Strategies of radioiodine ablation in patients with low-risk thyroid cancer.

BACKGROUND: It is not clear whether the administration of radioiodine provides any benefit to patients with low-risk thyroid cancer after a complete surgical resection. The administration of the smallest possible amount of radioiodine would improve care. METHODS: In our randomized, phase 3 trial, we compared two thyrotropin-stimulation methods (thyroid hormone withdrawal and use of recombinant human thyrotropin) and two radioiodine ((131)I) doses (i.e., administered activities) (1.1 GBq and 3.7 GBq) in a 2-by-2 design. Inclusion criteria were an age of 18 years or older; total thyroidectomy for differentiated thyroid carcinoma; tumor-node-metastasis (TNM) stage, ascertained on pathological examination (p) of a surgical specimen, of pT1 (with tumor diameter ≤1 cm) and N1 or Nx, pT1 (with tumor diameter >1 to 2 cm) and any N stage, or pT2N0; absence of distant metastasis; and no iodine contamination. Thyroid ablation was assessed 8 months after radioiodine administration by neck ultrasonography and measurement of recombinant human thyrotropin-stimulated thyroglobulin. Comparisons were based on an equivalence framework. RESULTS: There were 752 patients enrolled between 2007 and 2010; 92% had papillary cancer. There were no unexpected serious adverse events. In the 684 patients with data that could be evaluated, ultrasonography of the neck was normal in 652 (95%), and the stimulated thyroglobulin level was 1.0 ng per milliliter or less in 621 of the 652 patients (95%) without detectable thyroglobulin antibodies. Thyroid ablation was complete in 631 of the 684 patients (92%). The ablation rate was equivalent between the (131)I doses and between the thyrotropin-stimulation methods. CONCLUSIONS: The use of recombinant human thyrotropin and low-dose (1.1 GBq) postoperative radioiodine ablation may be sufficient for the management of low-risk thyroid cancer. (Funded by the French National Cancer Institute [INCa] and the French Ministry of Health; ClinicalTrials.gov number, NCT00435851; INCa number, RECF0447.).

Performance of FDG PET/CT at initial diagnosis in a rare lymphoma: nodular lymphocyte-predominant Hodgkin lymphoma.

PURPOSE: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare Hodgkin lymphoma distinguished from classical Hodgkin lymphoma (cHL) by the nature of the neoplastic cells which express B-cell markers. We wanted to determine the diagnostic performance of FDG PET/CT in initial assessment and its therapeutic impact on staging. METHODS: We retrospectively studied a population of 35 patients with NLPHL (8 previously treated for NLHPL, 27 untreated). All patients underwent an initial staging by pretherapeutic FDG PET/CT. The impact on initial stage or relapse stage was assessed by an independent physician. RESULTS: In a per-patient analysis, the sensitivity of the pretherapeutic FDG PET/CT was 100%. In a per-site analysis, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of pretherapeutic FDG PET/CT were 100%, 99%, 97%, 100% and 99%, respectively. Pretherapeutic FDG PET/CT led to a change in the initial stage/relapse stage in 12 of the 35 patients (34%). In contrast to previous results established without FDG PET/CT, 20% of patient had osteomedullary lesions. CONCLUSION: Pretherapeutic FDG PET/CT has excellent performance for initial staging or relapse staging of NLPHL.

Current molecular imaging of spinal tumors in clinical practice.

