Pathogenesis and causes
Immunological disorders in individuals with a genetic predisposition (often associated with the HLA-B8 antigen carrier state) play a leading role in the development of diffuse toxic goiter. Severe psychological trauma and stress frequently precede the manifestation of the disease. Women are affected more often.
Normally, hormone synthesis occurs in the follicles of the gland: dietary iodine binds to the high-molecular-weight glycoprotein thyroglobulin. Tyrosine is iodinated, forming thyroxine ($T_4$) and triiodothyronine ($T_3$). In Basedow's disease, this process gets out of control.
Hormones circulate in the blood bound to proteins (globulin, prealbumin), but only the free fraction is active. $T_3$ provides the main clinical effect ($T_4$ is converted into $T_3$ at the tissue level). High doses of thyroid hormones not only suppress the secretion of pituitary thyrotropin (TSH) via a negative feedback mechanism, but also sharply increase the sensitivity of adrenoceptors to catecholamines.
Clinical presentation
Patients complain of heat intolerance, sweating, nervousness, muscle weakness, and progressive weight loss, which paradoxically combines with a good appetite.
Local and systemic manifestations:
- Thyroid gland: diffusely enlarged (goiter). Sizes are variable—from thickening of the isthmus to a massive goiter that alters the neck contour or extends retrosternally (causing compression of the esophagus and trachea). Auscultation over the gland reveals a bruit due to increased blood supply.
- Eye signs: widening of the palpebral fissures. Classic signs are present: Graefe's sign (lag of the upper eyelid when looking down, exposing a white strip of sclera), Stellwag's sign (infrequent blinking), and Möbius sign (convergence weakness).
- Nervous system: fine tremor of the fingers (Marie's sign), increased excitability.
- Digestion and reproductive system: tendency toward diarrhea due to increased gastrointestinal motility, nausea, vomiting, and reproductive dysfunction.
Thyrotoxic heart
The cardiovascular system is among the first to suffer due to hyperreactivity to catecholamines and accelerated blood flow. Hemodynamics changes to a hyperdynamic type.
Characteristic features:
- Arrhythmias: persistent tachycardia (100–140 bpm) that does not disappear even during sleep. Atrial fibrillation frequently develops—initially paroxysmal, then permanent.
- Auscultation: loud heart sounds, functional systolic murmur heard.
- ECG: tachycardia, signs of atrial fibrillation, ST-segment and T-wave changes.
With prolonged untreated disease, myocardial dystrophy and hypertrophy develop, followed by chamber dilation and severe heart failure.
Diagnostics and treatment principles
Laboratory diagnostics include biochemistry (decreased cholesterol, increased calcium and protein-bound iodine) and a hormonal profile (high $T_3$ and $T_4$). Instrumental tests include ultrasound to assess size, technetium ($^{99}Tc$) scintigraphy, and radioactive iodine uptake tests.
Treatment strategy is divided into three approaches:
- Medical: the mainstay is antithyroid drugs (imidazole derivatives, e.g., thiamazole). For mild forms, iodine preparations and sedatives are added. Non-selective $\beta$-blockers (propranolol) are mandatory to relieve cardiac symptoms.
- Surgical: indicated for severe cases, giant goiter, or medical therapy failure.
- Radioactive iodine: used less frequently today due to the high risk of hypothyroidism developing 10 or more years after therapy.
Briefly: answers to topical questions
What grades of thyroid enlargement are distinguished upon palpation according to the WHO classification?
According to the WHO classification (2001), three grades of thyroid enlargement are distinguished.
- Grade 0 (Normal): no goiter. The volume of a lobe does not exceed the size of the distal phalanx of the patient's thumb; the gland is neither visible nor palpable.
- Grade 1 (Palpable goiter): the gland is not visible with the neck in a normal position, but is palpable (lobe size is larger than the phalanx). Any palpable nodules are also classified under this grade.
- Grade 2 (Visible goiter): the enlargement of the gland is clearly visible to the eye with the neck in a physiological position without the need for palpation.
What specific skin manifestations (dermopathy) are characteristic of Graves' disease?
A specific cutaneous manifestation of the disease is pretibial myxedema (mucinosis edema of the skin of the shins).
Characteristic features of dermopathy:
- Local mucosal edema of the soft tissues of the anterior shins (may be unilateral or bilateral).
- Tissue thickening due to edema and hyperpigmentation.
- Prominent hair follicles, giving the skin a specific "orange peel" appearance.
Overall, patients also exhibit warm, moist skin with increased sweating due to arterial hyperemia and elevated metabolism.
The classic triad of Basedow's disease is easy to remember by the rule of three "G"s in Russian, or in English by Goiter (enlarged neck), Glasses-like eyes (exophthalmos/bulging eyes), and Galloping pulse (tachycardia).
Class and exam questions
Why do patients with thyrotoxicosis lose weight despite having a good appetite?
Thyroid hormone excess drastically accelerates all types of metabolism. Energy is consumed so rapidly that even increased food intake fails to compensate for weight loss.
What is a thyrotoxic crisis and how does it manifest?
This is a life-threatening complication caused by a massive release of hormones into the blood during stress, trauma, or infection. It manifests with acute psychosis, hyperthermia, pronounced tachycardia, and abdominal syndrome (pain, nausea, diarrhea) mimicking an "acute abdomen".
Why are beta-blockers included in the treatment regimen?
Thyroid hormones repeatedly increase receptor sensitivity to adrenaline and noradrenaline. Non-selective beta-blockers (e.g., propranolol) protect the myocardium and effectively eliminate palpitations.
What else to study on this topic
- Negative feedback mechanism in the Pituitary-Thyroid axis
- ECG criteria and morphological stages of the thyrotoxic heart
- Specific ophthalmological symptoms: eponyms and mechanisms of development
- Pharmacodynamics of imidazole derivatives in the treatment of DTG
- Differential diagnosis of causes of atrial fibrillation
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