Acknowledging gray areas: 2015 vs. 2009 American Thyroid Association differentiated thyroid cancer guidelines on ablating putatively low-intermediate-risk patients.

PURPOSE: Typically formulated by investigators from "world centres of excellence," differentiated thyroid carcinoma (DTC) management guidelines may have more limited applicability in settings of less expert care and fewer resources. Arguably the world's leading DTC guidelines are those of the American Thyroid Association, revised in 2009 ("ATA 2009") and 2015 ("ATA 2015"). To further explore the issue of "real-world applicability" of DTC guidelines, we retrospectively compared indications for ablation using ATA 2015 versus ATA 2009 in a two-centre cohort of ablated T1-2, M0 DTC patients (N = 336). Based on TNM status and histology, these patients were low-intermediate risk, but many ultimately had other characteristics suggesting elevated or uncertain risk. METHODS: Working by consensus, two experienced nuclear medicine physicians considered patient and treatment characteristics to classify each case as having "no indication," a "possible indication," or a "clear indication" for ablation according to ATA 2009 or ATA 2015. The physicians also identified reasons for classification changes between ATA 2015 versus ATA 2009. Classification was unblinded, but the physicians had cared for only 138/336 patients, and the charts encompassed September 2010-October 2013, several years before the classification was performed. RESULTS: One hundred of 336 patients (29.8 %) changed classification regarding indication for ablation using ATA 2015 versus ATA 2009. Most reclassified patients (70/100) moved from "no indication" or "clear indication" to "possible indication." Reflecting this phenomenon, "possible indication" became the largest category according to the ATA 2015 classification (141/336, 42.0 %, versus 96/336, 28.6 %, according to ATA 2009). Many reclassifications were attributable to multiple clinicopathological characteristics, most commonly, stimulated thyroglobulin or anti-thyroglobulin antibody levels, multifocality, bilateral involvement, or capsular/nodal invasion. CONCLUSIONS: Regarding indications for ablation, ATA 2015 appears to better "acknowledge grey areas," i.e., patients with ambiguous or unavailable data requiring individualised, nuanced decision-making, than does ATA 2009.

Difficulties in deciding whether to ablate patients with putatively "low-intermediate-risk" differentiated thyroid carcinoma: do guidelines mainly apply in the centres that produce them? Results of a retrospective, two-centre quality assurance study.

PURPOSE: We determined the reasons for radioiodine thyroid remnant ablation, and the procedure's necessity based on postsurgical remnant size, in patients with putatively "low-intermediate-risk" differentiated thyroid carcinoma (DTC). We identified key clinicopathological, treatment and remnant characteristics, and factors associated with remnant size in 336 patients with pT1/2, M0 DTC ablated during the period September 2010 to October 2013 at one Cypriot or one Greek referral centre. METHODS: Clinicopathological/treatment characteristics were compiled from charts. Experienced nuclear medicine physicians rated the numbers/intensities of uptake foci in the thyroid bed on postablation planar scintigrams using scales of 0-4 points and 0-3 points, respectively. The product of these scores was taken as the "remnant score" that ranged from 0 (no remnant) to 12 (multiple remnants, intense uptake). RESULTS: DTC was predominantly papillary. The median [25th-75th percentile] longest primary tumour diameter was 1.0 cm [0.7-1.5 cm]. Despite favourable histotypes and primary tumour classifications, patients often had preablation characteristics suggesting elevated or uncertain risk: 31.0% of patients (104 of 336) had primary tumour multifocality, 22.0% (74) had confirmed cervical lymph node metastases, 37.2% (125) had unknown nodal status, and 38.1% (128) had antithyroglobulin antibody seropositivity. The median [25th-75th percentile] remnant score was 4 [2-6]; 39.9% of patients (134 of 336) had scores ≥6. For the entire cohort, T or N stages (r ≤ 0.174, P ≤ 0.05) correlated positively with the remnant score in a univariate Spearman analysis. The numbers of patients referred by the surgeon, cervical lymph nodes excised and metastatic nodes excised correlated negatively (r ≤ 0.243, P ≤ 0.038) with the remnant score, and the first two factors independently predicted the remnant score (P ≤ 0.037) in a multivariate analysis. CONCLUSION: Patients with putatively "low-intermediate-risk" DTC frequently had disease characteristics denoting high or uncertain risk, suggesting that "selective" radioiodine ablation in such patients may seldom be applicable outside international centres of excellence. Proxies for surgeon experience and surgical completeness correlated with remnant number/uptake intensity and may aid ablation-related decision-making.

