Silent thyroiditis following vaccination against COVID-19: report of two cases.

PURPOSE: It is well established that thyroiditis and other thyroid disorders can be induced by COVID-19 infection, but there is limited information about the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We report two cases of thyrotoxicosis following SARS-CoV-2 vaccine. METHODS AND RESULTS: Two young health care peoples (wife and husband) received a first dose of SARS-CoV-2 vaccine, and few weeks later developed clinical manifestations of thyroid hyperactivity, with increased thyroid hormone levels on thyroid function tests, suppressed thyroid-stimulating hormone and negative antithyroid antibodies, despite being healthy before vaccination. They were diagnosed at the 4th week after first dose of SARS-Cov-2 vaccine as silent thyroiditis and followed without treatment, since their symptoms were not severe. At the 6th week, the patients became wholly asymptomatic and their thyroid function returned to normal. CONCLUSIONS: Thyrotoxicosis can occur after SARS-CoV-2 vaccination probably related to silent thyroiditis.

Pregnancy-associated plasma protein A mRNA expression as a marker for differentiated thyroid cancer: results from a "surgical" and a "cytological" series.

PURPOSE: Pregnancy-associated plasma protein A (PAPPA) is a metalloproteinase initially described for its role during pregnancy. PAPPA regulates IGF ligands 1 (IGF1) bioavailability through the degradation of IGF-binding protein 4 (IGFBP4). After the cleavage of IGFBP4, free IGF1 is able to bind IGF1 receptors (IGF1R) triggering the downstream signaling. Recently, PAPPA expression has been linked with development of several cancers. No data have been published on thyroid cancer, yet. METHODS: We evaluated PAPPA, insulin-like growth factor (IGF1), IGF1 receptors (IGF1R) and IGF-binding protein 4 (IGFBP4) mRNA expression levels in a "Surgical series" of 94 thyroid nodules (64 cancers, 16 follicular adenomas and 14 hyperplastic nodules) and in a "Cytological series" of 80 nodules from 74 patients underwent to fine-needle aspiration cytology (FNAC). In tissues, PAPPA was also evaluated by western blot. RESULTS: We found that PAPPA expression was increased in thyroid cancer specimen at mRNA and protein levels and that, adenomas and hyperplastic nodules had an expression similar to normal tissues. When applied on thyroid cytologies, PAPPA expression was able to discriminate benign from malignant nodules contributing to pre-surgical classification of the nodules. We calculated a cut-off with a good specificity (91%) which reached 100% when combined with molecular biology. CONCLUSION: These results show that PAPPA could represent a promising diagnostic marker for differentiated thyroid cancer.

Indication for radioiodine remnant ablation in differentiated thyroid cancer patients: does 2018 Italian consensus change anything?

PURPOSE: We speculated that radioiodine remnant ablation (RRA) could be performed less frequently in differentiated thyroid cancer (DTC) patients, if the recommendations of the 2018 Italian Consensus (ITA) were applied in clinical practice. Therefore, we compared the ITA indications for RRA with the recommendations by the 2015 American Thyroid Association guidelines (ATA). METHODS: We retrospectively evaluated 380 consecutive DTC patients treated with surgery and RRA, followed at the Section of Endocrinology, University of Siena, Italy from January 2006 to December 2019. RESULTS: Using ITA a significant increase of DTC patients classified as low or high risk and a significant decrease of patients defined at intermediate risk were observed (p < 0.0001). Consequently, the percentage of patients without routinary indication for RRA (47.4%, versus 38.2%, p < 0.0001) and those with a definite indication for RRA (8.2 versus 1.8%, p < 0.0001) was significantly higher compared to ATA. Moreover, using ITA the percentage of patients with a selective use of RRA was lower in comparison to ATA (44.7% versus 60%, p < 0.0001). Nevertheless, the prevalence of distant metastases, at post-ablative whole body scan, in patients without indication for RRA, was not different using either ATA or ITA (2.1% and 1.1% respectively, p = 0.37). CONCLUSION: The use of ITA Consensus, in clinical practice, increases significantly the number of patients for whom RRA is not routinely indicated in comparison to ATA guidelines but without differences in delaying the diagnosis of distant metastatic disease.

