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The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 5 1519-1525
Copyright © 2008 by The Endocrine Society

APPROACH TO THE PATIENT

Approach to the Patient with a Positive Serum Thyroglobulin and a Negative Radioiodine Scan after Initial Therapy for Differentiated Thyroid Cancer

Richard T. Kloos

Departments of Internal Medicine and Radiology, Divisions of Endocrinology, Diabetes, and Metabolism and Nuclear Medicine, The Ohio State University, The Arthur G. James Cancer Hospital, and Richard J. Solove Research Center, and The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210

Address all correspondence and requests for reprints to: Richard T. Kloos, M.D., The Ohio State University, 446 McCampbell Hall, 1581 Dodd Drive, Columbus, Ohio 43210-1296. E-mail: richard.kloos{at}osumc.edu.


   Abstract
Top
 Abstract
Introduction
 Background
 Controversies and Areas of...
 Diagnostic and Therapeutic...
 Returning to the Patient
 Conclusions
 References
 
The 10-yr survival of differentiated thyroid cancer is about 76–93%, and at least 10% of patients manifest tumor persistence or recurrence, depending on their disease stage, after initial therapy, which typically includes total thyroidectomy and 131I ablation. Previously the realization of their residual/recurrent cancer often presented simultaneously with the additional surprise that they lacked pathological uptake on their diagnostic whole-body radioiodine image despite their elevated stimulated serum thyroglobulin (Tg) level, a scenario referred to as the scan-negative, Tg-positive patient. Now that serum Tg and neck ultrasonography have supplanted the diagnostic whole-body scan because of its inferior sensitivity, patients are often recognized to harbor residual disease without radioiodine imaging, and a new challenging scenario has emerged: the ultrasonography-negative, Tg-positive patient. Similarities and differences of these two patient populations aside, these Tg-positive patients are frequently encountered, and some are considered for additional 131I therapy, although now typically after negative anatomic ± 18F-fluorodeoxyglucose positron emission tomography imaging or in the setting of known or suspected distant metastases already localized by anatomic imaging. Thus, the scan-negative, Tg-positive patient of today differs from those of the past, but the term still has relevance to current practice. The optimal evaluation and treatment of these patients remain controversial, partly because many of these patients will not die from thyroid cancer, and there are no randomized trials to demonstrate that intervention could have prevented the deaths that do occur. Here a case is presented that adds the complexity of advanced age, and one approach to these challenging patients is offered.


   Introduction
Top
 Abstract
 Introduction
Background
 Controversies and Areas of...
 Diagnostic and Therapeutic...
 Returning to the Patient
 Conclusions
 References
 
An 85-yr-old widower presented with 6 yr of hoarseness, 1 yr of hypothyroidism, and recent dysphagia to solid foods. His past medical history was remarkable for hypertension and peptic ulcer disease. He had no history of prior head and neck radiation exposure. Computed tomography (CT) revealed a left-sided substernal goiter with compression of the esophagus and trachea with a normal-sized right thyroid lobe. Preoperative chest x-ray was remarkable only for an anterior mediastinal mass causing tracheal narrowing and deviation. The patient underwent a left lobectomy and isthmusectomy in November 1996. Final histology revealed a 5.7-cm tumor that was felt to represent either a well-differentiated encapsulated follicular variant of papillary thyroid carcinoma (PTC) or a minimally invasive (encapsulated) follicular thyroid carcinoma.

Neck ultrasonography (US) demonstrated no residual disease, and completion thyroidectomy was performed March 1997. Subsequently thyroid hormone withdrawal and hospital admission for remnant ablation was complicated by shortness of breath and new-onset atrial fibrillation with a rapid ventricular response, despite his serum TSH of 110 µIU/ml [and thyroglobulin (Tg) of 124 ng/ml]. The patient was acutely anticoagulated and his cardiac rate was controlled. An echocardiogram demonstrated mild enlargement of the left atrium and left ventricular hypertrophy without thrombus. Long-term full anticoagulation was deferred, given his unsteady gait and intermittent falls. He received 150 mCi of 131I in April 1997 with a serum creatinine of 1.5 mg/dl (0.9–1.3 mg/dl), and the posttherapy whole-body scan (WBS) demonstrated uptake in the right thyroid bed and isthmus with no evidence of metastatic disease.