TSH ≥30 mU/L may not be necessary for successful 131I remnant ablation in patients with differentiated thyroid cancer.

Purpose: To determine whether thyroid-stimulating hormone level ≥ 30 mU/L is necessary for radioiodine (131I) remnant ablation (RRA) in patients with differentiated thyroid cancer (DTC), as well as its influencing factors and predictors. Methods: A total of 487 DTC patients were retrospectively enrolled in this study. They were divided into two groups (TSH < 30 and ≥ 30 mU/L) and further divided into eight subgroups (0-<30, 30-<40, 40-<50, 50-<60, 60-<70, 70-<80, 80-<90, and 90-<100 mU/L). The simultaneous serum lipid level, successful rate of RRA and its influencing factors in different groups were analyzed. The receiver operating characteristic curves derived from pre-ablative thyroglobulin (pre-Tg) and pre-Tg/TSH ratio were compared for RRA success prediction performance. Results: There was no statistical difference in success rates of RRA between the two groups (P = 0.247) and eight subgroups (P = 0.685). Levels of total cholesterol (P < 0.001), triglyceride (P = 0.006), high-density lipoprotein cholesterol (P = 0.024), low-density lipoprotein cholesterol (P = 0.001), apolipoprotein B (P < 0.001), and apolipoprotein E (P = 0.002) were significantly higher while apoA/apoB ratio (P = 0.024) was significantly lower at TSH ≥ 30 mU/L group. Pre-Tg level, gender, and N stage were influencing factors for RRA. The area under the curve of pre-Tg level and pre-Tg/TSH ratio was 0.7611 (P < 0.0001) and 0.7340 (P < 0.0001) for all enrolled patients and 0.7310 (P = 0.0145) and 0.6524 (P = 0.1068) for TSH < 30 mU/L, respectively. Conclusion: TSH ≥ 30 mU/L may not be necessary for the success of RRA. Patients with higher serum TSH levels prior to RRA will suffer from severer hyperlipidemia. Pre-Tg level could be used as a predictor for the success of RRA, especially when TSH < 30 mU/L.

Radioiodine in Differentiated Thyroid Carcinoma: Do We Need Diagnostic Pre-Ablation Iodine-123 Scintigraphy to Optimize Treatment?

Changing insights regarding radioiodine (I-131) administration in differentiated thyroid carcinoma (DTC) stir up discussions on the utility of pre-ablation diagnostic scintigraphy (DxWBS). Our retrospective study qualitatively and semi-quantitatively assessed posttherapy I-131 whole-body scintigraphy (TxWBS) data for thyroid remnant size and metastasis. Findings were associated with initial treatment success after nine months, as well as clinical, histopathological, and surgical parameters. Possible management changes were addressed. A thyroid remnant was reported in 89 of 97 (92%) patients, suspicion of lymph node metastasis in 26 (27%) and distant metastasis in 6 (6%). Surgery with oncological intent and surgery by two dedicated thyroid surgeons were independently associated with a smaller remnant. Surgery at a community hospital, aggressive tumor histopathology, histopathological lymph node metastasis (pN1) and suspicion of new lymph node metastasis on TxWBS were independently associated with an unsuccessful treatment. Thyroid remnant size was unrelated to treatment success. All 13 pN1 patients with suspected in situ lymph node metastases on TxWBS had an unsuccessful treatment, opposite 19/31 (61%) pN1 patients without (p = 0.009). Pre-ablative knowledge of these TxWBS findings had likely influenced management in 48 (50%) patients. Additional pre-ablative diagnostics could optimize patient-tailored I-131 administration. DxWBS should be considered, especially in patients with pN1 stage or suspected in situ lymph node metastasis. Dependent on local surgical expertise, DxWBS is not recommended to evaluate thyroid remnant size.

Cervical thyroid remnant consistent with papillary carcinoma as an incidental finding in a patient with benign total thyroidectomy ten years prior.