Familial non-medullary thyroid cancer: a critical review.

BACKGROUND: Familial non-medullary thyroid carcinoma (FNMTC), mainly of papillary histotype (FPTC), is defined by the presence of the disease in two or more first-degree relatives in the absence of other known familial syndromes. With the increasing incidence of PTC in the recent years, the familial form of the disease has also become more common than previously reported and constitutes nearly 10% of all thyroid cancers. Many aspects of FNMTC are debated, concerning both clinical and genetic aspects. Several studies reported that, in comparison with sporadic PTCs, FPTCs are more aggressive at disease presentation, while other authors reported no differences in the clinical behavior of sporadic and familial PTCs. For this reason, recent guidelines do not recommend screening of family members of patients with diagnosis of differentiated thyroid cancer (DTC). FNMTC is described as a polygenic disorder associated with multiple low- to moderate-penetrance susceptibility genes and incomplete penetrance. At the moment, the genetic factors contributing to the development of FNMTC remain poorly understood, though many putative genes have been proposed in the recent years. PURPOSE: Based on current literature and our experience with FNMTC, in this review, we critically discussed the most relevant controversies, including its definition, the genetic background and some clinical aspects as screening and treatment.

Should familial disease be considered as a negative prognostic factor in micropapillary thyroid carcinoma?

PURPOSE: An increased aggressiveness of familial papillary thyroid carcinoma (FPTC) compared with sporadic form has been reported. On the contrary, the biological behavior of familial microPTC (FmPTC) is still debated. To assess if familial diseases should be considered as a negative prognostic factor in mPTC, the clinical presentation and outcome of FmPTC and sporadic mPTC (SmPTC) were compared. METHODS: We retrospectively analyzed 291 mPTC (SmPTC n = 248, FmPTC n = 43) patients followed for a median follow-up of 8.3 years. FmPTC was defined as the presence of PTC in two or more first-degree relatives, after excluding hereditary syndromes associated with PTC. RESULTS: FmPTC patients had more frequently bilateral tumor (32.6% versus 16.5%, p = 0.01) and lymph node metastases at diagnosis (30.2% versus 14.9%, p = 0.02). At the first follow-up, FmPTC patients had a higher rate of structural disease and a lower rate of remission compared to SmPTC (p = 0.01). Also in a multivariate model, using a "CHAID tree-building algorithm", familial disease correlated with a worse clinical presentation and outcome of mPTC patients. Familial disease was associated with a higher rate of intermediate risk patients in non incidental mPTC and with a higher rate of structural incomplete response in mPTC without lymph node metastases (p = 0.01). CONCLUSIONS: Like in macroPTC, the familial form of the diseases has been shown to be a negative prognostic factor also in mPTC, therefore, it should be highly regarded in the management of mPTC patients.

Small papillary thyroid carcinoma with minimal extrathyroidal extension should be managed as ATA low-risk tumor.

PURPOSE: According to American Thyroid Association (ATA) guideline, papillary thyroid cancer (PTC) with minimal extrathyroidal extension (mETE) is classified at "intermediate risk" of persistent/recurrent disease. However, the impact of mETE per se on patients' outcome is not fully understood. The aim of our study was to evaluate the prognostic significance of mETE in patients with PTC not submitted to therapeutic or prophylactic lymph node dissection, according to tumor size and other prognostic factors. PATIENTS AND METHODS: We retrospectively evaluated a total of 514 PTC patients: 127 (24.7%) had mETE (pT3Nx) and 387 (75.3%) had negative margins (pT1-2Nx). At a median follow-up of 9.1 years, patients were divided in two groups: patients with "good outcome" (no evidence of disease) and patients with "poor outcome" (persistent structural disease or recurrent disease or tumor-related death). RESULTS: The rate of patients with "poor outcome" was significantly higher in patients with mETE compared with patients with negative margins (11.8 versus 5.1%; OR 2.4576, 95% CI 1.2178-4.9594, p = 0.01). However, mETE was significantly associated with poor outcome only in patients with tumors larger than 1.5 cm. CONCLUSIONS: mETE is an unfavorable prognostic factor in tumors larger than 1.5 cm, suggesting that, in the absence of other unfavorable characteristics, smaller tumors with mETE should be classified and managed as "low risk" tumors.

