Persistent or Recurrent Disease in Thyroid Cancer Survivors Who Have Elevated Serum Antithyroglobulin Antibodies.

OBJECTIVE: Detection of residual differentiated thyroid cancer is important but difficult. A variety of imaging modalities and biochemical markers has been used with moderately good success. We hypothesized that elevated perioperative serum antithyroglobulin antibody (TgAb) levels would also be a predictive marker for persistent or recurrent thyroid cancer. METHODS: We performed a retrospective analysis of 277 differentiated thyroid cancer survivors divided into 2 groups: (1) those with low or normal serum TgAb (TgAb-) and (2) those with elevated serum TgAb (TgAb+). All patients were seen at one major academic medical center. Patients were followed for a median of 7.54 years. RESULTS: Patients in the TgAb+ group were more likely to have positive lymph nodes at initial surgery, to be assigned to a higher American Joint Committee on Cancer stage, and to have significantly higher incidence of persistent/recurrent disease. The higher incidence of persistent/recurrent cancer was significant under univariable and multivariable (including TgAb status, age, and sex) Cox proportional hazards model analysis. CONCLUSION: We conclude that individuals with elevated serum TgAb at the outset should be followed with a higher index of suspicion for persistent/recurrent thyroid cancer.

Clinical Features in Differentiated Thyroid Carcinoma Stratified By Lymph Node Status.

OBJECTIVE: Cervical lymph node (CLN) metastases (mets) often occur in differentiated thyroid cancer (DTC), especially in the central compartment, and are a major predictor of local recurrence. We examined clinical endpoints in three groups of patients based on status of lymph node involvement: those with definite lymph node involvement (N1), negative lymph nodes (N0), and no lymph nodes resected (Nx). We correlated these endpoints with clinical and pathologic features of these patients. METHODS: Medical records of 261 patients with DTC who underwent thyroidectomy between 2006 and 2018 at our center were reviewed. Lymph node status of patients was categorized based on American Joint Committee on Cancer (AJCC) 8th edition criteria as N1, N0, and Nx. We performed statistical analysis to assess the differences among these groups, using one-way analysis of variance. When significant differences were found, pairwise comparisons were conducted among the three groups. Statistical significance was defined as 2-tailed P<.05 for all tests. RESULTS: There were significant differences among the groups in tumor multicentricity, tumor category/size, AJCC stage, and the presence of thyroglobulin auto-antibodies (TgAbs). There were no difference in age, gender, or histopathology. N1 patients had a higher incidence of multicentricity, larger tumor sizes, and were more likely to have elevated TgAbs. There were no significant differences between the N0 and Nx groups. CONCLUSION: This study shows that larger and multi-centric tumors are associated with increased likelihood of CLN mets in DTC. We suggest increased vigilance for CLN mets in tumors >2 cm, multicentric tumors, and patients with elevated TgAbs. ABBREVIATIONS: AJCC = American Joint Committee on Cancer; CLN = cervical lymph node; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; mets = metastases; N0 = no cancer in any lymph nodes; N1 = cancer in a lymph node; N1a = cancer in a central compartment lymph node; N1b = cancer in a lateral neck lymph node; Nx = lymph nodes not resected or examined; PTC = papillary thyroid cancer; TgAb = thyroglobulin auto-antibody.

The Evolving Role of the Orthopaedic Surgeon in Combat Zones and Austere Deployed Locations Since the 2012 Troop Drawdown.

The purpose of this study was to evaluate the operative experience of orthopaedic surgeons in the various deployment locations since 2012. We also evaluated the implications of humanitarian surgical care and the impact of deployment on an orthopaedic practice. An emailed survey was sent to orthopaedic surgeons deployed after 2012. The survey was 48 questions. Most cases in Iraq, Afghanistan and Syria were emergent traumas. In other locations, however, most cases were elective/non-emergent cases. Of surgeons surveyed, 44% performed less than 10 cases during their deployment, and 50% considered humanitarian surgery part of their mission. Six weeks was needed to prepare for deployment, and 4.4 weeks to re-build a practice. Disparity exists in surgical case volume and types of cases performed by orthopaedic surgeons that is dependent on deployed location. This dichotomy in operative experience places surgeons deployed to such locations at risk of losing surgical skills. (Journal of Surgical Orthopaedic Advances 29(3):182-186, 2020).