BACKGROUND: Differential diagnosis of a cervical lesion corresponding with papillary thyroid carcinoma (PTC) after benign total thyroidectomy can be a real challenge. METHODS: A cervical thyroid remnant compatible with papillary carcinoma was incidentally found ten years after total thyroidectomy for a non-functional multinodular goitre. Histological analysis of fine needle puncture aspiration (FNPA) was highly suggestive for PTC. Surgical excision of the cervical lesion was performed. Specimen study demonstrated a classic variant of PTC contacting a peripheral margin, applying ablative treatment with radioactive iodine postoperatively. RESULTS: The patient did not present signs of recurrence during follow-up. Small thyroid remnants after benign thyroidectomy are often left behind, although their risk of malignancy is exceptional. CONCLUSIONS: It is important to individualize therapeutic approach when facing this rare entity. We decided to treat the patient by removing the lesion followed by ablation therapy with successful results. PTC: Papillary thyroid carcinoma FNPA: Fine needle puncture aspiration.

Less than 2% of the Low- and Intermediate-Risk Differentiated Thyroid Cancers Show Distant Metastases at Post-Ablation Whole-Body Scan.

BACKGROUND: Recently, there has been a trend to reduce the use of radioiodine remnant ablation (RRA) in patients with low-risk (LR) and intermediate-risk (IR) differentiated thyroid cancer (DTC). OBJECTIVES: The aim of this paper was to evaluate the diagnostic role of whole-body scan (ptWBS) performed after RRA in LR and IR DTC patients. METHODS: We analyzed 545 DTC patients treated with total thyroidectomy and RRA in hypothyroidism followed by a ptWBS. Neck ultrasound (US) and serum thyroglobulin measurement were performed. According to the American Thyroid Association guidelines, patients were classified as LR (n = 345) and IR (n = 200). RESULTS: In addition to the thyroid remnant, the ptWBS showed the presence of further areas of 131I uptake in 16/545 (2.9%) cases. ptWBS showed laterocervical lymph node metastases in 11/16 patients (10/11 were also detected by US), mediastinal uptake in 1/16, lung metastases in 3/16, and bone metastases in 1/16. Only 6/545 (1.1%) metastases were detected by ptWBS alone. After 7.8 years, 8/16 patients were free of disease, and 8 had persistent disease: 4 "biochemical" and 4 "structural." Remission was achieved in 3 cases after one single 131I course, in 1 case after surgery, and in the last 4 cases after several 131I courses. CONCLUSIONS: The ptWBS diagnostic role was clinically relevant for the therapeutic strategies of our patients only in 1.1% of the cases. The cost-effectiveness of performing RRA and ptWBS in all LR and IR patients to find 1-2% of the cases with distant metastases remains controversial.

Undetectable or low (<1 ng/ml) postsurgical thyroglobulin values do not rule out metastases in early stage differentiated thyroid cancer patients.

BACKGROUND: Differentiated thyroid cancer (DTC) work-up is based on (near)total-thyroidectomy plus thyroid remnant ablation (TRA) with 131-radioiodine in many patients, and long-life follow-up. 131I-post therapy whole body scan (pT-WBS) and serum thyroglobulin (Tg) are used in identifying metastatic patients. Some authors have evaluated the possibility of using post-surgical Tg (ps-Tg) values in deciding for or against TRA. The aim of our study was to verify the diagnostic accuracy of 131I-pT-WBS and SPECT/CT imaging (post-therapeutic imaging) compared to serum Tg levels in detecting metastases in early stage of DTC patients. RESULTS: Post-therapeutic imaging revealed metastases in 82 out of 570 (14.4%) patients. Metastases were successively confirmed by other diagnostic tools or by histology (sensitivity and PPV = 100%). Seventy-three out of 82 patients (90.2%) showed ps-Tg levels ≤1 ng/ml. In fifty-four per cent of patients, serum Tg levels at TRA remained ≤1 ng/ml. CONCLUSION: In conclusion, ps-Tg levels cannot be used in deciding for or against TRA. In early stage of DTC, post-therapeutic imaging (131I-pT-WBS and SPECT/CT) is an accurate method of detecting metastases, also in patients with stimulated serum Tg values ≤1 ng/ml. METHODS: We retrospectively reviewed the records of 570 consecutive patients affected by pT1-pT3 DTC (F = 450, M = 120), referred to our Nuclear Medicine Units in the last five years to perform TRA after (near)-total-thyroidectomy.All patients underwent TRA 3-4 months after thyroid surgery either in euthyroid or in hypothyroid state. Serum Tg values evaluated in post-surgical period and at TRA were matched with post-therapeutic imaging results.

