Increased Thyroglobulin Levels Research Articles

Submandibular lymph node metastasis of occult thyroid carcinoma first suspected to be a salivary gland tumor: a case report

BackgroundWhen diagnosing and treating neck masses, various diseases need to be considered, including benign or malignant tumors, lymph node-related diseases, and cysts. Thus, there may be cases in which making a definitive diagnosis is difficult on the basis of blood testing and imaging alone.Case presentationThe patient was an 80-year-old Japanese female who presented with swelling in the right submandibular area. Magnetic resonance imaging and ultrasonography revealed a solid tumor with inhomogeneous content continuous with the submandibular gland. Therefore, the clinical diagnosis was salivary gland tumor. Surgical treatment was performed, and intraoperative frozen-section examination demonstrated submandibular lymph node metastasis of thyroid carcinoma. After surgical treatment, blood test for thyroid gland function yielded normal results except for increased thyroglobulin levels. Further positron-emission tomography–computed tomography and ultrasonography were performed, in addition to fine-needle aspiration biopsy of the thyroid gland and other tests; however, no other thyroid abnormalities were observed. Fine-needle aspiration biopsy revealed no carcinomatous components. Close observational follow-up has been continued without thyroid gland treatment, and as of approximately 8 years postoperation, no recurrence, metastases, or thyroid carcinoma have developed.ConclusionThe mass was lymph node metastasis of occult thyroid carcinoma. In general, occult thyroid carcinoma metastasizes to level II–V. To the best of our knowledge, this is the first report of submandibular lymph node metastasis alone of occult thyroid carcinoma.

Analysis of diagnosis and treatment of 100 patients with Hürthle cell adenoma

Objective To summarize and analyze the clinical data and prognosis of the patients with Hurthle cell tumor (HCT) in order to raise the clinicians' awareness of the disease. Methods The clinical data on patients with histopathologically proven HCT, without other thyroid carcinomas, were collected retrospectively in Peking University First Hospital from January 2001 to February 2017. All the patients underwent surgery due to thyroid nodules. The follow-up information was also collected. Results A total of 100 patients were enrolled in the current study. All of them were diagnosed with Hurthle cell adenoma (HCA). There were 77 females and 23 males, with the male-to-female ratio of 1 : 3.3. The average age of these patients was (52±14) years at the time of operation. Fifty-one patients were found their thyroid nodules accidentally by ultrasonography during their health check-ups. 69.4% of the 49 symptomatic patients presented with painless cervical nodules. 83.0% HCA patients were combined with multinodular goiters (MNGs). 88.4% (76/86) patients were euthyroid and 53.8% (21/39) had increasing thyroglobulin levels. The mean longest diameter of HCAs was (3.2±1.5) cm (range: 0.9-7.3 cm) on ultrasonography. There were a series of sonographic features of HCA, such as larger, solidity, hypoecho, a smooth outline, intranodular vascularization, perinodular vascularization, absence of calcification in nodules and absence of enlarged cervical lymph nodes. Compared with the histological diagnosis, the diagnostic accuracy by frozen section (FS) during operation was 97.4%. Twenty-nine patients were followed up with an average period of (49.2±22.1) months and none of them had local recurrence or cervical lymph node metastasis. Six patients accepted thyroid hormone replacement treatment and one had thyrotoxicosis due to over-dose. Conclusion HCA is more common in women. It is often found accidentally by ultrasonography during their health check-ups or presented with painless cervical nodules. It is combined with MNG frequently. HCA exhibits numerous sonographic features but not unique. FS during operation is a reliable method to identify HCA with high diagnostic accuracy. Patients with thyroid hormone administration should be monitored for thyroid function after thyroid surgery.

Relapse-free survival after adjuvant radioactive iodine therapy in patients with differentiated thyroid carcinoma with a microscopically positive tumor margin.