By April 1998 he developed increasing dyspnea, congestive heart failure, and sick-sinus syndrome that prompted hospitalization, implantation of a dual-chamber cardiac pacemaker, and diuresis.

In September 1998 his serum Tg was less than 0.5 ng/ml with negative anti-Tg antibodies and a TSH of 0.07 µIU/ml. By September 1999 stimulated Tg testing and whole-body radioiodine imaging was recommended. Given his advanced age of 87 yr and comorbid diagnoses, Thyrogen (Genzyme Corporation, Cambridge, MA) stimulation (1) was suggested rather than hypothyroidism. The 4 mCi I-131 diagnostic WBS (DxWBS) was negative, whereas the basal serum Tg of 0.6 ng/ml (with a TSH of 0.14 µIU/ml) rose to 17.9 ng/ml.


   Background
Top
 Abstract
 Introduction
 Background
Controversies and Areas of...
 Diagnostic and Therapeutic...
 Returning to the Patient
 Conclusions
 References
 
In the not-too-distant past, patients were evaluated for disease persistence and recurrence by physical examination, chest x-ray, and whole-body radioiodine imaging without serum Tg. Currently most patients with differentiated thyroid cancer and an undetectable basal Tg (in the absence of anti-Tg antibodies) are evaluated by stimulated serum Tg and neck US without DxWBS, with additional testing considerations (such as the DxWBS) for those with interfering anti-Tg antibodies or the minority of patients with particularly aggressive tumor presentations (2). As the field shifted away from the DxWBS toward reliance on the serum Tg to more accurately determine disease status, it was recognized that about 10–15% of patients have elevated serum Tg levels despite negative a DxWBS (3). Currently whereas detectable stimulated serum Tg levels after remnant ablation are concerning for the possibility of disease, levels greater than 2 ng/ml are highly suspicious for persistent or recurrent disease (1, 4).

Stereotypically, old men with large tumors are notorious for adverse outcomes, and most thyroid cancer staging systems identify this patient’s increased risk for impaired cancer-specific survival (5, 6). Advanced age is recognized by most (7, 8), but not all (9), as a powerful predictor of thyroid cancer-related death. On the other hand, this patient’s advanced age is already a predictor of diminished long-term survival because the average survival for white men in the United States aged 85, 90, and 95 yr is 6, 4, and 3 yr, respectively (10). Thus, whereas cure of thyroid cancer with minimal morbidity may be ideal, it is often unobtainable and (thankfully) may be unnecessary in some circumstances. However, reliably identifying these circumstances without a crystal ball is often challenging, as in this case. Indeed, Links et al. (9) studied standardized survival time, which adjusted for the baseline mortality rate in the general population. They found that persistent disease reduced the life expectancy to 60%, a finding that was independent of initial tumor status or age.

An additional initial clue to this patient’s risk of persistence or recurrence of disease was his elevated serum Tg at the time of initial remnant ablation. Kim et al. (11) found that the positive predictive value for recurrence in patients having Tg levels at the time of ablation greater than 2 ng/ml, greater than 10 ng/ml, or greater than 30 ng/ml was 23, 42, and 70%, respectively. Others have also found that the preablation serum Tg predicted disease recurrence (12), disease-specific mortality, and disease-free survival (13). Ronga et al. (14) identified a Tg value of 30.3 ng/ml as the optimal cutoff to predict metastases with a sensitivity of 84%, specificity of 86%, and PPV of 65%. However, Heemstra et al. (15) reported from multivariate analysis that Tg levels 6 months or more after initial therapy were predictors of death (along with age and other factors), whereas the Tg level at the time of remnant ablation was not.

