hypothyroidism

hypothyroidism is due to underactivity of the thyroid gland, and results from its failure to secrete sufficient thyroid hormones into the bloodstream.

For normal function, the thyroid gland relies upon stimulation by a hormone from the pituitary gland known appropriately as thyroid stimulating hormone (TSH). Primary hypothyroidism is due to failure of the thyroid itself, whilst secondary hypothyroidism occurs when the pituitary secretes inadequate TSH. Primary hypothyroidism is the usual reason for thyroid underactivity.

There are several potential causes of primary hypothyroidism. It may for example be due to insufficient intake of iodine in the diet, since iodine is an essential constituent of thyroid hormones. This is a major health problem in many regions of the underdeveloped world and ranks first as a global cause of thyroid deficiency. In contrast, congenital hypothyroidism is due to a rare failure of the thyroid gland to develop during fetal life. Another infrequent cause of hypothyroidism is a failure in the complex biosynthetic pathway which leads to the secretion of its hormones by the thyroid gland (thyroid dyshormonogenesis). But if there is sufficient dietary iodine, the most common cause of hypothyroidism is autoimmune destruction of the cells which make up the basic functional unit of the thyroid gland — namely, the thyroid follicle. The thyroid gland is particularly prone to autoimmune disorders. Thus in Hashimoto's thyroiditis, which in the UK afflicts about 1 in 10 women, but only 1 in 100 men, there is progressive hypothyroidism with declining secretion of thyroid hormones. The thyroid is gradually infiltrated by lymphocytes and the follicular architecture of the gland breaks down. At the same time, the overall mass of the gland can increase, and if untreated a large multinodular goitre sometimes develops. Hashimoto's thyroiditis is named after the Japanese surgeon who gave the first clear description of the condition in 1912. In 1956 it was demonstrated by Doniach, Roitt, and Campbell in London that Hashimoto's thyroiditis is further characterized by the presence in the circulating blood of thyroid autoantibodies (anti-thyroglobulin and anti-thyroid peroxidase).

Most of the symptoms of hypothyroidism in adults are the result of lowered cellular metabolism, due to the inadequate output of thyroid hormones. Typically, the patient feels cold, lethargic, and depressed. There is often weight gain, a puffy appearance (myxoedema), dry hair, and maybe a goitre. The pulse tends to be slow, cardiac output is reduced, and in women (the majority of sufferers) there may be menstrual irregularities. In children, since thyroid hormones are required for growth, there is stunted growth along with lethargy and obesity. One of the particular problems of this condition is that because hypothyroidism develops slowly these symptoms are insidious; they can go unnoticed or be wrongly attributed, for example, to the menopause or to natural ageing.

Inadequacy of thyroid hormones is particularly serious for the fetus, because they are required for the development of the nervous system in utero. In iodine-deficient regions of the world, this leads to the birth of neurological cretins, who have suffered major and irreversible damage to their central nervous system. It is estimated that, even in these days, 100 000 such cretins are born each year. In contrast, the incidence of neonatal hypothyroidism in iodine-replete Western society — a condition often referred to as ‘sporadic cretinism’ — is about 1 in 4000 live births; this is due to failure of the fetal thyroid to develop. This congenital hypothyroidism, unlike the neurological cretin, is amenable to treatment with thyroid hormones.

Hypothyroidism can readily be treated by oral thyroxine, which is one of the two hormones synthesized by the thyroid gland. This was first demonstrated by George Murray, a physician in Hartlepool. In 1891 he reported to the Newcastle Medical Research Society the beneficial effects of administering extracts of sheep thyroids to his profoundly hypothyroid patients. This was the first example of hormone replacement therapy.

N. J. Marshall

See also goitre; hormones; thyroid.