In patients with differentiated thyroid carcinoma (DTC) with a microscopically positive tumor margin, the optimal first dose of I-131 during adjuvant radioactive iodine (RAI) therapy to improve relapse-free survival (RFS) is unclear. Due to the limited number of hospital beds, 1110MBq of I-131 is administered to such patients in Japan. This study primarily aimed to retrospectively determine the difference in RFS between high-dose (3700MBq) and low-dose (1110MBq) adjuvant RAI therapies in DTC patients with a microscopically positive tumor margin. The secondary aim was to investigate the background factors affecting RFS. Forty-eight consecutive patients (15 men and 33 women) who underwent total thyroidectomy between April 2007 and December 2017 for DTC without gross residual tumors and distant metastasis, and who were diagnosed with a positive margin histopathologically, followed by RAI therapy, were enrolled. We retrospectively investigated initial I-131 dose, classifying it into high-dose and low-dose groups. The primary endpoint was RFS. Relapse was considered in the following cases: patients with visible recurrent tumor and/or metastasis on neck ultrasound and/or computed tomography, and patients without visible tumor, but with clearly increasing thyroglobulin levels on follow-up every 3-6months. RFS outcomes were analyzed using the Kaplan-Meier method. Univariate analysis was performed using the log-rank test, and multivariate analysis was undertaken using the Cox proportional hazard model. There were nine cases of recurrence (52.9%) in the low-dose group and seven in the high-dose group (22.5%) during follow-up. The estimated median RFS was 69.4months in the low-dose group and 120.7months in the high-dose group. High-dose administration was associated with improved RFS, as demonstrated by Kaplan-Meier survival curves (log-rank test [P = 0.009]). Patient factors associated with worse RFS included low-dose administration (hazard ratio [HR] = 91.9; 95% confidence interval [CI] = 7.66-1102.79); P < 0.001), T4 stage (HR = 1.88; 95% CI = 0.44-8.10; P = 0.015), and presence of central lymph node metastases (HR = 190; 95% CI = 3.80-9496; P = 0.009). The most common type of recurrence was lymph node metastasis. Patients with microscopically positive tumor margins could benefit from RAI with high activities.

Association between Refractoriness to 131I Therapy for Differentiated Thyroid Carcinoma and 18F-FDG Accumulation in Lung Metastasis

Background: The purpose of this study was to retrospectively investigate the association between 2-[F-18]-fluoro-2-deoxy-D-glucose (18F-FDG) accumulation in lung metastasis (LM) before 131I therapy and refractoriness to 131I therapy for differentiated thyroid carcinoma (DTC) patients. Methods and Findings: Sixty-one DTC patients with LM who underwent Positron emission tomography/computed tomography using 18F-FDG (18F-FDG PET/ CT) before an initial 131I therapy were retrospectively evaluated. Maximum of standardized uptake value (SUVmax) in LM with the highest 18F-FDG accumulation was measured in each patient. The SUVmax was compared between patients with and without 131I-positive LM, and between patients with and without an increased level of thyroglobulin (tumor marker) 12 ± 2 months after 131I therapy using the Wilcoxon test. Discussion: Predictability for the patients with an increased thyroglobulin level was also analyzed by receiver-operating-characteristic (ROC) analysis. SUVmax of LM was significantly greater for patients without 131I-positive LM than for those with 131I-positive LM (5.9 ± 6.0 vs. 1.9 ± 2.0, p 3.8 showed an increased TG level after 131I therapy. Use of the optimal cutoff threshold for SUVmax of 1.6 differentiated patients with an increased level of TG from those without at a sensitivity of 74.2%, a specificity of 94.4%, an accuracy of 81.6% and an AUC of 0.91. Conclusion: 18F-FDG accumulation in LM from DTC can be one of predictors for refractoriness to 131I therapy.

Cardiac blood pool activity on postablation radioiodine imaging.