Energy metabolism measurements in spinal cord tumors, as well as in osseous spinal tumors/metastasis in vivo, are rarely performed only with molecular imaging (MI) by positron emission tomography (PET). This imaging modality developed from a small number of basic clinical science investigations followed by subsequent work that influenced and enhanced the research of others. Apart from precise anatomical localization by coregistration of morphological imaging and quantification, the most intriguing advantage of this imaging is the opportunity to investigate the time course (dynamics) of disease-specific molecular events in the intact organism. Most importantly, MI represents one of the key technologies in translational molecular neuroscience research, helping to develop experimental protocols that may later be applied to human patients. PET may help monitor a patient at the vertebral level after surgery and during adjuvant treatment for recurrent or progressive disease. Common clinical indications for MI of primary or secondary CNS spinal tumors are: (i) tumor diagnosis, (ii) identification of the metabolically active tumor compartments (differentiation of viable tumor tissue from necrosis) and (iii) prediction of treatment response by measurement of tumor perfusion or ischemia. While spinal PET has been used under specific circumstances, a question remains as to whether the magnitude of biochemical alterations observed by MI in CNS tumors in general (specifically spinal tumors) can reveal any prognostic value with respect to survival. MI may be able to better identify early disease and to differentiate benign from malignant lesions than more traditional methods. Moreover, an adequate identification of treatment effectiveness may influence patient management. MI probes could be developed to image the function of targets without disturbing them or as treatment to modify the target's function. MI therefore closes the gap between in vitro and in vivo integrative biology of disease. At the spinal level, MI may help to detect progression or recurrence of metastatic disease after surgical treatment. In cases of nonsurgical treatments such as chemo-, hormone- or radiotherapy, it may better assess biological efficiency than conventional imaging modalities coupled with blood tumor markers. In fact, PET provides a unique possibility to correlate topography and specific metabolic activity, but it requires additional clinical and experimental experience and research to find new indications for primary or secondary spinal tumors.

Parathyroid scintigraphy findings in chronic kidney disease patients with recurrent hyperparathyroidism.

BACKGROUND: Parathyroidectomy (PTX), either subtotal or total with forearm autografting, is a well-established treatment for refractory renal hyperparathyroidism (RHPT). However, 20-30% of patients develop persistent or recurrent disease. Obtaining accurate localization before reoperation is difficult. PATIENTS AND METHODS: The study group comprised 21 consecutive adult patients (18 undergoing haemodialysis and 3 with a renal graft) imaged using (99m)Tc-sestamibi/(123)I subtraction scintigraphy. Of the 21 patients, 12 had undergone one previous PTX and the other 9 between two and four parathyroid operations. All patients had symptoms and signs of severe RHPT. The mean serum PTH level was 1,142 pg/ml. (99m)Tc-Sestamibi and (123)I images were recorded simultaneously. Imaging views comprised a planar view of the neck and mediastinum, followed by a magnified pinhole view over the thyroid bed area. If parathyroid ectopy was detected, SPECT or SPECT-CT was performed. The forearm was imaged in case of autograft. RESULTS: Parathyroid scintigraphy was negative in one patient and positive in the other 20 (sensitivity 95.2%). One patient had uptake corresponding to two unresected parathyroid glands. Recurrence at the site of the partially resected gland or autograft was seen in 11 patients. However, six of them had a second (99m)Tc-sestamibi focus corresponding to a supernumerary parathyroid gland. Seven other patients had a supernumerary parathyroid gland as the sole cause of relapse. Three of the supernumerary glands showed major ectopy (intrathyroidal, low mediastinal, undescended within the vagus nerve). One patient had parathyromatosis with multiple parathyroid nodules scattered over the left side of the neck. Reoperation was possible in 13 patients, with no false-positive findings. CONCLUSION: Many patients referred with the hypothesis of hyperplasia of a subtotally resected parathyroid gland or autograft were found to harbour a supernumerary parathyroid gland missed at the initial surgery.

Effect of (18)F-FDG PET/CT imaging in patients with clinical Stage II and III breast cancer.