Graves' disease in a mediastinal mass presenting after total thyroidectomy for nontoxic multinodular goiter: a case report.

BACKGROUND: Thyrotoxicosis after total thyroidectomy is mostly iatrogenic. Rarely, a hyperfunctional thyroid remnant or ectopic tissue may be the cause. There are few cases of Graves' disease arising from thyroid tissue located in the mediastinum and none in which Graves' disease was diagnosed only after surgery. We report the case of a patient with Graves's disease in a mediastinal thyroid mass presenting 7 years after total thyroidectomy for nontoxic goiter. CASE PRESENTATION: A 67-year-old Caucasian woman presented with palpitations, fatigue and weight loss. She had a history of total thyroidectomy for nontoxic multinodular goiter at the age of 60 without any signs of malignancy on microscopic examination. She had been medicated with levothyroxine 100 µg/day since the surgery without follow-up. She was tachycardic, had no cervical mass or eye involvement. Her thyroid-stimulating hormone levels were suppressed (0.000 µU/mL) and her free thyroxine (3.22 ng/dL) and free triiodothyronine (8.46 pg/mL) levels increased. Neither mediastinal enlargement nor trachea deviation was found on chest roentgenogram. Levothyroxine treatment was stopped but our patient showed no improvement on free thyroxine or free triiodothyronine 10 days later. Thyroglobulin was increased to 294 mg/mL. A cervical ultrasound scan revealed no thyroid remnant. Her anti-thyroid-stimulating hormone receptor antibodies were high (19.7 U/L). Corporal scintigraphy demonstrated increased intrathoracic radioiodine uptake. A computed tomography scan confirmed a 60 × 40 mm mediastinal mass. Methimazole 10 mg/day was started. Three months later, her thyroid function was normal and she underwent surgical resection. Microscopic examination showed thyroid tissue with no signs of malignancy. CONCLUSIONS: Although thyrotoxicosis after total thyroidectomy is mostly due to excessive supplementation, true hyperthyroidism may rarely be the cause, which should be kept in mind. The presence of thyroid tissue after total thyroidectomy in our patient may correspond to a remnant or ectopic thyroid tissue that became hyperfunctional in the presence of anti- thyroid-stimulating hormone receptor antibodies.

Transient early increase in thyroglobulin levels post-radioiodine ablation in patients with differentiated thyroid cancer.

OBJECTIVES: Treatment of differentiated thyroid cancer (DTC) includes surgical thyroidectomy and, in most cases, radioactive iodine (RAI) ablation. Measurement of serum thyroglobulin (Tg) levels is used for assessing disease burden and identifying persistent-recurrent DTC. This prospective study determined the Tg profile before and after RAI-ablation in patients with DTC. DESIGN AND METHODS: Fifty-five DTC patients with complete resection received RAI-ablation and were assessed for Tg at baseline (non-stimulated), pre-ablation (stimulated), 7 days post-ablation (stimulated) and at 6 months (stimulated). Stimulation of Tg was achieved by thyroid hormone withdrawal to achieve serum thyroid stimulating hormone (TSH) ≥30 mU/L. Thyroid remnant size was estimated from whole body scintigraphy. Similar protocols were implemented for nine patients with incomplete resection/metastatic disease for comparison. RESULTS: Mean stimulated Tg levels for DTC patients with complete resection at 7 days post-RAI increased 13-fold from 13.7 to 175.5 µg/L (p<0.0001), and the Tg levels reduced to 2.3 µg/L (p<0.0001 versus post-RAI) by follow-up. None of the patients had recurrence of disease. For the nine patients with incomplete resection/metastases, Tg levels were higher throughout compared to the patients with complete resection. There was no increase in Tg between pre- and post-RAI. We did not observe a significant correlation between the remnant size and Tg increase. CONCLUSIONS: This study confirms a prominent transient early increase in Tg post-RAI ablation in DTC patients with complete resection, with the Tg levels falling below baseline by 6 months. This is presumed to reflect RAI-induced thyroid tissue destruction/inflammation with subsequent release of Tg from the thyroid remnant. Recognizing this transient phenomenon is important for post-ablation Tg interpretation and patient management.