There are reports on physiologic and pathologic mediastinal uptake on radioiodine imaging in patients with thyroid carcinoma. The most commonly reported physiologic causes of mediastinal uptake are esophageal retention of salivary secretion and uptake by hyperplastic or normal thymus gland. In this study, we evaluated physiologic cardiac blood pool (CBP) activity and its associated findings on radioiodine imaging. Cardiac blood pool activity was evaluated in 186 postablation and 32 posttherapy scans. After oral radioiodine administration, imaging was initiated on day 7. Thyroglobulin, anti-thyroglobulin and TSH blood level determination was carried out in all patients. Whole-body scans were inspected with regard to residual thyroid uptake, esophageal uptake, CBP activity, hepatic activity and metastatic iodine uptake. Uptake in the residual thyroid tissue was graded visually as mild (m), moderate (M) and significant (S). Whenever CBP activity was detected on visual inspection, its intensity was graded as mild (1), moderate (2), and significant (3). Cardiac blood pool activity was detected in 61 postablation scans (33 %). Residual thyroid uptake was observed in all patients with CBP. A significant correlation existed between the intensity of uptake and the presence of CBP (p < 0.05). The mean Tg in patients with CBP was significantly higher than those without CBP (p < 0.05). Cardiac blood pool activity was not observed in any posttherapy scans and in those scans with distant metastases in the postablation group. Linear or irregular activity pattern thought to be due to esophagus was detected in 4 % of postablation scans. The results have revealed CBP to be common on postablation scans. Its presence correlated with the intensity of residual thyroid uptake and had a significant association with increased thyroglobulin levels. Its absence on posttherapy scans despite increased Tg levels suggested that this activity is due to labeled thyroid hormones released by the residual thyroid tissue. Its presence might imply a high level of blood radiation dose.

Analysis of the Thyroid Phenotype in 42 Patients with Pendred Syndrome and Nonsyndromic Enlargement of the Vestibular Aqueduct

Pendred syndrome (PS), a recessive disorder caused by mutations in the SLC26A4 (PDS) gene, is associated with deafness and goiter. SLC26A4 mutations have also been identified in patients exhibiting isolated sensorineural hearing loss without apparent thyroid abnormality (nonsyndromic enlargement of the vestibular aqueduct; nonsyndromic EVA). Our aim was to describe systematically the thyroidal phenotypes and the SLC26A4 genotypes of patients presenting with PS or nonsyndromic EVA. Nineteen patients with PS and 23 patients with nonsyndromic EVA, aged 5-53 years, were included. They underwent thyroid evaluation (physical examination, biological thyroid function tests, measurement of thyroglobulin level, thyroid ultrasonography, and thyroid (123)I scintigraphy with perchlorate discharge test), otological evaluation, and SLC26A4 mutation screening. In 19 patients with PS, goiter was identified in 15 (79%) and hypothyroidism in 15 (79%); hypothyroidism was subclinical in four patients and congenital in six patients. The perchlorate discharge test (PDT) was positive in 10/16 (63%). Morphological evaluation of the inner ear using MRI and/or CT showed bilateral EVA in 15/15 PS patients. Mutation screening revealed two SLC26A4 mutant alleles in all 19 PS patients that were homozygous in two families and compound heterozygous in 12 families. In the 23 patients with nonsyndromic EVA, systematic thyroid evaluation found no abnormalities except for slightly increased thyroglobulin levels in two patients. SLC26A4 mutations were identified in 9/23 (39%). Mutations were biallelic in two (compound heterozygous) and monoallelic in seven patients. The thyroid phenotype is widely variable in PS. SLC26A4 mutation screening is needed in patients exhibiting PS or nonsyndromic EVA. PS is associated with biallelic SLC26A4 mutations and nonsyndromic EVA with no, monoallelic, or biallelic SLC26A4 mutations. Systematic thyroid evaluation is recommended in patients with nonsyndromic EVA associated with one or two SLC26A4 mutations. We propose using a combination of three parameters to define and diagnose PS: (i) sensorineural deafness with bilateral EVA; (ii) thyroid abnormality comprising goiter and/or hypothyroidism and/or a positive PDT; (iii) biallelic SLC26A4 mutations.

Esophageal Metastasis From Papillary Thyroid Cancer

We report a case of esophageal metastasis from papillary thyroid cancer diagnosed by I SPECT/CT. A 70-year-old man presented with increasing thyroglobulin levels 13 years after thyroidectomy and ablation with I for thyroid cancer. The whole-body radioiodine scan demonstrated marked tracer uptake in the mediastinum, and SPECT/CT could clearly localize the activity to the esophagus. Subsequent surgical resection with histopathologic evaluation revealed an esophageal metastasis from papillary thyroid cancer. I SPECT/CT is a valuable tool for evaluation and precise anatomical localization of the foci of radionuclide activity in thyroid cancer, enabling adequate treatment.

