Hyperthyroidism

2011

Pathophysiology

Hyperthyroidism, or thyrotoxicosis, is the result of excessive levels of circulating thyroid hormones. It is characterized by elevated total T4, free T4, free thyroxine index, and/or tri-iodothyronine and tri-iodothyronine resin uptake. Low thyroid-stimulating hormone and normal levels of tri-iodothyronine and thyroxine characterize subclinical hyperthyroidism, and it has the same causes as overt hyperthyroidism. Graves’ disease, an autoimmune disorder in which stimulatory anti-TSH receptor antibodies are formed, comprises the majority of hyperthyroid cases. In fact, the strongest risk factor for both hypothyroidism and hyperthyroidism is the presence of thyroid peroxidase antibodies. These antibodies are directed toward the receptors in the cell membrane of the thyroid gland, causing the gland to increase growth, size, and function. Graves’ disease is characterized by several common features, including thyrotoxicosis, goiter, exophthalmos, and pretibial myxedema. Graves’ disease is eight times more common in women than men, typically presents between the ages of 20 and 40 years old, and the most common presentation is a diffuse nonpain-ful goiter. It may be more prevalent in some genetic HLA haplotypes.

There are several types of thyroiditis that can cause hyperthyroidism, including Hashimoto’s thyroiditis, subacute thyroiditis, painless thyroiditis, postpartum thyroiditis, and radiation thyroiditis. Other contributing factors include stress, smoking, and iodine supplements/ excessive iodine intake, drug-induced hypothyroidism, higher pregnancy frequency, being postpartum, and microbial infections. Hyperthyroid patients have a significantly lower exposure to exogenous estrogens than euthyroid patients.

Toxic adenoma is a solitary nodule within the thyroid that produces excessive amounts of thyroid hormones. It typically occurs in the middle-aged and older populations.

Thyroid storm, or thyrotoxic crisis, can occur as a result of a serious stressor, such as surgery, infection, or trauma in a poorly managed case. The mortality rate is approximately 25% even with proper medical treatment.

Hyperthyroidism and subclinical hyperthyroidism affect quality of life, producing symptoms mimicking adrenergic overactivity. Subclinical hyperthyroidism exerts significant effects on the cardiovascular system. It is associated with a higher heart rate and increased risk of supraventricular arrhythmias, and with an increased left ventricular mass, often accompanied by impaired diastol-ic function and sometimes by reduced systolic performance on effort and decreased exercise tolerance. These changes usually precede the onset of more severe cardiovascular disease, thus potentially contributing to increased cardiovascular morbidity and mortality. Subclinical hyperthyroidism may accelerate the development of osteoporosis and hence increased bone vulnerability to trauma, particularly in postmenopausal women with a pre-existing predisposition. Fortunately, subclinical hyperthyroidism and its symptoms are readily preventable, and reversible with timely treatment.

Signs and Symptoms

Symptoms of hyperthyroidism are listed in Signs and Symptoms of Hyperthyroidism. Menstrual symptoms associated with hyperthyroidism can vary, and may range from amenorrhea to oligome-norrhea, but menstrual cycles also may appear normal. Anxiety, nervousness, and depression rates are higher in hyperthyroid patients than in euthyroid controls. Graves’ disease is characterized by a triad of hyperthyroidism, exophthalmos, and pretibial myxedema. Hyperthyroidism symptoms in postmenopausal women present differently than in younger women. Symptoms are usually confined to a single organ system, particularly the cardiovascular or central nervous system. Goiter is usually absent in 40% of cases, and in older women, a co-occurring disease such as infection of coronary heart disease is usually predominant. The triad of weight loss, constipation, and appetite loss occurs in about 15% of older patients, whereas ophthalmic disease is rare. Practitioners may notice failure to thrive in older patients, with signs of heart disease, unexplained weight loss, and mental or psychological changes signaling possible hyperthyroidism.

Signs and Symptoms of Hyperthyroidism

  • Diaphoresis
  • Diarrhea
  • Exercise intolerance
  • Exophthalmia
  • Goiter
  • Hair loss
  • Heart palpitations
  • Heat intolerance
  • Increased appetite
  • Nervousness
  • Onycholysis (separation of the nail from the bed)
  • Personality/psychological changes
  • Pretibial myxedema
  • Skin changes
  • Tachycardia
  • Thyroid bruit (murmur)
  • Tremor
  • Weakness
  • Weight loss

Diagnosis

Definitive laboratory diagnosis is based on elevated serum free T4, total T4, free thyroxine index, and tri-iodothyronine resin uptake. If these are borderline elevated, the tri-iodothyronine should be checked as it is often elevated out of proportion to the T4. Thyroid-stimulating hormone is typically decreased. Test for Graves’ disease using the serum thyroid-stimulating hormone receptor antibodies (TSH-R-Ab) test. If nodular goiter presents, a thyroid scan to rule out cancer is recommended. As with hypothyroidism, controversy exists as to whether to routinely screen for subclinical hyperthyroidism. Proponents of screening advocate for the potential benefit via prevention of atrial fibrillation, osteoporotic fractures, and other complications of overt hyperthyroidism. Controlled studies of the treatment of subclinical disease have not been conducted.