Rare diseases in clinical endocrinology: a taxonomic classification system.

PURPOSE: Rare endocrine-metabolic diseases (REMD) represent an important area in the field of medicine and pharmacology. The rare diseases of interest to endocrinologists involve all fields of endocrinology, including rare diseases of the pituitary, thyroid and adrenal glands, paraganglia, ovary and testis, disorders of bone and mineral metabolism, energy and lipid metabolism, water metabolism, and syndromes with possible involvement of multiple endocrine glands, and neuroendocrine tumors. Taking advantage of the constitution of a study group on REMD within the Italian Society of Endocrinology, consisting of basic and clinical scientists, a document on the taxonomy of REMD has been produced. METHODS AND RESULTS: This document has been designed to include mainly REMD manifesting or persisting into adulthood. The taxonomy of REMD of the adult comprises a total of 166 main disorders, 338 including all variants and subtypes, described into 11 tables. CONCLUSIONS: This report provides a complete taxonomy to classify REMD of the adult. In the future, the creation of registries of rare endocrine diseases to collect data on cohorts of patients and the development of common and standardized diagnostic and therapeutic pathways for each rare endocrine disease is advisable. This will help planning and performing intervention studies in larger groups of patients to prove the efficacy, effectiveness, and safety of a specific treatment.

Familial non-medullary thyroid carcinoma displays the features of clinical anticipation suggestive of a distinct biological entity.

Non-medullary thyroid carcinoma (NMTC) is mostly sporadic, but familial clustering is described. We aimed to compare the features of patients with sporadic and familial NMTC (FNMTC) patients and to assess whether FNMTC patients with parent-child relationship exhibit the 'anticipation' phenomenon (earlier age at disease onset and increased severity in successive generations). Among 300 NMTCs followed in the Section of Endocrinology (University of Siena, Italy), 34 (11.3%) patients, all with the papillary histotype, (16 kindred), met the criteria of FNMTC. Twenty-seven of them (79.4%) exhibited a parent-child relationship and seven (20.6%) a sibling relationship. These patients were compared with 235 patients with sporadic papillary thyroid cancer (PTCs). To analyze the features of FNMTC of the first and second generations, we cumulated the series of Siena with 32 additional FNMTC patients (15 kindred) from the Department of Endocrinology-Endocrine Oncology, Thessaloniki, Greece. Significant difference between sporadic PTC and FNMTC patients included more frequent tumor multifocality (P=0.001) and worse final outcome in FNMTC patients (P=0.001). Among 47 FNMTC with parent-child relationship, we found an earlier age at disease presentation (P<0.0001), diagnosis (P<0.0001), and disease onset (P=0.04) in the second generation when compared with the first generation. Patients in the second generation were more frequently males (P=0.02); their tumors were more frequently multifocal (P=0.003) and bilateral (P=0.01), had higher rate of lymph node metastases at surgery (P=0.02) and worse outcome (P=0.04) when compared with the first generation. In conclusion, FNMTC displays the features of clinical 'anticipation' with the second generation acquiring the disease at an earlier age and having more advanced disease at presentation.

Limited value of repeat recombinant human thyrotropin (rhTSH)-stimulated thyroglobulin testing in differentiated thyroid carcinoma patients with previous negative rhTSH-stimulated thyroglobulin and undetectable basal serum thyroglobulin levels.