Unusual Muscular Metastases From Papillary Thyroid Carcinoma Detected by Fluorine-18-Fluorodeoxyglucose PET/MRI

A 50-year-old woman with papillary thyroid carcinoma (PTC) [pT3(m),pN1a], treated by surgery and radioiodine ablation (6.2 GBq) 22 years before, was referred to our center for restaging due to increased serum thyroglobulin levels (65 ng/mL) after a 5-year period in which she has been lost at follow-up. Neck ultrasonography (US), thoracic computed tomography (CT), and I-whole-body scan were negative for recurrences. Fluorine-18-fluorodeoxyglucose (F-FDG) positron emission tomography (PET)/CT showed 2 areas of increased uptake in the left trapezius and right subscapularis muscles without abnormal findings at coregistered CT. Therefore, the patient underwent a F-FDG-PET/magnetic resonance imaging (MRI), which showed increased uptake in 2 hyperdense lesions in the left trapezius (4.2 cm) and right subscapularis muscles (2.5 cm) (Figure 1). Based on these findings, the patient underwent a biopsy of the muscle lesions. Histopathological pattern was consistent with muscular metastases from PTC (Figure 2), and the patient was addressed to surgery. PTC is a slowly progressive cancer with a high 10-year survival rate (85–95%). Distant metastases are seen in 3–15% of PTC patients, mostly in the lungs, followed by the bone. Muscular metastases of PTC are very rare, but detecting them has a significant impact on the clinical management and prognosis of patients (1, 2). The usefulness of F-FDG-PET/CT for detecting PTC recurrences in patients with increased thyroglobulin levels and negative I-whole-body scan is well known (3). Conversely, only 1 article, limited to the study of the neck, reported the usefulness of F-FDG-PET/MRI in this setting (4). This emerging technique (5) has been useful in our case to detect unusual PTC metastases.

A CT Scan Aspect of “Hypodense Thyroid Gland” after Sunitinib Treatment for Metastatic Carcinoma of the Kidney

A 63-yr-old woman was admitted for a painful goiter. She had no medical history, except a renal carcinoma. She developed pulmonary metastases 2 yr after diagnosis. Administration of sunitinib (50 mg/d) included six repeated cycles with 4 wk of treatment followed by 2 wk without treatment. A swelled and painful neck appeared 5 months after treatment with sunitinib. The patient had no signs of thyrotoxicosis but had an irregular goiter. TSH was suppressed (0.06 mU/liter; normal, 0.27– 4.20), with elevated free T4 (131 pmol/liter; normal, 12.0– 22.0) and free T3 (9.2 pmol/liter; normal, 3.5–6.5). Antithyroid antibodies were absent. C-reactive protein level was 3.27 mg/ml (normal, 5), sedimentation rate was 35 mm/h (normal, 0–20), and thyroglobulin level was 42.3 ng/ml (normal, 2.5–30). Contrast computed tomography (CT) revealed an unusual aspect of the thyroid [36 Hounsfield unit (HU) density] (Fig. 1, A–C). Ultrasonography confirmed goiter (65 cm) (Fig. 1D). Beta-blockers were started. After 10 d, free T4 and free T3 decreased (7.91 and 1.78 pmol/liter, respectively), TSH increased (17.31 mU/liter), thyroid peroxidase antibody emerged (81 U/ml; normal, 60), sedimentation rate was 24 mm/h, and thyroglobulin was 27.9 ng/ml. Ultrasonography didn’t change. L-Thyroxine was required (75 g/d) and normalized thyroid function. Sunitinib is a tyrosine kinase inhibitor with antiangiogenic and antiproliferative effects (1). Sunitinib is one of the first-line treatments of advanced renal carcinoma (2). Thyroid dysfunction due to sunitinib is usual, but mechanisms remain unclear. Hyperthyroidism was reported in 25% of patients preceding hypothyroidism. Increased thyroglobulin level, decreased iodine uptake, and cytological data suggested destructive thyroiditis (3–5). In this observation, a thyroid cytotoxic or ischemic effect of sunitinib could explain the transient thyrotoxicosis and CT scan picture.

