Printer Friendly

Diffuse hyperplasia of the thyroid gland (Graves' disease).


Widely known by its eponym Graves' disease, diffuse hyperplasia of the thyroid gland is an autoimmune condition in which excess thyroid hormone production is unchecked by the normal feedback loop between the thyroid and the pituitary gland. The immune-system abnormality is mediated by antibodies to the thyrotropin receptor found on follicular epithelial cells. When the most specific antibody, known as thyroid-stimulating immunoglobulin (TSI), is bound to the thyrotropin receptor, the TSI mimics the action of pituitary thyrotropin and stimulates the follicular epithelium to produce hormone. The clinical effect of this autoimmune process is (1) thyrotoxicosis accompanied by diffuse thyroid enlargement and an infiltrative ophthalmopathy and (2) a spectrum of the systemic effects of excessive thyroid hormone production.

Graves' disease is the most common cause of spontaneous hyperthyroidism, representing up to 80% of all cases in the United States. Patients usually present in the third and fourth decades of life. Graves' disease is much more common in women than men (10:1). The wide spectrum of symptoms includes weight loss, heat intolerance, fatigue, weakness, palpitations, dyspnea on exertion, stridor secondary to tracheal compression, hoarseness, chest pain, dysphagia, oligomenorrhea, hair loss or a change in hair texture, a gritty sensation in the eyes, proptosis, conjunctivitis, memory loss, poor attention span, emotional lability, muscle weakness, and irritability or agitation. In addition to hair loss and a wide-eyed stare or proptotic appearance, physical findings may include localized myxedema (particularly pretibial), irritative keratoconjunctivitis, lid lag, diplopia, tachycardia, hyperactive reflexes, and smooth, warm, and velvety skin. The thyroid is diffusely enlarged, although nodules may be seen in longstanding or treated disease. Laboratory evaluation will show an elevated serum free thyroxine ([T.sub.4]) or triiodothyronine ([T.sub.3]) level and a markedly suppressed thyroid-stimulating hormone level.

The appearance of the thyroid on low-power magnification in Graves' disease is remarkable for the accentuation of its normal lobular pattern (figure 1). This change in appearance is attributable to an increase in the amount of fibrous tissue in the interlobular septa. A patchy lymphocytic infiltrate is often present. Moreover, the entire gland is affected by papillary hyperplasia, with the cell growth showing both hyperplasia and hypertrophy. The thyroid follicles are lined with columnar epithelial cells with basally located round nuclei and relatively dense chromatin; the cytoplasm is granular and eosinophilic (figure 2). The nuclei are not irregular. The hyperplastic follicular epithelium forms infoldings into the lumen of the follicle, producing a stellate outline. Vacuoles are noted along the apical aspect of the follicular cells, giving the colloid a scalloped appearance. Sometimes Graves' disease is mistaken for papillary carcinoma or Hashimoto's thyroiditis, but other histologic features will help make the distinction.


Most cases of Graves' disease show treatment effect, specifically related to medical management or radioactive iodine. Potassium iodide causes involution, as follicular cells revert to their normal cuboidal or flattened appearance, alternating with areas that have retained some of the features of hyperplasia (figure 3, A). However, the failure rate with medical therapy is 40%, so most patients are forced to consider radioactive iodine or surgery. Radioactive iodine may produce a nodular gland; the nodules are often quite cellular and may exhibit striking nuclear atypia (figure 3, B). Beta blockers are used to ameliorate symptoms before surgery.


The overall prognosis for patients with Graves' disease is excellent. However, thyroid storm is a life-threatening exacerbation of thyrotoxicosis. Patients exhibit severe central nervous system and cardiac manifestations. Thyroid storm requires rapid treatment, usually with antithyroid drugs for initial control.

Suggested reading

Cooper DS. Antithyroid drugs for the treatment of hyperthyroidism caused by Graves' disease. Endocrinol Metab Clin North Am 1998;27(1):225-47.

Dabon-Almirante CL, Surks MI. Clinical and laboratory diagnosis of thyrotoxicosis. Endocrinol Metab Clin North Am 1998;27(1):25-35.

McIver B, Morris JC. The pathogenesis of Graves' disease. Endocrinol Metab Clin North Am 1998;27(1):73-89.

Lester D.R. Thompson, MD, FASCP

From the Department of Pathology, Woodland Hills Medical Center, Southern California Permanente Medical Group, Woodland Hills, Calif.
COPYRIGHT 2007 Vendome Group LLC
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2007, Gale Group. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:Thompson, Lester D.R.
Publication:Ear, Nose and Throat Journal
Date:Nov 1, 2007
Previous Article:Retropharyngeal carotid artery.
Next Article:Tympanometry.

Related Articles
Learn to answer troublesome questions about thyroid tests.
Primary parathyroid hyperplasia. (Pathology Clinic).
Clinical utility of autoantibodies directed against TSH-R.
Oncocytoma of the parotid gland.
Dyshormonogenetic goiter of the thyroid gland.
Hypothyroidism following hemithyroidectomy for benign nontoxic thyroid disease.
Bilateral multinodular oncocytomas of the parotid arising in a background of bilateral oncocytic nodular hyperplasia.
Radiotherapy-associated euthyroid Graves ophthalmopathy following floor-of-mouth surgery: a case report.

Terms of use | Privacy policy | Copyright © 2022 Farlex, Inc. | Feedback | For webmasters |