CONTEXT: One year after initial treatment, low-risk differentiated thyroid cancer (DTC) patients undergo recombinant human (rh)TSH-stimulated serum thyroglobulin (Tg) (rhTSH-Tg) and neck ultrasound (US). OBJECTIVE: The need for more rhTSH-Tg in these patients is controversial. We evaluated the utility of a second rhTSH-Tg in DTC patients 2-3 yr after their first evaluation. RESULTS: At the first rhTSH-Tg, basal and stimulated serum Tg was undetectable in 68 of 85 patients. Neck US was unremarkable in all but one, who had evidence of lymph node disease. Seventeen of 85 patients had undetectable serum Tg that became positive after rhTSH, with negative imaging in 10 and evidence of disease in seven. Patients with no evidence of disease were reevaluated 2-3 yr later (second rhTSH-Tg). In patients in which the first stimulated Tg was undetectable, all had undetectable basal serum Tg, which remained undetectable after rhTSH in 66 of 67 patients (98.5%) and became detectable in one (1.5%) (positive neck US). In the 10 patients with detectable stimulated Tg in the first test, basal serum Tg and US were negative at the second test, but rhTSH-Tg became detectable in six. Compared with the first rhTSH-Tg, the second stimulated Tg in these six patients decreased in one, increased in three, and stabilized in two patients. CONCLUSIONS: The second rhTSH-Tg was informative in patients who had first stimulated Tg detectable but not in those who had undetectable Tg at the first test, in which the only patient with recurrence was diagnosed by neck US. Thus, rhTSH-Tg should be repeated only in patients who have had a positive first rhTSH-Tg and negative imaging.

Increasing incidence of thyroid cancer in Basilicata: an Italian study.

OBJECTIVE: In recent years many authors have reported an increase in thyroid cancer (TC) incidence in several countries. The cause of such phenomenon remains unclear. DESIGN: This study was designed to estimate the incidence of TC in Basilicata, the smallest region of Southern Italy with a population of 596,546 people, between 2001 and 2004. MAIN OUTCOME: A total of 302 cases of TC were identified. The annual incidence of TC changed over the years, from 10.0 per 100,000 people in 2001 to 15.7 per 100,000 people in 2004. The number of new TC cases per 100,000 people increased an average of 16% per yr. Median age at diagnosis was 49 yr. The most frequent histotype was papillary TC (PTC) (73.2%). In 20 (6.6%) patients with PTC, we identified at least one first-degree relative affected by differentiated TC. CONCLUSIONS: The present study shows a high incidence of sporadic and familial non-medullary TC in Basilicata. The reason for this finding may be related to several factors discussed in the paper. Further studies evaluating the trends in the incidence of TC in Basilicata in the future could provide some answers for the potential pathogenetic hypothesis.

Diagnostic 131-iodine whole-body scan may be avoided in thyroid cancer patients who have undetectable stimulated serum Tg levels after initial treatment.

The follow-up of differentiated thyroid cancer after total thyroidectomy and thyroid ablation is commonly based on serum Tg determination and 131-iodine ((131)I) diagnostic whole-body scan (WBS) performed in the hypothyroid state, 6-12 months after thyroid ablation. Based on the greater sensitivity of Tg measurement, with respect to WBS, the diagnostic yield of diagnostic WBS has been questioned in patients who are off L-T(4) therapy and have undetectable Tg levels. The aim of the present retrospective study was to evaluate the diagnostic relevance of (131)I WBS performed after thyroid remnant ablation, in patients with undetectable serum Tg and off thyroid hormone therapy. The study included 315 of 662 consecutive patients (47.6%) treated in our department between 1980 and 1990, who, at the first control WBS after thyroid ablation, had undetectable serum Tg levels in the hypothyroid state. There were 54 men (17%) and 261 women (83%), with a mean age of 40.9 +/- 13.1 yr (range, 12-76), followed for a mean of 12 +/- 2.8 (range, 9-19) yr. The control WBS was negative in 225 (71.4%) patients and positive for persistent areas of thyroid bed uptake, frequently of very low significance, in 90 (28.6%). No local or distant metastases were discovered. At the last follow-up visit (1999-2000), 281 (89.2%) patients showed complete remission, with undetectable serum Tg off L-T(4) and negative WBS. Persistent thyroid bed uptake, with undetectable levels of Tg, was observed in 29 patients (9.2%) studied during L-T(4) withdrawal. Only 2 patients (0.6%) experienced local recurrence (lymph-node metastases) during their follow-up. In conclusion, our data suggest that the presence of undetectable levels of serum Tg off L-T(4) at the time of the first control WBS after initial treatment, is highly predictive of complete and persistent remission. With the exception of detecting persistent thyroid bed uptake in a minority of cases, the control WBS has never given information that could influence the following therapeutic strategy. On this basis, we propose that the diagnostic (131)I WBS may be avoided in patients with undetectable levels of Tg off L-T(4). These patients may be monitored with clinical examination, neck ultrasound, and serum Tg measurements on L-T(4).