Differentiated thyroid cancer – 2009

Three years ago continental guidelines were published referring management and follow-up of low risk thyroid cancer patients. The aim of this paper is to summarize the changes and new directions in this field. High risk patients require another protocol. Neck ultrasound plays important role in differential diagnosis and in detecting recurrences. Some new ultrasound techniques are discussed, too. FDG-PET can help to solve the problem of patients having negative scan and increased thyroglobulin level. In recent years there was an expansion of our knowledge about the pathomechanism of thyroid cancer. It appears that genetic alterations frequently play a key role in carcinogenesis. There are molecular methods that allow the detection of these genetic events in thyroid fine needle aspirations samples providing important information for diagnosis, management and prognosis. Instead of diagnostic whole body scanning the posttherapeutic scan became preferable but in high risk cases the diagnostic whole body scintigrams serve useful data. Primary therapy of thyroid cancer is an adequate surgery: total thyreoidectomy and, if necessary, lymph node dissection or limited surgery in selected cases. Nowadays radioguided surgery can help to improve the results. Radioiodine therapy (e.g. rest ablation) proved to be a safe and effective method to complete surgery. It can prevent relapses and results in longer survival. Thyroid hormone withdrawal or recombinant human thyrotropin stimulation can increase thyrotropin level before radioiodine treatment. These two methods have similar success rate of rest ablation but irradiation burden of blood is lower in the case of exogenous stimulation which avoids hypothyroid state and preserves quality of life. Since tumor cells fail to maintain the ability to perform physiological functions they undergo dedifferentiation. Therefore, an important aim is to reactivate some function of differentiated cells, e.g. iodine uptake, production of thyroperoxydase and thyroglobulin. Opportunities for this therapeutic effort are also mentioned. Restoration of iodine uptake enables radioisotope treatment. Until now there has been little interest in the development of new drugs for the treatment of thyroid cancer. However, advances in our understanding of tumor cell biology will lead to a paradigm shift in the therapy that is likely to benefit patients who have high risk disease and who do not almost have any therapeutic option. There are new drugs in clinical trials that appear to be more effective than earlier cytotoxic agents. Probably modern chemotherapy of advanced thyroid cancer will have significant results in the near future.

Molecular imaging in thyroid cancer

Molecular imaging plays an important role in the evaluation and management of thyroid cancer. The routine use of thyroid scanning in all thyroid nodules is no longer recommended by many authorities. In the initial work-up of a thyroid nodule, radioiodine imaging can be particularly helpful when the thyroid stimulating hormone level is low and an autonomously functioning nodule is suspected. Radioiodine imaging can also be helpful in the 10–15% of cases for which fine-needle aspiration biopsy is indeterminate. Therapy of confirmed thyroid cancer frequently involves administration of iodine-131 after surgery to ablate remnant tissue. In the follow-up of thyroid cancer patients, increased thyroglobulin levels will often prompt the empiric administration of 131I followed by whole body radioiodine imaging in the search for recurrent or metastatic disease. 131I imaging of the whole body and blood pharmacokinetics can be used to determine if higher doses of 131I can be given in thyroid cancer. The utility of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) is steadily increasing. FDG is primarily taken up by dedifferentiated thyroid cancer cells, which are poorly iodine avid. Thus, it is particularly helpful in the patient with an increased thyroglobulin but negative radioiodine scan. FDG PET is also useful in the patient with a neck mass but unknown primary, in patients with aggressive (dedifferentiated) thyroid cancer, and in patients with differentiated cancer where histologic transformation to dedifferentiation is suspected. In rarer types of thyroid cancer, such as medullary thyroid cancer, FDG and other tracers such as 99mTc sestamibi, [11C]methionine, [111In]octreotide, and [68Ga]somatostatin receptor binding reagents have been utilized. 124I is not widely available, but has been used for PET imaging of thyroid cancer and will likely see broader applicability due to the advantages of PET methodology.

Sunitinib-Induced Thyrotoxicosis Followed by Persistent Hypothyroidism with Shrinkage of Thyroid Volume