PANCREAS METASTASES FROM PAPILLARY THYROID CARCINOMA: A REVIEW OF THE LITERATURE.

OBJECTIVE: Although locoregional metastases occur in 5 to 10% of patients with papillary thyroid cancer (PTC), distant metastases are rare, especially to the pancreas. Here we review the literature regarding metastases to the pancreas from PTC and present an illustrative patient. METHODS: The literature search was performed through using the PubMed database. The information regarding our illustrative case was obtained from the medical records of our institution. RESULTS: Since 1991, 11 cases of pancreas metastases of PTC have been reported. The average age at diagnosis was 55.3 years. There were 8 males and 3 females. Three had classic PTC histology, 2 had tall cell variant, and 2 had follicular variant. Four had T4 tumors, and 2 had T3 tumors. Seven had thyroid cancer spread to regional lymph nodes. One had distant metastasis. Pancreas metastases were diagnosed from 1 month to 13 years after primary PTC was detected; the average was 7 years. Our patient was an 84-year-old female diagnosed with PTC with a BRAFV600E mutation following total thyroidectomy. A whole-body scan after radioactive iodine (RAI) remnant ablation was negative for metastases. A pancreatic tumor was identified 2 years later on a fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan. A biopsy of the tumor was histologically similar to PTC and positive for thyroglobulin, thyroid transcription factor-1, and the BRAFV600E mutation. CONCLUSION: The biological reasons why PTCs metastasize to the pancreas remain to be elucidated. Older patients with non-RAI avid, FDG-PET-positive metastases, and symptoms of pancreatitis are at increased risk of this rare entity. ABBREVIATIONS: FDG = fluorodeoxyglucose FNA = fine-need aspiration PTC = papillary thyroid cancer RAI = radioactive iodine Tg = thyroglobulin TgAb = antithyroglobulin antibodies TNM = tumor-node-metastasis.

LOWER RATES OF RESIDUAL/RECURRENT DISEASE IN PATIENTS WITH INCIDENTALLY DISCOVERED THYROID CARCINOMA.

OBJECTIVE: Incidentally discovered thyroid cancers (IDTCs) have contributed to the rapid rise in thyroid cancer incidence over the past 20 years. Since death rates from thyroid cancer are not increasing, we hypothesized that IDTCs are less aggressive compared to clinically apparent thyroid cancer (CATC). METHODS: A retrospective study of patients and tumor characteristics of IDTCs and their rates of residual/recurrent (R/R) disease were determined at a median follow-up of 27 months in the setting of a large academic medical center. Patient analysis groups (IDTC [n = 46] and CATC [n = 126]) were based upon how the cancer was initially discovered. Patients were followed clinically and by biochemical testing and ultrasonography. We also compared time to progression between these groups. RESULTS: Patients in the two groups had similar demographic and tumor characteristics. At the close of the study, R/R status in the IDTC group was 6.7%, compared to 20.8% in the CATC group (P = .04). Of the 28 individuals in our overall cohort who had R/R disease, 3 were from the IDTC group and 25 were from the CATC group (P = .04). All three of the IDTC recurrences occurred within the first 6 months of follow-up. Using Kaplan-Meier analysis, there was a nonsignificant trend for longer progression-free survival in the IDTC group (P = .08). CONCLUSION: Compared to CATC patients, IDTC patients have a significantly less aggressive course and a trend toward longer progression-free survival. If confirmed by further studies, it may be reasonable to subject them to less intense surveillance and more conservative therapeutic approaches. ABBREVIATIONS: CATC = clinically apparent thyroid cancers CT = computed tomography HMH = Houston Methodist Hospital IDTC = incidentally discovered thyroid cancer MRI = magnetic resonance imaging PET = positron emission tomography PTMC = papillary thyroid microcarcinoma R/R = residual/recurrent RRA = radioiodine remnant ablation Tg = thyroglobulin TgAb = anti-thyroglobulin antibody TSH = thyroid-stimulating hormone US = ultrasonography.