Prediction of disease status by recombinant human TSH-stimulated serum Tg in the postsurgical follow-up of differentiated thyroid carcinoma.

Stimulation with recombinant human TSH (rhTSH) has been introduced in clinical practice as an effective alternative to thyroid hormone withdrawal for the diagnostic follow-up (Tg measurement and 131-iodine whole-body scan) of patients with differentiated thyroid cancer. The present study was specifically aimed to evaluate the utility of rhTSH-stimulated serum Tg measurements in patients with undetectable serum Tg values, on L-T(4) therapy, as the only test to differentiate patients with persistent disease from patients who are disease-free. We studied 72 consecutive patients with differentiated thyroid cancer, previously treated with near-total thyroidectomy and 131-I thyroid ablation. Admission criteria were: an undetectable (<1 ng/ml) serum Tg, on L-T(4) therapy, and negative anti-Tg antibodies. The study design consisted of a Tg-stimulation test after rhTSH, during L-T(4), followed by diagnostic WBS and serum Tg measurement off L-T(4). After rhTSH, serum Tg remained undetectable in 41 of 72 patients (56.9%). A negative rhTSH Tg test agreed with an undetectable hypo-Tg in 36 of 41 cases (87.8%), all without evidence of metastatic disease at hypo-WBS. In 5 of 41 cases (12.2%), hypo-Tg was detectable (1.1-7.8 ng/ml), in association with negative hypo-WBS or faint uptake in the thyroid bed. Serum Tg converted from undetectable to detectable after rhTSH in 31 of 72 patients (43.1%), with a peak Tg ranging between 1.2 and 23.0 ng/ml. Hypo-Tg was always detectable in these patients (100% concordance), and it was significantly higher than rhTSH-stimulated Tg (P < 0.0002). Hypo-WBS was positive in 23 of 31 patients (74.2%), showing thyroid residues in 12, cervical lymph nodes in 7, and lung metastases in 4 cases. In 8 of 31 cases, hypo-WBS was negative, despite detectable serum Tg. Thus, rhTSH-stimulated Tg was able to detect all cases of documented local or distant metastases. In conclusion, our data indicate that, in patients with undetectable basal levels of serum Tg, rhTSH-stimulated Tg represents an informative test to distinguish disease-free patients (not requiring WBS) from diseased patients (requiring further diagnostic and/or therapeutic procedures).

RET protein expression has no prognostic impact on the long-term outcome of papillary thyroid carcinoma.

BACKGROUND: RET proto-oncogene rearrangements (RET/PTC) are causative events in the pathogenesis of a subset of papillary thyroid cancer (PTC). The prevalence of RET/PTC varies in different countries and according to specific clinical features: it is higher after radiation exposure and it is claimed to be higher in young patients. Conflicting results are reported regarding the prognostic role of RET/PTC activation. OBJECTIVE: To investigate the prognostic meaning of RET/PTC rearrangement on the long term outcome of PTC. METHODS: We have studied the expression of the RET encoded protein in 127 papillary thyroid carcinomas by immunohistochemistry using a polyclonal antibody against the tyrosine-kinase domain of the RET protein. These cases have been collected during 1970-1985, and have a mean (+/-S.D.) period of follow-up of 18.6+/-3.7 years (range 12-27 years). The results have been compared with the patients' outcome. RESULTS: The tyrosine-kinase domain of RET was expressed in 82 (64.6%) papillary carcinomas. Among them, RET was highly expressed in 65 (51.2%) cases and moderately expressed in 17 (13.4%). RET expression was absent in 45 (35.4%) cases. No correlation was found between RET expression and other parameters such as sex, age at diagnosis, tumor class and histological variant. Follow-up analysis showed no influence of RET expression on patients' outcome. By multivariate analysis, age (>45 years) and tumor class IV, but not sex and RET expression were adverse prognostic indicators of death. CONCLUSION: In conclusion, our analysis indicates that RET expression is frequently found in PTC, and has no influence on tumor outcome.

