Lymphocytic Hypophysitis - Types, Symptoms, Diagnosis, and Treatment

Introduction

Lymphocytic hypophysitis is also known as autoimmune hypophysitis, a rare autoimmune condition affecting the pituitary gland. Lymphocytic hypophysitis mainly involves the pituitary gland and, in some instances, the pituitary stalk. Due to the rare incidence and nature of the disease, it is difficult to diagnose and treat it. However, once diagnosed correctly with the help of blood examinations and imaging techniques, the condition is treatable with medical therapy, surgery, and radiosurgery. Unfortunately, more than 72 % of patients with lymphocytic hypophysitis would require lifelong hormone replacement treatment.

What Is Lymphocytic Hypophysitis?

• Lymphocytic hypophysitis is a rare autoimmune condition characterized by infiltration of the pituitary gland by lymphocytes (a type of white blood cell), leading to hypopituitarism.

• Hypopituitarism is when the pituitary gland either does not produce enough hormones or fails to produce any hormone. In addition, autoimmune disease is when the body's immune system starts attacking healthy cells.

• Lymphocytic hypophysitis is a noncancerous condition of the pituitary gland, and it causes signs and symptoms of hypopituitarism due to inflammation of the pituitary gland or sellar mass lesion.

• In lymphocytic hypophysitis, the pituitary gland is infiltrated by T lymphocytes and B lymphocytes.

Is Lymphocytic Hypophysitis a Common Disease?

• Lymphocytic hypophysitis is a rare condition with a rate of incidence equal to one in nine million population.

• Initially, it was believed that lymphocytic hypophysitis is a condition affecting women during the third trimester of pregnancy or the postpartum period. However, later it was reported that this autoimmune condition of the pituitary gland could also affect non-pregnant women and men.

• Women are more frequently affected by lymphocytic hypophysitis as compared to men. The risk is eight times higher in women.

• Cases of lymphocytic hypophysitis have been reported in individuals of varying ages. However, the average age of occurrence in men is 45 years, and in women, it is 34 years.

• In about 20 % to 50% of the cases, lymphocytic hypophysitis is associated with other autoimmune conditions.

What Are the Types of Lymphocytic Hypophysitis?

Based on their cause, lymphocytic hypophysitis can be classified as:

• Primary Lymphocytic Hypophysitis: This type describes pituitary gland inflammation itself.

• Secondary Lymphocytic Hypophysitis: This type describes pituitary gland inflammation due to a specific disease. These diseases include sarcoidosis (abnormal growth of the small collection of inflammatory cells known as granulomas in parts of the body), hemochromatosis (excess iron in the body), tuberculosis, syphilis, etc. In addition, the action of certain drugs can also cause secondary lymphocytic hypophysitis.

What Causes Lymphocytic Hypophysitis?

Lymphocytic hypophysitis is an autoimmune disease, meaning the body's immune system erroneously starts attacking its healthy cells. The exact cause of autoimmune diseases is unknown. However, certain genetic and familial conditions can make an individual prone to autoimmune diseases.

What Are the Symptoms of Lymphocytic Hypophysitis?

Lymphocytic hypophysitis can result in a deficiency of one or more pituitary hormones.

• If the posterior pituitary is affected, it can lead to central diabetes insipidus. It is a condition in which the secretion of the pituitary hormone, vasopressin, is impaired.

• If the anterior pituitary is affected, it can lead to central hypothyroidism and central adrenal insufficiency. Hypothyroidism is defined as an underactive thyroid gland, and adrenal insufficiency refers to a condition that is caused by impaired production of corticotrophin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH).

Therefore, the symptoms of lymphocytic hypophysitis depend on which part of the pituitary gland is affected. The symptoms include:

• If adrenocorticotropic hormone-producing cells are damaged, then symptoms are; extreme fatigue, weight loss, decreased appetite, darkening of skin or hyperpigmentation, reduced blood pressure, craving for salt, abdominal pain, nausea, etc.

• If thyroid-stimulating hormone cells are damaged, symptoms are; intolerance to cold, fatigue, tiredness, unusual weight gain, puffiness of the face, dryness of skin and scalp, constipation, muscle weakness, hoarseness of the voice, etc.

