Plummer’s disease is an endocrine pathology caused by the development of thyroid adenoma, which actively produces thyroid hormones. It is manifested by symptoms of hyperthyroidism: weight loss, shortness of breath, weakness, drowsiness, tachycardia, arrhythmia. The diagnostic complex includes consultation and examination of an endocrinologist, ultrasound and thyroid scintigraphy, blood test for thyroxine, triiodothyronine and thyroid-stimulating hormone. Treatment is carried out by surgical methods (less often medicamentally), elderly patients are shown therapy with radioiodine, ethanol sclerodestruction of thyroid nodes.
ICD 10
E05.2 Thyrotoxicosis with toxic nodular goiter
Meaning
Plummer’s disease (thyrotoxic adenoma, toxic multinodular goiter) got its name from the surname of the American physiologist, endocrinologist Henry Stanley Plummer. In 1913, he published a paper in which he described a pathological condition manifested by thyrotoxicosis, but devoid of some classic signs of diffuse toxic goiter and different from it in the mechanisms of origin. Women are more susceptible to morbidity, the gender ratio is 4:1. Rare cases of toxic adenoma are registered among adolescents and children. General epidemiological indicators are higher in areas endemic to goiter.
Causes
The nature of thyrotoxic adenoma is polyetiological and cannot always be established reliably. It is believed that the main role in the occurrence of endocrinopathy is played by somatic mutations of the gland cells and external provoking effects (intoxication, ionizing radiation). The occurrence of gene changes leading to the development of the syndrome is increasing in regions with iodine deficiency. Presumably, mutations trigger the activation of the pTSH in thyrocytes regardless of the strength of the natural regulatory signals of the pituitary gland and autoanatibodies to TSH receptors detected in autoimmune trieopathies. Mutations of TSH receptors located on the epithelium of the thyroid gland lead to hyperactivation of individual secretory cells, which begin to autonomously and uncontrollably produce thyroid hormones.
Pathogenesis
Plummer’s disease is accompanied by thyrotoxicosis, which is caused by excessive production of iodized hormones by cells of the autonomous adenoma. The key link in the pathogenesis are mutations of thyrotropin receptors, leading to their autoactivation – the ability to absorb more iodine and synthesize thyroxine (T4), triiodothyronine (T3) without the regulatory effect of thyroid-stimulating hormone. Hyperplasia and hyperfunction of individual epithelial cells develop. In the future, under the influence of growth factors, thyrocytes proliferate, forming a benign hormone-active epithelial tumor – toxic thyroadenoma. Another pathogenetic mechanism of tumor formation is changes in the G–protein gene, which increases the functional activity of individual follicles.
Thyrotoxicosis occurs mainly due to the influence of triiodothyronine. The level of TSH and tyroliberin remains normal or decreases. With a prolonged course of the disease, the production of thyrotropin by the pituitary gland is suppressed – the feedback law is triggered. At the morphological level, the microfollicular structure of adenomas is characteristic of Plummer’s disease. If a multi-node formation is formed, macrofollicular tumors may occur in parallel with characteristic microfollicular tumors.
Symptoms
A distinctive feature of the disease is the predominance of cardiac arrhythmias and myopathy in the clinical picture. Patients are diagnosed with sinus tachycardia and atrial flutter – cardiological syndromes that are subjectively experienced as palpitations, discomfort, a feeling of heaviness or pain in the heart area. With a severe course of the disease, there is a feeling of lack of air, shortness of breath, weakness, dizziness, decreased performance.
Thyrotoxic myopathy is manifested by muscle weakness, hypotrophy, trembling, less often – myalgia. A decrease in the tone of the diaphragmatic muscle increases shortness of breath. The previously habitual physical exertion becomes unbearable. Ophthalmic disorders are represented by the Grefe symptom (separation of the upper eyelid from the iris when looking up) and the Mobius symptom (inability to focus on closely located objects).
The emotional state of patients changes: they become overly excitable, emotionally unbalanced, often cry, provoke conflicts, experience unreasonable fear and anxiety. The purposefulness of behavior decreases, speech and thought processes accelerate, but the concentration of attention worsens. There is fussiness, insomnia, tremor of the fingers.