Lowest effective 131I activity for thyroid remnant ablation of differentiated thyroid cancer patients. Dosimetry-based model for estimation.

AIM: A theoretical dosimetry-based model was applied to estimate the lowest effective radioiodine activity for thyroid remnant ablation of low-risk differentiated thyroid cancer patients. PATIENTS, METHODS: The model is based on the distribution of the absorbed (radiation) dose per administered radioiodine activity and the absorbed dose threshold of 300 Gy for thyroid remnants, the level believed to destroy most thyroid remnants. For this purpose, ¹²4I PET/CT images of 49 thyroidectomised patients were retrospectively analysed to measure the distribution of the (average) absorbed doses to thyroid remnant per administered ¹³¹I activity. The fraction of thyroid remnants that received at least 300 Gy was determined for standard activities between 0.37 and 5.55 GBq. The lower activity was considered to be equally effective to that obtained with higher activity if the (absolute) fraction difference was below 5%. RESULTS: A total of 62 thyroid remnants were included. The medians and ranges (in parentheses) for the absorbed dose per unit 131I activity were 359 Gy/GBq (34 to 1825 Gy/GBq). The fractions of thyroid remnants receiving more than 300 Gy at different therapy activities (within parentheses) were 60% (1.11 GBq), 76% (1.85 GBq), 79% (2.22 GBq), and 81-82% for activities between 2.59 and 3.70 GBq. The therapy activity of 1.11 GBq is considerably less effective than that of 1.85 or 2.22 GBq; therapy activities were equally effective in the range between 2.22 to 3.70 GBq. CONCLUSION: On the basis of the model and the patients' data included, the lowest effective therapy activity appears to be approximately 2.2 GBq to ablate thyroid remnants. The results of this study may help to guide the design of prospective clinical studies.

Semi-quantitative analysis of the effect of 131I on residual thyroid tissue in patients with differentiated thyroid cancer / 中华地方病学杂志

Objective To evaluate the effect of postoperative thyroid residual tissue on 131I treatment of differentiated thyroid carcinoma (DTC) metastases in patients with DTC.Methods Patients with thyroid residual tissue and lymph node metastases or distant organ metastases were confirmed by 131I whole body scan after 131I treatment of DTC from January 2004 to January 2013 in Dalian.The clinical data were divided into the cured group and the non-cured group according to the final results of mI treatment.The per unit area count value (Kc/cm2) of residual thyroid remnant (NTR),lymph node metastases (LNM) and distant metastases (DM) were measured and performed semi-quantitative analysis.The thresholds of the analysis results were calculated by the Bootstrap method.Results A total of 114 patients were studied,aged from 14 to 80 years old,including 47 males and 67 females;the ratio of males to females was 1.0:1.4.There were significant differences in NTR unit area counts (0.25 vs 1.29 Kc/cm2) between the cured group and the non-cured group (72 in the cured group and 42 in the non-cured group,U =0.001,P ＜ 0.05);there was no significant difference in LNM unit area counts (0.21 vs 0.41 Kc/cm2) between the cured group and the non-cured group (U =0.052,P ＞ 0.05).Those with the ratio of residual area to lymph node metastases (N/L) and the ratio of residual area to distant metastases(N/D) less than 1.7 had a better 131I treatment;unit area N/L greater than 4.9 and unit area N/D greater than 8.0 had a poor therapeutic effect.Conclusion Excessive residual tissue after surgery results in poor efficacy of 131I treatment;semi-quantitative analysis for whole body scan after 131I treatment can predict the efficacy of 131I treatment.

Use of Pre-Ablation Radioiodine-131 Scan to Assess the Impact of Surgical Volume and Specialisation following Thyroidectomy for Differentiated Thyroid Carcinoma.