PURPOSE: To investigate the potential effect of using (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in the initial assessment of patients with clinical Stage II or III breast cancer. METHODS AND MATERIALS: During 14 consecutive months, 39 patients (40 tumors) who presented with Stage II or III breast cancer on the basis of a routine extension assessment were prospectively included in this study. PET/CT was performed in addition to the initial assessment. RESULTS: In 3 cases, PET/CT showed extra-axillary lymph node involvement that had not been demonstrated with conventional techniques. Two of these patients had hypermetabolic lymph nodes in the subpectoral and infraclavicular regions, and the third had a hypermetabolic internal mammary node. PET/CT showed distant uptake in 4 women. Of these 4 women, 1 had pleural involvement and 3 had bone metastasis. Overall, of the 39 women, the PET/CT results modified the initial stage in 7 (18%). The modified staging altered the treatment plan for 5 patients (13%). It led to radiotherapy in 4 patients (bone metastasis, pleural lesion, subpectoral lymph nodes, and internal mammary nodes) and excision of, and radiotherapy to, the infraclavicular lymph nodes in 1 patient. CONCLUSIONS: PET/CT can provide information on extra-axillary lymph node involvement and can uncover occult distant metastases in a significant percentage of patients. Therefore, initial PET/CT could enable better treatment planning for patients with Stage II and III breast cancer.

Plasma exchanges overcome persistent iodine overload to enable 131I ablation of differentiated thyroid carcinoma.

BACKGROUND: Amiodarone has a high iodine content that can induce persistent iodine excess and may prevent radioiodine (RI) treatment. PATIENT: A 55-year-old obese man had taken amiodarone (200 mg/d) for 3 years and stopped 2 years earlier. He underwent total thyroidectomy for papillary cancer with extrathyroidal extension and a metastatic central lymph node, requiring RI treatment. But iodine overload, with no other documented iodinated drug intake, was found (urinary iodine excretion = 472 microg/24 h; normal < 150 microg/24 h), and persisted 3 months later. Plasma exchanges (PE) were prescribed. INTERVENTIONS AND RESULTS: Eight PE over 4 weeks were needed to eliminate 39,295 nmol of iodine. Urinary iodine excretion and serum iodine concentrations, before PE and after eight sessions were, respectively: 230 and 84 nmol/mmol of creatinine, and 811 and 71 nmol/L, enabling RI treatment (4 GBq (131)I). Post-therapy whole-body scan revealed cervical uptake (0.48% of the total administered dose) corresponding to usual thyroid remnants. Ablation efficacy was confirmed 6 and 24 months later by cervical ultrasonography combined with an undetectable serum thyroglobulin level after recombinant human thyrotropin stimulation. CONCLUSIONS: When spontaneous iodine elimination is too slow to allow RI treatment of high-risk thyroid carcinoma within a reasonable time after thyroidectomy, PE are reliable and effective to overcome iodine overload.

Successful Treatment of Differentiated Thyroid Carcinoma with Transaxillary Robotic Surgery and Radioiodine: The First European Experience.

OBJECTIVES: Transaxillary robotic thyroidectomy surgery (TARS) has been reported to be a safe approach in patients with differentiated thyroid carcinoma, and oncological responses are promising. STUDY DESIGN: This study aimed to evaluate the oncological outcomes of TARS followed by radioiodine (RAI) therapy in patients with differentiated thyroid carcinoma. Between 2011 and 2016, patients treated for differentiated thyroid carcinoma by TARS in a single institution, followed by RAI, were retrospectively included. The oncological response was performed according to the 2015 American Thyroid Association (ATA) guidelines 6-12 months later and at the last available visit. RESULTS: A total of 42 patients (30 females) were included, with a median tumor size of 20 mm (12 cases of N1a and 5 cases of N1b on initial pathology report). According to ATA classification of recurrence risk after surgery, 17 and 25 patients were classified as low and intermediate risk, respectively. After RAI, all patients had a normal posttherapeutic whole body scan (except 1 patient, who had pathological lymph node uptake), but no unusual uptake was seen. At the 6- to 12-month evaluation (n = 37), 24 patients had excellent response, 8 had indeterminate response, and 5 had incomplete response (2 biological and 3 structural); no distant metastasis was found. At the last evaluation (median follow-up 15.9 months), 35 patients had no evidence of disease and 1 patient had a structural incomplete response. In total, a second open surgery was necessary for 3 patients to treat persistent lymph nodes (all intermediate risk). CONCLUSION: In this study, TARS followed by RAI therapy seems to be curative, even for patients with lymph node metastases, after good preoperative staging. More studies are required to confirm the findings.

