Thyroid cancer in pregnancy is a malignant tumor lesion of thyroid tissue diagnosed during gestation. It often proceeds without symptoms. It can manifest itself with nodular formations and pain in the neck, an increase in cervical lymph nodes, a change in voice, difficulty breathing and swallowing, paroxysmal cough, shortness of breath, suffocation. It is diagnosed by ultrasound, fine-needle thyroid biopsy, determination of the content of thyrogormones. Treatment involves subtotal or total removal of the affected tissues, followed by thyroxine replacement therapy.
C73 Malignant neoplasm of the thyroid gland
According to statistics, over the past 20 years, there has been an almost twofold increase in the prevalence of malignant thyroid diseases with a continuing trend towards an increase in the incidence of such tumors. This is due both to the increased radiation pollution of the environment, the endemicity of most regions of Russia for iodine deficiency, and with the use of modern diagnostic methods that allow detecting the disease at the preclinical stage. Although thyrocarcinomas are not pathogenetically associated with pregnancy, the more frequent development of tumors in women of reproductive age and the high survival rate of patients after radical treatments increases the likelihood of a combination of the disease with gestation.
The etiology of malignant degeneration of thyroid tissue has not been established. Probable provoking factors are hyperproduction of thyrotropin by the pituitary gland, exposure to ionizing radiation. Neoplasia is significantly more often diagnosed in pregnant women with pathology of the reproductive organs, benign thyroid tumors, chronic thyroiditis, nodular goiter. A genetic predisposition to the occurrence of some forms of malignant neoplasms of the thyroid gland has been established: 2.5-6.3% of cases of papillary and follicular carcinomas and up to 35% of medullary cancers are familial. In some patients, neoplasia is associated with other hereditary diseases (Gardner and Turcot syndromes, Carney complex, Cowden’s disease). Predisposing factors are determined in 84-86% of sick women, and their combination was detected in 60.5% of patients.
Specific prerequisites for the occurrence or faster progression of the disease in pregnant women, according to the results of numerous studies in the field of oncology, obstetrics and gynecology, have not been established. However, the clinical manifestation of the oncological process in the gestational period can be facilitated by such physiological changes as:
- Stimulation with chorionic gonadotropin. hCG produced by the placenta is structurally similar to thyroid-stimulating hormone, which stimulates thyrocytes. Under the action of chorionic gonadotropin, hyperplasia of both normal and degenerated thyroid gland tissues occurs, as a result, nodular formations become more noticeable and are easier to detect on palpation.
- Increased concentration of estrogens. Estrogen and progesterone receptors were found in thyroocytes. Estrogens, whose level in pregnant women increases by 30 times, are one of the growth factors of normal and malignant thyroid cells. At the same time, the inhibition of mitogenesis of malignated thyrocytes by antiestrogenic drugs has been experimentally confirmed.
- Iodine deficiency. The pregnant woman’s body lacks iodine due to the increased excretion of trace elements in the urine, its transplacental transfer and deioding of thyroid hormones by the placenta. In response to a violation of thyroid hormone metabolism in a pregnant woman, TSH production increases, which leads to compensatory tissue hyperplasia and activation of foci (nodes).
Thyroid carcinoma is a monoclonal formation originating from a single malignated cell. In the presence of a congenital defect of the met, ras, p53 genes or their mutation under the influence of damaging factors, a tumor transformation of a thyrocyte occurs, less often a calcitonin—producing C-cell. Against the background of a decrease in the suppressor effects of cytokines, interferon, tumor necrosis factor and an increase in the concentration of fibroblast growth factor, ectodermal growth factor, and other stimulators of mitogenesis, uncontrolled division of a cancer cell and expansive tumor growth begins.
The systematization of forms of thyroid cancer in pregnancy is carried out according to the same principles and criteria as outside the gestational period. When determining the stage of the disease, a TNM classification is used, taking into account the size of the carcinoma, germination into the parathyroid tissue, surrounding tissues and organs (parathyroid glands, prevertebral fascia, cervical muscles, carotid, thyroid arteries, mediastinal vessels), lesion of regional and distant lymph nodes, the presence of metastases. To predict the outcome of cancer and the choice of tactics for accompanying pregnancy, histological classification of thyroid tumors is usually used, according to which they are distinguished:
- Highly differentiated forms of cancer. They are represented by papillary and follicular carcinomas, which originate from glandular thyroid cells and are detected in 75-88% of pregnant women. They are characterized by low progrediency and often low functional activity. For a long time localized in the tissues of the gland, spread mainly lymphogenically. They have a favorable prognosis, which allows them to continue gestation.
- Low-grade forms of cancer. They include medullary carcinomas formed by calcitonin-producing C cells and anaplastic neoplasia. The prevalence of tumors with low differentiation ranges from 10 to 13%. The prognosis of anaplastic and medullary cancer is extremely unfavorable. Their detection is an unconditional indication for termination of pregnancy and the appointment of active treatment with the use of radiation techniques.
Symptoms of thyroid cancer in pregnancy
Thyroid cancer in pregnancy is usually asymptomatic. Its first sign may be the appearance of one or more bulky formations in the lower part of the neck above the projection of thyroid cartilage, an increase in cervical lymph nodes, a feeling of pressure, a “lump in the throat”. The nodes shift together with the larynx when swallowing. With the progression of cancer and the involvement of tissues surrounding the gland in the process, soreness occurs in the affected area, the pregnant woman begins to experience difficulty swallowing, breathing. There may be hyperemia or cyanosis of the skin, increased vascular pattern, dilation of the cervical veins. In the later stages, hoarseness of voice, coughing attacks, shortness of breath, which increases with head turns, suffocation, tachycardia occur. The occurrence of cancer intoxication is indicated by increased fatigue, weakness, loss of appetite, weight loss.
