James R. Hurley

COMPLICATIONS OF RADIOIODINE TREATMENT OF HYPERTHYROIDISM.

Radioactive iodine was introduced for the treatment of hyperthyroidism 25 yr ago. It has proved to be effective, inexpensive, and convenient for both the patient and the physician, and it is widely considered to be the treatment of choice for most patients with hyperthyroidism. Several hundred thousand patients have been treated since the 1940s, and serious complications have been rare. In a small percentage of susceptible individuals, acute radiation effects may lead to mild thyroiditis or an exacerbation of hyperthyroidism. The fear of possible leukemogenesis or carcinogenesis raised by the use of radiation in the treatment of a benign disease led the early workers to restrict the use of 131 I therapy for uncomplicated hyperthyroidism to those patients above the age of 45. These fears have been dissipated by time and familiarity, and now many laboratories routinely treat all patients over age 25 with 131 I. These younger patients will remain at risk for a longer period, and the possibility of leukemia or thyroid cancer must be reevaluated in terms of this longer period of risk. The possible genetic effects of radioiodine treatment during the childbearing years can probably never be satisfactorily evaluated, yet they remain an issue that cannot be completely ignored in evaluating this form of treatment in younger individuals. Approximately 15 yr passed before the significant incidence of hypothyroidism after radioiodine treatment was fully appreciated. It is now apparent that a regular annual increment of hypothyroidism follows treatment with radioactive iodine. By 10 yr, the incidence of hypothyroidism has reached 50% in some scries, and this appears to be the most serious consequence of treatment. Hypothyroidism is easily treated, but it must first be recognized. Its irregular appearance in as many (or as few) as 50% of the radioiodine treated patients presents special epidemologic problems.

Historical Note: TSH Suppression for Thyroid Cancer

The earliest use of thyroid hormone to treat thyroid cancer was reported by a surgeon, Sir Thomas Dunhill, in the Lettsomian Lectures given under the auspices of the Medical Society of London in 1937 (1). At the end of his three lectures Dunhill described his experience with two children. One had been operated on twice at age 8 years and had also received deep X-ray treatment. A neck mass recurred at age 11 years and increased in size. At age 13 years, the girl was placed on ‘‘fairly large doses of thyroid’’ by Dunhill and the mass disappeared. The second child was operated on at age 5 years and developed a recurrent neck mass at age 22 years. It failed to respond to surgery or insertion of radium needles. Dunhill treated her with thyroid as well, and the mass resolved completely. In a 1956 communication to Dr. George Crile, Jr., he reported that both patients remained alive and well and mentioned two additional patients successfully treated with thyroid, one of which had diffuse pulmonary metastases that completely disappeared (2). Dunhill did not give a rationale for treating his thyroid cancer patients with thyroid hormone. However, thyroid extracts had been used to treat other thyroid conditions for some time. The first reports on the treatment of myxedema appeared in the l890s and in 1894 there were several reports of patients whose goiters shrank or disappeared when given raw sheep or calf thyroid (3). Parenthetically, in 1894 von Eiselberg reported evidence that a thyroid cancer metastasis could produce thyroid hormone. His patient was a 38-year-old woman who developed myxedema following a total thyroidectomy for thyroid cancer. Growth of her sternal metastasis was associated with a return to euthyroidism (4). In his Lettsomian Lectures Dunhill said in apparent reference to von Eiselberg’s patient, ‘‘a metastatic deposit from a malignant thyroid can function sufficiently to supply the body’s needs after the thyroid gland has been extirpated, and that subsequent removal of the deposit has resulted in myxoedema. Metastatic carcinoma of the thyroid has also shown physiological activity in the tadpole test’’ (1). By the 1930s the ability of pituitary thyrotropin (TSH) to stimulate the thyroid was well understood and both crude preparations of TSH and bioassays for TSH were available (5). Dunhill was aware of this evidence. Possibly, in vague reference to a relationship between thyroid hormone status and thyroid carcinoma, he speculates that ‘‘papilliferous hyperplasia’’ (which he believed might be a precursor of ‘‘papilliferous adenocarcinoma’’) might be due to stimulation of the thyroid by ‘‘ordinary physiologic demands’’ and that such changes might not occur if the physiologic demands of the body could be kept at a lower level (1). The availability of radioiodine in the early 1940s led to rapid advances in the diagnosis and treatment of thyroid disease. It was soon discovered that some thyroid cancers concentrated radioiodine and that others could be induced to do so by rendering the patient hypothyroid or injecting TSH (6–8). It became common practice to subject patients with metastases to prolonged periods of hypothyroidism, and it was observed that this often caused the metastases to grow more rapidly (2,9). In the early 1950s Greer and Astwood studied the effect of TSH suppression on thyroid function and growth. In 1951 Greer reported that 3–5 grains of desiccated thyroid suppressed the thyroidal uptake of radioiodine to less than 10% in most normal volunteers (10), and in 1953 Greer and Astwood reported a series of 50 patients with thyroid enlargement or nodules who were treated with 2–3 grains of desiccated thyroid daily with complete regression in 40% (3). They hypothesized that ‘‘thyroid.will decrease the secretion of TSH and, in turn, the size of the goiter.’’ However, no patients with known thyroid cancer were included in their study. In 1954 Balme published the first well-documented case in which function and growth of metastatic thyroid cancer was suppressed by administration of thyroid hormone (11). The patient was a 37-year-old woman with diffuse pulmonary metastases. She was treated with 100 mCi of iodine 131 (I) and retained 46% in her chest. Nine months later an I study showed a chest uptake of 56%. She was then placed on l-thyroxine 0.7 mg daily, which reduced her chest uptake to zero. Four weeks after l-thyroxine was stopped, the chest uptake was 20%. She was then maintained on 0.5 mg of l-thyroxine daily with clearing of her chest X-ray and improvement in pulmonary function. Balme commented that suppression of uptake in the lungs was probably due to suppression of TSH and quotes Greer’s 1951 paper (10). The chief advocate of a major role for TSH suppression in the treatment of thyroid cancer was also a surgeon, George Crile, Jr. In his initial report in 1955 (12), he described seven patients treated with 3–4 grains of desiccated thyroid for 1–5 years. Five with pulmonary metastases showed improvement in their chest X-ray and two with solitary bone metastases (who were also treated with X-ray) remained stable and showed recalcification. He was inspired by a patient who had both lung metastases from Hürthle cell thyroid cancer and