Sunitinib, a tyrosine kinase inhibitor, has been approved for the treatment of cancers, such as advanced renal cell carcinoma (RCC). On the other hand, sunitinib treatment is known to induce thyroid dysfunction in a substantial proportion of patients treated for advanced RCC; in fact, hypothyroidism is a frequent complication. However, little is known about sunitinib-induced thyrotoxicosis and destructive thyroiditis. Here, we report a patient with RCC who developed transient overt thyrotoxicosis followed by hypothyroidism due to sunitinib treatment. A 58-year-old woman, who had been treated with chronic thyroiditis, was diagnosed as having left RCC with bone metastasis to the rib. The patient underwent resection of the left kidney and the bone metastasis lesion. However, 3 months later, bone metastasis to the rib recurred, and sunitinib treatment was started. At 6 weeks of sunitinib therapy, the patient developed transient thyrotoxicosis, followed by persistent hypothyroidism. In the thyrotoxic phase, the patient was diagnosed as having destructive thyroiditis based on an increased thyroglobulin level, a low radioactive iodine uptake, increased free thyroxine level, and suppressed thyroid-stimulating hormone level. The thyroid volume in the hypothyroid phase was 68% of that in the thyrotoxic phase. In conclusion, the present report suggests that sunitinib-induced persistent hypothyroidism may be a consequence of preceding destructive thyroiditis with transient thyrotoxicosis. The decreased volume of the thyroid during the hypothyroid phase indicates irreversible organ damage in the present patient, thereby resulting in persistent hypothyroidism. Thus, periodic surveillance of thyroid function is mandatory during sunitinib therapy.

Sunitinib in patients with refractory advanced thyroid cancer: the THYSU phase II trial

6058 Background: There is no standard treatment for advanced thyroid cancer refractory to radioactive iodine (RTC). There are arguments for implication of angiogenesis in TC. Methods: In this phase II study, sunitinib (Su) was given at 50 mg/d for 4 weeks every 6 weeks. Patients (pts) had anaplastic, medullar or differentiated RTC being progressive during the last 6 months. Primary endpoint was objective response and secondary endpoints were safety, overall survival and time to progression. A 20% response rate is expected. A two-stage design was proposed to include 21 (+20) and 11 (+4–7) assessable pts in the non medullar and medullar RTC group during the 1st period, respectively. Results: Seventeen pts were included in 3 months. Eight pts had papillary, 4 medullar, 1 anaplastic and 4 miscellaneous. Median age was 64.3 years old. Median time from primary tumor to inclusion was 7.3 months (range: 2–240). Metastatic sites were lung (15pts), lymph nodes (8pts) and bone (5pts). Three pts had an increased thyroglobulin levels. Median number of Su cycles was 2.1 (range 1–4). Four pts needed a decrease of Su to 37.5mg/d. Toxicities were mainly hypertension, asthenia (7pts each), mucositis (5pts), hand foot syndrome (2pts), and thrombopenia (2pts). Grade 3/4 events were hypertension, asthenia, mucositis and hand foot syndrome. Fifteen pts were evaluable for response: 1 pt had a PR, 12 pts had a stable disease with 1 pt with > 90% decrease of thyroglobulin and 1 pt with a dramatic decrease of symptoms. Conclusion: Sunitinib appeared feasible in pts with RTC and efficacy evaluation has to be confirmed in the entire population of the study. Results from the 1st period will be presented at the ASCO meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Pfizer Bayer, Pfizer Bayer, Pfizer

Is thyroglobulin the stronger indicator for progressive disease than the other conventional factors in same age patient groups with differentiated thyroid cancer?

To determine the thyroglobulin cut-off value as an indicator for progressive disease and to research relationships between sex, histological type, extra-capsular invasion and progressive disease in differentiated thyroid cancer. Four hundred and eight patients were evaluated retrospectively. One hundred and fifty-eight patients (group 1) treated for progressive disease and 166 patients (group 2) that were ablated for thyroid remnant were included in our study. Sex, age, histological type, presence of extra-capsular invasion at the diagnosis and L-thyroxine off thyroglobulin values (6-12 months after the ablation) were obtained. Data were analysed by statistical methods. There was no statistically significant difference for ages (group 1, 45.3+/-16.1 years; group 2, 47+/-12 years, P>0.05). The chi-squared test revealed statistically significant differences for histological type (P>0.05) and extra-capsular invasion (P<0.001) but not for sex (P>0.05). Feasible cut-off level, sensitivity and specificity were found as a 10 ng.ml thyroglobulin value, 79% and 97%, respectively. However, sensitivity and specificity were 80%, 92% for 5 ng.ml and 82% for 2 ng.ml thyroglobulin levels. Multivariate analysis showed that a 10 ng.ml thyroglobulin cut-off value and extra-capsular invasion were independent prognostic factors. Increased thyroglobulin level, extra-capsular invasion and follicular type were poor prognostic factors but sex was not, whereas only extra-capsular invasion and increased thyroglobulin level were independent prognostic indicators for our groups. A 10 ng.ml thyroglobulin level was a feasible cut-off and seemed to be a stronger factor than other indicators to predict progressive disease.

