"Tumour sink effect" on the diagnostic or posttreatment radioiodine scan due to sequestration into large-volume functioning metastasis of differentiated thyroid carcinoma influencing uptake in smaller metastatic sites or remnant thyroid tissue: An uncommon but possible phenomenon in thyroid cancer practice.

Two patients of differentiated thyroid carcinoma are illustrated demonstrating "sink effect" in posttherapeutic and diagnostic radioiodine (I-131) study: (a) in the first case, it masked the other small-volume metastatic sites (pulmonary and paratracheal nodes) in the posttreatment scan, which were clarified following metastatectomy of the large-volume skeletal metastatic lesion, and (b) in the second, interestingly, it masked the remnant thyroid uptake in the first postoperative diagnostic radioiodine study. In both the situations, large-volume highly functioning skeletal metastasis was the cause for the observed "sink effect" and is presented as learning illustrations to the attending physicians. Although uncommon, this is a possible phenomenon in thyroid cancer practice.

The feasibility of low-dose oral lithium therapy and its effect on thyroidal radioiodine uptake, retention, and hormonal parameters in various subcategories of hyperthyroid patients: a pilot study.

BACKGROUND: Radioactive iodine (I) (RAI) is used widely for the treatment of hyperthyroidism either as a first-line treatment or following relapse after antithyroid drug treatment. Intrathyroidal retention of RAI is considered an important determinant of its effectiveness, which is believed to be prolonged by lithium. AIMS AND OBJECTIVES: To study the impact of low-dose oral lithium therapy on RAI uptake and retention parameters in different subgroups of hyperthyroidism patients, and thus explore its potential role in enhancing the therapeutic efficacy of RAI in these groups of patients. MATERIALS AND METHODS: A total of 28 patients (age range=18-70 years) who were being considered for RAI therapy were included in this prospective pilot study. The patients were divided into two groups: (i) those who had not received any RAI therapy before were included in 'group I' (n=22), whereas (ii) 'group II' (n=6) included patients who were found to be persistently hyperthyroid on biochemical and clinical follow-up despite previous RAI therapy for hyperthyroidism. Patients in group I were further divided into four subgroups on the basis of the underlying etiopathology: (a) subgroup Ia - diffuse toxic goiter (n=15), (b) subgroup Ib - autonomous functioning module (n=2), (c) subgroup Ic - toxic multinodular goiter (n=4), and (d) subgroup Id - nontoxic multinodular goiter (n=1) on the basis of scintigraphic and clinical findings. All patients first underwent 25 µCi I uptake estimation at 2, 24, and 48 h and values thus obtained were considered the baseline for further evaluation. After biochemical assessment of normal renal and liver functions, patients received 900 mg lithium per day in three divided doses orally, and on the fourth day after starting tab lithium, the serum lithium level was estimated with continued lithium administration. On the fifth, sixth, and seventh day, patients underwent lithium-primed 25 µCi I uptake estimation at 2, 24, and 48 h. Retention index (RI) was calculated using the formula [RI=(48 h uptake-24 h uptake)/24 h uptake×100]. A day after completion of uptake study, that is, on the third day from diagnostic (25 µCi I) RAI administration, patients received a fixed 5 mCi therapeutic RAI dose after their suitability for the same was ascertained using clinical, biochemical, and scintigraphic findings as the criteria. Lithium administration was stopped 5 days after therapy. RESULTS: Lithium priming resulted in a significantly reduced serum FT4 level in subgroup Ia (diffuse goiter) of group I. Similarly, lithium priming resulted in a statistically significant increase in the radioiodine RI in subgroup Ia. Lithium priming resulted in increased retention of radioiodine and reduced serum FT4 level in the rest of the study population also, but the difference was not statistically significant (likely because of fewer patients in these subgroups). The low-dose lithium priming regimen used in the present study was found to be feasible and safe. The mean serum lithium concentration was 0.6 mEq/l with the dose protocol administered and hence was considered safe. Only one patient had achieved a level of 1.5 mEq/l, without any obvious side effects, and it was clinically uneventful. One patient experienced headache necessitating dose reduction. CONCLUSION: The results of this study, carried out in different groups of patients with hyperthyroidism, suggested that a short course of lithium is safe and could be beneficial for hyperthyroid patients considered for RAI therapy as it increased the RAI retention in thyroid, and thus had the potential to increase the effect of RAI therapy. Alternatively, it is proposed that lithium priming could help reduce the dose of RAI administered without compromising on therapeutic efficacy, with possible potential implications for cost reduction, radiation safety precautions, and lowered radiation dose to nontarget organs.

