Thyrotropinoma is a benign neoplasm of the pituitary gland that produces thyroid—stimulating hormone. It is manifested by symptoms of hyperthyroidism, ophthalmic disorders, intracranial hypertension, secondary hypopituitarism. Diagnosis is carried out according to anamnesis, hormonal examination, visometry, perimetry, brain MRI, ultrasound of thyroid tissue. Conservative therapy includes the appointment of thyrotropin secretion inhibitors. Surgical treatment consists in a complete adenomectomy, if it is impossible, a radiosurgical operation is performed.
ICD 10
D35.2 Benign neoplasm of the pituitary gland
General information
Thyrotropinoma refers to rare types of functional pituitary adenoma. It accounts for about 0.5-3% of all adenomas. Neoplasm cells secrete thyroid-stimulating hormone (TSH), which leads to the development of thyrotoxicosis. The first description of thyrotoxicosis of central genesis occurs in 1960. Since then, about 460 cases of the disease have been presented in the literature. The prevalence of pathology does not exceed 1 case per 1 million population. The average age of the patients is 50-60 years. Gender differences in morbidity are not observed.
Causes
The etiological factors leading to changes in normal thyrotropin-producing cells are unknown. Oncogenes characteristic of many tumors, disorders in receptor genes in thyrotropinomas have not been detected. The monoclonality of tumor cells suggests the stimulation of pathological proliferation of thyrotrophs by a certain trigger with the subsequent occurrence of mutations. Mutagen triggers can be:
- Physical factors. They include ultraviolet radiation, radioactive exposure, excessive fluctuations in ambient temperature. These factors can lead to breaks in the DNA molecule.
- Chemicals. These include asbestos, nitric acid, colchicine, benzapyrene, nicotine, drugs, alcohol and others. They enter the human body with food, water, and inhaled air. The mutagens in the soil pass into plants that are eaten.
- Biological factors. The most common opinion is about the mutagenic effects of viruses. Mutations can occur after an infectious disease, especially when the virus persists.
Pathogenesis
Under the influence of mutagenic environmental factors, changes occur in the genome of individual thyrotrophs, leading to a violation of the limitation of division and uncontrolled proliferation of affected cells with the formation of a tumor. Mutated cells synthesize TSH regardless of the level of peripheral hormones thyroxine (T4) and triiodothyronine (T3). It is possible that the insensitivity of abnormal thyrotrophs to a high content of thyroid hormones, normally inhibiting the production of TSH, is associated with changes in their receptors resulting from mutation.
Morphologically, thyrotropinoma is a benign neoplasm of fibrous structure. In most cases, the tumor has a large size (macroadenoma) and is characterized by invasive growth. The microscopic structure is usually represented by highly differentiated adenomatous transformed thyrotrophic cells. Low-differentiated formations consist of spindle-shaped cells with heterochromic nuclei, a small number of secretory granules.
Classification
Among all the observed cases, thyrotropin revealed tumors with increased production of only TSH and neoplasms with hyperproduction and other pituitary hormones. This fact was the basis of the clinical classification widely used in endocrinology. According to it , the following forms of thyrotropinoma are distinguished:
- TSH is secreting. It makes up to 80% of all thyrotropins. It is characterized by increased secretion of exclusively thyroid-stimulating hormone. In the clinic, manifestations of hyperthyroidism come to the fore.
- Mixed. It occurs in 20-25% of cases. Along with TSH, it produces other pituitary hormones, more often prolactin, somatostatin. The symptoms of hyperthyroidism are often masked by clinical manifestations of hyperprolactinemia, acromegaly.
Symptoms
The disease debuts with signs of hyperthyroidism. Patients report palpitations, anxiety, weight loss, sweating. It is characterized by emotional lability, irritability, acceleration of thinking with a decrease in the ability to concentrate attention. Insomnia occurs, which cannot be corrected by sleeping pills.
Increased metabolism is manifested by hyperthermia, increased sweating, increased appetite. Thinning of the skin and hair is observed. The skin becomes warm and moist. Possible instability of the chair, polyuria. Exophthalmos, as a rule, is weakly expressed or absent. Moderate severity of thyrotoxicosis symptoms is typical.
With mixed thyrotropinomas, increased production of somatotropic hormone is clinically manifested by symptoms of acromegaly with hypertrophy of the nose, cheekbones, auricles, brow arches, an increase in the size of the hands and feet. Hyperproduction of prolactin in women leads to galactorrhea, a violation of the menstrual cycle. The latter is also observed in 30% of patients with pure TSH-secreting tumors.
Macroadenomas due to their large mass lead to compression of the visual pathways, which is manifested by visual disorders. There is a decrease in visual acuity, narrowing of visual fields, diplopia. An increase in thyrotropinoma is accompanied by an increase in intracranial pressure, in connection with which patients note the occurrence of cephalgia, a feeling of heaviness of the eyelids, pressure on the eyeballs. Headache has a dull diffuse character, sometimes occurs with nausea.