BACKGROUND: We evaluated the relationship between thyroid remnant size following thyroidectomy for differentiated thyroid carcinoma and surgical volume and specialisation by assessing pre-ablation radioiodine-131 ((131)I) thyroid bed uptake (TBU) scanning as a surrogate for residual thyroid tissue. METHODS: We analysed data of 651 patients in our thyroid cancer database. Patients' data were included if the following criteria were met: (1) diagnosis of differentiated thyroid carcinoma, (2) total or near-total thyroidectomy, (3) pre-ablation (131)I scan prior to radioiodine ablation (RAI), (4) no distant metastasis, and (5) >3,000 MBq ablative dose of (131)I. (131)I diagnostic whole-body scans and measurement of thyroglobulin levels were carried out 3-9 months after RAI. 305 patients were included in the final analysis. RESULTS: Four endocrine, 19 otolaryngology and 25 general surgeons performed thyroidectomies with median pre-ablation (131)I TBU values of 1.0, 1.8 and 2.9%, respectively (p = 0.0031). There was a statistically significant relationship between number of thyroidectomies performed and median pre-ablation (131)I TBU values up to the optimal number of 11 operations beyond which there was no further significant difference between surgeons. There were differences in remnant size between endocrine and general surgeons (p = 0.001), otolaryngology and general surgeons (p = 0.023) but not between endocrine and otolaryngology surgeons (p = 0.167). CONCLUSION: Using the pre-ablation (131)I uptake scan as a surrogate for thyroid remnant quantification following thyroidectomy demonstrates the relationship between the surgical volume and size of thyroid remnant. The study also demonstrated beneficial effects of specialisation with specialist surgeons achieving the smallest thyroid remnant.

Approach to the patient with parathyroid adenoma and thyroid remnant goiter / 中华内分泌代谢杂志

Parathyroid adenoma is the main cause of primary hyperparathyroidism and often associated with thyroid nodular goiter.Thyrothymic thyroid rest belong to the ectopic thyroids which are classified into 4 grades according to the state of their connection with the proper neck thyroid gland.Thyrothymic thyroid remnant can also develop into nodular goiter and may be difficult to be distinguished from parathyroid adenoma.We present herewith the diagnosis and treatment of a rare case of parathyroid adenoma accompanied by thyrothymic thyroid remnant nodular goiter in order to remind clinicians of the attention to the thyrothymic thyroid remnant disease.

Detection for Residual Thyroid Tissue and Metastatic Lesion after Total Thyroidectomy in Patients with Differentiated Thyroid Cancer: Comparison between Tc-99m Pertechnetate Scan and High Dose I-131 Therapy Scan / 대한핵의학회잡지

PURPOSE: To evaluate diagnostic sensitivity of nuclear imaging in the detection of residual thyroid tissue and metastatic lesion, we have compared neck scintigrams with Tc-99m pertechnetate (Tc-99m scan) and high dose I-131 iodide (I-131 scan) in patients with differentiated thyroid cancer. SUBJECTS AND METHODS: One hundred thirty-five thyroidectomized patients for differentiated thyroid cancer were enrolled in this study. Twenty-three had a previous history of radioiodine therapy. Planar and pin-hole images of anterior neck with Tc-99m were acquired at 20 minutes after injection, followed by I-131 scan three days after high-dose radioiodine therapy within 7 days interval. Patients were asked to discontinue thyroid hormone replacement more than 4 weeks. RESULTS: All subjects were in hypothyroid state. Seventy out of 135 patients (51.9%) showed concordant findings between Tc-99m and I-131 scans. I-131 scan showed higher number of uptake foci in all of 65 patients showing discordant finding. Tc-99m scan showed no thyroid bed uptake in 34 patients, whereas 23 of them (67.6%) showed bed uptake in I-131 scan. Tc-99m scan did not show any uptake in thyroid bed in 11 of 112 patients without previous history of radioiodine therapy, but 9 of them showed bed uptake in I-131 scan. Tc-99m scan showed no bed uptake in all of the 23 patients with previous history of radioiodine therapy, in contrast 14 of them (60.9%) showed bed uptake in I-131 scan. CONCLUSION: These results suggest that Tc-99m scan has poor detectability for residual thyroid tissue or metastatic lesion in thyroidectomized differentiated thyroid cancer patients, compared to high dose I-131 therapy scan. Tc-99m scan could not detect any remnant tissue or metastatic lesion in patients with previous history of radioiodine treatment, especially.