Outcome after ablation in patients with low-risk thyroid cancer (ESTIMABL1): 5-year follow-up results of a randomised, phase 3, equivalence trial.

BACKGROUND: In ESTIMABL1, a randomised phase 3 trial of radioactive iodine (131I) administration after complete surgical resection in patients with low-risk thyroid cancer, 92% of patients had complete thyroid ablation at 6-10 months, defined as a recombinant human thyroid-stimulating hormone (rhTSH)-stimulated serum thyroglobulin concentration of 1 ng/mL or less and normal findings on neck ultrasonography. Equivalence was shown between low-activity (1·1 GBq) and high-activity (3·7 GBq) radioactive iodine and also between the use of rhTSH injections and thyroid hormone withdrawal. Here, we report outcomes after 5 years of follow-up. METHODS: This multicentre, randomised, open-label, equivalence trial was done at 24 centres in France. Between March 28, 2007, and Feb 25, 2010, we randomly assigned (1:1:1:1) adults with low-risk differentiated thyroid carcinoma who had undergone total thyroidectomy to one of four strategies, each combining one of two methods of thyrotropin stimulation (rhTSH or thyroid hormone withdrawal) and one of two radioactive iodine activities (1·1 GBq or 3·7 GBq). Randomisation was by computer-generated sequence, with variable block size. Follow-up consisted of a yearly serum thyroglobulin measurement on levothyroxine treatment. Measurement of rhTSH-stimulated thyroglobulin and neck ultrasonography were done at the discretion of the treating physician. No evidence of disease was defined as serum thyroglobulin of 1 ng/mL or less on levothyroxine treatment and normal results on neck ultrasonography, when performed. This study was registered with ClinicalTrials.gov, number NCT00435851. FINDINGS: 726 patients (97% of the 752 patients originally randomised) were followed up. At a median follow-up since randomisation of 5·4 years (range 0·5-9·2), 715 (98%) had no evidence of disease. The other 11 had either structural disease (n=4), raised serum thyroglobulin concentration (n=5), or indeterminate findings on neck ultrasonography (n=2). At ablation, six of these patients had received 1·1 GBq radioactive iodine (five after rhTSH and one after withdrawal) and five had received 3·7 GBq (two after rhTSH and three after withdrawal). TSH-stimulated (either after rhTSH injections or thyroid hormone withdrawal according to the treatment group) thyroglobulin concentration measured at the time of ablation was prognostic for structural disease status at ablation, ablation status at 6-10 months, and the final outcome. INTERPRETATION: Our findings suggest that disease recurrence was not related to the strategy used for ablation. These data validate the use of 1·1 GBq radioactive iodine after rhTSH for postoperative ablation in patients with low-risk thyroid cancer. FUNDING: French National Cancer Institute (INCa), French Ministry of Health, and Sanofi Genzyme.

Bone metastases of differentiated thyroid cancer: impact of early 131I-based detection on outcome.