MEN1 in a Patient With Nonsyndromic Familial Nonmedullary Thyroid Carcinoma.

Clinical syndromes involving multiple endocrine glands have been well recognized for over a century. Multiple reports describing hereditary multiple endocrine neoplasia (MEN) syndromes involving pituitary, parathyroid, and pancreatic neuroendocrine tumors have been published. Differentiated (nonmedullary) thyroid cancer can also present as a hereditary syndrome with or without a specific genetic predisposition. We report the case of a man with nonsyndromic familial nonmedullary thyroid carcinoma, a pituitary adenoma, hyperparathyroidism, an adrenal adenoma, and pancreatic adenocarcinoma. Genetic testing did not reveal mutations in the commonly reported genes associated with MEN syndromes. MEN1 is characterized by endocrine neoplasia in at least 2 of the following glands: pituitary, parathyroid, and the gastro-entero-pancreatic (GEP) tract. Co-occurrence of MEN1 with familial nonmedullary thyroid carcinoma, however, has not been reported in the medical literature. This unique case of MEN1 co-existing in a patient with nonsyndromic familial thyroid carcinoma was not associated with any common MEN syndrome germline mutations.

Myxedema Coma Associated with Macroprolactinoma: Case Report and Review of the Literature.

Myxedema coma is a rare life-threatening presentation of severe hypothyroidism associated with a high mortality rate. Although most cases are due to primary thyroid failure, a minority have central hypothyroidism as the underlying cause. We report the case of a 69-year-old man who presented with obtundation, hypoglycemia, and hyponatremia. The patient's initial thyroid-stimulating hormone (TSH) was within normal limits. Subsequent evaluation revealed critical anterior pituitary insufficiency due to a macroprolactinoma and a diagnosis of myxedema coma after appropriate workup The finding of a normal serum TSH should not eliminate the possibility of myxedema coma.

A sequence-specific exopeptidase activity test (SSEAT) for "functional" biomarker discovery.

One form of functional proteomics entails profiling of genuine activities, as opposed to surrogates of activity or active "states," in a complex biological matrix: for example, tracking enzyme-catalyzed changes, in real time, ranging from simple modifications to complex anabolic or catabolic reactions. Here we present a test to compare defined exoprotease activities within individual proteomes of two or more groups of biological samples. It tracks degradation of artificial substrates, under strictly controlled conditions, using semiautomated MALDI-TOF mass spectrometric analysis of the resulting patterns. Each fragment is quantitated by comparison with double labeled, non-degradable internal standards (all-d-amino acid peptides) spiked into the samples at the same time as the substrates to reflect adsorptive and processing-related losses. The full array of metabolites is then quantitated (coefficients of variation of 6.3-14.3% over five replicates) and subjected to multivariate statistical analysis. Using this approach, we tested serum samples of 48 metastatic thyroid cancer patients and 48 healthy controls, with selected peptide substrates taken from earlier standard peptidomics screens (i.e. the "discovery" phase), and obtained class predictions with 94% sensitivity and 90% specificity without prior feature selection (24 features). The test all but eliminates reproducibility problems related to sample collection, storage, and handling as well as to possible variability in endogenous peptide precursor levels because of hemostatic alterations in cancer patients.

A BRAF V600E Mutation in RET-Negative Medullary Thyroid Cancer.