Thyroid cancer in pregnancy can be complicated by metastasis to the bones, lungs, liver, brain. In the future, a relapse of the disease with the development of a tumor in the remaining thyroid tissue is possible. Obstetric complications usually occur when the balance of thyrogormones is disturbed. When cancer is combined with hyperthyroidism, the frequency of early toxicosis, gestosis, spontaneous miscarriages increases, intrauterine fetal hypoxia is detected in 20-22% of cases, more than a third of women in labor have anomalies of labor activity. 18% of pregnant women have premature labor.
With hypothyroidism developed against the background of cancer or its therapy, almost 68% of newborns have signs of perinatal encephalopathy, 27% — anemia, 23% — hypotrophy. 18-25% of children are diagnosed with developmental abnormalities with predominant damage to the central nervous system (functional disorders, microcephaly, hydrocephalus) or endocrine pathology (congenital hypothyroidism, thyrotoxicosis).
Timely diagnosis of malignant neoplasia of the thyroid gland is complicated by the asymptomatic course of the disease and the absence of obvious pathognomonic signs. If one or more nodular formations are detected in the structure of thyroid tissue, enlarged cervical lymph nodes of a pregnant woman, the following studies are recommended:
- Ultrasonography. During ultrasound of the thyroid gland, it is possible to visualize nodes whose dimensions exceed 0.5 mm. The sensitivity of the method is 80-92%, the specificity is 50-92%. Cancer foci usually look like hypoechoic areas with uneven contours without clear boundaries. The method allows to identify microcalcinates, violation of the integrity of the thyroid capsule, affected lymph nodes. In the course of ultrasound Dopplerography, the features of the blood supply to the tumor are investigated.
- Biopsy. The detection of nodular neoplasia serves as a direct indication for obtaining cellular material by fine needle biopsy. To increase the information content, the material is taken under the control of ultrasound, which allows us to examine non-palpable formations and areas of interest in palpable tumors. Aspiration biopsy is also performed when suspicious regional lymph nodes are detected. The sensitivity of the TAB ultrasound reaches 78-95%, the specificity exceeds 62%.
- Determination of hormone levels. The laboratory study is aimed at assessing the functional viability of thyroid tissue. Most pregnant women suffering from thyroid carcinoma have elevated TSH levels. To detect possible hyperthyroidism or hypothyroidism, the content of triiodothyronine (T3), thyroxine (T4) is determined. A specific marker of highly differentiated forms of cancer is an increase in the concentration of thyroglobulin in the blood.
As additional methods, MRI of the thyroid gland can be recommended to obtain a three-dimensional image of the organ, the determination of hTERT, ECM1, TMPRSS4, and other cancer markers in the puncture material. CT, PET, radioisotope scintigraphy of the affected organ is not prescribed due to the high risk of damaging effects on the fetus. An MRI of the whole body is recommended to detect possible cancer metastases. Differential diagnosis is carried out with nodular goiter, acute and chronic thyroiditis, fibrous goiter of Riedel, syphilitic and tuberculous organ damage. According to the patient’s indications, in addition to an oncologist and an endocrinologist, a surgeon, a venereologist, an infectious disease specialist consult.
In most cases, gestation can be prolonged until the fetus is sufficiently viable. Medical abortion or early delivery by caesarean section followed by therapy according to standard oncological protocols are indicated for medullary, aplastic cancer variants, common highly differentiated neoplasia with germination into surrounding organs and metastasis. Pregnant women with diagnosed thyroid cancer are recommended:
- Surgical treatment. The volume of intervention depends on the stage of the disease, and in papillary carcinomas — on the course variant. The operation is recommended to be performed in the second trimester. Most often, a thyroidectomy or subtotal resection of the thyroid gland is performed. If the lymph nodes are affected, lymph node dissection is additionally performed. To remove small tumors that are located in the thickness of the gland and do not germinate the capsule, hemithyroidectomy can be recommended.
- Hormone replacement therapy. To maintain euthyroidism, all pregnant women operated on for malignant nodular formation of the thyroid gland are prescribed L-thyroxine in high dosages. The drug not only prevents the development of a hypothyroid condition that is dangerous for the development of the fetus, but also prevents the recurrence of the disease by suppressing the secretion of thyroid-stimulating hormone. Treatment is carried out under laboratory control of TSH, T3, T4 levels.
Radioiodotherapy and radiation treatment methods are allowed to be used only after the end of gestation. Natural delivery is recommended for patients with highly differentiated thyroid cancer of stage I-II. Cesarean section is performed in the presence of obstetric indications (preeclampsia, anatomically and clinically narrow pelvis, oblique, transverse fetal position, etc.), severe extragenital pathology.
Prognosis and prevention
With timely diagnosis and adequate treatment of follicular and papillary thyroid carcinomas, the survival rate exceeds 90%. The prognosis of medullary and especially anaplastic cancer is unfavorable. Primary prevention is aimed at preventing iodine deficiency, eliminating radiation effects, blocking the assimilation of radioactive iodine during the release of radiation by taking potassium iodide. Regular ultrasound screening is recommended for patients with thyropathology. In the presence of hereditary syndromes that increase the risk of medullary cancer, preventive thyroidectomy is possible.