Bone is the second most frequent target of distant metastases in patients with differentiated thyroid cancer, and such forms carry a very poor prognosis. The impact of (131)I therapy in this setting is controversial. We describe the diagnostic circumstances and outcome of patients with bone metastases recently managed in two institutions. Among 921 consecutive thyroid cancer patients who had total thyroidectomy and (131)I ablation between January 2000 and December 2004 and who were subsequently monitored, bone metastases had been diagnosed in 16 patients. In three cases, the bone metastases were non-functioning (negative (131)I uptake) . These patients were treated with surgery and radiotherapy but progressed rapidly. The other 13 patients had functioning (positive (131)I uptake) bone metastases. In five of them, thyroid cancer was revealed by signs of distant involvement (bone pain, n = 4; dyspnea, n = 1). The bone metastases progressed in these five patients, despite local therapy and multiple courses of (131)I. The bone metastases in the remaining eight patients were discovered on the post-surgery (131)I therapy scan. Complementary radiological studies were negative except in one patient in whom one of the metastases (a 5 mm lesion of the right humerus) was visible on magnetic resonance imaging (MRI). Six of these patients showed a good response to (131)I therapy, with (131)I uptake and Tg levels becoming undetectable or showing a sharp fall. One patient refused (131)I therapy; bone metastases became visible on MRI within 1 year and the Tg level rose tenfold. The disease progressed in one patient despite (131)I therapy. Post-surgical (131)I ablation can contribute to early detection of bone metastases at a time when the Tg level may be only moderately elevated, when other radiological studies are negative, and when the disease is potentially curable by (131)I therapy.

Distant metastases of differentiated thyroid cancer: diagnosis, treatment and outcome.

The remarkably good prognosis and long-term survival in differentiated thyroid cancer (DTC) are significantly reduced in patients with distant metastasis (DM). Multi-site metastases are associated with a high mortality rate reaching 92% at 5 years necessitating early diagnosis and treatment. The most common site of metastases are the lungs, followed by the bone, with the former having better prognosis than the latter due to late detection. A number of factors contribute to the development of DM including large and multifocal primary tumour, extrathyroidal extension, aggressive histology and advanced age. In patients with good (131)I uptake, (131)I therapy appears highly effective and should be offered up to a cumulative activity of 22 GBq. Other measures such as surgery, radiotherapy, arterial embolisation and cementoplasty may be required. If there is low or no (131)I uptake, FDG-PET should be obtained due to its prognostic impact. It may help in selecting patients for other modalities such as cytotoxic chemotherapy and redifferentiation therapy by 13-cis retinoic acid. The development of tyrosine kinase inhibitors has raised hopes in providing alternative therapy for bone metastasis, especially in older age groups with poorly differentiated tumours with no (131)I uptake but good uptake of FDG.

Assessing Bone Marrow Activity in Patients with Myelofibrosis: Results of a Pilot Study of 18F-FLT PET.

An emerging noninvasive approach to assess tissue proliferation uses the PET tracer 3'-deoxy-3'-18F-fluorothymidine (18F-FLT). To evaluate the diagnostic value of this technique in myelofibrosis, 18F-FLT PET imaging results were compared with bone marrow histology and bone marrow scintigraphy (BMS), the gold standard techniques in this clinical situation. Methods: Fifteen patients with histology-proven myelofibrosis were included consecutively in the study. Tracers' distributions were assessed using a visual grading assessment score of the uptake in the axial skeleton, proximal and distal limbs, liver, and spleen. This visual score was used to define patterns of tracer distribution and to compare the information provided either by PET or by BMS. A semiquantitative analysis with determination of SUVmax in the same localizations was performed for 18F-FLT PET. Results: The histology grade of fibrosis correlated with the SUVmax in the axial skeleton (spine and iliac crests) and proximal limbs. 18F-FLT uptake in these areas was much lower in patients with grade 3 fibrosis than in patients with grade 1 or 2 fibrosis. 18F-FLT PET showed the same distribution of uptake as BMS in 13 of 14 patients (1 patient did not undergo BMS). In 1 patient, 18F-FLT PET clearly showed an intense abnormal splenic uptake, whereas spleen uptake was inconclusive with BMS. Conclusion:18F-FLT PET appears to be a reliable and convenient technique to assess hematopoietic activity in bone marrow. It yields results close to those observed with BMS. In our study population, 18F-FLT uptake in the axial skeleton and proximal limbs assessed by SUVmax correlated with the grade of fibrosis. Thus, 18F-FLT PET may be a useful tool to measure the severity of myelofibrosis, and to monitor noninvasively the patients' status during follow-up. Finally, 18F-FLT PET may be foreseen as an alternative to BMS.

