The relative frequency in which empiric dosages of radioiodine would potentially overtreat or undertreat patients who have metastatic well-differentiated thyroid cancer.

The dosage of (131)I for the treatment of metastatic well-differentiated thyroid cancer is typically selected empirically. Benua and Leeper implemented a method to estimate the maximum dosages of (131)I that could be administered to a patient so as not to exceed a maximum tolerated radiation absorbed dose (MTD), which was defined as 200 rads (cGy) to the blood. The objective of this study was to determine the frequency of (131)I treatments in which the patient (1) would have exceeded the MTD (i.e., overtreatment) or (2) would have been able to receive higher dosages of (131)I thereby delivering a potentially higher radiation absorbed dose to their metastases (i.e., undertreatment) had the patient been administered various assumed empiric dosages of (131)I. The dosimetrically-determined maximum tolerated radioactivities (MTA) to deliver 200 rads to the blood (MTD) were tabulated at our facility. Data were then grouped to determine the percentage of patients who would have received less than or more than the MTD for various assumed empiric dosages of (131)I. A total of 127 dosimetries were performed. For assumed empiric dosages of (131)I (100 mCi, 150 mCi, 200 mCi, 250 mCi, and 300 mCi), the percentage of treatments for which patients would have exceeded the MTD were less than 1%, 5%, 11%, 17%, and 22%, respectively, and could have received a higher dosage of (131)I were more than 99%, 95%, 89%, 83%, and 78%, respectively. A significant number of patients receiving various empiric dosages of (131)I may exceed 200 rads (cGy) to the blood (potential overtreating). Likewise, the majority of patients may be able to receive much higher dosages of (131)I relative to empiric dosages thereby delivering potentially higher radiation absorbed doses to the metastases without exceeding 200 rads (cGy) to the blood (potential undertreating).

A consensus report of the role of serum thyroglobulin as a monitoring method for low-risk patients with papillary thyroid carcinoma.

Recent studies have provided new information regarding the optimal surveillance protocols for low-risk patients with differentiated thyroid cancer (DTC). This article summarizes the main issues brought out in a consensus conference of thyroid cancer specialists who analyzed and discussed this new data. There is growing recognition of the value of serum thyroglobulin (Tg) as part of routine surveillance. An undetectable serum Tg measured during thyroid hormone suppression of TSH (THST) is often misleading. Eight studies show that 21% of 784 patients who had no clinical evidence of tumor with baseline serum Tg levels usually below 1 micro g/liter during THST had, in response to recombinant human TSH (rhTSH), a rise in serum Tg to more than 2 micro g/liter. When this happened, 36% of the patients were found to have metastases (36% at distant sites) that were identified in 91% by an rhTSH-stimulated Tg above 2 micro g/liter. Diagnostic whole body scanning, after either rhTSH or thyroid hormone withdrawal, identified only 19% of the cases of metastases. Ten studies comprising 1599 patients demonstrate that a TSH-stimulated Tg test using a Tg cutoff of 2 micro g/liter (either after thyroid hormone withdrawal or 72 h after rhTSH) is sufficiently sensitive to be used as the principal test in the follow-up management of low-risk patients with DTC and that the routine use of diagnostic whole body scanning in follow-up should be discouraged. On the basis of the foregoing, we propose a surveillance guideline using TSH-stimulated Tg levels for patients who have undergone total or near-total thyroidectomy and (131)I ablation for DTC and have no clinical evidence of residual tumor with a serum Tg below 1 micro g/liter during THST.

Thyroid function in the intensive care unit setting.

In sum, there is no convincing evidence yet published supporting the utility of T4 or T3 administration in patients with nonthyroidal illness. The authors recognize that evidence accrued in one disease state may not be applicable to others and that, although these studies are difficult to perform, further large scale prospective studies need to be performed. The issue of T3 treatment will not be resolved satisfactorily until more definitive data are available. Until that time, there may be rare circumstances when a clinician may think it best to treat an individual patient with T4 or T3. For the majority of patients, however, there will be little indication for the administration of thyroid hormones until the potential benefits can be shown to outweigh the risks.

The controversy of the treatment of critically ill patients with thyroid hormone.