Contralateral papillary thyroid cancer is frequent at completion thyroidectomy with no difference in low- and high-risk patients.

Total (or near-total) thyroidectomy (TT) is considered by many as the most adequate treatment for papillary thyroid carcinoma (PTC). In patients who have undergone lobectomy, the necessity of performing a completion thyroidectomy (CT) is still discussed. The aim of this retrospective study was to evaluate tumor bilaterality in patients initially treated with partial thyroidectomy for PTC and who then underwent CT. We studied 182 patients treated with CT after lobectomy and/or isthmectomy for PTC diagnosed from 1969-1998. Mean age at diagnosis was 40+/-14.5 years and mean interval between partial thyroidectomy and CT was 19.8+/-56.8 months. At CT, 80 of 182 patients (44%) had one or more foci of tumor in the remaining thyroid lobe, always of the same papillary histotype, associated with ipsilateral lymph node metastases in 22 cases. In addition, 10 patients with no tumoral foci in the thyroid specimen had evidence of lymph node metastases. The rate of bilateral tumor was not different when patients were analyzed according to the classification of "low-" or "high-risk." Among several clinical features, the presence of lymph node metastases at the first surgical treatment and time interval between first treatment and CT were correlated with higher frequency of bilaterality (p = 0.033 and p = 0.044, respectively). The postsurgical 131I whole-body scan revealed the presence of persistent lymph node metastases or diffuse micronodular lung metastases in 7 and 6 patients, respectively. In conclusion, PTC was frequently bilateral in our series and this bilaterality was independent from the "low-" or "high-risk" classification. On these bases, we believe that PTC should be treated with TT when diagnosed before surgery and submitted to CT, if partial surgery was the initial intervention.

Outcome of differentiated thyroid cancer with detectable serum Tg and negative diagnostic (131)I whole body scan: comparison of patients treated with high (131)I activities versus untreated patients.

Detectable serum Tg levels associated with negative diagnostic (131)I whole body scan are not infrequently found in patients with differentiated thyroid cancer. Several researchers have shown that in these patients the administration of high (131)I activity (100 mCi or more) increases the sensitivity of a posttherapy diagnostic (131)I whole body scan performed a few days later and allows the detection of neoplastic foci not seen with diagnostic doses of (131)I. Empirical radioiodine treatment has also been advocated by some researchers, but its therapeutic effect is controversial. In our institute, positive serum Tg/negative diagnostic (131)I whole body scan patients were not treated with high (131)I activities before 1984; afterward, almost all patients with positive serum Tg/negative diagnostic (131)I whole body scan patients were treated with radioiodine, and a posttherapy diagnostic (131)I whole body scan was performed. In the present retrospective study we compared the outcome of these two groups of patients, 42 treated and 28 untreated, followed for mean periods of 6.7 +/- 3.8 and 11.9 +/- 4.4 yr, respectively. In the treated group the first posttherapy diagnostic (131)I whole body scan was negative in 12 patients and positive in 30 patients. (131)I treatment was further administered only in the latter group. At the end of follow-up in treated patients a complete remission (normalization of serum Tg off L-thyroxine and negative diagnostic (131)I whole body scan) was observed in 10 patients (33.3%). In 9 cases (30%) posttherapy diagnostic (131)I whole body scan became negative, and serum Tg was reduced but still detectable; in 11 patients (36.6%) serum Tg was detectable, and posttherapy diagnostic (131)I whole body scan was positive. The resolution of (131)I uptake in lung metastases was observed in 8 of 9 cases (88.8%) and in cervical node metastases in 11 of 18 cases (61.1%). In patients treated only once because the posttherapy diagnostic (131)I whole body scan was negative (n = 12), 2 patients (16.7%) were in apparent remission, 7 (58.3%) had detectable Tg values without evidence of disease, 2 (16.7%) showed lymph node metastases in the mediastinum, and 1 patient (8.3%) died because of lung metastases. Of the 28 untreated patients, none with radiological evidence of disease, serum Tg off L-thyroxine therapy became undetectable in 19 cases (67.9%), significantly reduced in 6 cases (21.4%), and unchanged or increased in 3 patients (10.7%), 1 of whom developed lung metastases 14 yr after the diagnosis. In summary, our results indicate that in patients with detectable serum Tg and negative diagnostic (131)I whole body scan, treatment with high doses of (131)I may have therapeutic utility in patients with lung metastases and, to a lesser extent, in those with lymph node metastases. However, in view of the frequent normalization of Tg values in untreated patients, we believe that treatment with (131)I should be considered according to the result of the first posttherapy scan. If positive in the lung, (131)I treatment should be continued up to total remission; surgical treatment should be preferred in patients with node metastases, and no treatment should be used in those with thyroid bed uptake or no uptake.

