Pathophysiology
Summary
Hyperthyroidism is a condition marked by excessive production of thyroid hormones, specifically T3 & T4, leading to a hypermetabolic state. Clinically, this manifests as weight loss, increased body temperature, flushed skin, and increased heat production and sweating. Thyrotoxic myopathy can also occur, characterized by proximal muscle weakness without elevated creatine kinase levels or muscle atrophy.
Cardiovascular effects are significant, with increased beta adrenergic receptor expression causing sympathetic overstimulation. This leads to tachycardia, hypertension, and increased cardiac output, sometimes by up to 250%. There's also an elevated risk for cardiac conduction abnormalities, particularly atrial fibrillation.
Neurological and psychological symptoms include anxiety, irritability, and tremors due to sympathetic overactivity. Patients may also display a widened gaze and lid lag, along with brisk and exaggerated deep tendon reflexes.
Gastrointestinal are related increased motility, causing symptoms like diarrhea & malabsorption, which in turn contribute to rapid weight loss. Metabolic symptoms such as hypercalcemia are also common, which increases the risk of osteoporosis, especially in older women.
Thyroid storm is a critical complication of untreated severe hyperthyroidism characterized by massive sympathetic stimulation, leading to extreme fever, severe tachycardia, GI symptoms like vomiting and diarrhea, and CNS dysfunction, which can range from agitation to coma. It can also precipitate acute congestive heart failure and tachyarrhythmias, elevating the risk of sudden cardiac death. Triggers include infection, trauma, and surgery.
Graves disease is most common cause of hyperthyroidism, especially among women, and is linked to HLA antigens B8 & DR3. In Graves' disease, activating autoantibodies target TSH receptors, stimulating excessive thyroid hormone production even in the presence of low TSH levels. This results in a diffuse, nontender goiter.
Extrathyroidal symptoms in Graves disease include Graves ophthalmopathy, where cytokines released by helper T cells stimulate orbital fibroblasts to produce excess glycosaminoglycans resulting in edema and eye protrusion, and pretibial myxedema, characterized by waxy edema on the anterior leg. Histological features reveal diffuse follicular cell hyperplasia and T-cell lymphocytic infiltration, with a "scalloped" appearance on colloid examination.
Alternative causes of hyperthyroidism are toxic multinodular goiters and toxic adenomas. Both conditions autonomously produce thyroid hormones without TSH stimulation. In toxic adenomas, an activating TSH receptor mutation may be present, leading to autonomous hormone production and low TSH levels. If the adenoma's capsule is invaded, it can progress to follicular carcinoma.
For diagnosis, radioactive iodine scans help differentiate causes. Cold nodules are more likely to be cancerous, while 'hot' nodules suggest benign conditions like toxic adenomas or Graves disease.
Lesson Outline
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FAQs
Hyperthyroidism is characterized by an overproduction of thyroid hormones T3 and T4, leading to a hypermetabolic state in the body. This condition results in symptoms such as weight loss, increased temperature, sweating, flushed skin from peripheral vasodilation, and proximal muscle weakness. Other signs include symptoms of sympathetic overstimulation such as tachycardia, hypertension, diaphoresis, anxiety, irritability, tremor, cognitive impairments, and confusion. Increased sympathetic activation also causes widened gaze and lid lag. Patients with hyperthyroidism may also experience increased heart rate and palpitations, heightened deep tendon reflexes, and gastrointestinal issues like diarrhea and malabsorption syndromes.
Hyperthyroidism can significantly affect the cardiovascular system. It leads to an increase in heart rate and palpitations due to heightened sympathetic activity, and results in hypertension because of increased cardiac contractility and sympathetic tone. Patients with hyperthyroidism are at an increased risk of cardiac conduction abnormalities, especially atrial fibrillation. Severe untreated hyperthyroidism can also lead to life-threatening conditions like a thyroid storm, which can cause acute congestive heart failure.
Hyperthyroidism can have a detrimental impact on bone health by increasing bone resorption, which can lead to hypercalcemia. Elevated calcium levels can suppress parathyroid hormone (PTH) and vitamin D, increasing the risk of osteoporosis, especially in older women.
Graves disease is an autoimmune form of hyperthyroidism. It is characterized by activating autoantibodies that stimulate TSH receptors, leading to excess thyroid hormone production. Graves disease can lead to follicular hypertrophy and hyperplasia causing a diffuse, non-tender goiter. It can also exhibit ophthalmopathy or exophthalmos due to the activation of helper T-cells leading to inflammation, fat, and glycosaminoglycan accumulation, causing the eyes to bulge outward. Less commonly, it can cause infiltrative dermopathy or pretibial myxedema as a result of excess accumulation of glycosaminoglycans in the dermis of the anterior leg. In some cases, Graves disease is associated with HLA antigens B8 and DR3.
Although multinodular goiters are more commonly associated with hypothyroidism, tissue in this condition can begin producing thyroid hormone autonomously, leading to hyperthyroidism. Similarly, toxic multinodular goiters and toxic adenomas, which are solitary nodules, can produce excess thyroid hormone without the need for TSH stimulation, causing hyperthyroidism. Some toxic adenomas have an activating TSH receptor mutation, further promoting the autonomous production of thyroid hormone. In both cases, abnormal thyroid tissues will take up radioactive iodine, giving them a more localized ‘hot’ appearance on scans, unlike the diffuse uptake seen in Graves disease.