Conventional Treatment

The primary goal of conventional medicine is to limit the amount of thyroid hormone production by the thyroid gland. Three main treatment methods are available: (1) antithyroid drug therapy, (2) surgery, or (3) radioactive iodine therapy. Although Graves’ disease is an autoimmune disorder, conventional treatment of the disorder is aimed at managing the hyperthyroidism.

Antithyroid drug therapy seems to be most useful in young patients with mild disease. The drugs propylthiour-acil, carbimazole, and methimazole may be given until spontaneous remission occurs. Twenty to forty percent of patients have spontaneous remission within 6 months to 15 years duration. There is a fifty to sixty percent relapse rate in patients treated with this method of therapy.’

Thyroidectomy is the treatment of choice for those patients with large or multinodular goiters. The patient is given antithyroid drugs for 6 weeks to bring the gland to a euthyroid state. The patient is also given potassium iodine for 2 weeks prior to surgery to diminish the vas-cularity of the gland and simplify the surgery. Subtotal thyroidectomy is preferred over total thyroidectomy. Patients generally require supplementation with thyroid hormone following surgery.

In radioactive iodine therapy, radioactive iodine is given in one dose, following which the gland shrinks and the patient becomes euthyroid over a period of 6 to 12 weeks. The major complication of this method of therapy is hypothyroidism, which develops in 80% of patients treated.

In mild cases of hyperthyroidism, beta-blockers may be given to provide symptomatic relief of adrenergic symptoms, including arrhythmia, tremor, tachycardia, and anxiety. They also provide minimal prevention of peripheral conversion of thyroxine to T3. As beta-blockers have no effect on inhibition on the production or release of thyroid hormone, they are an adjunctive therapy alongside of one of the more invasive therapies described in the preceding.

Hyperthyroidism: Botanical Treatment

Nutritional Considerations

The risk of oxidative damage is increased in the hyper-thyroid patient because of a higher metabolic rate. Lipid peroxidation is increased and activities of antioxi-dant enzymes are altered. Dietary changes involve an emphasis on goitrogens, foods that naturally block thyroid hormone synthesis, and the avoidance of certain foods, particularly those high in iodine content such as seaweeds. Dietary goitrogens include broccoli, cauliflower, Brussels sprouts, cabbage, kohlrabi, sweet potatoes, almonds, pine nuts, millet, peaches, and peanuts.

• Include a complex daily antioxidant supplement.

Flavonoid-containing substances have been shown to decrease serum thyroxine concentrations and inhibit both conversion of thyroxine to tri-iodothyronine and 5′-deiodinase activity. Foods and botanical medicines that are high in flavo-noid compounds include those fruits and vegetables of yellow-orange, red, and purple color, such as blueberries, purple grapes, and cherries. Botanical medicines that provide flovanoid compounds include hawthorne berry, astragalus, gingko, licorice, and chamomile.

Calcium metabolism is altered in hyperthyroidism, making Graves’ patients more susceptible to osteoporosis. Adequate prevention of osteoporosis should be an important part of the patient’s treatment plan.

Selenium deficiency substantially alters the conversion of thyroxine to tri-iodothyronine in peripheral tissues such as the liver and kidneys. In a randomized, prospective, blinded study 36 patients with autoimmune thyroiditis were supplemented 200 |ig of selenium for 3 months, thyroid-specific TPOAb concentrations significantly decreased from 100% to 63%, 9 of the 36 had complete normalization of TPOAb concentrations.

Zinc needs are increased in hyperthyroid patients because of greater urinary zinc excretion.

Additional Therapies

Stress reduction methods include biofeedback, meditation, tai chi, yoga and prayer therapy, and should be included in a plan for hyperthyroid treatment.

Treatment Summary

• Achieve symptomatic relief of heart palpitations and anxiety with herbs.

• Use herbs and antioxidant supplements to protect the liver against the oxidative stress effects of increased metabolism caused by this condition.

• Ensure adequate nutritional intake, metabolism is significantly increased in patients with hyperthyroidism.

• Increase intake of dietary goitrogens to help reduce excessive thyroid function.

Severe hyperthyroidism requires medical management

Case History: Hyperthyroidism