We report the case of a woman with a sporadic medullary thyroid carcinoma. Genomic analysis found that her tumor did not contain any common RET mutations but did harbor a BRAF V600E mutation. Only one other well-confirmed example of the BRAF V600E mutation has been reported in an MTC patient. We conclude that this common BRAF mutation may independently drive neoplastic transformation of human parafollicular C cells.

Features of Multiple Endocrine Neoplasia Type 1 and 2A in a Patient with Both RET and MEN1 Germline Mutations.

The coexistence of multiple endocrine neoplasia type 1 (MEN1) and type 2A (MEN2A) is a rare occurrence and has been reported only twice in the literature. We present a patient with primary hyperparathyroidism and medullary thyroid cancer with strong family history of both MEN1- and MEN2A-associated conditions. Genetic testing showed the patient had a novel MEN1 loss-of-function mutation, c0.525_526insTT (p.Ala176Leufs*10), and an uncommon Cys630Tyr RET mutation. This case highlights the importance of obtaining a detailed family history when heritable endocrine disorders are suspected.

Recombinant human TSH-assisted radioactive iodine remnant ablation achieves short-term clinical recurrence rates similar to those of traditional thyroid hormone withdrawal.

UNLABELLED: Recent studies have confirmed that radioactive iodine therapy after recombinant human TSH (rhTSH) stimulation effectively ablates the normal thyroid remnant. However, no published study has determined the effectiveness of rhTSH preparations on the important endpoint of disease recurrence. METHODS: Disease recurrence was retrospectively assessed a median of 2.5 y after radioiodine remnant ablation (RRA) in 394 consecutive thyroid cancer patients (93% papillary, 71% female, 47+/-15 y old [mean +/- SD], median (131)I dose of 3,996 MBq [108 mCi]). RESULTS: Similar rates of clinically evident disease recurrence (4% rhTSH vs. 7% thyroid hormone withdrawal [THW], P=not statistically significant) and residual thyroid bed uptake without other evidence of persistent disease (4% rhTSH vs. 7% THW, P=not statistically significant) were seen in the 320 patients undergoing rhTSH-assisted RRA and the 74 patients prepared for RRA by THW. When the definition of no clinical evidence of disease included a suppressed thyroglobulin level of less than 1 ng/mL and a stimulated thyroglobulin level of less than 2 ng/mL, rhTSH-assisted RRA was associated with significantly higher rates of no clinical evidence of disease (74% rhTSH vs. 55% THW, P=0.02) and significantly lower rates of persistent disease (19% rhTSH vs. 32% THW, P=0.02) than was RRA after THW. Patients selected for rhTSH-assisted RRA were older (48+/-15 vs. 44+/-15 y, P=0.03) and received a slightly higher administered activity of (131)I (median, 4,033 MBq [109 mCi] vs. 3,811 MBq [103 mCi], P=0.01) but did not differ with respect to sex, histology, disease stage, or mean time to recurrence (19+/-9 mo for rhTSH vs. 20+/-16 mo for THW). CONCLUSION: rhTSH-assisted RRA is associated with rates of clinically evident disease recurrence and persistent uptake in the thyroid bed that are similar to those for traditional THW.

Comparison of Direct Patient Care Costs and Quality Outcomes of the Teaching and Nonteaching Hospitalist Services at a Large Academic Medical Center.

