Annick Van den Bruel

Riedel's thyroiditis and retroperitoneal fibrosis in multifocal fibrosclerosis: Positron emission tomographic findings

Purpose The authors describe F-18 fluorodeoxyglucose positron emission tomographic (FDG PET) imaging features of Riedel’s thyroiditis and retroperitoneal fibrosis in a patient with multifocal fibrosclerosis. Materials and Methods A 41-year-old woman in whom Riedel’s thyroiditis had been diagnosed 7 months earlier was examined for fatigue, anorexia, and lower back pain, irradiating to the abdomen. Abdominal sonography and computed tomography showed a retroperitoneal mass. A biopsy of this mass showed histopathologic findings of retroperitoneal fibrosis. FDG PET was performed to evaluate the activity of the retroperitoneal fibrosis and to screen for other areas of fibrosclerosis. Results The FDG-PET images showed an intense hypermetabolic abdominal mass surrounding the aorta and increased glucose metabolism in the thyroid. No other sites of abnormal FDG metabolism were noted. These abnormalities disappeared after 4 months of steroid therapy. Conclusions Sites of multifocal fibrosclerosis can be demonstrated by FDG PET, probably as a result of active inflammation involving lymphocytes, plasma cells, and fibroblast proliferation. FDG PET can help to establish the diagnosis of multifocal fibrosclerosis and evaluate the activity and patient response to corticosteroid therapy.

Regional Variation in Thyroid Cancer Incidence in Belgium Is Associated With Variation in Thyroid Imaging and Thyroid Disease Management

CONTEXT Increased thyroid cancer incidence is at least partially attributed to increased detection and shows considerable regional variation. OBJECTIVE We investigated whether regional variation in cancer incidence was associated with variations in thyroid disease management. DESIGN We conducted a retrospective population-based cohort study that involved linking data from the Belgian Health Insurance database and the Belgian Cancer Registry to compare thyroid-related procedures between regions with high and low cancer incidence. MAIN OUTCOME MEASURES Primary outcome measures were rates of TSH testing, imaging, fine-needle aspiration cytology (FNAC), and thyroid surgery. Secondary study outcomes were proportions of subjects with thyrotoxicosis and nodular disease treated with surgery, of subjects treated with surgery preceded by FNAC or with synchronous lymph node dissection, and of thyroid cancer diagnosis after surgery. RESULTS The rate of TSH testing was similar, but the rate of imaging was lower in the low incidence region. The rate of FNAC was similar, whereas the rate of surgery was lower in the low incidence region (34 [95% CI 33; 35 ] vs 80 [95% CI 79; 81 ] per 100,000 person years in the high incidence region; P < .05). In the low incidence region compared to the high incidence region, surgery represented a less chosen therapy for euthyroid nodular disease patients (47% [95% CI 46; 48] vs 69% [95% CI 68; 70]; P < .05), proportionally more surgery was preceded by FNAC, more cancer was diagnosed after total thyroidectomy, and thyroid cancer patients had more preoperative FNAC and synchronous lymph node dissection. CONCLUSION Regional variation in thyroid cancer incidence, most marked for low-risk disease, is associated with different usage of thyroid imaging and surgery, supporting variable detection as a key determinant in geographic variation.

Altered expression of key players in vitamin D metabolism and signaling in malignant and benign thyroid tumors.

1,25-DihydroxyvitaminD3 (1,25(OH)2D3), the active form of vitamin D, mediates antitumor effects in various cancers. The expression of key players in vitamin D signaling in thyroid tumors was investigated. Vitamin D receptor (VDR) and CYP27B1 and CYP24A1 (respectively activating and catabolizing vitamin D) expression was studied (RT-PCR, immunohistochemistry) in normal thyroid, follicular adenoma (FA), differentiated thyroid cancer (DTC) consisting of the papillary (PTC) and follicular (FTC) subtype, and anaplastic thyroid cancer (ATC). VDR, CYP27B1, and CYP24A1 expression was increased in FA and DTC compared with normal thyroid. However, in PTC with lymph node metastasis, VDR and CYP24A1 were decreased compared with non-metastasized PTC. In ATC, VDR expression was often lost, whereas CYP27B1/CYP24A1 expression was comparable to DTC. Moreover, ATC with high Ki67 expression (>30%) or distant metastases at diagnosis was characterized by more negative VDR/CYP24A1/CYP27B1 staining. In conclusion, increased expression of key players involved in local 1,25(OH)2D3 signaling was demonstrated in benign and differentiated malignant thyroid tumors, but a decrease was observed for local nodal and especially distant metastasis, suggesting a local antitumor response of 1,25(OH)2D3 in early cancer stages. These findings advocate further studies with 1,25(OH)2D3 and analogs in persistent and recurrent iodine-refractory DTC.