Thymus uptake of 131I in patients with differentiated thyroid carcinoma: Three different case scenarios and patterns of uptake and the importance of its recognition in thyroid cancer practice.

The importance of recognizing thymic radioiodine uptake as the cause of a false-positive mediastinal focus in the whole-body 131I scan, done for the evaluation of post-thyroidectomy cases of differentiated thyroid carcinoma, is illustrated with the corresponding clinicoradiorological correlation. The pattern of mediastinal uptake could vary based upon the pattern of thymic hyperplasia in an individual case. Three different patterns of mediastinal uptake were observed in the cases described in the present report. Recognizing the patterns and the clinical settings (where this was to be suspected by the treating physician) was important to obviate unnecessary aggressive treatment, such as, surgery or radioiodine therapy. In a review of the literature, we found that a majority of the cases were reported in the young population (related to the thymus reaching its peak size during adolescence and gradual atrophy in the following decades) and in patients undergoing a six-month follow-up whole body diagnostic scan after thyroid remnant ablation treatment, and also in patients receiving a second course of 131-iodine treatment for a persistently elevated thyroglobulin (Tg) level. The indicators that should raise the suspicion of false-positive radioiodine uptake to the attending physician include: (a) undetectable/low serum thyroglobulin level (although this may not be always the case, depending on the clinical setting), (b) a well-controlled disease with no other abnormal focus in the rest of the body,

The use of 99mTc-HYNIC-TOC and 18F-FDG PET/CT in the evaluation of duodenal neuroendocrine tumor with atypical and extensive metastasis responding dramatically to a single fraction of PRRT with 177Lu-DOTATATE.

This report describes a case of extensive diffuse bone marrow involvement with bilateral breast metastases from duodenal neuroendocrine tumor giving rise to a superscan-like appearance on somatostatin receptor-targeted (99m)Tc-hydrazinonicotinamide-TOC scintigraphy. The metastatic lesions demonstrated partial concordance with (18)F-FDG PET/CT findings, signifying varying tumor biology and heterogeneity among metastatic lesions in the same individual, as illustrated with a dual-tracer approach. There was a dramatic symptomatic and biochemical response and better health-related quality of life with a single fraction of peptide receptor radionuclide therapy with (177)Lu-DOTATATE, and radiologically there was stable disease at that point.

Comparative evaluation of 24-hour thyroid 131I uptake between γ camera-based method using medium-energy collimator and standard uptake probe-based method.

UNLABELLED: The objective of the study was to make a quantitative comparison of 24-h thyroid uptake calculated by γ camera-based and thyroid uptake probe-based methods after administration of a diagnostic (131)I capsule in patients with benign thyroid disorders. METHODS: The study group comprised 66 patients, of whom 26 were male (28-67 y old) and 40 female (20-65 y old). These patients had benign thyroid disorders (primarily hyperthyroidism [thyrotoxicosis]), most of whom had been referred for evaluation before radioiodine treatment. (131)I (25 µCi [925 MBq]) was administered, and 24-h thyroid uptake was calculated using a probe-based method and a camera-based method with a medium-energy parallel-hole collimator. The paired t test was used to check the variation in values obtained by these 2 methodologies. RESULT: Of the 66 patients included in this study, 45 had clinical thyrotoxicosis and 21 had nonthyrotoxic multinodular goiter. In the group with thyrotoxicosis, neck uptake ranged from 40.13% to 97.1% by the probe-based method and 36.89% to 95.9% by the camera-based method. In the group with clinically nonthyrotoxic goiter, neck uptake ranged from 1.4% to 38.4% by the probe-based method and 0.6% to 34.8% by the camera-based method. Paired t testing was performed on both groups of patients, and P values were less than 0.05, showing good agreement within the 2 groups of data. CONCLUSION: The camera-based method is a good substitute for the probe-based method; though not producing identical results, the former could be used to derive useful quantitative information on thyroid function.

Examining recombinant human TSH primed ¹³¹I therapy protocol in patients with metastatic differentiated thyroid carcinoma: comparison with the traditional thyroid hormone withdrawal protocol.

