Pituitaritis is an inflammatory lesion of the pituitary gland, often having an autoimmune character. Among the clinical manifestations, cephalgia, visual impairment, and symptoms of hypopituitarism come to the fore. Diagnostics includes a study of hormone levels, an antibody test, an ophthalmological examination, a cerebral MRI, and, if possible, a histology of a biopsy sample. Conservative methods of treatment include the use of corticosteroids and cytostatic drugs, hormone replacement therapy. If they are ineffective, surgical resection or stereotactic surgery is indicated.
E23 Hypofunction and other pituitary disorders
The term “pituitaritis” unites all inflammatory diseases of the pituitary gland. A detailed description of the granulomatous form was made in 1917 by the German physician and pathologist Morris Simmonds. The description of the lymphocytic form was presented in 1962. The number of cases of pituitaritis recorded during the year does not exceed 1 in 7-9 million people. Pathology accounts for less than 1% of all pituitary diseases. According to various data, in 8-20% of cases it is observed against the background of autoimmune diseases. With lymphocytic pituitaritis, the incidence of women is 3 times higher than that of men.
The etiological triggers of the primary form of the disease are not exactly known. It is assumed that the dysfunction of the immune system can be caused by harmful environmental influences: chemicals, increased insolation, viruses, bacterial toxins. The role of genetic factors cannot be excluded. According to researchers, hereditary predisposition is associated with alleles HLA DR4, HLA DR5, HLA DQ8, HLA DR53.
Secondary pituitaritis develops as a result of damage to the pituitary region by various pathological processes. The etiofactors of pituitary inflammation are:
- Cellaric formations. The most commonly observed cyst of the Ratke pocket, germinoma, adenoma, craniopharyngioma. Volumetric processes of the chiasmal-cellular zone, sprouting and /or squeezing the pituitary gland, provoke its inflammation.
- Autoimmune pathology. Systemic diseases such as Wegener’s granulomatosis, sarcoidosis, Takayasu’s disease, histiocytosis, occur due to autoimmune disorders. The systematic nature of the process leads to the formation of antibodies against pituitary antigens.
- Infectious diseases. Tuberculosis, viral diseases on the background of immunodeficiency, syphilis can lead to damage to pituitary cells. Pathogens are able to overcome the blood-brain barrier with the development of infectious inflammation of the pituitary tissues.
- Immunomodulatory therapy. The use of monoclonal antibodies in the treatment of malignant tumors in some cases provokes autoimmune processes, including pituitary gland damage. Pituitaritis occurs several months after the start of antitumor immunotherapy.
The autoimmune mechanism is characteristic of primary forms, secondary lesions on the background of autoimmune diseases, the intake of immuno-oncological pharmaceuticals. At the same time, pathological changes in the immune system are accompanied by the synthesis of antibodies against the pituitary cells’ own antigens. Autoantibodies affect cellular structures, causing an inflammatory reaction.
Neoplasms of the cellular region provoke inflammatory changes due to compression or tissue damage during the spread of the tumor process. Infectious agents, damaging cells, trigger a humoral immune mechanism that leads to the development of inflammation. Morphologically, the result of the inflammatory process is swelling, cellular infiltration and heterogeneity of pituitary tissues.
Over time, an inflammatory lesion leads to a decrease in the number of hormone-producing cells, which is accompanied by a violation of certain endocrine functions or panhypopituitarism. In a number of patients, the phenomenon of hyperprolactinemia is observed, presumably due to antibody-mediated activation of prolactin synthesizing cells, damage to dopamine receptors with a decrease in its inhibitory effect.
Etiopathogenetically, pituitaritis is divided into primary, occurring idiopathically, and secondary — occurring against the background of an existing underlying disease. There are also 2 morphological classifications: anatomical and histological. According to the first one , they distinguish:
- Adenohypophysitis is a lesion of only the anterior lobe. It accounts for about 65% of all cases.
- Infundibuloneirohypophysitis — inflammation spreads to the legs and neurohypophysis. It is observed in 10% of cases.
- Panhypophysitis — inflammatory changes cover all parts of the pituitary gland. It occurs in 25% of patients.
Microscopic examination makes it possible to identify various types of changes occurring in the pituitary gland, in connection with which a histological classification was developed. It is widely used to verify the diagnosis in patients who have undergone surgical treatment, and includes the following options:
- Lymphocytic. It is diagnosed in 68% of patients with pituitary. Lymphocytes predominate in the cellular infiltrate. It is characterized by the appearance of symptoms during pregnancy or in the first months after childbirth.
- Granulomatous. It ranks second in prevalence after lymphocytic. Along with lymphocytes, multinucleated giant cellular elements are found in inflammatory tissues.
- Xanthomatous. It is about 3%. Typically, an increased content of lipids in the pituitary tissues, the formation of fatty inclusions.
- IgG4 is associated. The inflammatory infiltrate contains a large number of IgG4-positive plasmocytes. In the later stages, fibrosis develops.
- Necrotizing. It differs in the presence of necrosis sites. Difficult differentiation of necrotizing pituitaritis from secondary, caused by a cyst of the pituitary course.
- Mixed. It is a variable combination of various histological forms. It is quite rare.