PURPOSE: To compare costs of care and quality outcomes between teaching and nonteaching hospitalist services, while testing the assumption that resident-driven care is more expensive. METHOD: Records of inpatients with the top 20 Medicare Severity Diagnosis-Related Groups admitted to the University Teaching Service (UTS) and nonteaching hospitalist service (NTHS) at Houston Methodist Hospital from 2014-2015 were analyzed retrospectively. Direct costs of care, length of stay (LOS), in-hospital mortality (IHM), 30-day readmission rate (30DRR), and consultant utilization were compared between the UTS and NTHS. Propensity score matching and case mix index (CMI) were used to mitigate differences in baseline characteristics. To compare outcomes between matched groups, the Wilcoxon rank sum test and chi-square test were used. A sensitivity analysis was conducted using multivariable regression analysis. RESULTS: From the overall study population of 8,457 patients, 1,041 UTS and 3,123 NTHS patients were matched. CMI was 1.07 for each group. The UTS had lower direct costs of care per case ($5,028 vs. $5,502, P = .006), lower LOS (4.7 vs. 5.2 days, P = .0002), and lower consultant utilization (1.0 vs. 1.6, P ≤ .0001) versus the NTHS. The UTS and NTHS 30DRR (17.2% vs. 19.3%, P = .110) and IHM (2.9% vs. 3.7%, P = .206) were comparable. The multivariable regression analysis validated the matched data and identified an incremental cost savings of $333/UTS patient. CONCLUSIONS: Patients of an academic hospitalist service had significantly shorter LOS, fewer consultants, and lower direct care costs than comparable patients of a nonteaching service.

Cardiovascular Disease in Acromegaly.

In patients with acromegaly, chronic excess of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) leads to the development of acromegalic cardiomyopathy. Its main features are biventricular hypertrophy, diastolic dysfunction, and in later stages, systolic dysfunction and congestive heart failure. Surgical and/or pharmacological treatment of acromegaly and control of cardiovascular risk factors help reverse some of these pathophysiologic changes and decrease the high risk of cardiovascular complications.

Real-time prognosis for metastatic thyroid carcinoma based on 2-[18F]fluoro-2-deoxy-D-glucose-positron emission tomography scanning.

CONTEXT/OBJECTIVE: Approximately 15% of thyroid cancer patients develop subsequent metastases. The clinical course of patients with metastatic thyroid carcinoma is highly variable. We hypothesized that the metabolic activity of metastatic lesions, as defined by retention of 2-[(18)F]fluoro-2-deoxyglucose (FDG), would correlate with prognosis. DESIGN/PATIENTS: The initial FDG-positron emission tomography (PET) scans from 400 thyroid cancer patients were retrospectively reviewed and compared with overall survival (median follow-up, 7.9 yr). We examined the prognostic value of clinical information such as gender, age, serum thyroglobulin, American Joint Committee on Cancer (AJCC) stage, histology, radioiodine avidity, FDG-PET positivity, number of FDG-avid lesions, and the glycolytic rate of the most active lesion. RESULTS: Age, initial stage, histology, thyroglobulin, radioiodine uptake, and PET outcomes all correlated with survival by univariate analysis. However, only age and PET results continued to be strong predictors of survival under multivariate analysis. The initial American Joint Committee on Cancer stage was not a significant predictor of survival by multivariate analysis. There were significant inverse relationships between survival and both the glycolytic rate of the most active lesion and the number of FDG-avid lesions. CONCLUSIONS: FDG-PET scanning is a simple, expensive, but powerful means to restage thyroid cancer patients who develop subsequent metastases, assigning them to groups that are either at low (FDG negative) or high (FDG positive) risk of cancer-associated mortality. We propose that the aggressiveness of therapy for metastases should match the FDG-PET status.

Diagnostic accuracy and prognostic value of 18F-FDG PET in Hürthle cell thyroid cancer patients.

