Undetectable thyroglobulin makes 123I whole-body scan and stimulated thyroglobulin obsolete in follow-up care of differentiated thyroid cancer: a retrospective study

Background Differentiated thyroid cancer (DTC) is a common malignancy with increasing incidence. Follow-up care for DTC includes thyroglobulin (Tg) measurement and ultrasound (US) of the neck, combined with 131I remnant ablation when indicated. Diagnostic precision has evolved with the introduction of the new high-sensitive Tg-assays (sensitivity ≤0.1 ng/mL). The aim of the study was to determine the prognostic utility of high-sensitive Tg and the need for other diagnostic tests in DTC. Methods This was a retrospective, observational study. Patients with pathologically confirmed DTC, treated with total thyroidectomy and 131I remnant ablation, who had their complete follow-up care in our institution were selected (October 2013–December 2018). Subjects with possible thyroglobulin autoantibody interference were excluded. Statistical analysis was performed using the IBM SPSS® Statistics 24 software package. Results Forty patients were eligible for analysis. A total of 24 out of the 40 patients (60%) had an undetectable high-sensitive Tg 6 months after total thyroidectomy. None of these patients had a stimulated Tg above 1 ng/mL, or remnant on the 123I Whole-Body Scan (WBS) after 1 year of follow-up. Ultrasound of the neck, performed between 6 and 12 months postoperative, was negative in 21 out of the 24 patients. Conclusions This study shows that an undetectable high-sensitive Tg can change the management of patients with DTC and decrease the use and need of stimulated Tg and 123I WBS.

Median 10 years follow-up of patients with covert Cushing’s syndrome: a case series

Background Ectopic adrenocorticotropic hormone secretion syndrome occurs in 10% of all patients with adrenocorticotropic-hormone-dependent hypercortisolism. It is usually associated with overt malignancies or with occult and indolent tumors. This study aims to confirm the source of ectopic adrenocorticotropic hormone in four patients with ectopic Cushing’s syndrome over time. Case presentation A 38-year-old Iranian man with Cushing’s syndrome underwent bilateral adrenalectomy since the source of ectopic adrenocorticotropic hormone secretion was not localized and pituitary imaging was normal. A whole-body scan revealed a right-lung tumoral mass with mediastinal lymph node metastasis. The mass was assumed a lung carcinoid tumor with mediastinal adenopathy. Right-lung mid-zone lobectomy and mediastinal lymphadenectomy were done. In a 47-year-old Iranian man with Cushing’s syndrome, whole-body computed tomography scan revealed a pulmonary nodule in the posterior segment of the left lower lobe of the lung. The third case was a 25-year-old Iranian man who presented with symptoms and signs of Cushing’s syndrome. Pituitary magnetic resonance imaging revealed a microadenoma 5 × 9 mm. Whole-body scan showed abnormal focal somatostatin receptors analog avid lesion in the posterior aspect of inferior third of right lung, highly suggestive of ectopic adrenocorticotropic-hormone-producing tumor. The last case was a 43-year-old Iranian woman with Marfan syndrome with a history of mitral and aortic valve replacement and chronic dissection of the aorta, who presented with symptoms and signs of Cushing’s syndrome. She underwent bilateral adrenalectomy 1 year later owing to failure to locate ectopic adrenocorticotropic hormone syndrome. Whole-body scan showed abnormally increased radiotracer uptake in the midline of the skull base and posterior aspect of the middle zone of left hemithorax and bed of left lobe of thyroid. Conclusion The clinical spectrum of ectopic adrenocorticotropic hormone secretion syndrome is wide, and distinguishing Cushing’s disease from ectopic adrenocorticotropic hormone secretion syndrome is difficult. Initial failure to identify a tumor is common. Pulmonary carcinoid or occult source of ectopic adrenocorticotropic hormone secretion syndrome is usually the cause. In occult cases of ectopic adrenocorticotropic hormone in which the tumor cannot be localized, serial follow-up with serial computed tomography, magnetic resonance imaging, or scintigraphy is recommended for several years until the tumor can be localized and treated.