Management of Thyroid Cancer: Radioiodine Ablation, “Stunning,” and Treatment of Thyroglobulin-Positive, 131I Scan-Negative Patients

To present an overview of three controversial issues in the management of thyroid cancerradioiodine ablation, "stunning," and treatment of thyroglobulin-positive, (131)I scan-negative patients. Pertinent studies from the literature and personal experience are reviewed. Radioiodine is commonly administered after thyroidectomy to destroy residual normal thyroid cells, a procedure known as thyroid ablation. Currently, use of radioiodine for ablation has been shown to decrease the risk of recurrence, increase the sensitivity of postablation whole-body scanning with radioiodine, and increase the sensitivity of serum thyroglobulin testing. With use of conventional criteria, administration of 30,000 rad to the thyroid remnant will successfully ablate approximately 95% of remnants that are 2 g or less, but the success rate is lower in patients with larger remnants. The same degree of success can be achieved by administration of 50 mCi of (131)I. The use of larger amounts of radioiodine does not increase the number of patients with successful thyroid ablation. If recurrence is used as the endpoint, no difference has been observed between patients who were given 29 to 50 mCi and those given 50 to 100 mCi for ablation. Stunning occurs when (131)I administered for preablation imaging causes a decrease in uptake of radioiodine subsequently given for ablation. Scanning doses of 2 mCi or less have not been shown to cause stunning, but the risk increases progressively with larger amounts. Therapeutic radioiodine is being given to patients with detectable thyroglobulin but negative (131)I whole-body scans with increasing frequency. Although posttherapy scans show abnormal uptake in most cases, no available evidence indicates that these patients benefit from treatment. Radioiodine ablation after thyroidectomy decreases the risk of recurrent thyroid cancer and facilitates subsequent radioiodine treatment. Stunning can be avoided by use of a maximal scanning dose of 2 mCi. It seems reasonable to treat patients who have progressively increasing thyroglobulin levels but to continue careful observation in those with stable or decreasing thyroglobulin concentrations.

Utility of fluorine-18-fluorodeoxyglucose positron emission tomography in differentiated thyroid carcinoma with negative radioiodine scans and elevated serum thyroglobulin levels

Background: This study aimed to determine the role of fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in the follow-up of patients who underwent total thyroidectomy and iodine-131 ( 131I) ablation therapy for differentiated thyroid cancer and presented increased thyroglobulin levels with negative 131I and thallium-201 ( 201Tl) scans. Methods: Two patients with follicular carcinoma and eight with papillary tumors underwent total thyroidectomy and 131I therapy until the 131I scan was negative. 131I and 201Tl scans were performed with negative results in all cases, while serum thyroglobulin measurements were all positive with negative thyroglobulin autoantibodies. One week after the 131I scans, all the patients underwent FDG-PET whole-body scans. Results: The FDG-PET scan detected in 4 patients, a single focal increase of FDG uptake in one lymph node metastasis (subsequently confirmed histologically); in 1 patient, multiple pathological focal uptakes in brain, neck, and chest; and in 1 patient, two mild focal uptakes in the mediastinum, close to the tracheal branch. In 2 other patients, pathological FDG uptakes in cervical spine and mediastinum were not confirmed by other imaging techniques, and in the 2 remaining patients the scan results were inconclusive. The sensitivity of FDG-PET whole-body scan for detecting metastatic thyroid cancer was 60%. Conclusions: This study indicates that the FDG-PET whole-body scan is a useful tool in the follow-up of patients with differentiated thyroid cancer, negative 131I and 201Tl scans and elevated serum thyroglobulin levels. The FDG-PET scan detects metastatic disease in 60% of patients with differentiated thyroid cancer, enabling surgical therapy to be performed on accessible lesions.