The disease manifests with general cerebral symptoms in the form of cephalgic syndrome and visual function disorder associated with compression of the visual tracts by an enlarged pituitary gland. The headache is permanent, accompanied by nausea. More than 50% of patients report vomiting. Neuro-ophthalmological symptoms include decreased visual acuity, impaired color perception, narrowing or loss of visual fields. With secondary pituitaritis, manifestations of the underlying disease are observed.
As the severity of inflammation fades and its transition to the chronic stage, symptoms of pituitary insufficiency begin. The nature of endocrine dysfunction depends on the etiology and form of pituitaritis. Adenohypophysitis and pangypophysitis occur with a deficiency of ACTH, thyrotropin, gonadotropins. Hypocorticism leads to weight loss, hyperpigmentation of the skin and mucous membranes, asthenia. Reduced production of thyrotropin leads to hypothyroidism, manifested by dry skin, bradycardia, memory impairment.
Hypogonadism causes a decrease in libido, in women — menstrual disorders up to amenorrhea. In 23% of cases of adenohypophysitis, hyperprolactinemia is observed, accompanied by galactorrhea. An obligatory symptom of infundibuloneirohypophysitis is diabetes insipidus, manifested by insatiable thirst, polyuria. With pangypophysitis, pangypopituitarism is noted.
A formidable complication of hypocorticism is acute adrenal insufficiency, which without timely medical care can lead to death. Polyuria in diabetes insipidus is complicated by dehydration, increased blood viscosity, and electrolyte imbalance. In the absence of treatment, severe dehydration threatens the development of collapse, heart failure. Progressive hypogonadism is complicated by infertility.
When collecting anamnesis, attention is paid to the recent weight loss, the presence of concomitant pathology, the passage of antitumor immunotherapy. A general examination reveals dryness and hyperpigmentation of the skin. After consultation with a neurologist and an endocrinologist, patients are recommended:
- Ophthalmological examination. Includes visual acuity assessment, ophthalmoscopy, perimetry. Examination of the visual fields diagnoses their narrowing. Ophthalmoscopy is performed to exclude other ophthalmological pathology.
- Immunological studies. Antibodies to pituitary structures are detected using enzyme immunoassay, immunoblotting, and immunofluorescence. The presence of antibodies confirms autoimmune changes, but is not specific to the pituitary gland.
- Hormonal studies. The study of pituitary and peripheral hormones diagnoses their partial or total decrease. The exception is prolactin, the level of which is increased in some patients.
- MRI of the brain. In the phase of acute inflammation, an increase, heterogeneity of the structure, blurring of the contours of the pituitary gland, thickening of the funnel is visualized. When the process becomes chronic, fibrosis and a decrease in the pituitary gland are detected.
- Histology of the biopsy. Histopathological verification of pituitary tissue samples remains the gold standard for pituitary diagnosis. However, the complexity and invasiveness of the procedure limit its use.
Pituitaritis should be differentiated from pituitary tumors, Sheehan syndrome. MRI signs may be similar to neoplasms, the asymmetry of the lesion indicates in favor of the tumor. Unlike neoplasms, pituitaritis starts with adrenal insufficiency, followed by the addition of deficiency of other hormones. Like lymphocytic pituitaritis, Sheehan’s syndrome manifests in the postpartum period. However, it is characterized by a lack of lactation. The MRI images show swelling of the chiasm, hemorrhagic foci in the pituitary gland.
Basic medical treatment is aimed at relieving the inflammatory process, compensating for the missing endocrine function. The rarity of the disease, the lack of a wide sample to obtain reliable clinical data leads to the lack of clear recommendations on the choice and dosage of the drugs used. Treatment is prescribed individually, includes 2 main components:
- Immunosuppression. It is necessary for the relief of autoimmune mechanisms underlying pituitaritis. It is used during an acute inflammatory reaction. It is recommended to start treatment with glucocorticoids, with the ineffectiveness of which to proceed to the appointment of cytostatics.
- Hormone therapy. It is of a substitutive nature. The selection of the drug and dose is carried out individually, in accordance with the level of hormones. First of all, correction of hypocorticism is necessary. Replacement therapy of hypogonadism is carried out in the chronic phase.
The indication for surgery is a pronounced compression of the visual pathways and chiasm resistant to drug therapy, clinically manifested by visual disorders. Partial resection of the pituitary gland by transsphenoidal access is performed. Important attention is paid to the removal of inflammatory masses with gentle resection of viable areas. In the postoperative period, glucocorticoid therapy is recommended.
The recurrence of pituitaritis, which is not amenable to conservative treatment, is an indication for stereotactic radiosurgery. Targeted radiation therapy is a modern minimally invasive intervention widely used in practical neurosurgery. After the destructive effects of radiation, replacement therapy may be required.
Prognosis and prevention
The positive effect of immunosuppressive therapy is observed in 40-50% of patients. In some cases, complete restoration of hormone-producing function is possible. Relapse was observed in 38% of patients after drug treatment. The recurrence rate after surgery is 11-25%. Due to the unclear etiology, prevention of primary pituitaritis is difficult. Prevention of secondary forms is based on the treatment of causal disease.