Especially for non-low-risk patients, tumor recurrence has historically been a more significant event than just the need for another operation or 131I treatment. Tumor recurrence has been recognized as a significant predictor of cancer-specific death (16), and some have reported that this risk is independent of initial tumor status (9). Grant et al. (17) reported that the 30-yr cumulative risk of death due to PTC after the first recurrence as neck nodal metastases, local recurrence, or distant metastases were less than 10, 48, and 70%, respectively, with the majority of these deaths occurring within the first 10 yr of the tumor recurrence. Whether these data are applicable to patients of today is unknown. Current sensitive Tg assays and modern imaging technology are likely to detect recurrent disease at a much earlier point in time compared with even a decade ago.


   Controversies and Areas of Uncertainty
Top
 Abstract
 Introduction
 Background
 Controversies and Areas of...
Diagnostic and Therapeutic...
 Returning to the Patient
 Conclusions
 References
 
There is controversy as to the optimal approach to patients with DxWBS-negative, Tg-positive disease (3, 18). Previously it was common to administer an empiric dose of 131I as the first step with a goal of tumor localization and treatment (19, 20). Unfortunately, many of those patients had a negative posttreatment WBS (RxWBS), and few were rendered free of disease (3). Some have noted that the majority of these patients have a favorable outcome, especially when the Tg level is only modestly elevated (3, 21). Given this patient’s advanced age and comorbid conditions, a conservative approach that followed the patient’s basal Tg level would not be unreasonable, recognizing that a rising level would indicate tumor growth, given the direct relationship between tumor burden and the serum Tg level (22).

For most DxWBS-negative, Tg-positive patients, however, there has been an increasing shift toward more anatomic (2) ± functional [18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)] imaging as a first step to direct potentially curative surgery, alternative interventions [such as 131I therapy, external beam radiation therapy (EBRT), ethanol ablation (23, 24), or radiofrequency ablation (24)], or follow-up (25). However, exactly which imaging modalities should be used and when has remained uncertain, and the role and timing of 131I therapy in these patients has remained controversial. My current approach is outlined in Fig. 1Go and is discussed below. Deviations from this approach are present in this particular case and reflect the evolution of the field over time and patient-specific factors that are difficult to incorporate into an algorithm and include the individual wishes of the patient.


Figure 1
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  		FIG. 1. Evaluation and treatment algorithm for the 131I scan-negative, Tg-positive patient. See another reference (65 ) for protocols outlining simultaneous acquisition of stimulated FDG PET and DxWBS with the option of 131I therapy. *, Get brain magnetic resonance imaging if macroscopic pulmonary metastases. TH, thyroid hormone; THW, thyroid hormone withdrawal; RFA, radiofrequency ablation.

 

   Diagnostic and Therapeutic Strategies
Top
 Abstract
 Introduction
 Background
 Controversies and Areas of...
 Diagnostic and Therapeutic...
Returning to the Patient
 Conclusions
 References
 
Neck US

In our experience, biochemical cure is more likely after reoperation, compared with treatment with additional 131I (26). Thyroid bed recurrences and regional lymph node metastases are the most common and most treatable sites of disease. Typically they are associated with a detectable serum Tg during TSH suppression and/or stimulation, although this biochemical abnormality is absent in a small number of such patients (27, 28). For most thyroid cancer centers, the most sensitive test for local lymph node metastases is skilled US of the neck to include the central compartment, the lateral neck compartments and the superior mediastinum (3, 29). Neck US in skilled hands has the potential to identify malignant lymph nodes as small as 3–4 mm, whereas lymph nodes in the 5- to 7-mm range are more easily found. Unfortunately, this level of expertise is not routinely available.

Whereas some experts elect to follow small foci of metastatic disease (25), others (including myself) advocate surgical resection via compartmental lymph node dissection (in the absence of distant metastases) in an attempt for biochemical cure in most patients. A few studies have suggested that 19–67% of these patients can be rendered free of disease with additional surgery, although the criteria used to determine disease-free status are inconsistent among these studies (30, 31, 32). In a series of patients from The Ohio State Thyroid Cancer Unit with a detectable stimulated serum Tg who underwent reoperation for persistent or recurrent disease after initial therapy, biochemical complete remission, defined stringently as an undetectable stimulated Tg, was achieved in 23% after one or two reoperations, including 33% of operations when the preoperative basal Tg was undetectable, compared with 11% of operations when the basal Tg was detectable (P = 0.023, Fisher’s exact test) (Kloos, RT, unpublished data). Patients that decline surgery, have nonthreatening cervical disease and distant metastases, or have persistent cervical disease despite one or two surgical reoperations for attempted cure may be candidates for observation of the cervical disease or ethanol ablation under US guidance (24, 33). More threatening cervical disease that is not amendable to surgical resection should be considered for EBRT.