Radioiodine treatment of metastatic differentiated thyroid cancer in patients on L-thyroxine, using recombinant human TSH.

OBJECTIVE: This study tested the hypothesis that administration of human recombinant thyroid-stimulating hormone (rhTSH: Thyrogen, thyrotropin alpha) could promote iodine-131 ((131)I) uptake in the therapy for metastatic or locally invasive differentiated thyroid cancer (DTC), obviating L-thyroxine suppressive therapy (L-T4) withdrawal and hypothyroidism in patients with advanced disease. METHODS: Twelve totally (or almost completely) thyroidectomized adults, nine of whom had received earlier therapy after L-T4 withdrawal, underwent (131)I treatment while euthyroid on L-T4, after rhTSH administration. Nine underwent diagnostic whole-body scanning (WBS) after two consecutive daily i.m. injections (0.9 mg) of rhTSH. They then received an identical second course of rhTSH to promote therapeutic (131)I uptake. Post-therapy WBS was performed one week later. Three patients received only rhTSH (131)I therapy. RESULTS: Administration of rhTSH promoted (131)I uptake in all patients, as demonstrated by post-therapy WBS. Administration of rhTSH also promoted a significant increase in serum thyroglobulin (Tg) concentrations. According to the most recent measurements, 3-12 months after therapy, serum Tg levels fell in four, and stabilized in two out of eleven patients. Upon additional rhTSH-WBS 8 months post-study, a reduction in one metastatic site was noted in one patient. The rhTSH was well tolerated, with mild, transient fever and/or nausea occurring in only a minority of patients. Individuals with bone metastases experienced degrees of peritumoral pain and swelling that were similar (though more short-lived) to those seen in the same or other patients after L-T4 withdrawal. CONCLUSIONS: Administration of rhTSH is a safe, successful tool for inducing (131)I uptake in local and metastatic DTC lesions, and avoids L-T4 withdrawal, preserving metabolic homeostasis and preventing the debilitating effects of hypothyroidism.

Use of surgical gamma probe for the detection of lymph node metastases in differentiated thyroid cancer.

BACKGROUND: Patients with differentiated thyroid cancer (DTC) after total or near-total thyroidectomy require 131I therapy. After surgery the persistence of lymph node metastases in our series of patients was frequent (30%). Such patients are preferentially treated with radioiodine and shifted to surgical reintervention when the nodal lesions persist after two 131I treatments. AIM: Use of an intraoperative radioactive probe (C-TraK) to allow a more radical surgical approach in thyroid cancer patients submitted to surgery for lymph node metastases. METHODS AND RESULTS: After adequate withdrawal of L-thyroxine suppressive therapy six patients were given high 131I doses followed by post-therapy WBS which demonstrated cervical activity in 5 patients and peri-jugular activity in 1. Surgery with the help of a gamma probe allowed to detect and remove all metastatic nodes. After excision all surgical specimens showed higher radioactive counts with respect to the background. The post-surgical scan showed the disappearance of all areas of 131I uptake. Histology confirmed the presence of metastatic lesions from papillary thyroid cancer. CONCLUSIONS: We conclude that the use of a gamma probe can be successful in patients with metastatic neck lesions resistant to 131I treatment, particularly in patients with nonpalpable lesions.