A new approach to imprinting mutation detection in GNAS by Sequenom EpiTYPER system

BACKGROUND Pseudohypoparathyroidism type Ib (PHPIb) results from abnormal imprinting of GNAS. Familial and sporadic forms of PHPIb have distinct GNAS imprinting patterns: familial PHPIb patients have an exon A/B-only imprinting defect and an intragenic STX16 deletion, whereas sporadic PHPIb cases have abnormal imprinting of the three differentially methylated regions (DMRs) in GNAS without the STX16 deletion. Overall GNAS methylation defects have recently been detected in some PHPIa patients. METHODS This study describes the first quantitative methylation analysis of multiple CpG sites for three different GNAS DMRs using the Sequenom EpiTYPER in 35 controls, 12 PHPIb patients, 2 PHPIa patients and 2 patients without parathormone (PTH) resistance but having only hypocalcemia and hyperphosphatemia. RESULTS All patients have GNAS methylation defects typically with NESP hypermethylation versus XL and exon A/B hypomethylation while the imprinting of SNURF/SNRPN was normal. PHPIa patients showed an abnormal methylation in the three DMRs of GNAS. For the first time, a marked abnormal GNAS methylation was also found in 2 patients without PTH resistance but having hypocalcemia and hyperphosphatemia. CONCLUSIONS The Sequenom EpiTYPER proves to be very sensitive in detecting DNA methylation changes. Our analysis also suggests that GNAS imprinting defects might be more frequent and diverse than previously thought.

A Progress Report of the IFCC Committee for Standardization of Thyroid Function Tests

Background: The IFCC Committee for Standardization of Thyroid Function Tests aims at equivalence of laboratory test results for free thyroxine (FT4) and thyrotropin (TSH). Objectives: This report describes the phase III method comparison study with clinical samples representing a broad spectrum of thyroid disease. The objective was to expand the feasibility work and explore the impact of standardization/harmonization in the clinically relevant concentration range. Methods: Two sets of serum samples (74 for FT4, 94 for TSH) were obtained in a clinical setting. Eight manufacturers participated in the study (with 13 FT4 and 14 TSH assays). Targets for FT4 were set by the international conventional reference measurement procedure of the IFCC; those for TSH were based on the all-procedure trimmed mean. The manufacturers recalibrated their assays against these targets. Results: All FT4 assays were negatively biased in the mid- to high concentration range, with a maximum interassay discrepancy of approximately 30%. However, in the low range, the maximum deviation was approximately 90%. For TSH, interassay comparability was reasonable in the mid-concentration range, but worse in the pathophysiological ranges. Recalibration was able to eliminate the interassay differences, so that the remaining dispersion of the data was nearly entirely due to within-assay random error components. The impact of recalibration on the numerical results was particularly high for FT4. Conclusions: Standardization and harmonization of FT4 and TSH measurements is feasible from a technical point of view. Because of the impact on the numerical values, the implementation needs careful preparation with the stakeholders.

A thyroid thriller: acute transient and symmetric goiter after fine-needle aspiration of a solitary thyroid nodule

OBJECTIVE To report a case of a patient who developed an acute and transient, tender, and bilateral swelling of the thyroid that occurred during fine-needle aspiration (FNA) of a solitary nodule in the left thyroid lobe; to add accurate ultrasound measurements to support our clinical observation; and to analyze a possible underlying mechanism of this rare condition. RESULTS AND CLINICAL FOLLOW-UP: The calculated thyroid volume increased from 23 to 57 mL before and at 4 minutes, respectively, after the needle aspiration, but the thyroid volume returned to prediagnostic level after 4 hours. Cytology, serum calcitonin, and histology were concordant, and the nodule was diagnosed as a medullary thyroid carcinoma. Immunohistochemistry was positive for calcitonin, chromogranin, and the very potent vasodilator calcitonin gene-related peptide (CGRP). CONCLUSION This is a rare case of acute and transient thyroid swelling during a common procedure as FNA of a thyroid nodule. This is the first case with documented acute volume expansion quantified by ultrasound measurements supporting our clinical observation, which is in accordance with two historical case reports. The clinical and ultrasound data support the hypothesis of vasodilation as the underlying mechanism, possibly evoked by the release of the vasodilator CGRP.