Chest CT

To exclude distant metastases that may alter therapy, I obtain a helical thin-cut chest CT without contrast for patients with a stimulated serum Tg greater than 2 ng/ml. Pulmonary metastases are the most common distant site of differentiated thyroid carcinoma metastasis and lesions in the 1- to 3-mm range are commonly identified on CT, whereas FDG PET has decreased sensitivity for miliary pulmonary disease (34, 35, 36). Indeed, one study of pulmonary metastases from various malignancies reported the sensitivity of FDG PET for lesions less than 5, 5–7, 8–10, and 11–28 mm as 0, 41, 78, and 94%, respectively (37). Many patients will have a few small noncalcified pulmonary nodules of unknown etiology. In the absence of convincing evidence of pulmonary metastases, I proceed as if the CT is negative and typically follow up on these small nodules at 6- to 12-month intervals for 2–3 yr, and if the serum Tg is rising. Chest CT can also identify mediastinal and bone metastases that often require therapy or close follow-up.

FDG PET

In patients with negative neck US and chest CT or in patients whose serum Tg is out of proportion to the identified disease, I obtain FDG PET imaging. The median sensitivity and specificity of FDG PET imaging has been reported as 77 and 78%, respectively (38), although FDG PET may be more robust for Hürthle cell thyroid cancer as opposed to PTC and follicular thyroid carcinoma (39, 40, 41).

FDG PET scans are more likely to be positive when the Tg is greater than 10 or 15 ng/ml (42, 43, 44, 45). In one study, true positive images were found in 11, 50, 80, 63, and 93% of those with Tg less than 10, 10–20, 20–50, 50–100, and greater than 100 ng/ml, respectively (with or without TSH stimulation) (46). Another study reported that patients with positive FDG PET scans had an average Tg of 293 ng/ml (range 26–747), whereas those with negative scans had an average Tg of 30 ng/ml (range 3–44) (47). Current data suggest that PET/CT fusion studies provide increased accuracy and modify the treatment plan in a significant number of cases when compared with PET images alone (36, 48). Shammas et al. (49) found a correlation between the rate of positive scans with PET/CT and the serum Tg and a more encouraging rate of detection at lower Tg levels. They reported positive PET/CT images in 14, 45, and 62% of patients with Tg levels less than 5, 5–10, and greater than 10 ng/ml, respectively, which changed clinical management in 44% of patients. It is unclear, however, how often management would have been changed had a neck US and chest CT been performed before the PET/CT as suggested in Fig. 1Go.

There have been conflicting reports regarding the additional benefit of FDG PET imaging during TSH stimulation with hypothyroidism (50, 51, 52). Taken together, however, these studies suggest a possible modest benefit to TSH-stimulated FDG PET scans, which may be most relevant when the baseline serum Tg is low. Other authors have reported that FDG PET scans are modestly improved by simultaneous TSH stimulation and T4 therapy using recombinant human (rh) TSH (Thyrogen) (53, 54). Importantly, no studies have directly compared the utility of FDG PET scans after rhTSH to those stimulated by thyroid hormone withdrawal.

