Click here for Frequently Asked Questions on a Hot Nodule.
A hot nodule is defined as a nodular region of the thyroid gland that takes up large amounts of radioactive iodine relative to the rest of the thyroid gland, hence it is visualized as a "hot spot" on the thyroid scan. The majority of hot nodules function autonomously, and have lost their normal ability to be regulated by TSH. Accordingly, they often produce excess amounts of thyroid hormone, and eventually result in the development of hyperthyroidism. In mild cases, the hot nodule may not be producing sufficient amounts of thyroid hormone to suppress TSH production and secretion from the pituitary, hence the TSH may be normal or towards the lower end of the normal range. As the nodule enlarges, becomes more metabolically active and produces increasing amounts of thyroid hormone, the TSH will become gradually lower, and if hyperthyroidism ensues, the TSH will be suppressed.
If a hot nodule is producing excess amounts of thyroid hormone, the remainder of the thyroid gland may in fact be "turned off" and appear cold or absent on a thyroid scan. This is a normal compensatory response to the development of hyperthyroidism and a low TSH.
A hot nodule may become clinically apparent because of an increase in size and the detection of a nodule in the neck. Alternatively, the nodule may become apparent in the course of investigating a patient for hyperthyroidism.
If a hot nodule is biopsied in the course of investigating a patient for the presence of a single thyroid nodule, the cytology result may be interpreted as highly abnormal, since follicular cells from a metabolically active hot nodule may appear abnormal and resemble thyroid cancer cells under the microscope. For this reason, it is important to always have the result of a TSH when investigating a patient for a thyroid nodule. Some physicians will also advocate carrying out a thyroid scan (to detect a hot versus cold nodule) prior to recommending surgery for a patient with abnormal thyroid cytology.
Although mostly benign, thyroid cancer has been detected in a small percentage of hot nodules, generally in less than 5% of reported cases, but up to 10% in some series. This can be difficult to diagnose, since fine needle aspiration biopsy of hot nodules will often show follicular thyroid cells, and may not be suggestive of thyroid cancer even if this turns out to be the final diagnosis. Persistently enlarging nodules, or nodules that are irregular or large should prompt a higher suspicion for the presence of thyroid cancer in the setting of a hot nodule. For an overview of recent literature linking hot nodules and thyroid cancer, See Pathology of the autonomously functioning (hot) thyroid nodule. Ann Diagn Pathol. 2002 Feb;6(1):10-9.
If the hot nodule is small, the patient has no symptoms, and the TSH is normal, there is no immediate reason to recommend or institute treatment. The risk of thyroid cancer development in a hot nodule is extremely low, but rare cases of functioning hot nodules that turned out to be follicular cancers of the thyroid have been reported.
Alternatively, if the nodule is quite large, if it causes compressive symptoms, or if clinical hyperthyroidism is present, then treatment of the hot nodule needs to be considered. In North America, the principal treatment options for management of thyroid nodules are radioactive iodine versus surgery. The surgical option may be superior if one wishes to completely remove a large nodule that may be causing compressive symptoms. Radioactive iodine will often result in resolution of the hyperthyroidism, but may not always result in a significant decrease in size or disappearance of the nodule.
My friend in Italy had her nodule injected and avoided radioactive iodine and surgery. Why can't I have this treatment?
In some centers, more often in Europe, injection of a thyroid nodule with alcohol may produce effective treatment and reduction in nodule size. Occasionally, if alcohol leaks out into the surrounding tissues, severe neck pain and inflammation may ensue. This procedure has not become popular in North America, despite continuing reports from Europe that it may be effective treatment for some patients. For example, see Radioiodine and percutaneous ethanol injection in the treatment of large toxic thyroid nodule: a long-term study. Thyroid. 2000 Nov;10(11):985-9.
How and why do hot nodules develop?
Although the answer to this question remains unclear, a substantial proportion of hot nodules exhibit genetic mutations in genes that control the growth and function of the thyroid cell. The mutations are generally somatic and not germline, that is they are found in the thyroid nodule only, and not in all cells of the body. Hence, the risk of developing hot nodules is usually not transmitted genetically from parents to children. These mutations invariably lead to a perpetual state of increased cell function (increased iodine uptake and thyroid hormone synthesis) and cell growth. To review the types of genetic mutations that have been detected in hot nodules, see Functioning and nonfunctioning thyroid adenomas involve different molecular pathogenetic mechanisms. J Clin Endocrinol Metab. 1999 Nov;84(11):4155-8 and Hyperfunctioning thyroid nodules in toxic multinodular goiter share activating thyrotropin receptor mutations with solitary toxic adenoma. J Clin Endocrinol Metab. 1998 Feb;83(2):492-8 and Somatic mutations in the thyrotropin receptor gene and not in the Gs alpha protein gene in 31 toxic thyroid nodules. J Clin Endocrinol Metab. 1997 Nov;82(11):3885-91. and Activating thyrotropin receptor mutations are present in nonadenomatous hyperfunctioning nodules of toxic or autonomous multinodular goiter. J Clin Endocrinol Metab. 2000 Jun;85(6):2270-4.
Will I become hypothyroid after radioactive iodine treatment for my hot nodule?
Although many patients will not develop hypothyroidism, some patients will, depending on the size of the nodule and the dose of radioactive iodine administered. In some instances the rate of hypothyroidism after treatment of a hot nodule can eventually approach 50-60%, as outlined in Outcome of radioiodine-131 therapy in hyperfunctioning thyroid nodules: a 20 years' retrospective study. Clin Endocrinol (Oxf). 2005 Mar;62(3):331-5. To review studies that examines this issue, see Efficacy of low doses of radioiodine in the treatment of autonomous thyroid nodules: importance of dose/area ratio. Thyroid 1997 Jun;7(3):357-61 and Determinants of long-term outcome after radioiodine therapy for solitary autonomous thyroid nodules Endocr Pract. 2008 Jul-Aug;14(5):543-9