UNLABELLED: Hürthle cell carcinoma is an uncommon and occasionally aggressive differentiated thyroid cancer associated with increased mortality compared with other differentiated thyroid malignancies. Because it generally has lower iodine avidity, 18F-FDG PET has been suggested as a more accurate imaging modality. However, there is limited information with regard to the true diagnostic accuracy and prognostic value of 18F-FDG PET in this disease. METHODS: All patients with Hürthle cell thyroid cancer who underwent their first 18F-FDG PET scan between May 1996 and February 2003 were identified retrospectively. 18F-FDG PET scans were reviewed and compared with all available imaging studies, including CT, ultrasound, and radioiodine scintigraphy (RIS). Abnormal 18F-FDG uptake was assessed visually and by measuring the maximum standardized uptake value (SUVmax) of the most intense lesion. Clinical follow-up for at least 1 y or until death was required for inclusion. RESULTS: Forty-four patients met inclusion criteria. The median follow-up was 2.9 y. There were 24 positive and 20 negative 18F-FDG PET scans with 1 false-positive and 1 false-negative study, resulting in a diagnostic sensitivity of 95.8% and a specificity of 95%. In 5 of 11 patients who had both positive CT and 18F-FDG PET findings, 18F-FDG PET revealed additional sites of disease. Furthermore, 18F-FDG PET correctly classified as negative 3 patients with false-positive CT findings. In 3 of 6 patients with positive RIS, 18F-FDG PET revealed additional sites of metastatic disease. Ten patients with positive 18F-FDG PET had negative RIS. Only 1 patient with negative 18F-FDG PET had positive RIS. The SUVmax also provided prognostic information: In a stepwise fashion, each increase in intensity by SUVmax unit was associated with a 6% increase in mortality (P < 0.001). The 5-y overall survival in patients with SUVmax < 10 was 92%; it declined to 64% in those with SUVmax > 10 (P < 0.01). CONCLUSION: 18F-FDG PET has excellent diagnostic accuracy in Hürthle cell thyroid cancer patients, improving on CT and RIS. Intense 18F-FDG uptake in lesions is an indicator of a poor prognosis. Our data suggest that all patients with Hürthle cell thyroid cancer should undergo 18F-FDG PET as part of their initial postoperative staging and periodically to screen for occult recurrence, particularly in patients with elevated serum thyroglobulin.

Empiric radioactive iodine dosing regimens frequently exceed maximum tolerated activity levels in elderly patients with thyroid cancer.

UNLABELLED: Although 131I-iodine (RAI) therapy is a mainstay in the treatment of metastatic thyroid cancer, there is controversy regarding the maximum activity that can safely be administered without dosimetric determination of the maximum tolerable activity (MTA). At most institutions, a fixed empiric dosing strategy is often used, with administered activities ranging from 5.55 to 9.25 GBq (150-250 mCi). In our experience with dosimetry, we have observed that this empiric dosing strategy often results in administered RAI activities exceeding the MTA safety limit of 200 cGy (rads) to the blood or bone marrow in many patients with metastatic thyroid cancer. METHODS: We retrospectively analyzed 535 hypothyroid dosimetry studies performed as part of routine clinical care in 328 patients with apparently normal renal function. RESULTS: The MTA was less than 5.18 GBq (140 mCi) in 3%, less than 7.4 GBq (200 mCi) in 8%, and less than 9.25 GBq (250 mCi) in 19%. Analysis of MTA values by age at the time of dosimetry revealed little change in the MTA until the age of 70 y, when a significant decrease occurred. An empiric administered activity of 7.4 GBq (200 mCi) would exceed the MTA in 8%-15% of patients less than 70 y old and 22%-38% of patients 70 y old or older. However, administration of 9.25 GBq (250 mCi) would exceed the MTA in 22% of patients less than 70 y old and 50% of patients 70 y old or older. Factors associated with a lowering of MTA to less than 9.25 GBq (250 mCi) were age at dosimetry greater than 45 y, the female sex, subtotal thyroidectomy, and RAI-avid diffuse bilateral pulmonary metastases. CONCLUSION: Administered RAI activities of less than 5.18 GBq (140 mCi) rarely exposed blood to more than 200 cGy except in the very elderly. However, administered activities of 7.4-9.25 GBq (200-250 mCi) frequently exceeded the calculated MTA in patients 70 y old or older. Therefore, dosimetry-guided RAI therapy may be preferable to fixed-dose RAI treatment strategies in older patients with thyroid cancer and in patients with RAI-avid diffuse bilateral pulmonary metastases, even when renal function is normal.