Important additional information derived from FDG PET imaging (besides the opportunity for tumor localization) includes insight into the tumor’s likelihood of concentrating therapeutic 131I (55). Thyroid carcinomas with low iodine avidity tend to have higher glucose metabolism and are more likely to be positive on FDG PET imaging (a marker of tumor dedifferentiation). Conversely, those tumors that concentrate radioiodine well are unlikely to yield a positive FDG PET scan (56). Thus, I withhold empiric 131I therapy for FDG PET-positive patients, whereas I consider 131I therapy for those who are FDG PET scan negative with stimulated Tg levels greater than 5 or 10 ng/ml after rhTSH or thyroid hormone withdrawal, respectively, especially if the Tg is rising (2). Pathological uptake on the RxWBS may be therapeutic, or at least help localize the residual disease to direct additional anatomic imaging or therapy, including sites in the neck, lungs, bones, and brain. In the past, empiric 131I therapies in the range of 100–200 mCi have been considered for nearly all patients with elevated or rising serum Tg levels to aid in tumor localization or for therapy of surgically incurable disease (2). Recent data, however, have demonstrated that empiric high-activity therapies may exceed accepted patient safety limits more commonly than previously recognized (57, 58). For example, one study demonstrated that for empiric activities of 100, 150, 200, 250, and 300 mCi, the percentage of treatments for which patients would have exceeded 200 cGy to the blood or bone marrow was less than 1, 5, 11, 17, and 22%, respectively. Pertinent to the current case, Tuttle et al. (57) demonstrated that these rates were substantially higher in the elderly. For patients 80 yr old or older with serum creatinine values less than 2 mg/dl, the 200 cGy to the blood or bone marrow threshold would be exceeded if given 140 or 200 mCi in 13 and 38%, respectively. Thus, in the absence of dosimetry (59), past and future 131I therapy for this elderly man likely should have been limited to less than 140 mCi.

FDG PET imaging also provides prognostic information about the patient’s survival over the coming years. One study found the 3-yr survival of patients with FDG-avid tumor metastases volumes of 125 ml or less was 96%, compared with 18% in patients with FDG tumor volumes greater than 125 ml (60). Recently an expanded series of 400 thyroid cancer patients who underwent FDG PET imaging was analyzed using multivariate analysis that included age at imaging, American Joint Committee on Cancer stage, histopathology, gender, serum Tg during TSH suppression, radioiodine avidity, FDG avidity, number of FDG-avid lesions, and site of metastases (61). The results indicated that only age, FDG status, number of FDG lesions, and maximum standardized uptake value (SUVmax) were significant predictors of survival. The median survival for FDG-positive patients was 53 months after the PET scan, compared with only two deaths from the 180 FDG-negative patients. Thus, FDG PET scan-positive patients should strongly be considered for therapies other than 131I or clinical trials (www.thyroidtrials.org).


   Returning to the Patient
Top
 Abstract
 Introduction
 Background
 Controversies and Areas of...
 Diagnostic and Therapeutic...
 Returning to the Patient
Conclusions
 References
 
The stimulated serum Tg of 17.9 ng/ml was recognized to suggest residual disease; however, it was also recognized that given the patient’s advanced age, it was important to balance the risks and benefits of further therapy. A goal of TSH suppression was set for the 0.05 to 0.1 µIU/ml range (2, 5, 62). The patient’s physical examination revealed no evidence of palpable disease and no bone pain to percussion. Anatomic imaging was undertaken to identify potentially treatable disease and equally important to exclude potentially harmful lesions. Neck US was negative but limited by kyphosis and very limited ability to extend the neck, and therefore, US was supplanted by less sensitive neck CT imaging. Renal function was assessed, followed by negative CT imaging of the neck and chest with contrast to optimize imaging of the neck and mediastinum, despite the fact that this would delay the option of radioiodine imaging and therapy.

By January 2000 the basal Tg had risen to 3.4 ng/ml, suggesting tumor growth (22, 63). In May 2000 a hypothyroid DxWBS demonstrated asymmetric salivary gland uptake (likely resulting from his initial 131I ablation) and vague/questionable uptake in the left lower medial thorax. The serum TSH was greater than 200 µIU/ml and the Tg was 224.5 ng/ml. The blood urea nitrogen and creatinine were elevated at 25 and 2.1 mg/dl, respectively. The white blood count was normal at 7.2 K/µl (4.5–11.0 K/µl), but the hematocrit and platelets were low at 36.5% (39–49%) and 143 K/µl (150–400 K/µl), respectively. The patient was treated with 181 mCi I-131 orally, and the 8-d RxWBS was negative. The posttherapy course was complicated by side effects of 131I (64) that included throat pain, decreased oral intake, a dry mouth, and postural hypotension that required withholding of his diuretic for a few days about 3 wk after therapy. Concurrently the patient developed a slow oozing nose bleed that resolved on its own, but he presented to the emergency room for difficulty breathing through his nose that responded to speculum and forceps removal of old blood clots. Six weeks after therapy, he presented to the emergency room for severe joint pain and slight mental confusion and was hospitalized and diagnosed with dehydration and pseudogout. During this admission the white blood count, hematocrit, and platelet nadirs were 4.1 K/µl, 26.8%, and 98 K/µl, respectively. He was discharged to a nursing home for convalescence during which his levothyroxine dose was decreased because of his low TSH, apparently not recognizing the role of TSH suppression in the setting of active metastatic thyroid cancer (2, 5). The platelets returned to normal within 6 months of therapy, although the hematocrit remained reduced in the 30–34% range.