MERAIODE: A Redifferentiation Phase II Trial With Trametinib and Dabrafenib Followed by Radioactive Iodine Administration for Metastatic Radioactive Iodine Refractory Differentiated Thyroid Cancer Patients With a BRAFV600E Mutation (NCT 03244956)

Background: Two-thirds of patients with metastatic differentiated thyroid cancer (DTC) become refractory to radioactive iodine (RAIR). The inhibition of the MAP-kinase pathway that is activated in case of BRAFV600E mutation might increase RAI incorporation into metastatic foci and reverse the RAI refractoriness. MERAIODE is a prospective multicentric open-label phase II trial, using a one-stage Fleming design, evaluating the efficacy and tolerance of trametinib (a MEK inhibitor) and dabrafenib (a BRAF inhibitor) treatment followed by the administration of RAI in metastatic RAIR DTC patients. Methods: Patients with BRAFV600E mutated RAIR metastatic DTC with RECIST progression within 18 months prior to enrollment and no lesion > 3 cm were included. A baseline rhTSH-stimulated diagnostic whole body scan (dc WBS) was performed prior to treatment initiation. Patients were treated with dabrafenib (150 mg bid) and trametinib (2 mg per day) for 42 days. At day 28, a second rhTSH-stimulated dc WBS was performed. After 35 days, a therapeutic activity of RAI (5.5 GBq) was administered. Primary endpoint was objective response rate (ORR) at 6 months according to RECIST v1.1 (central review). Patients: Among the 24 patients (mean age 67 years, 15 females) with a BRAFV600E mutated RAI refractory papillary DTC included between March 2018 and January 2020 in 8 French centers from the TUTHYREF netwok, 24 patients were treated and 21 patients were evaluable for the principal outcome at 6 months. Results: Abnormal RAI uptake was present in only 1 of the 21 patients (5%; 95%CI 0-24%) on a RAI diagnostic whole body scan (dc-WBS) performed prior to treatment initiation, in 11 patients, 11/17 (65%; 95%CI 38-86) on a dc-WBS performed 4 weeks after dabrafenib-trametinib initiation and in 20/21 (95%; 95%CI 76-100) on the post-therapeutic WBS performed after 5.5 GBq of RAI. The RECIST 6-months tumor response (central review) was partial response (PR) in 38% (95%CI 18-61), stable disease (SD) in 52% (95% CI 30-74) and progressive disease (PD) in 10% (95% CI 1-30). The median change in the sum of target lesions was -22% (range: -79 to +46) at 6 months after baseline. The 6-month fluorodesoxyglucose metabolic PET response was PR in 11/17 (65% 95%CI 38-86), SD in 4/17 (23%) (95% CI 7-50) and PD in 2/17 (12%; 95% CI 1-36). Among the 15 patients without Tg antibodies, 7 (47%) patients had a decrease of serum thyroglobulin level on T4 treatment by more than 50%All patients experienced at least one grade 1-2 adverse event, mainly asthenia, nausea, fever, diarrhea and cutaneous eruption. Nine grade 3 toxicities occurred in 6 treated patients. No grade 4-5 adverse event occurred Conclusion: The association of dabrafenib and trametinib in BRAFV600E mutated patients is effective for restoring RAI uptake and is followed by a tumor control in 90% of patients and by tumor response in 38% with limited adverse events. (PHRC 2015, NCT 03244956)