PURPOSE: Recombinant human thyroid-stimulating hormone (rhTSH)-based protocol is a promising recent development in the management of differentiated thyroid carcinoma (DTC). The objectives of this prospective study were: (1) to assess the feasibility and efficacy of the rhTSH primed (131)I therapy protocol in patients with DTC with distant metastatic disease, (2) to perform lesional dosimetry in this group of patients compared to the traditional protocol, (3) to document the practical advantages (patient symptoms and hospital stay) of the rhTSH protocol compared to the traditional thyroid hormone withdrawal protocol, (4) to document and record any adverse effect of this strategy, (5) to compare the renal function parameters, and (6) to compare the serum TSH values achieved in either of the protocols in this group of patients. METHODS: The study included 37 patients with metastatic DTC having lung or skeletal metastases or both. A comparison of lesional radiation absorbed dose, hospital stay, renal function tests, and symptom profile was undertaken between the traditional thyroid hormone withdrawal protocol and rhTSH-based therapy protocol. Dosimetric calculations of metastatic lesions were performed using lesion uptake and survey meter readings for calculation of effective half-life. Non-contrast-enhanced CT was used for assessment of tumor volume. Quality of life was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QOL forms. A comparison of pretreatment withdrawal thyroglobulin (TG) was done with the withdrawal TG level 3 months after treatment. RESULTS: The mean effective half-life of (131)I in metastatic lesions was less during the rhTSH protocol (29.49 h) compared to the thyroid hormone withdrawal protocol (35.48 h), but the difference was not statistically significant (p = 0.056). The mean 24-h % uptake of the lesions during the traditional protocol (4.84 %) was slightly higher than the 24-h % uptake during the rhTSH protocol (3.56 %), but the difference was not found to be statistically significant (p = 0.301). The mean tumor radiation absorbed dose per mCi was less during the rhTSH protocol (6.04 rad/mCi) than during the thyroid hormone withdrawal protocol (8.68 rad/mCi), and the difference was statistically significant (p = 0.049), though visual analysis of the rhTSH posttherapy scans showed avid concentration of (131)I in the metastatic sites and revealed more lesions in 30 % of the patients compared to the traditional large dose scan and equal number of lesions in 65 % of the patients. Visual analysis of the traditional large dose scan, rhTSH pretreatment scan, and rhTSH posttherapy scans showed that the traditional large dose scan is better compared to the rhTSH 1 mCi scan as it showed more lesions in 19 of 37 patients (51.35 %). rhTSH posttherapy scans were better compared to the traditional large dose scans and rhTSH pretreatment scans. More lesions were seen on rhTSH posttherapy scans in 11 of 37 patients (29.7 %) compared to the traditional large dose scans and in 24 of 37 (64.86 %) patients compared to the rhTSH 1 mCi scans. Our findings demonstrate that the rhTSH primed pretreatment scan undertaken at 24 h after diagnostic dose is suboptimal to evaluate whether a metastatic lesion concentrates (131)I. The majority of these lesions demonstrated radioiodine accumulation in the posttreatment scan. Quality of life as assessed using EORTC QOL-3 forms clearly showed that rhTSH improved the quality of life of patients compared to the thyroid hormone withdrawal protocol. Functional scale and global health status were significantly better in the rhTSH protocol compared to the thyroid hormone withdrawal protocol (p < 0.001). The mean symptom scale score was significantly higher in the thyroid hormone withdrawal protocol (45.25) compared to the rhTSH protocol (13.59) (p < 0.001). Of the 20 patients, 4 (20 %) had more than 25 % increase in the TG value on follow-up. The median hospital stay of patients receiving (131)I therapy with the rhTSH protocol was shorter (2 days, range 2-8 days) compared to the thyroid hormone withdrawal protocol (3 days, range 1-8 days) and the difference was found to be statistically significant (p = 0.007). The mean serum creatinine level was significantly lower in the rhTSH protocol (0.826 mg/dl) than the thyroid hormone withdrawal protocol (0.95 mg/dl) (p = 0.013), though the mean blood urea level of patients during the rhTSH therapy protocol was slightly higher (22.81 mg/dl) than during the thyroid hormone withdrawal protocol (21.91 mg/dl) without statistical significance (p = 0.55). The mean serum TSH on day 2 of the rhTSH protocol was 140.99 µIU/ml (range 71-176 µIU/ml) compared to 72.62 µIU/ml (range 2.05-154 µIU/ml) in the traditional protocol after around 4-6 weeks of thyroid hormone withdrawal (p < 0.05). CONCLUSION: Overall, the rhTSH primed (131)I therapy protocol was found to be feasible and a good alternative to the thyroid hormone withdrawal protocol in patients with metastatic DTC. The lesional dosimetry findings need to be further examined in subsequent studies. The rhTSH primed pretreatment scan at 24 h after diagnostic dose is suboptimal to determine whether a metastatic lesion concentrates (131)I and the posttreatment scan is important for the correct impression.