By August 2000 the TSH had risen to 1.01 µIU/ml and the serum Tg had reduced to 0.8 ng/ml (compared with 3.4 ng/ml before therapy, despite the negative RxWBS). Additional imaging options, including FDG PET, were discussed with the patient and his son; however, balancing the patient’s medical condition and his wishes resulted in a plan for TSH suppression and observation. Over the next year, the patient’s greatest complaint was weight loss with TSH suppression. Despite the desire for conservative care, a rise in the suppressed serum Tg to 17 ng/ml prompted CT imaging of the head, neck, and chest, which revealed a possibly new slightly spiculated 7-mm right lower lung nodule that was judged inaccessible to biopsy via CT guidance or bronchoscopy. The patient was considered noniodine avid, so no additional radioiodine imaging or therapy was considered. Chest CT follow-up 4 months later was without change.

By January 2003 the Tg had steadily risen to 171.5 ng/ml with a TSH of 0.02 µIU/ml. The patient expressed a desire to avoid surgery and aggressive treatment, so that conservative follow-up was continued. However, by July 2003 at age 91 yr, the serum Tg had risen as high as 534 ng/ml, and additional discussions included anatomic and functional imaging (FDG PET) to exclude impending harmful lesions that would be amenable to EBRT as well as experimental thyroid cancer clinical trials if desired, although it was expected that he would do poorly with EBRT to the neck as well as the typical side effects from chemotherapy and currently available experimental compounds. CT imaging of the neck and chest were without change, and FDG PET (without CT fusion) imaging revealed mild uptake (SUVmax = 2.2) in the periphery of the left lung without a corresponding anatomic abnormality on the CT.

In February 2005, at age 93 yr, the patient tripped at home and sustained a left hip fracture. His preoperative chest x-ray was negative and his hip fracture was addressed surgically. He was discharged to an extended care facility for 4 months for rehabilitation, and his levothyroxine dose was again erroneously decreased by the admitting physician because of TSH suppression.

By February 2006 the serum Tg had risen to 2410 ng/ml with a TSH of less than 0.04 µIU/ml. Additional extensive discussions were held with the patient and his son regarding options of tumor localization, treatment, quality of life, and his anticipated limited long-term overall survival. In April 2006 the patient developed a 3-d history of cough and congestion that prompted a chest x-ray that demonstrated a soft tissue pleural-based mass in the left lateral hemithorax. A chest CT demonstrated the stable 7-mm nodule and a chest wall mass measuring 5.8 x 3.3 cm with osseous destruction of the left seventh rib. Fused FDG PET/CT showed increased size and uptake (SUVmax = 7) in the chest wall lesion, compared with the previous study (Fig. 2Go), uptake in the T7 vertebral body (SUVmax = 2.8), and no uptake in the lung nodule. On review, the patient was asymptomatic from these lesions except occasional pain in the chest wall. Options of observation and EBRT were discussed, and EBRT was recommended, given the anatomic and biochemical progression (Tg doubling time ~1 yr). The patient received 3000 cGy in 12 fractions to the left chest wall and T7 vertebral body.


Figure 2
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  		FIG. 2. FDG PET/CT images. Left chest wall mass measuring 5.8 x 3.3 cm with osseous destruction of the seventh rib. A, B, and C, Demonstration of FDG PET image, CT image, and fusion FDG PET/CT image, respectively.