Modeling therapeutic response to radioiodine in metastatic thyroid cancer: a proof-of-concept study for individualized medicine.

PURPOSE: Radioiodine therapy (RAI) has traditionally been used as treatment for metastatic thyroid cancer, based on its ability to concentrate iodine. Propositions to maximize tumor response with minimizing toxicity, must recognize the infinite possibilities of empirical tests. Therefore, an approach of this study was to build a mathematical model describing tumor growth with the kinetics of thyroglobulin (Tg) concentrations over time, following RAI for metastatic thyroid cancer. EXPERIMENTAL DESIGN: Data from 50 patients with metastatic papillary thyroid carcinoma treated within eight French institutions, followed over 3 years after initial RAI treatments, were included in the model. A semi-mechanistic mathematical model that describes the tumor growth under RAI treatment was designed. RESULTS: Our model was able to separate patients who responded to RAI from those who did not, concordant with the physicians' determination of therapeutic response. The estimated tumor doubling-time (Td was found to be the most informative parameter for the distinction between responders and non-responders. The model was also able to reclassify particular patients in early treatment stages. CONCLUSIONS: The results of the model present classification criteria that could indicate whether patients will respond or not to RAI treatment, and provide the opportunity to perform personalized management plans.

Molecular Pathology of Anaplastic Thyroid Carcinomas: A Retrospective Study of 144 Cases.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a rare tumor, with poorly defined oncogenic molecular mechanisms and limited therapeutic options contributing to its poor prognosis. The aims of this retrospective study were to determine the frequency of anaplastic lymphoma kinase (ALK) translocations and to identify the mutational profile of ATC including TERT promoter mutations. METHODS AND MATERIALS: One hundred and forty-four ATC cases were collected from 10 centers that are a part of the national French network for management of refractory thyroid tumors. Fluorescence in situ hybridization analysis for ALK rearrangement was performed on tissue microarrays. A panel of 50 genes using next-generation sequencing and TERT promoter mutations using Sanger sequencing were also screened. RESULTS: Fluorescence in situ hybridization was interpretable for 90 (62.5%) cases. One (1.1%) case was positive for an ALK rearrangement with a borderline threshold (15% positive cells). Next-generation sequencing results were interpretable for 94 (65.3%) cases, and Sanger sequencing (TERT) for 98 (68.1%) cases. A total of 210 mutations (intronic and exonic) were identified. TP53 alterations were the most frequent (54.4%). Forty-three percent harbored a mutation in the (H-K-N)RAS genes, 13.8% a mutation in the BRAF gene (essentially p.V600E), 17% a PI3K-AKT pathway mutation, 6.4% both RAS and PI3K pathway mutations, and 4.3% both TP53 and PTEN mutations. Nearly 10% of the cases showed no mutations of the RAS, PI3K-AKT pathways, or TP53, with mutations of ALK, ATM, APC, CDKN2A, ERBB2, RET, or SMAD4, including mutations not yet described in thyroid tumors. Genes encoding potentially druggable targets included: mutations in the ATM gene in four (4.3%) cases, in ERBB2 in one (1.1%) case, in MET in one (1.1%) case, and in ALK in one (1.1%) case. A TERT promoter alteration was found in 53 (54.0%) cases, including 43 C228T and 10 C250T mutations. Three out of our cases did not harbor mutations in the panel of genes with therapeutic interest. CONCLUSION: This study confirms that ALK rearrangements in ATC are rare and that the mutational landscape of ATC is heterogeneous, with many genes implicated in the follicular epithelial cell dedifferentiation process. This may explain the limited effectiveness of targeted therapeutic options tested so far.

Late liver metastasis of medullary thyroid cancer with low calcitonin levels - successfully cured by radiofrequency.