Recombinant human thyrotropin-assisted radioiodine therapy for patients with metastatic thyroid cancer who could not elevate endogenous thyrotropin or be withdrawn from thyroxine.

The value of recombinant human thyrotropin (rhTSH) as preparation for radioiodine therapy was assessed in 115 patients with metastatic thyroid cancer. Patients who were either unable to elevate endogenous TSH during thyroxine withdrawal, or in whom thyroxine withdrawal was contraindicated for medical reasons were eligible. Their physicians requested rhTSH as part of the Thyrogen Compassionate Use Program. This is a retrospective summary of the nonrandomized uncontrolled experience. We assessed the ability of rhTSH to elevate the serum TSH; to avoid the complications of hypothyroidism; to stimulate radioiodine uptake; and to stimulate the serum thyroglobulin. Disease response and adverse events were also assessed. After rhTSH, the serum TSH levels rose to >or=25mU/L in every patient in whom levels were measured (n = 112). Hypothyroid complications were avoided in 22 of 25 patients who had experienced them in the past, and in 47 of 51 patients who were at high risk for hypothyroid complications. Radioiodine uptake was present on whole-body scans (WBS) in 105 of the 115 patients. Serum thyroglobulin levels were lower than baseline in 73% of patients assessed at 12 months. Cancer-related symptoms were improved in approximately 25%. Two patients had serious adverse events that were thought to be related to rhTSH. rhTSH elevates serum TSH and facilitates radioiodine uptake in patients who cannot produce endogenous TSH or who cannot tolerate hypothyroidism.

The evolving role of (131)I for the treatment of differentiated thyroid carcinoma.

The use of radioactive iodine ((131)I) for the treatment of thyroid carcinoma has changed over the past 50 y. These changes are based on increasing awareness of the biophysical properties of (131)I and new discoveries concerning the biology of iodine handling by thyroid cells. The therapeutic administration of (131)I for thyroid remnant ablation and for metastases requires an appreciation of iodine clearance kinetics, of factors that can alter the occupancy time of (131)I within lesions, and of the role of thyroid-stimulating hormone in stimulating the sodium-iodide symporter. The potential complications and adverse events associated with (131)I are discussed. (131)I will continue to be a major weapon in the fight against metastatic thyroid carcinoma. Its future role will be modified by expanding knowledge of its relative risks and benefits.

Is the serum thyroglobulin response to recombinant human thyrotropin sufficient, by itself, to monitor for residual thyroid carcinoma?

The serum thyroglobulin (Tg) response to elevated TSH is one of the most sensitive indexes of residual thyroid carcinoma. We have explored the possibility that this test alone would be sufficient to detect residual thyroid carcinoma in thyroid cancer patients after total thyroidectomy and radioiodine remnant ablation. We used recombinant human TSH (rhTSH) to elevate serum TSH, rather than withdraw the patients from thyroid hormone. Routine evaluations, including diagnostic radioiodine whole body scans (DxWBS) and serum Tg, were performed on 366 patients after preparation by rhTSH, over a 2-yr interval. A retrospective analysis of the data from these patients revealed that 76% of those whose stimulated Tg rose to more than 2 microg/liter had evidence for residual thyroid carcinoma, whereas the same was true for only 13% of those whose stimulated Tg was 2 microg/liter or less. Using risk group stratification, we analyzed outcomes in a low risk subset (which excluded patients with elevated Tg levels on suppression, known metastatic disease, and clinical or histological evidence of aggressive disease). In this low risk group, we found that a stimulated Tg of 2 microg/liter or less had a 91.7% negative predictive value. No low risk patient who had had a prior negative DxWBS and a stimulated Tg of 2 microg/liter or less had any evidence of residual thyroid carcinoma. We conclude that the stimulated Tg alone is not sufficient by itself to screen unselected patients, but that it may be sufficient in low risk patients, especially those who have had a prior negative DxWBS.