Hypothyroidism

Introduction

The vast majority of patients have primary hypothyroidism due to thyroid gland failure from chronic autoimmune thyroiditis (Hashimoto’s disease). Defects in suppressor T lymphocyte function led to survival of a randomly mutating clone of helper T lymphocytes directed against antigens on the thyroid membrane. The resulting interaction stimulates B lymphocytes to produce thyroid antibodies.

CLINICAL PRESENTATION

• Symptoms of hypothyroidism include dry skin, cold intolerance, weight gain, constipation, weakness, lethargy, fatigue, muscle cramps, myalgia, stiffness, and loss of ambition or energy. In children, thyroid hormone deficiency may manifest as growth or intellectual retardation.
• Physical signs include coarse skin and hair, cold or dry skin, periorbital puffiness, bradycardia, and slowed or hoarse speech. Objective weakness (with proximal muscles affected more than distal muscles) and slow relaxation of deep tendon reflexes are common. Reversible neurologic syndromes such as carpal tunnel syndrome, polyneuropathy, and cerebellar dysfunction may also occur.
• Most patients with secondary hypothyroidism due to inadequate TSH production have clinical signs of generalized pituitary insufficiency, such as abnormal menses and decreased libido, or evidence of a pituitary adenoma, such as visual field defects, galactorrhea, or acromegaloid features.
• Myxedema coma is a rare consequence of decompensated hypothyroidism manifested by hypothermia, advanced stages of hypothyroid symptoms, and altered sensorium ranging from delirium to coma. Mortality rates of 60% to 70% necessitate immediate and aggressive therapy.

DIAGNOSIS

• A rise in TSH level is the first evidence of primary hypothyroidism. Many patients have a free T4 level within the normal range (compensated hypothyroidism) and few, if any, symptoms of hypothyroidism. As the disease progresses, the free T4 drops below normal. The T3 concentration is often maintained in the normal range despite low T4 . Antithyroid peroxidase antibodies and antithyroglobulin antibodies are usually elevated. The RAIU is not useful in evaluation of hypothyroidism because it can be low, normal, or elevated.
• Pituitary failure (secondary hypothyroidism) should be suspected in patients with decreased T4 levels and inappropriately normal or low TSH levels.

TREATMENT OF HYPOTHYROIDISM

Goals of Treatment: Restore thyroid hormone concentrations in tissue, provide symptomatic relief, prevent neurologic deficits in newborns and children, and reverse the biochemical abnormalities of hypothyroidism.

• Levothyroxine (l-thyroxine, T4 ) is the drug of choice for thyroid hormone replacement and suppressive therapy because it is chemically stable, relatively inexpensive, free of antigenicity, and has uniform potency.
• Thyroid USP (or desiccated thyroid) is usually derived from pig thyroid gland. It may be antigenic in allergic or sensitive patients. Inexpensive generic brands may not be bioequivalent.
• Liothyronine (synthetic T3 ) has uniform potency but has a higher incidence of cardiac adverse effects, higher cost, and difficulty in monitoring with conventional laboratory tests.
• Liotrix (synthetic T4 :T3 in a 4:1 ratio) is chemically stable, pure, and has a predictable potency but is expensive. It lacks therapeutic rationale because ~35% of T4 is converted to T3 peripherally