Dual malignancies in the setting of differentiated thyroid carcinoma: their synchronous or metachronous nature, impact of radioiodine treatment on occurrence of second malignancy and other associated variables.

PURPOSE: The primary objective of the study was to assess the risk for second primary malignancy after radioiodine treatment for differentiated thyroid carcinoma (DTC). Other objectives were to study the different variables associated with the occurrence of synchronous or metachronous dual malignancies in association with DTC. MATERIALS AND METHODS: The patient population studied comprised patients with histopathologically proven DTC referred for radioactive iodine treatment after thyroidectomy followed up at a single centre during the period from January 1963 to March 2011. The data collected were analysed with respect to different variables associated with two primary tumours in the setting of DTC. RESULTS: Out of the total 8614 patients studied from 1963 to March 2011, 44 dual malignancies in association with DTC were detected, showing a prevalence rate of 0.5%. The most common site of second primary malignancy was the head and neck (H&N) in men and the breast in women. Of the 44 dual malignancies, 18 were synchronous in nature and 26 were metachronous. In the metachronous group, thyroid carcinoma was the first primary malignancy in only 5/26 patients, whereas the remaining 21 patients had thyroid carcinoma as the second primary malignancy. In 5/26 patients in whom carcinoma of the thyroid was the first primary malignancy, the second primary malignancy was breast carcinoma in two cases, renal cell carcinoma in one case, colorectal carcinoma in one case and metastatic NET of unknown primary in one case. All these five patients received radioiodine treatment with different activities. In 21/26 patients in whom thyroid carcinoma was the second primary malignancy, the most common first primary malignancy comprised H&N tumours. In this group, 12 patients had a history of external beam radiotherapy (EBRT). Among synchronous malignancies (18/44 patients), H&N tumours were the most commonly associated. CONCLUSION: There was no significant risk for second primary malignancy after radioactive iodine treatment in patients with DTC. There is increased risk for thyroid malignancy after EBRT delivered for other primary tumours, especially in children. Hence, any thyroid abnormality on long-term follow-up of patients after EBRT for other tumours should be considered carefully. H&N malignancies are the most common synchronous, metachronous and overall associated second malignancy with thyroid carcinoma.

The added clinical value of 18F-FDG PET/CT in evaluating intratracheal recurrence of differentiated thyroid carcinoma: implications for planning surgery, assessing its completeness, and planning radioiodine therapy.

In selected patients with differentiated thyroid carcinoma, (18)F-FDG PET/CT has been shown to have added value. We present 2 clinical examples in the settings of both iodine-concentrating and non-iodine-concentrating lesions with tracheal involvement with special reference to its importance in planning of surgery or radioiodine therapy and assessing completeness of surgery. We believe that the use of PET/CT should be considered on a case-by-case basis and specifically when SPECT/CT is unavailable or has inconclusive findings.

A Logical levothyroxine dose Individualization: Optimization Approach at discharge from Radioiodine therapy ward and during follow-up in patients of Differentiated Thyroid Carcinoma: Balancing the Risk based strategy and the practical issues and challenges: Experience and Views of a large volume referral centre in India.

In this communication, the authors discuss the issue of individualization of thyrotropin suppressive therapy in differentiated thyroid carcinoma (DTC) patients and share their views with respect to optimizing the dose of levothyroxine (LT) prescription both during discharge from radioiodine therapy ward and during follow-up. The changing management paradigm at our Institute during post-thyroidectomy period and during the preparation for radioiodine scan is also briefly highlighted. Five factors can be identified as important determinants for the dose individualization approach: (1) Persistence or absence of metastatic disease, (2) the risk characteristics of the patient and the tumor (3) patient's clinical profile, symptomatology, and contraindications (4) the feasibility to ensure a proper thyroid stimulating hormone TSH suppression level (depends on patient's socio-economic and educational background, the connectivity with the local physician and his expertise) (5) time period elapsed since initial diagnosis. While discussing each individual case scenario, the authors, based upon their experience in one of the busiest thyroid cancer referral centers in the country, discuss certain unaddressed points in the current guideline recommendations, deviations made and some challenges toward employing them into practice, which could be situation and center specific. In addition to these, the value of clinical examination, patient profile and detailed enquiry about clinical symptomatology by the attending physician in each follow-up visit cannot be overemphasized. According to the authors, this aspect, quite important for dose determination in an individual, is relatively underrepresented in the present guidelines. It would also be worthwhile to follow a conservative approach (till clear data emerges) in patients who have characteristics of "high-risk" disease, but are clinically and biochemically disease free, if no medical contraindications exist and patient tolerates the suppressive therapy well. This would be particularly applicable in the presence of aggressive histopathological variants, where, in the event of recurrence/metastasis, the disease demonstrates adverse prognosis and higher incidence of radioiodine refractoriness. At the end, certain important and noteworthy concepts pertaining to LT prescription that has definitive practical implications for the suppressive therapy in DTC patients are described.

