crucial, as this is the most immediately dangerous complication. If diabetes insipidus is suspected, specific tests, such as a water deprivation test, may be necessary to confirm the deficiency of antidiuretic hormone.
Magnetic Resonance Imaging (MRI) is the preferred imaging modality for visualizing the pituitary gland and is crucial for diagnosis. Typical MRI findings suggestive of LH include symmetrical enlargement of the pituitary gland and a thickened pituitary stalk. The inflamed tissue often shows intense, homogeneous enhancement after contrast injection, and sometimes a specific “dural tail sign” is visible. These features help distinguish LH from pituitary adenomas, which are typically asymmetric and have different enhancement patterns. A definitive diagnosis requires a tissue biopsy, but this invasive procedure is usually avoided unless the diagnosis remains uncertain or surgical decompression is necessary.
Management and Long-Term Care
The treatment of lymphocytic hypophysitis has two goals: reducing the inflammation causing the mass effect and replacing hormones the damaged gland can no longer produce. Acute treatment for inflammation, especially when visual symptoms or severe headaches are present, involves high-dose glucocorticoids, such as methylprednisolone or prednisone. Glucocorticoids are highly effective at quickly reducing the size of the inflamed gland and reversing mass effect symptoms due to their anti-inflammatory properties. This initial high-dose therapy is followed by a gradual reduction over several months, depending on the clinical and radiological response.
Surgical intervention is reserved for cases where vision is rapidly deteriorating or when medical therapy fails to relieve the mass effect. Surgery, usually a transsphenoidal procedure, aims to decompress the optic chiasm and relieve pressure. It also offers the advantage of obtaining tissue for a definitive pathological diagnosis, which confirms LH with certainty.
Long-term management of LH focuses on hormone replacement therapy (HRT) for any permanent pituitary deficiencies. Even after successful treatment of the inflammation, a majority of patients, often more than 70%, require lifelong HRT. This replacement includes cortisol (glucocorticoids) for ACTH deficiency, thyroid hormone for TSH deficiency, and sex hormones for hypogonadism. Patients with central diabetes insipidus require desmopressin to manage fluid balance. Long-term monitoring with regular endocrine follow-up and repeat imaging is necessary, as some patients can experience inflammation recurrence or develop new hormonal deficits over time.