Severe Thyrotoxicosis Following Topical Iodine Application

Background: Exposure to iodine can lead to iodine-induced hyperthyroidism in patients with underlying thyroid disease. Clinical Case: A 67 year-old woman with a history of nontoxic multinodular goiter and atrial fibrillation presented with fatigue, palpitations, weight loss, and tremor. Laboratory evaluation demonstrated new-onset profound biochemical hyperthyroidism (FT4 > 7.77 ng/dL, n 0.8 – 1.8 ng/dL; FT3 >27.0 pg/mL, n 2.0-4.4 pg/mL). She was treated with beta-blocker, high doses of methimazole, and cholestyramine while further evaluation was pursued. She declined SSKI due to reported iodine allergy and steroids due to concerns about impact on wound healing following recent hip arthroplasty. TSI and TRAb were negative, and thyroid ultrasound showed stable nodules at 1.7cm. Pelvic ultrasound and MRI were obtained due to concern for non-thyroidal etiology, and revealed a 3.7cm septated cystic ovarian lesion, raising suspicion for struma ovarii. Whole body scan to localize site of thyroid hormone production could not be obtained due to high risk of clinical deterioration off methimazole, as she had persistent clinical and biochemical thyrotoxicosis on high doses (up to 90mg/day). She ultimately required 3 sessions of plasma exchange to lower her thyroid hormone levels, and then underwent bilateral salpingo-oophorectomy. Final pathology revealed mucinous cystadenoma without ectopic thyroid tissue. Post-operatively, her thyroid hormone levels were persistently elevated but improved compared to pre-operative levels, allowing for brief cessation of methimazole and completion of whole body scan. Imaging demonstrated a single focus of radioactive iodine uptake in the lower right thyroid lobe, correlating with the dominant 1.7 cm nodule on prior ultrasound, consistent with a toxic adenoma. Additionally, she was found to have an elevated urine iodine level (1200 mcg/24 hours, n 75 – 851 mcg/24 hours). Patient endorsed low iodine diet due to allergy history, and denied recent contrasted imaging study, dietary supplements, or amiodarone use. Upon further inquiry, she recalled using povidone-iodine solution to care for her surgical site post-arthroplasty, approximately a week before the onset of her initial symptoms. Her clinical presentation was ultimately attributed to toxic adenoma, with severe thyrotoxicosis exacerbated by iodine load. She underwent total thyroidectomy and is doing well on levothyroxine post-operatively. Conclusions: Topical iodine administration can contribute to iodine-induced hyperthyroidism in patients with underlying thyroid disease, and its use should be carefully considered in these patients. When evaluating a patient with new thyrotoxicosis, a detailed history of oral, IV, and topical iodine use should be obtained.

Simplification of Dosimetry in 90Y-Radioembolization Therapy Using Dual Planar Images.

Aim: The purpose was to provide practical and effective method for performing 90Y dosimetry with 99mTc-MAA. The impact of scatter and attenuation correction (AC) on the injected 90Y activity and absorbed doses to critical organs was also further target beyond this study.Material and Methods: 18 patients (F: 3, M: 15) were subjected to 90Y therapy. 99mTc-MAA (111-222 MBq) was injected into the targeted liver, followed by a whole-body scan (WBS) with peak-window at 140 keV (15% width), and one down-scatter window. SPECT/CT scan was acquired over the lungs and liver regions. The lung shunt fractions were fashioned from the standard WBS, scatter corrected WBS, only scatter corrected SPECT and SPECT/CT with attenuation and scatter correction. The absorbed doses to tumor and surrounding healthy tissue were estimated with alternative approaches involving AC-SC (SPECT/CT), NoAC-SC (SPECT), NoAC-NoSC+LSF (SC-WBS), AC-SC+LSF (WBS), and NoAC-NoSC+LSF (WBS).Results: The average LSF deviations between the standard LSF and those obtained from AC-SC, NoAC-SC, and SC-WBS was -50% (-29/-71), -32%(-8/-67), and -45%(-13/80), respectively. The prescribed 90Y activity (GBq/Gy) was decreased by a range of 2-11%, 1-9%, and 2-7% with using LSFs from AC-SC, NoAC-SC, SC-WBS images. The absorbed dose to tumour and healthy liver tissue were calculated as 112±90 Gy and 30±18 Gy/GBq by AC-SC (SPECT/CT), 117±108 and 30±22 by NoAC-SC (SPECT), 110±100 and 31±21 Gy/GBq by NoAC-NoSC+LSF (SC-WBS), 106±84 and 28±17 Gy/GBq by AC-SC+LSF (WBS), while the absorbed dose was 90±85 and 28±20 Gy/GBq by using NoAC-NoSC+ LSF (WBS). Overall, no significant difference (p< 0.05) in the tomour and the health liver dose between all the approaches with/and without scatter correction. However, the scatter correction caused a significant difference in the lung shunt fractions (p <0.05).Conclusion: Scatter correction has a significant effect on the lung shunt fractions, planned activity and number of 90Y treatments. However, a minimal or negligible change was occurred on the absorbed dose to tumours and surrounding healthy liver. The good agreement between SPECT/CT approach, and scatter corrected whole-body scan might be practical and effective route for 90Y dosimetry.