A 16-year-old girl is brought to the office by her mother due to concern about excessive weight loss. The patient has lost 4.5 kg (10 lb) over the past 2 months, but thinks she still appears overweight, and is worried about gaining weight. She does not use tobacco, alcohol, or illicit drugs. Her mother has hypothyroidism. Blood pressure is 130/70 mm Hg, and pulse is 105/min and regular. There are no orthostatic changes. BMI is 22 kg/m2. On examination, the patient appears anxious. The thyroid is small and without palpable nodules. There is a fine tremor seen in the fingers when the arms are outstretched. Deep tendon reflexes are 3+ diffusely. The skin is warm and moist. Laboratory results show decreased TSH, elevated free thyroxine (T4), and undetectable thyroglobulin levels. Which of the following is most likely to be seen on thyroid biopsy of this patient?
This patient's symptoms (eg, weight loss, tachycardia, and tremors), elevated free thyroxine (T4), and suppressed TSH are indicative of thyrotoxicosis. However, her thyroid is small and serum thyroglobulin is undetectable, which suggests an exogenous source of thyroid hormone. Thyroglobulin is a glycoprotein produced by thyroid follicular cells that makes up a substantial component of follicular colloid and serves as the substrate for the formation of thyroid hormone. A small amount is released by the thyroid in normal function. Low levels, as in this patient, suggest noninflammatory suppression of thyroid activity.
In light of her mother's hypothyroidism, which suggests a possible source of levothyroxine tablets, this patient is likely surreptitiously taking thyroid hormone in an attempt to lose weight. Exogenous thyrotoxicosis can also occur in patients taking over-the-counter supplements containing animal thyroid tissue and in erroneous dosing of thyroid replacement therapy. Excess T4 supplementation suppresses TSH, which decreases iodine organification and colloid formation resulting in atrophy of thyroid follicles.
(Choice B) Histopathology in chronic autoimmune (Hashimoto) thyroiditis is characterized by a mononuclear infiltrate consisting of lymphocytes and plasma cells, often with germinal centers. Hashimoto thyroiditis typically presents with primary hypothyroidism (elevated TSH, low free T4) and goiter; although Hashimoto's can occasionally present with an initial hyperthyroid phase, these patients will have elevated thyroglobulin levels due to inflammatory disruption of thyroid follicles.
(Choice C) Subacute granulomatous (de Quervain) thyroiditis is characterized by disruption of follicles and a mixed cellular infiltrate with occasional multinucleated giant cells. Patients may have hyperthyroidism but typically have a painful, tender thyroid gland and high levels of thyroglobulin due to destructive thyroiditis.
(Choice D) Medullary thyroid cancer is a neuroendocrine tumor that arises from calcitonin-secreting parafollicular C cells. Microscopy shows nests or sheets of polygonal or spindle-shaped cells with extracellular amyloid deposits (derived from calcitonin). Clinical features include diarrhea, flushing, and thyroid nodules, but TSH and free T4 are normal.
(Choice E) Graves disease presents with a diffusely enlarged thyroid gland associated with hyperthyroidism, exophthalmos, and pretibial myxedema. The thyroid follicular epithelium is tall and crowded with hyperactive reabsorption, causing scalloping around the edges of the colloid. However, high serum levels of thyroglobulin would be seen due to increased thyroid metabolic activity.
Educational objective:
Exogenous hyperthyroidism is characterized by elevated free thyroxine (T4), suppressed TSH, and low/undetectable thyroglobulin. It can occur with surreptitious levothyroxine misuse, animal-sourced thyroid supplements, and erroneous dosing of thyroid replacement therapy. Over time, the lack of TSH stimulation causes the thyroid follicles to become atrophic.