Localized Manifestations of Subacute Thyroiditis Presenting as Solitary Transient Cold Thyroid Nodules

Eleven patients, each with a painful solitary cold nodule of the thyroid were evaluated. All patients had subacute thyroiditis associated with neck pain and tenderness. Despite elevated sedimentation rate and increased thyroglobulin levels, nine of the patients were euthyroid, and I-131 uptake was normal in six. In all patients, thyroid scintigraphy demonstrated a solitary cold nodule that resolved regardless of anti-inflammatory therapy. Granulomatous subacute thyroiditis is characterized by decreased I-131 uptake accompanied by transient hyperthyroidism. The uncommon localized variant of this entity may present with a painful solitary nodule, normal or only moderately decreased I-131 uptake, and should be suspected even in euthyroid patients.

Advances in the management of patients with thyroid disease

Discoveries related to thyroid immunology, especially concerning the thyroid-stimulating hormone (TSH) receptor, may facilitate new immunologic approaches to the therapy of Graves' disease and the thyroiditis syndromes. Advances in genetics are being applied to the thyroid hormone resistance syndromes and papillary and medullary carcinomas. The development of ever more sensitive TSH assays has led to the detection of subclinical thyroid disease, which has special implications for the sick and elderly patients. Sensitive TSH assays also allow more precise titration of levothyroxine (T4) dosages, especially for patients with a past history of thyroid cancer. Evidence continues to accumulate suggesting that postmenopausal women on T4 doses that suppress the TSH level below 0.1 ulU/mL have lower bone mineral density than matched patients with healthy TSH levels. Also, pregnant hypothyroid women need higher T4 doses to normalize the TSH levels. In the evaluation of thyroid nodules, fine-needle aspiration biopsy is the single most definitive modality in selecting the patients for surgery. Scintigraphy provides a complimentary role, especially in defining autonomously functioning thyroid adenomas (AFTA), because these should not be treated with T4 suppression. Ultrasound-guided needle biopsy is occasionally helpful with nodules that are difficult to palpate. Concern for possible tracheal compression after treatment of toxic multinodular goiter with large doses of radioactive iodine (I-131) in the range of 50 to 150 mCi (1.85 to 5.5 GBq) does not seem warranted. Work, primarily out of Italy, suggests AFTA can be ablated with repeat ethanol injections. Residual tissues after thyroidectomy for differentiated carcinoma can be "stunned" by tracer doses of 131I greater than 3.0 mCi (111 MBq), which diminishes the uptake and effectiveness of a subsequent therapy dose. Positron emission tomograph, imaging with thallium-201, and Technetium 99m Sestamibi can identify a small number of patients shown to have metastases from differentiated thyroid carcinoma by increasing thyroglobulin levels in the absence of 131I uptake. Several groups have recently advocated treating such patients empirically with 131I.

Knochenmarkveränderungen bei Patienten mit Schilddrüsenkarzinom

In 62 patients with thyroid carcinoma 79 MRI bone marrow examinations and 48 bone marrow scintigraphies were recorded before or following radioiodine therapy, to study the extent of bone marrow expansion. The results of both methods were the same. In 34/79 investigations normal findings were seen, in 18 the bone marrow expanded to the middle third and in 26 to the distal third of the femur. One patient showed bone marrow expansion to the tibia. These results were compared with the following data: histology of tumor, TNM- staging, time passed since thyroidectomy, accumulated doses of radioiodine therapy, results of131I scintigraphy, hematological changes, thyroglobulin level, age and sex. No significant correlations were found between these and the bone marrow imaging results. Bone marrow changes in patients before radioiodine therapy were similar to those in patients treated with up to 48 GBq 131I. Blind biopsy of the posterior iliac crest in five patients showed slightly pathological reactive changes. In only 2/17 follow-up studies an increase of bone marrow expansion was seen. In 8 patients localized findings indicating malignant infiltration were observed. In 4/8 patients metastases of thyroid carcinoma were known or confirmed by pathological radioiodine uptake and in 2/8 metastatic involvement was assumed because of an increased thyroglobulin level.

Serum thyroglobulin levels: the physiological decrease in infancy and the absence in athyroidism.

The cord serum thyroglobulin levels of 218 neonates are much higher than the levels after the first year of life and show a wide range. A relation exists between a shorter gestational age and increased thyroglobulin levels. The serum thyroglobulin levels decrease within a few months after birth, but throughout the first year of life, these levels are still higher than the normal values at later ages (5-35 ng/ml). IN 3 athyroid children, thyroglobulin is undetectable in serum.