Thyroid suppression and stimulation testing: The place of scanning in the evaluation of nodular thyroid disease

In the past, T3 suppression testing was often required to confirm the presence of autonomous thyroid function in patients with borderline clinical and laboratory findings suggestive of hyperthyroidism or in euthyroid patients with the stigmata of Graves disease. Similarly, TSH stimulation testing was used to document the presence of low thyroid reserve in patients with borderline clinical and laboratory findings suggestive of hypothyroidism. The current availability of radioimmunoassays for triiodothyronine (T3) and thyrotorpin (TSH) plus the ability to evalate pituitary responsiveness by performing a TRH stimulation test permits a definitive diagnosis to be made in the majority of borderline situations without recourse to the more cumbersome suppression and stimulation tests. Suppression and stimulation thyroid scanning retain a unique position in the evaluation of localized areas in increased uptake of radionuclide (hot nodules), especially in patients who are euthyroid. Proof that such nodules are autonomously functioning thyroid adenomas (AFTN) greatly decreases the possibility that they represent malignant thyroid tumors. Suppression and stimulation scanning have a more limited role in the evaluation of patients with hyperthyroidism arising in a multinodular goiter, where TSH stimulation scanning may help to differentiate between toxic multinodular goiter and Graves disease arising in a preexisting goiter.

Clear-Cell Follicular Adenoma of Ectopic Thyroid in the Submandibular Region.

A case of clear-cell follicular adenoma arising in ectopic thyroid tissue is reported. The 2.0-cm tumor arose in the submandibular region in a 29-yr-old female. The diagnosis was established on the basis of light microscopic morphology, a positive thyroglobulin immunohistology, and the presence of normal thyroid tissue surrounding the mass. Preoperative computed tomography (CT) scan, and postoperative ultrasound studies revealed a normal orthotopic thyroid gland. No additional tumors have since been detected. The patient is free of recurrent or metastatic disease 54 mo following excision of the mass. Only eight previously published reports have described ectopic thyroid tissue in the submandibular region, all but one of which lacked an orthotopic thyroid gland. In this article, we describe the pathological features of our case and review the existing literature on the subject.

Less is More: The Impact of Multidisciplinary Thyroid Conference on the Treatment of Well-Differentiated Thyroid Carcinoma

BackgroundIn 2006, a multidisciplinary thyroid conference (MDTC) was implemented to better plan management of thyroid cancer patients at our institution. This study assessed the clinical impact of a MDTC on radioactive iodine (RAI) treatment patterns.MethodsA prospective database (2003–2014) collected patient and tumor characteristics, RAI doses, and tumor recurrences. Patients treated with total thyroidectomy for differentiated thyroid carcinoma ≥1xa0cm were stratified based on American Thyroid Association (ATA) risk classification. RAI regimens were compared before initiation of MDTC (2003–2005, nxa0=xa088), after establishment of MDTC (2007–2009, nxa0=xa095), and after the release of 2009 ATA guidelines (2011–2014, nxa0=xa0181). RAI doses were defined as low (≤75xa0mCi), intermediate (76–150xa0mCi), and high (>150xa0mCi).ResultsThere was a significant decrease in the number of patients who received high-dose RAI after implementation of MDTC compared to before initiation of MDTC in the intermediate and high-risk patient groups (pxa0=xa00.04 and pxa0<xa00.01) without an associated increase in tumor recurrence (11 vs. 7%, pxa0=xa00.74). On multivariable analysis, presentation of a patient at MDTC was a negative predictor for receiving high-dose RAI (pxa0=xa00.002). As might be expected, there was also a significant decrease in use of RAI after the 2009 ATA guidelines were issued compared to after implementation of MDTC (pxa0<xa00.01).ConclusionIn conjunction with implementation of a thyroid malignancy multidisciplinary conference, we observed significantly decreased postoperative dosing of RAI without increased tumor recurrence. The 2009 ATA guidelines were associated with a further decrease in RAI administration. Treatment for patients with thyroid carcinoma is optimized by a multidisciplinary approach.