FDG uptake in unilateral breast related to breastfeeding practice in a patient of pulmonary hydatid cyst.

Unusual FDG uptake in unilateral breast on FDG PET study in a 32-year-old lactating woman with recent diagnosis of left upper lobe hydatid cyst is described. The FDG PET study demonstrated uptake in the periphery of the lesion corresponding to the hydatid cyst. In addition, there was an unusually intense FDG tracer uptake in the right breast. She was questioned about her breastfeeding practice in view of the unilateral uptake, and she gave a history of feeding her child from the right breast only. This case gives insight into the fact that there is differential glucose transporter activity in lactating women related to breastfeeding practice as evidenced by unilateral FDG uptake in breast.

Detection by (18)F-FDG PET of unsuspected extensive bone marrow metastases in a case of basosquamous carcinoma of the cheek.

Basosquamous carcinoma (BSC) is a rare type of malignancy with features of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with a potential for aggressive behaviour infiltration and destruction. First reported by MacCormac in 1910 in a series of rodent ulcers, this entity does have an increased risk of recurrence and metastases as well, which distinguish it from other forms of basal cell carcinoma. The overall incidence of basosquamous carcinoma ranges from 1.2% to 2.7%. An unusual case of basosquamous carcinoma (BSC) is presented where 18- fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) scan diagnosed unsuspected extensive metastatic disease in the bone marrow, which was further proven histopathologically. The patient was a 32 years old man with history of recently diagnosed basosquamous carcinoma of left cheek involving left lower eyelid and left eyeball. Contrast enhanced computed tomography(ceCT) of the head and neck demonstrated involvement of the left cheek skin by the malignancy along with erosion of zygomatic bone and phthisis bulbi of the left eye. The serum alkaline phosphatase was elevated (255units, normal range 50-150units). The patient was referred for (18)F-FDG PET, for disease status evaluation. The scan showed intense tracer uptake in the left zygomatic region, the site of known primary disease. Intense tracer uptake was noted in the multiple lesions of bone marrow of axial as well as appendicular skeleton. The scan appearance was highly suggestive of metastatic bone marrow involvement. A bone marrow biopsy was performed to confirm the scan findings. Guided by the (18)F-FDG PET scan findings, bone marrow biopsy was performed and metastatic basosquamous carcinoma was diagnosed. We believe this is the first reported case of basosquamous carcinoma where extensive metastatic bone marrow disease was diagnosed with the aid of (18)F-FDG PET. At first diagnosis, an advanced stage of BSC is often present. Due to its metastatic potential, extensive primary surgical resection of BSC, possibly completed by radiation or photodynamic adjuvant treatment is recommended. Given the aggressive nature of basosquamous carcinoma, whole body (18)F-FDG PET is very useful in diagnosing metastatic BSC. In conclusion, this is the first reported case of the use of (18)F-FDG PET study for diagnosing metastatic bone marrow disease in a patient with basosquamous carcinoma.

'Reverse discordance' between 68Ga-DOTA-NOC PET/CT and 177Lu-DOTA-TATE posttherapy scan: the plausible explanations and its implications for high-dose therapy with radiolabeled somatostatin receptor analogs.

In this technical note, an unusual discordance between diagnostic and posttherapeutic scan resulting from the use of different somatostatin receptor ligands in two settings is described. Such observation, we believe, is multifactorial, but most importantly arises due to different receptor affinity profile of the ligands and different somatostatin receptor subtype expression in different tumors. It is important for the treating physician to be aware of this phenomenon that would aid in improving our understanding of complex ligand-receptor interactions in various somatostatin receptor-positive tumors with its possible implications for therapeutic decision making with radiolabeled somatostatin receptor analogues.