Back to ENDOCRINOLOGYThyrotoxicosis are the clinical, physiologic and biochemical syndromes that result when tissues are exposed to, and respond to high levels of thyroid hormone. In most instances, thyrotoxicosis is due to hyperactivity of thyroid gland, or hyperthyroidism (hypermetabolism). Occasionally, thyrotoxicosis may be due to other causes such as excessive ingestion of thyroid hormone or secretion form ectopic sites. There are various forms of thyrotoxicosis and the most common is Graves’ Disease.
Graves’ disease, also known as Parry’s or Basedow’s disease or diffuse toxic goiter, is a disorder with three major manifestations: hyperthyroidism with diffuse goiter, ophthalmopathy, and dermopathy. They do not appear together. Indeed, one or two need never appear, and moreover, the three may run courses that are largely independent of one another.
It is the most common form of thyrotoxicosis. It affects as many as 1.9 per cent of the female population. The ratio of women to men is as high as 7:1. It reaches its peak incidence between the third and forth decades and the reason for the female predominance in this as in all thyroid diseases is unknown. Genetic factors play an important role, since there is an increased frequency haplotypes HLA-B8 and -DRw3 in Caucasian, HLA-Bw36 in Japanese, and HLA-Bw46 in Chinese patients with the disease.
Graves’ disease is currently viewed as an autoimmune disease of unknown cause. Hyperthyroidism is its principal manifestation, yet TSH is suppressed and no intrinsic abnormalities in the gland have been identified.
In Graves’ disease, T lymphocytes become sensitized to antigens within the thyroid gland and stimulate B lymphocytes to synthesize antibodies to these antigens. One such antibody is directed against the TSH receptor site in the thyroid cell membrane and has the capacity to stimulate the thyroid cell to increased growth and function.
The presence of these antibodies is positively correlated with active disease and with relapse of the disease. There is an underlying genetic predisposition, but it is nor clear what “triggers” the acute episodes. Some factors that may incite the immune response: pregnancy, particularly the postpartum period; iodine excess, particularly in areas of iodine deficiency; lithium therapy; viral or bacterial infections; glucocorticoid withdraw.
The etiology and pathogenesis of Graves’ ophthalmopathy is not known. It may involve cytotoxic lymphocytes and cytotoxic antibodies sensitized to a common antigen in orbital fibroblasts, orbital muscle, and thyroid tissue, which would cause inflammation, resulting in proptosis of the globes. The pathogenesis of dermopathy may also involve this mechanism. Patients with exophthalmos and particularly those with dermopathy almost always have high titers of circulating TSH receptor antibodies, suggesting that these two clinical manifestations represent the most severe form of this disease.
Many symptoms of thyrotoxicosis suggest a state of catecholamine excess, but circulating levels of epinephrine are normal; thus, in Graves’ disease, the body appears to be hyperactive to catecholamines and this may be due in part to a thyroid hormone-mediated increase in cardiac catecholamine receptors.
The thyroid gland id diffused enlarged, hypercellular, soft and vascular. There is a parenchymatous hypertrophy and hyperplasia. Usually there is little or no colloid present with lymphocytic infiltration and in some cases it is impossible to distinguish the microscopic picture from Hashimoto’s thyroiditis. The disease is associated with generalized lymphoid hyperplasia and infiltration and occasionally with enlargement of the spleen and thymus. There may be degeneration of skeletal muscle fibers, enlargement of the heart, fatty infiltration or diffuse fibrosis of the liver, decalcification o the skeleton, and loss of body tissue.
The ophthalmopathy is characterized by and inflammatory infiltrate of the orbital contents. The dermopathy is characterized by thickening of the dermis, which is infiltrated with lymphocytes and with hydrophilic, metachromatically staining mucopolysaccarides.
The common clinical manifestations of hyperthyroidism are: palpitations, nervousness, easy fatigability, hyperkinesia, tremors, diarrhea, excessive sweating, intolerance to heat, preference for cold. There is often marked weight loss without loss of appetite. Proximal muscle weakness and loss of muscle mass may be so severe that the patient cannot rise from a chair without assistance. The patients often speaks very rapidly. The thyroid gland is diffused enlarged, and may be asymmetric or lobular. There may be a bruit over the thyroid that signifies that the patient is thyrotoxic. The patient often doesn’t note the neck swelling and comes to the doctor because of the other signs and symptoms.
The eye signs of Graves’ disease may be divided in two components: the spastic and the mechanical. The former includes the stare, lid lag, and lid retraction and accounts for the “frightened” facies. The mechanical component consists of proptosis of varying degree with ophthalmoplegia and congestive oculopathy characterized by chemosis, conjunctivitis, periorbital swelling, and the potential complications of corneal ulceration, optic neuritis, and optic atrophy. Exophthalmos(photo) may be unilateral early but usually progresses to bilateral involvement.
The dermopathy consists of thickening of the skin(photo), particularly over the lower tibia. It is relatively rare and is usually associated with ophthalmopathy. The skin cannot be picked between the fingers. Body involvement, with subperiosteal bone formation and swelling is particularly evident in the metacarpal bones, but this is also rare. Amore common finding is separation of the fingernails from their beds, or onycholysis(photo).
Part 2 will consist of the clinical management of the patient with Graves’ disease, including laboratory diagnosis, differential diagnosis, treatment and prognosis.
References
Back to ENDOCRINOLOGY
Back to SPECIALTIES
Back to MEDSTUDENTS HOMEPAGE