• If luteinizing hormone or follicle-stimulating hormone-producing cells are damaged (hypogonadism), then the symptoms are; infertility, erectile dysfunction, loss of bone mass, low sex drive, growth of breasts in men (gynecomastia), irregular menstrual cycles or absent cycles, hot flashes, loss of body hair, galactorrhea (milk discharge unrelated to pregnancy or lactation), etc.

• Headaches.

• Visual field disturbances.

How Is Lymphocytic Hypophysitis Diagnosed?

Diagnosis of lymphocytic hypophysitis is made with the help of the following tests and examinations:

• Biopsy: A tissue biopsy is necessary for a definitive diagnosis of lymphocytic hypophysitis.

• Hormone Function Evaluation: Patients who present with signs and symptoms of hypopituitarism are advised to take a pituitary hormone function test. During this test, growth hormone, cortisol, and glucose levels are measured in the blood, and then fast-acting insulin is administered intravenously. This test cannot be interpreted correctly unless less than 2.2 mmol/L (millimoles per liter) blood sugar level is achieved.

• Hormone Levels: Serum levels of several hormones are evaluated, including prolactin, adrenocorticotropic, cortisol, insulin-like growth factor-1, growth hormone, thyroid-stimulating hormone, and free thyroxine (T4), luteinizing hormone, follicle-stimulating hormone, and testosterone. Electrolyte levels, antidiuretic hormone, and urine osmolality are also tested to check for diabetes insipidus.

• Tests For Autoimmune Diseases: Lymphocytic hypophysitis is often associated with or precipitated by the pence of other autoimmune conditions. Complete blood count, complete metabolic panel, C-reactive protein, erythrocyte sedimentation rate, and different antibodies are checked in the blood to assess these diseases.

• Gadolinium-Enhanced MRI (magnetic resonance imaging): Gadolinium-enhanced MRI (magnetic resonance imaging) of the pituitary gland is the imaging technique for diagnosing lymphocytic hypophysitis. A gadolinium-enhanced MRI of the pituitary gland helps tell the difference between lymphocytic hypophysitis and pituitary adenoma. An MRI of a pituitary adenoma reveals asymmetrical pituitary growth and a pituitary stalk.

How Is Lymphocytic Hypophysitis Treated?

The cornerstone of lymphocytic hypophysitis treatment is managing and restoring pituitary hormone levels and treating any mass-like lesion that may have developed due to pituitary gland enlargement.

• Steroids are used as the first line of treatment for lymphocytic hypophysitis. There is no agreement on the dosage and duration of glucocorticoid treatment. A daily dose of 20 to 500 mg (milligrams) of Prednisolone, comparable to glucocorticoids for four days to a year, is recommended. As adverse side effects have increased, steroids should be tapered off gradually.

• In patients with compressive symptoms, surgery becomes the first line of treatment for lymphocytic hypophysitis. Trans-sphenoidal surgery to resect part or all of the pituitary mass is advised. This will give the tissue needed for a conclusive pathological diagnosis.

• Although a modality with limited experience, radiosurgery helps treat recurrent cases of lymphocytic hypophysitis. Gamma Knife radiosurgery and stereotactic radiotherapy are helpful in intractable issues.

What Are the Possible Complications of Lymphocytic Hypophysitis?

Untreated lymphocytic hypophysitis can lead to:

• Diabetes insipidus (a rare condition in which there is water and fluid imbalance in the body due to vasopressin deficiency).

• Panhypopituitarism (a rare condition in which the pituitary gland fails to make most or all pituitary hormones).

• Secondary adrenal insufficiency (when the pituitary gland does not produce enough of the hormone ACTH, secondary adrenal insufficiency develops. The adrenal glands do not have enough cortisol as a result.).

• Neurological problems like visual field defects.

Conclusion

After medical and surgical therapy, lymphocytic hypophysitis has a good prognosis, but the chances of recurrence are high. Lifelong hormone replacement therapy is required in about 72 % of the cases. Recognizing and treating adrenal insufficiency associated with lymphocytic hypophysitis is critical because it has a high morbidity and mortality rate. The diagnosis and treatment of lymphocytic hypophysitis will continue to be complicated. This intriguing endocrinological condition necessitates in-depth investigation and diagnosis. Results can be successful with diligent follow-up and appropriate sequential therapy when needed, allowing the patients to live everyday lives.