Thyroid hormone deficiency can result in a wide variety of clinical and physiological disturbances in virtually every organ system (Table 1). The classic disease state is myxedema; the accumulation of mucinous edema results in facial periorbital and peripheral edema involving both the hands and feet. The periorbital edema con tributes to the patient’s haggard appearance and includes a droop of the upper eyelid. Table 2 lists the major causes of hypothyroidism.
Table1. Some Clinical Features of Disturbed Thyroid Hormone Status
Table2. Causes of Hypothyroidism
In areas where dietary iodide is sufficient, the most common cause of hypothyroidism is Hashimoto’s dis ease, an autoimmune thyroid disease in which the subject has circulating antibodies against intracellular antigens of the thyroid gland. Hashimoto’s disease is characterized by lymphocytic infiltration of the thyroid gland with destruction of the thyroid follicles so that thyroid hormone production and secretion is decreased. The low circulating levels of T4 and T3 result in increased TSH secretion from the pituitary, leading to growth of the thy roid tissue or goiter. The intracellular antigens are most commonly thyroglobulin (Tg) and thyroid peroxidase (TPO). Hashimoto’s patients may also have antibodies against TSHR and Graves’ disease patients may have antibodies against TPO and Tg. Thus, these two dis eases can be considered a single autoimmune entity with Hashimoto’s on one end and Graves’ on the other end of a spectrum of conditions.
There are a variety of hereditary diseases in which there are defects in one or more of the many steps required for the biosynthesis of thyroid hormone. These include defects in (a) iodide uptake, (b) iodination of thyroglobulin, (c) thyroglobulin biosynthesis, (d) iodotyrosine dehalogenase biosynthesis, and (e) thyroid gland insensitivity to TSH. Perturbation of the hypothalamic-pituitary-thyroid axis may occur so that there is a deficiency or total lack of pituitary-derived TSH or thyrotropin-releasing hormone (TRH).
The goal in treatment of a deficiency of T4 (and therefore T3) from any of these causes is replacement of the missing hormone, which can be done quite readily with levothyroxine, the L isomer of the hormone which was first synthesized in 1927. With careful establishment and monitoring of the drug dose, treatment can be highly successful in ameliorating the symptoms of hormone deficiency.
Without question, in many sections of the world the prime cause of hypothyroidism is dietary insufficiency of iodine. Growth of the thyroid gland is triggered by increased TSH secretion, which attempts to stimulate the iodide-trapping mechanisms and subsequent steps in the intrathyroidal metabolism of iodine. The morphological consequence is the development of a goiter. Endemic cretinism is the most severe outcome of IDD. After birth, neither supplying I− nor replacing T4 has significant effect on the neurological and skeletal results of I− deprivation during development.