A 28-year-old female consulted in 1994 for a left thyroid nodule known for two years with documented progression. Left lobe resection was performed initially followed by total thyroidectomy without lymph node dissection in September 1994. Pathological examination concluded on unilateral 10 × 40 mm medullary thyroid carcinoma (MTC). RET mutation was negative. Basal and pentagastrin-stimulated CT levels had been normal from 1994 to 2008 when her CT level was found to be elevated at 33 ng/L and increased subsequently to 111 ng/L in 2010. In accordance with guidelines, cervical ultrasound was performed repeatedly with negative results. After discussion in a multidisciplinary meeting and with patient's consent, an F-Dopa PET scan was proposed in disagreement with guidelines. This scan showed unique uptake in liver segment VI, which was confirmed by MRI. CT levels reached to 253 ng/L when she finally accepted treatment. In February 2013 we performed radiofrequency ablation of the lesion, which allowed normalisation of CT levels. This observation highlights the possibility of late recurrence of MTC. We could propose that for MTC patients with low-calcitonin levels-recurrences F-DOPA-PET/CT is a good diagnostic tool to use in case of repeatedly negative US neck studies. (Endokrynol Pol 2016; 67 (3): 326-329).

Quality of life, clinical outcomes and safety of early prophylactic levothyroxine administration in patients with Graves' hyperthyroidism undergoing radioiodine therapy: a randomized controlled study.

OBJECTIVE: While radioiodine therapy is commonly used for treating Graves' disease, a prolonged and clinical hypothyroidism may result in disabling symptoms leading to deterioration of quality of life (QoL) of patients. Introducing levothyroxine (LT4) treatment in the early post-therapeutic period may be an interesting approach to limit this phenomenon. METHODS: A multicenter, prospective, open-label randomized controlled trial enrolled 94 patients with Graves' hyperthyroidism randomly assigned to the experimental group (n=46) (group A: early prophylactic LT4 treatment) or the control group (n=48) (group B: standard follow-up). The primary endpoint was the 6-month QoL. The secondary endpoints were other QoL scores such as Graves' ophthalmopathy (GO) outcomes, thyroid function tests and safety. RESULTS: The primary endpoint at 6 months was achieved: the mental composite score (MCS) of Short Form 36 (SF-36) was significantly higher in group A compared to group B (P=0.009). Four other dimension scores of the SF-36 and four dimension scores of the thyroid-specific patient-reported outcome (ThyPRO) significantly differed between the two groups, indicating better QoL in group A. After adjustment for variables, the early LT4 administration strategy was found as an independent factor for only two scores of SF-36: the MCS and the general health (GH) score. There were no differences in GO, final thyroid status and changes in the anti-TSH receptor antibodies (TRAbs) levels between the two groups. No adverse cardiovascular event was reported. CONCLUSION: Early LT4 administration post-radioactive iodine (RAI) could represent a safe potential benefit for patients with regard to QoL. The optimal strategy taking into account administered RAI activities and LT4 treatment dosage and timing remains to be determined.

Management of Graves' disease during pregnancy: the key role of fetal thyroid gland monitoring.

BACKGROUND: Fetuses from mothers with Graves' disease may experience hypothyroidism or hyperthyroidism due to transplacental transfer of antithyroid drugs (ATD) or anti-TSH receptor antibodies, respectively. Little is known about the fetal consequences. Early diagnosis is essential to successful management. We investigated a new approach to the fetal diagnosis of thyroid dysfunction and validated the usefulness of fetal thyroid ultrasonograms. METHODS: Seventy-two mothers with past or present Graves' disease and their fetuses were monitored monthly from 22 wk gestation. Fetal thyroid size and Doppler signals, and fetal bone maturation were determined on ultrasonograms, and thyroid function was evaluated at birth. Thyroid function and ATD dosage were monitored in the mothers. RESULTS: The 31 fetuses whose mothers were anti-TSH receptor antibody negative and took no ATDs during late pregnancy had normal test results. Of the 41 other fetuses, 30 had normal test results at 32 wk, 29 were euthyroid at birth, and one had moderate hypothyroidism on cord blood tests. In the remaining 11 fetuses, goiter was visualized by ultrasonography at 32 wk, and fetal thyroid dysfunction was diagnosed and treated; there was one death, in a late referral, and 10 good outcomes with normal or slightly altered thyroid function at birth. The sensitivity and specificity of fetal thyroid ultrasound at 32 wk for the diagnosis of clinically relevant fetal thyroid dysfunction were 92 and 100%, respectively. CONCLUSION: In pregnant women with past or current Graves' disease, ultrasonography of the fetal thyroid gland by an experienced ultrasonographer is an excellent diagnostic tool. This tool in conjunction with close teamwork among internists, endocrinologists, obstetricians, echographists, and pediatricians can ensure normal fetal thyroid function.