The metabolic rate increases, so patients experience hot flashes, often sweat, do not tolerate heat and high humidity, lose weight, despite the fact that their appetite increases, and the caloric content of the diet increases. Body temperature is normal or elevated to subfebrile values. Sexual functions are disrupted: men’s potency decreases, women’s menstrual cycle becomes irregular, monthly bleeding is accompanied by severe pain, fainting. Representatives of both sexes have an increased risk of infertility.
Complications
With the proliferation of adenoma and the absence of treatment for Plummer’s disease, the risk of degeneration of benign tumor tissue into malignant increases. Follicles are transformed into carcinomatous clones, which serve as the basis for the development of thyroid cancer, especially its aggressive forms. According to statistics, the frequency of this complication among adult patients ranges from 2 to 5%. Another problem is the side effects of radioiodine treatment. Pathophysiologists suggest that such therapy can serve as a provoking factor of autoimmune thyroopathy, for example, Graves-Bazedov disease, Hashimoto’s thyroiditis. The combination of these diseases with Plummer’s disease occurs in 2-4% of cases of all autoimmune pathologies of the thyroid gland.
Diagnostics
The examination of patients is carried out by an endocrinologist. The main diagnostic tasks are the determination of thyrotoxicosis and differentiation of Plummer’s disease with clinically similar autoimmune thyropathies – Graves’ disease, Hashimoto’s thyroiditis. A comprehensive study includes the following methods:
- Clinical survey. Patients present complaints characteristic of thyrotoxicosis – fatigue, a feeling of heat, attacks of palpitations, increased thirst and appetite, fever. It is characteristic that among the symptoms, disorders from the cardiovascular system are particularly emphasized.
- Physical examination. Palpation of the neck area reveals the formation of a rounded shape with smooth, clear contours. The knot is often elastic, smooth, does not cause pain, shifts at the moment of swallowing. During auscultation, tachycardia is diagnosed. The examination does not reveal endocrine ophthalmopathy and/or pretibial myxedema.
- Instrumental examination. According to the results of ultrasound of the thyroid gland, a rounded neoplasm is determined (a clear rim, a homogeneous hyperechoic structure). With radionuclide examination, there is a low accumulation or complete absence of the drug in the tissue that is not part of the node.
- Laboratory tests. According to the results of blood tests, elevated or high levels of triiodothyronine, normal or moderately elevated thyroxine concentration are detected. Indicators of the TSH level are reduced. Titers of autoantibodies to thyroperoxidase and thyroglobulin do not exceed the norm.
Treatment
The therapy scheme is always selected individually. To date, in clinical endocrinology, the most common methods of treating adenoma are conservative, surgical and radioactive. The expediency and safety of an intervention is assessed by the doctor individually, depending on the volume of the tumor, the progression of pathology, and the age of the patient. Four tactical approaches are known:
- Medical treatment. Conservative therapy is carried out with thyrostatic drugs in cases when the activity of the tumor process is insignificant, the neoplasm is small, there is no growth dynamics, and also if it is necessary to achieve remission before surgery. The action of thyrostatics is aimed at inhibiting individual stages of biosynthesis of iodine-containing hormones.
- Surgical operation. Most patients are shown surgical removal of the tumor. The volume of the operation depends on the size of the adenoma, its localization. Enucleation of the node, resection of the lobe of the gland or thyroidectomy is performed. After the operation of the function, the functioning of glandular tissues is gradually restored (except in the case of thyroidectomy).
- Radioiodotherapy. If there are contraindications to surgery, patients over 50-60 years of age are prescribed therapy with radioactive iodine. The disadvantages of this method are the risk of hypothyroidism and the addition of autoimmune thyropathies.
- Ethanol destruction of nodes. With small toxic adenomas, percutaneous sclerosing injections of ethanol can be used. The intervals between sessions and the amount of alcohol injected are determined during the course of procedures. This method of treatment is relatively new, studies of its effectiveness and safety are continuing.
Prognosis and prevention
With timely diagnosis and the appointment of adequate therapy, Plummer’s disease does not pose a danger to the health and life of the patient. Surgical and conservative methods can completely eliminate the tumor and restore the functions of glandular tissue, and adenoma malignancy is a fairly rare phenomenon. There are a number of measures that can reduce the likelihood of developing this disease. It is recommended to adhere to a diet with a sufficient intake of iodine, take iodine-containing drugs as prescribed by a doctor, avoid ionizing radiation, the entry of toxins into the body.