The invasive growth of the neoplasm is accompanied by the destruction of the surrounding healthy hormone-producing cells with the development of hypopituitarism. Secondary hypogonadism develops more often than other syndromes of hormonal insufficiency. Clinically, there is a decrease in libido. Male hypogonadism is manifested by a decrease in the size of the testicles, erectile dysfunction, violation of spermatogenesis. Female hypogonadism is accompanied by a disorder of menstrual function, amenorrhea.
Complications
Possible cardiovascular complications in the form of atrial fibrillation, atrial fibrillation, heart failure. However, they develop much less frequently than with Graves’ disease. A complication of hypogonadism is infertility. Isolated cases of transformation of thyrotropinoma into malignant, actively metastasizing carcinoma are described.
Diagnostics
When collecting anamnestic data, long-term hyperthyroidism is detected in many patients. The rarity of thyrotropinoma causes frequent erroneous diagnosis of Graves’ disease, as a result of which individual patients have a history of data on performed thyroidectomy or radioiodine therapy. The list of examinations necessary for the diagnosis of thyrotropinoma includes:
- Neurologist’s examination. In the neurological status, signs of intracranial hypertension, tremor of the fingers in the Romberg pose are determined. Attention is drawn to the lability of the emotional sphere.
- Hormonal studies. An increased content of thyroid hormones and TSH in the blood is detected. When stimulated with thyroliberin, an insufficient response is determined in 90% of cases. To diagnose mixed forms of thyrotropinoma, it is necessary to study the concentration of all pituitary hormones.
- Radiography. With aggressively growing TSH-producing adenoma, it allows you to identify indirect signs of a tumor. Osteoporosis and destruction of the Turkish saddle indicate the presence of adenoma.
- MRI of the brain. It is more informative than radiography. Allows you to visualize an intracellular pituitary tumor, determine its size, and the invasiveness of growth. Adenoma is characterized by a change in the size, structure and shape of the Turkish saddle.
- Ophthalmological examination. Visometry diagnoses visual acuity disorder. With a pronounced increase in intracranial pressure, ophthalmoscopy reveals congestion on the fundus, swelling of the macula.
- Ultrasound of the thyroid gland. It is indicated for the purpose of differential diagnosis with thyroid pathology. Thyrotropinoma is characterized by diffuse hypertrophy of the thyroid gland due to constant stimulation of TSH.
Differential diagnosis
Thyrotropinoma must be differentiated from hyperthyroidism associated with thyroid diseases: diffuse toxic goiter, nodular goiter, thyroiditis. The main distinguishing feature of these diseases is a reduced level of TSH. An increase in thyroid-stimulating hormone along with T3 and T4, except for thyrotropinoma, is observed in thyroid hormone resistance syndrome. The latter is characterized by a family of cases, a normal response to thyrooliberin, and the absence of changes in the MRI of the Turkish saddle area.
Treatment
Conservative therapy
Drug treatment is aimed at pharmacological suppression of TSH hyperproduction. It leads to a significant regression in the size of the neoplasm, restoration of visual function. Therapy requires long-term constant medication. The main groups of pharmaceuticals recommended by modern neuroendocrinology for the treatment of the disease are:
- Somatostatin analogues. Suppress the secretion of TSH, normalize the level of thyroid hormones in 90% of cases. Side effects of therapy are stone formation in the biliary tract, hyperglycemia. In some cases, resistance to somatostatin therapy is possible.
- Dopamine agonists. Inhibit the production of thyrotropin by affecting the dopamine receptors of thyrotropinoma cells. However, in most patients, suppression is partial. Therapy is indicated in case of ineffectiveness or the development of adverse reactions during treatment with somatostatin preparations.
Surgical treatment
Operative removal of thyrotropinoma is considered the most radical method. Complete removal of the adenoma is recommended. The impossibility of total resection may be due to the extrasellar spread of the neoplasm, a pronounced fibrous component of the tumor. The main options for surgical treatment are:
- Surgical removal. Complete resection is possible in 100% microadenom and 60% macroadenom. Adenomectomy is performed by transsphenoidal and subfrontal access. Complete removal of the neoplasm leads to normalization of pituitary function and euthyroidism.
- Radiosurgical operation. It is indicated mainly with a small size of thyrotropinoma. With large formations, only partial removal is possible, which leads to temporary improvement. The radiosurgical method is resorted to if there are indications for surgical removal and the ineffectiveness of conservative treatment.
Prognosis and prevention
In general, thyrotropinoma has a more benign course than toxic goiter, is not accompanied by severe hyperthyroidism and complications. Timely surgical and drug treatment leads to normalization of the hormonal background with regression of symptoms. Complications arise due to incorrect diagnosis and treatment of neoplasms as Graves’ disease.
Primary prevention consists in eliminating the influence of mutagenic factors on the human body. Secondary prevention is aimed at preventing relapses. It includes the most complete possible resection of thyrotropinoma during surgical treatment, constant drug therapy aimed at suppressing the synthesis of thyrotropin.