Prevalence of monoclonal gammopathy in patients with primary hyperparathyroidism: a prospective study.

BACKGROUND: The association between primary hyperparathyroidism (PHPT) and monoclonal gammopathy has been reported, but whether it is fortuitous remains unsettled. We conducted a prospective study to determine the prevalence of monoclonal gammopathies in patients with surgically proved PHPT. METHODS: In 101 consecutive patients with PHPT, serum immunoglobulins were systematically studied using agarose gel electrophoresis and immunofixation before and, when appropriate, after parathyroid surgery. The PHPT population was compared with a control series of patients with other diseases requiring surgery and with a group of patients with benign disease of the thyroid gland matched for age and sex to the PHPT population. RESULTS: Monoclonal immunoglobulin was detected in 10 (10%) of 101 patients with PHPT (including 2 with multiple myeloma) compared with 2 (2%) of 127 patients who underwent other surgery (P =.005) and 3 (3%) of 101 patients with benign thyroid diseases (P =.04). CONCLUSIONS: The prevalence of monoclonal gammopathies is high in patients with PHPT. At minimum, sensitive serum protein electrophoresis should be performed routinely in all patients with PHPT. Conversely, in patients with monoclonal gammopathy who have hypercalcemia but no other symptoms of progressive disease, clinicians must seek PHPT.

Quality of Life and Cost-Effectiveness Assessment of Radioiodine Ablation Strategies in Patients With Thyroid Cancer: Results From the Randomized Phase III ESTIMABL Trial.

PURPOSE: In the ESTIMABL phase III trial, the thyroid ablation rate was equivalent for the two thyroid-stimulating hormone (TSH) stimulation methods (thyroid hormone withdrawal [THW] and recombinant human TSH [rhTSH]) and the two iodine-131 ((131)I) activities (1.1 or 3.7 GBq). The objectives of this article were to present health-related quality-of-life (HRQoL) results and a cost-effectiveness evaluation performed alongside this trial. PATIENTS AND METHODS: HRQoL and utility were longitudinally assessed, from random assignment to the follow-up visit at 8 ± 2 months for the 752 patients with thyroid cancer, using the Short Form-36 and the EuroQoL-5D questionnaires, respectively. A cost-effectiveness analysis was performed from the societal perspective in the French context. Resource use (hospitalization for (131)I administration, rhTSH, sick leaves, and transportation) was collected prospectively. We used the net monetary benefit approach and computed cost-effectiveness acceptability curves for both TSH stimulation methods and (131)I activities. Sensitivity analyses of the costs of rhTSH were performed. RESULTS: At (131)I administration, THW caused a clinically significant deterioration of HRQoL, whereas HRQoL remained stable with rhTSH. This deterioration was transient with no difference 3 months later. rhTSH was more effective than THW in terms of quality-adjusted life-years (QALYs; +0.013 QALY/patient) but more expensive (+€474/patient). The probability that rhTSH would be cost effective at a €50,000/QALY threshold was 47% in France. The use of 1.1 GBq of (131)I instead of 3.7 GBq reduced per-patient costs by €955 (US$1,018) but with slightly decreased efficacy (-0.007 QALY/patient). CONCLUSION: rhTSH avoids the transient THW-induced deterioration of HRQoL but is unlikely to be cost effective at its current price.