There is currently a vast literature available on the changes in thyroid function tests that occur during non-thyroidal illness. The aetiology of these changes is, however, controversial, especially with respect to whether they play an adaptive role for the organism in order to cope with stress or whether they represent primary pathology of the pituitary-thyroid axis. This is particularly true for critically ill patients, in whom the most significant changes in thyroid function are observed. The changes include low levels of thyroxine and very low levels of tri-iodothyronine, which would, on the surface, appear to indicate hypothyroidism. Therapy with thyroid hormone, as either L-T4 or L-T3, has therefore been suggested because of these low values for thyroid hormones in the blood. It is, however, unclear whether treating these patients with thyroid hormone is beneficial or harmful. Multiple studies have addressed this issue with patients with cardiac disease, sepsis, pulmonary disease (e.g. acute respiratory distress syndrome) or severe infection, or with burn and trauma patients. In spite of a very large number of published studies, it is very difficult to form clear recommendations for treatment with thyroid hormone in the intensive care unit. Instead, we find the evidence far from compelling, and would advise withholding thyroid hormone therapy in the critical care setting in the absence of clear clinical or laboratory evidence for hypothyroidism.

Ultrasound-guided fine-needle aspiration and thyroid disease.

BACKGROUND: Fine-needle aspiration represents a critical diagnostic test in determining proper management of thyroid disease and the use of ultrasound-guided fine-needle aspiration (USGFNA) has increased over the years. METHODS: A retrospective chart review of patients undergoing USGFNA. Two hundred fifteen patients underwent 234 procedures with 362 nodules aspirated within a 2 (1/2)-year period. RESULTS: The mean ages of women and men were 51.9 and 57.8, respectively. The average size of nodules was 2.1 cm. A difficult to assess gland or nodule was the most common indication for USGFNA (33%). The sensitivity was 88.2%, specificity was 80.0%, the PPV was 65.2%, the negative predictive value was 94.1%, and the accuracy was 82.5%. The cancer yield, inadequacy, and complication rates were 44%, 10.5%, and 8.5%, respectively. CONCLUSIONS: USGFNA aspiration is a safe and effective diagnostic modality in the management of thyroid disease, especially for nodules that are difficult to palpate.

The role of radioactive iodine in salivary gland dysfunction.

The use of radioactive iodine has become an important adjunct to the treatment of thyroid cancer. Many normal tissues--including salivary glands, gastrointestinal mucosa, gonads, and lactating breast tissue--have the ability to concentrate radioactive iodine under normal circumstances. Although the mechanism is just beginning to be elucidated, it is this ability that might contribute to the immediate and long-term complications associated with radioactive iodine treatment. In some patients, the salivary complications can be permanent and might compromise daily functioning. In this article, we examine the salivary gland complications associated with radioactive iodine therapy, and we suggest potential protective mechanisms to circumvent these problems.

Hyperthyroid heart disease.

The heart is an organ sensitive to the action of thyroid hormone, and measurable changes in cardiac performance are detected with small variations in thyroid hormone serum concentrations. Most patients with hyperthyroidism experience cardiovascular manifestations, and the most serious complications of hyperthyroidism occur as a result of cardiac involvement. Recent studies provide important insights into the molecular pathways that mediate the action of thyroid hormone on the heart and allow a better understanding of the mechanisms that underlie the hemodynamic and clinical manifestations of hyperthyroidism. Several cardiovascular conditions and drugs can interfere with thyroid hormone levels and may pose a difficulty in interpretation of laboratory data in patients with suspected thyroid heart disease. The focus of this report is a review of the current knowledge of thyroid hormone action on the heart and the clinical and hemodynamic laboratory findings as well as therapeutic management of patients with hyperthyroid heart disease.

Prognostic importance of vascular invasion in papillary thyroid carcinoma.

BACKGROUND: The prognostic importance of vascular invasion has not been extensively studied in patients with papillary thyroid cancer. OBJECTIVE: To determine whether the presence of vascular invasion in papillary thyroid carcinoma, even within the thyroid gland, is associated with more aggressive disease at diagnosis and a higher incidence of tumor recurrence. PATIENTS AND METHODS: We identified 410 patients who had been diagnosed with papillary thyroid cancer since 1986 who had a follow-up period of longer than 1 year (median follow-up, 5.5 years). Pathology reports were reviewed and patients were separated into 3 groups: no vascular invasion, intrathyroidal vascular invasion, and extrathyroidal vascular invasion. MAIN OUTCOME MEASURES: Statistical comparison was performed by univariate and multivariate analysis. RESULTS: Patients with intrathyroidal vascular invasion were more likely to have distant metastasis at the time of diagnosis (26.1% vs 2.2%, P = .001). Similarly, patients with extrathyroidal vascular invasion had a higher incidence of distant metastases at diagnosis (40% vs 4.4%, P = .02). Patients with tumors identified to have intrathyroidal vascular invasion were more likely to develop distant recurrence (20% vs 3%, P = .002). CONCLUSIONS: These associations were found to be independent by multiple regression analysis. Patient age, sex, palpable or fixed lymph nodes, radiation exposure, and race did not differ between the patient group with and those without vascular invasion. Preliminary analysis of our data suggests that the presence of vascular invasion in papillary, thyroid carcinoma, even within the thyroid gland, is associated with more aggressive disease at diagnosis and with a higher incidence of tumor recurrence.

