GRAVES’ DISEASE AND PRETIBIAL MYXEDEMA
Graves’ disease is the form of hyperthyroidism that is most often seen in the young adult population. It is an autoimmune disease that causes the thyroid gland to produce thyroid hormones. This results in the clinical manifestations.
Clinical Findings: Graves’ disease is seen in females more frequently than males, in a ratio of approximately 7:1. Most patients have an insidious onset of symptoms. Heat intolerance and nervousness are two of the early and more common findings. Anxiety and emotional difficulties can be life altering. Patients often complain of difficulty sleeping. Constitutional symptoms can manifest as weight loss, increased appetite, increased sweating, and profound nervousness. Women may suffer from menstrual irregularities. Cardiac arrhythmias are common as the disease progresses. Hypertension and tachycardia can be two of the earliest cardiovascular signs of the disease. As the disease progresses, exophthalmos becomes prominent, a goiter can be seen or felt, and patients develop pretibial myxedema.
The exophthalmos may lead to intermittent double vision and a feeling of posterior ocular pressure. Photophobia can be a part of the disease, as can frequent tearing and a feeling of “sand” in the eyes that causes frequent tearing and pain. Goiter may be noticeable to the patient, and it may be appreciated initially because of difficulty buttoning one’s collar. The goiter is diffuse in nature. The thyroid is easily palpable and is firm to the touch. On occasion, the astute clinician can auscultate a bruit over the thyroid gland; this represents the increased blood flow to the growing gland.
Pretibial myxedema is the most widely recognized skin finding in Graves’ disease. It begins as small, indurated papules that coalesce into plaques on the anterior shin. The plaques indent easily when palpated and clinically act like lymphedema, causing a nonpitting edema. Pretibial myxedema can occur in other areas of the body, but this is a rare finding. The skin is typically warm to the touch and can have a velvety feel. Increased sweating is noticeable most often as warm, moist palms and soles, similar to what is observed in patients with hyperhidrosis. Clubbing of the fingers is seen in a small proportion of affected individuals. Facial flushing with an increase in sweating is also seen. Females may develop breast enlargement, and males may develop gynecomastia.
Laboratory testing is needed to help define the condition. Radioactive iodine uptake imaging shows a diffuse, symmetric uptake of iodine in the patient with Graves’ disease. The pattern of uptake is very different from that seen in patients with a “hot” thyroid nodule, in which the radioactive signal is dramatically increased in the nodule. Thyroid antibody testing is very helpful in differentiating Graves’ disease from other forms of thyrotoxicosis. Antithyroglobulin, anti- microsomal, and anti–thyroid-stimulating hormone (TSH) receptor antibodies can be evaluated.
Pathogenesis: Graves’ disease is an idiopathic auto- immune disease that causes autoantibodies against the TSH receptor. The antibodies act as agonists to the receptor and cause non-stop activation of the TSH receptor on the thyroid. This leads to increased production of thyroid hormones, both triiodothyronine (T3) and (T4), by the thyroid. The increase in metabolic functioning of the thyroid leads to diffuse enlargement and goiter. The increased production of thyroid hormones and their effects on target tissues lead to the clinical findings.
Histology: Biopsy specimens of the pretibial skin show large amounts of mucin deposits within the middle and lower dermis, between collagen bundles. The mucin is so thick that it causes the dermal collagen bundles to be splayed apart. Overlying hyperkeratosis can be appreciated. Biopsy specimens from clinically nonaffected skin may show some of the same histological findings but on a lesser scale.
Treatment: Treatment of Graves’ disease is predicated on stopping the excessive thyroid hormone production. Ablation of the thyroid can be achieved with radiation therapy or surgical removal. Medications such as β-blockers are used to lessen the symptoms of the disease until it is rendered under control. Medical management of Graves’ disease can be achieved with propylthiouracil or methimazole, both of which act to decrease thyroid hormone production.