 
Four months after EBRT, the chest wall mass was decreased to 3.3 x 2.5 cm on chest CT, and the serum Tg reached a nadir of 440 ng/ml with a TSH of less than 0.04 µIU/ml. The patient did reasonably well over the next 5 months but was frail, and his overall health declined. In April 2007 the patient was admitted to the hospital with dysphasia. The hospitalization was complicated by respiratory failure thought to result from aspiration pneumonia and diastolic dysfunction with pulmonary edema. He required intubation, mechanical ventilation, and vasopressor therapy. Swallowing studies demonstrated cricopharyngeus hypertrophy and aspiration. He was eventually discharged to a skilled nursing facility, and a percutaneous endoscopic gastrostomy tube was placed for nutritional support and hydration. Two weeks later he returned to the hospital with hypoxia and deterioration. Neck and chest CT images were remarkable for large bilateral pleural effusions, extensive atelectasis, more numerous subcentimeter pulmonary nodules, and an unchanged chest wall metastasis. His Tg had risen to 1393 ng/ml (a concurrent serum TSH level was not obtained). The patient was awake but not very alert. His responses to questions were limited and incoherent. His prognosis was deemed very poor. The son elected hospice care; however, the patient died before discharge at age 95 yr, 10.5 yr after his initial thyroid cancer surgery, 11 months after EBRT, and unrelated to his thyroid cancer.


   Conclusions
Top
 Abstract
 Introduction
 Background
 Controversies and Areas of...
 Diagnostic and Therapeutic...
 Returning to the Patient
 Conclusions
References
 
The percentage of thyroid cancer survivors recognized to be living with persistent (or less commonly recurrent) disease has increased as a result of improvements in serum Tg assay sensitivity. Finding the location(s) of their disease and providing therapy is challenging, as witnessed by the fact that most of these patients are not rendered free of disease with additional treatment (including surgery), and most have negative diagnostic radioiodine imaging. Perhaps early intervention on these patients with low-volume residual disease offers the best outcome; however, no randomized clinical trials have been performed to confirm or refute this assertion, and clinical judgment remains useful. Many scan-negative, Tg-positive patients live for years with persistent (and often stable) disease, whereas some progress and require occasional therapeutic interventions. However, some patients manifest more obvious progressive and life-threatening disease. In a patient with progressive disease that is not amenable to cure, one of the goals is to intervene on disease that is likely to cause harm. When this disease fails to respond to local surgery or systemic 131I, treatment options are currently limited to localized palliative therapies or clinical trials with systemic agents. Whereas treatments offering cure with no morbidity are ideal, interventions (or lack thereof) that allow patients to live out their natural life span with minimal morbidity may be the next best option.


   Footnotes
 
Disclosure Statement: Within the past 2 yr, the author has received lecture fees and grant support from Genzyme Corp.

Abbreviations: CT, Computed tomography; DxWBS, diagnostic WBS; EBRT, external beam radiation therapy; FDG, 18F-fluorodeoxyglucose; PET, positron emission tomography; PTC, papillary thyroid carcinoma; rh, recombinant human; RxWBS, posttreatment WBS; SUVmax, maximum standardized uptake value; Tg, thyroglobulin; US, ultrasonography; WBS, whole-body scan.

Received October 23, 2007.

Accepted January 30, 2008.


   References
Top
 Abstract
 Introduction
 Background
 Controversies and Areas of...
 Diagnostic and Therapeutic...
 Returning to the Patient
 Conclusions
 References
 

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S. Leboulleux, P. R. Schroeder, N. L. Busaidy, A. Auperin, C. Corone, H. A. Jacene, M. E. Ewertz, C. Bournaud, R. L. Wahl, S. I. Sherman, et al.
Assessment of the Incremental Value of Recombinant Thyrotropin Stimulation before 2-[18F]-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography/Computed Tomography Imaging to Localize Residual Differentiated Thyroid Cancer
J. Clin. Endocrinol. Metab., April 1, 2009; 94(4): 1310 - 1316.
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