The Sensitivity and Specificity of the Glucose Challenge Test in a Universal Two-Step Screening Strategy for Gestational Diabetes Mellitus Using the 2013 World Health Organization Criteria

The International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommends a universal one-step screening strategy with the 75-g oral glucose tolerance test (OGTT) for gestational diabetes mellitus (GDM) (1). Since the adoption of the IADPSG recommendation by the World Health Organization (WHO), the IADPSG criteria are commonly referred to as the 2013 WHO criteria (2). The IADPSG recommendation remains controversial due to the significant increase in GDM prevalence, increased workload, the need for a fasting test, and the risk for increased medicalization of care (3). Several professional associations therefore still recommend a universal two-step screening strategy, using a nonfasting 50-g glucose challenge test (GCT) to determine whether an OGTT should be performed (3). The GCT is easier to perform and is generally better tolerated than an OGTT. In addition, a two-step screening strategy with a GCT could limit the number of OGTTs. The GCT has been used in combination with the 100-g OGTT or the 75-g OGTT with various diagnostic criteria, but data are lacking on the sensitivity and specificity of the GCT in conjunction with the 2013 WHO criteria for GDM. We performed a multicentric prospective cohort study, the Belgian Diabetes in Pregnancy Study (BEDIP-N), between 2014 and 2017, enrolling 2,006 women between 6 and 14 weeks of pregnancy (4). Participants without prediabetes or diabetes in early pregnancy (defined by …

A Modified Two-Step Screening Strategy for Gestational Diabetes Mellitus Based on the 2013 WHO Criteria by Combining the Glucose Challenge Test and Clinical Risk Factors

This study determines if a modified two-step screening strategy with a glucose challenge test (GCT) ≥ 7.2 mmol/L and clinical risk factors improves the diagnostic accuracy for gestational diabetes mellitus (GDM), based on 2013 WHO criteria, while limiting the number of oral glucose tolerance tests (OGTT). This was a prospective multicentric cohort study with 1811 participants receiving both GCT and 75 g OGTT in pregnancy. Participants and health care providers were blinded for GCT. Characteristics were analyzed across four glucose tolerance groups: abnormal (≥7.2 mmol/L), GCT GDM (n = 165), normal GCT GDM (n = 63), abnormal GCT normal glucose tolerant (NGT) (n = 472); normal GCT NGT (n = 1113). Compared to normal GCT NGT women, normal GCT GDM women had increased rates of obesity (23.8% vs. 10.5%, p < 0.001), ethnic minority background (19.3% vs. 8.2%, p < 0.001) and a history of GDM (13.8% vs. 4.6%, p = 0.03). By combined screening of GCT ≥ 7.2 mmol/L with these risk factors, sensitivity increased to respectively, 74.1–78.1% using one risk factor, and to 82.9% using any of these risk factors with a specificity of 57.5%. By using a modified two-step screening strategy, the number of women needing both a GCT and OGTT would be reduced to 25.5%, and 52.6% of all OGTTs could be avoided, compared to a universal one-step approach.

Evolution in the management of thyroid cancer: an observational study in two referral centres in Belgium

ABSTRACT Objective Thyroid cancer incidence is increasing. The rise is most pronounced for microcancers (≤10 mm, T1a). In 2006, landmark European and American guidelines for the management of thyroid cancer were published. We studied thyroid cancer characteristics and initial management before and after 2006. Methods We conducted a retrospective observational study of non-medullary thyroid cancer patients that underwent thyroidectomy in two Belgian referral centres comparing pre-, per- and post-operative management in a cohort before and after 2006. Results Cancer subtypes and dimensions in cohort 1 (C1, n = 69) and cohort 2 (C2, n = 60) were comparable, with papillary thyroid cancer (PTC) as main subtype (86 and 82%, respectively), and T1a as main dimension (30 and 38%). In C2, a comparable proportion presented as incidentaloma (20 vs. 14% in C1). Pre-surgical fine needle aspiration (FNA) was performed in 75% in C1 and 83% in C2. The indications for thyroidectomy were comparable, with Bethesda 5–6 as main indication (43% in C1, 52% in C2). No differences were observed for execution of lymph node dissection in the PTC subgroup, hypoparathyroidism and recurrent nerve paresis after 1 year. Less radioiodine was administered in C2 (57 vs 74% in C1, p = 0.04). More neck ultrasonography at 1 year was performed in >T1aN0/x patients (73 vs 49% in C1, p = 0.02). Conclusion The use of FNA is high and established. The proportion of T1a cancers is stable. A shift in the post-operative management is observed towards more restrictive use of radioiodine and increased use of ultrasonography, in accordance with the international guidelines.

Bone scan alterations in aromatase inhibitor-treated patients.

We report bone scan changes in 3 patients receiving aromatase inhibitors as adjuvant treatment for postmenopausal hormone receptor-positive breast cancer. Compared with bone scans before treatment, repeated scans after at least 10 months of aromatase inhibitor treatment showed increased activity in the peripheral skeleton and the skull. In 2 patients, these alterations could be correlated with increased markers of bone turnover. They probably result from high bone turnover induced by estrogen depletion caused by aromatase inhibitors. This effect should be taken into account in the differential diagnosis of a bone scan pattern suggestive of hyperparathyroidism, which was ruled out.