Tall cell variant: an aggressive form of papillary thyroid carcinoma.

Twenty-four cases of the tall cell variant (TCV), a subset of papillary thyroid carcinoma, were identified in a group of 624 patients with thyroid cancer. All pathology specimens were reviewed, and each patient's carcinoma was categorized according to characteristics on presentation, local recurrence, distant metastases, follow-up, and tumor-related mortality. The TCV group was compared with a historical control group (Mazzaferri and Jhiang: 1355 patients). The TCV group had a statistically higher percentage of stage 3 and 4 carcinoma, extrathyroidal invasion, and tumor size less than 1.5 cm than the control group. There was no statistical relationship between age greater than 50 years and stage in the TCV group. No relationship could be found between TCV histology and recurrence or mortality. These findings, combined with those of studies that link stage on presentation to poor outcomes, have led to our conclusion that TCV is an aggressive malignancy warranting appropriate treatment and close follow-up.

Quantitative reverse transcription-polymerase chain reaction of circulating thyroglobulin messenger ribonucleic acid for monitoring patients with thyroid carcinoma.

Patients with thyroid cancer are monitored for disease recurrence by measurement of serum thyroglobulin (Tg) and iodine-131 (131I) scanning. To enhance sensitivity and to circumvent antibodies that interfere with Tg immunoassays, we have developed RT-PCR assays that detect circulating thyroid messenger RNA (mRNA) transcripts. We now report results using a sensitive quantitative Tg mRNA assay (Taqman; ABI, Foster City, CA) in comparison with immunoassay in patients previously treated for thyroid cancer. We evaluated 107 patients: 84 during T4 therapy, 14 after T4 withdrawal, and 9 at both time points. All patients had near-total thyroidectomy, and 92% received postoperative 131I. Serum TSH, Tg protein, and Tg mRNA were measured. Patients were grouped based on most recent 131I scan or pathologically confirmed disease as having no detectable thyroid tissue (n = 33), thyroid bed uptake (n = 37), cervical/regional adenopathy (n = 21), or distant metastases (n = 16). During T4 therapy, median (range) Tg mRNA values (pg Tg Eq/microg thyroid RNA) for the groups were 1.5 (0-26.8), 9.4 (0.5-90.0), 15.4 (0.2-92), and 12.4 (1.9-16.6), respectively. Using a value of 3 pg Tg Eq/microg thyroid RNA as cut-point, Tg mRNA was positive in 38% of patients with no uptake, 75% with thyroid bed uptake, 84% with cervical/regional disease, and 94% with distant metastases. The median Tg mRNA value for patients with no uptake was lower than the median values for patients with thyroid bed uptake (P = 0.009) or with detectable thyroid tissue at any site (P = 0.010). Patients with negative 131I whole body scans were also less likely to have detectable Tg mRNA levels than were patients with thyroid bed uptake (P < 0.001) or any detectable thyroid tissue at any location (P < 0.001). Similar differences between these groups were seen after T4 withdrawal and for the 23 patients with circulating anti-Tg antibodies, when analyzed separately. Eight of the nine patients studied with low and high TSH concentrations displayed greater amounts of circulating Tg mRNA after T4 withdrawal. In three patients followed prospectively, the amount Tg mRNA correlated with the presence and absence of cervical metastases. In conclusion, we have demonstrated that a quantitative Tg mRNA assay can identify thyroid cancer patients with recurrent or residual thyroid tissue with greater sensitivity and similar specificity to Tg immunoassay during T4 therapy. The assay was unaffected by anti-Tg antibodies, responded to TSH-stimulation, and was reduced after surgical removal of metastases. These data suggest that this quantitative Tg mRNA assay may be a sensitive marker of tumor recurrence or response to therapy, particularly in patients with anti-Tg antibodies.