Impact of scatter correction on personalized dosimetry in selective internal radiotherapy using 166Ho-PLLA: a single-center study including Monte-Carlo simulation, phantom and patient imaging.

BACKGROUND: Developments in transarterial radioembolization led to the conception of new microspheres loaded with holmium-166 (166Ho). However, due to the complexity of the scatter components in 166Ho single photon emission computed tomography (SPECT), questions about image quality and dosimetry are emerging. The aims of this work are to investigate the scatter components and correction methods to propose a suitable solution, and to evaluate the impact on image quality and dosimetry including Monte-Carlo (MC) simulations, phantom, and patient data. METHODS: Dual energy window (DEW) and triple energy window (TEW) methods were investigated for scatter correction purposes and compared using Contrast Recovery Coefficients (CRC) and Contrast to Noise Ratios (CNR). First, MC simulations were carried out to assess all the scatter components in the energy windows used, also to confirm the choice of the parameter needed for the DEW method. Then, MC simulations of acquisitions of a Jaszczak phantom were conducted with conditions mimicking an ideal scatter correction. These simulated projections can be reconstructed and compared with real acquisitions corrected by both methods and then reconstructed. Finally, both methods were applied on patient data and their impact on personalized dosimetry was evaluated. RESULTS: MC simulations confirmed the use of k = 1 for the DEW method. These simulations also confirmed the complexity of scatter components in the main energy window used with a high energy gamma rays component of about half of the total counts detected, together with a negligible X rays component and a negligible presence of fluorescence. CRC and CNR analyses, realized on simulated scatter-free projections of the phantom and on scatter corrected acquisitions of the same phantom, suggested an increased efficiency of the TEW method, even at the price of higher level of noise. Finally, these methods, applied on patient data, showed significant differences in terms of non-tumoral liver absorbed dose, non-tumoral liver fraction under 50 Gy, tumor absorbed dose, and tumor fraction above 150 Gy. CONCLUSIONS: This study demonstrated the impact of scatter correction on personalized dosimetry on patient data. The use of a TEW method is proposed for scatter correction in 166Ho SPECT imaging.

Autonomously functioning thyroid nodules present intermediate malignancy risk according to European Thyroid Imaging Reporting and Data System (EU-TIRADS) and yield indeterminate cytology results.

Objectives: The aim was to evaluate the clinical, ultrasound (US) and, when indicated, the cytological and histological characteristics of autonomously functioning thyroid nodules (AFTN) in consecutive patients. Methods: A prospective, single-centre study was conducted between March 2018 and September 2021. In total, 901 consecutive patients were referred for thyroid workup and of 67 AFTN were evaluated. All enrolled patients underwent 99mTcO4 - scintigraphy, additional 123I scintigraphy only in case of normal serum TSH, evaluation of thyroid function, US examination using European Thyroid Imaging and Reporting Data System (EU-TIRADS), and US-guided fine needle aspiration (FNA) cytology when indicated. All indeterminate FNA samples were subjected to DNA sequencing analysis. Results: More than half of the evaluated patients with AFTN were euthyroid; median serum TSH was 0.41 (IQR: 0.03-0.97) mU/L. The median AFTN size measured by US was 27.0 (IQR: 21.1-35.0) mm. 28.4% of AFTN were classified as EU-TIRADS score 3 and 71.6% as EU-TIRADS score 4, indicating that the majority of AFTN had intermediate risk for malignancy according to US. Out of the 47 AFTN subjected to cytological evaluation, 24 (51%) yielded indeterminate FNA results. DNA sequencing revealed pathogenic TSHR and GNAS mutations in 60% of cases. No malignancy was detected at final histology in surgically excised AFTN (n = 12). Conclusions: Of the 67 AFTN evaluated in this study, 50% presented with normal serum TSH, 70% displayed ultrasound features suggesting an intermediate malignancy risk and 50% of the AFTN submitted to cytology yielded indeterminate results. No malignant AFTN was detected.

Clinical impact of 99mTc-MAA SPECT/CT-based personalized predictive dosimetry in selective internal radiotherapy: a real-life single-center experience in unresectable HCC patients.

BACKGROUND: Recent data demonstrated that personalized dosimetry-based selective internal radiotherapy (SIRT) is associated with better outcome for unresectable hepatocellular carcinoma (HCC). AIM: We aim to evaluate the contribution of personalized predictive dosimetry (performed with Simplicity90® software) in our population of HCC patients by comparing them to our historical cohort whose activity was determined by standard dosimetry. METHODS: This is a retrospective, single-center study conducted between February 2016 and December 2020 that included patients with HCC who received SIRT after simulation based on either standard dosimetry (group A) or, as of December 2017, on personalized dosimetry (group B). Primary endpoints were best overall response (BOR) and objective response rate (ORR) evaluated by mRECIST at 3 months. Safety and toxicity profiles were evaluated at 1- and 3-months post-treatment. For group A we compared the activity to be administered determined a posteriori using Simplicit90Y® and the activity actually administered determined by the standard approach. RESULTS: Between February 2016 and December 2020, 66 patients received 69 simulations leading to 40 treatments. The median follow-up time was equal for both groups, 21 months (range 3-55) in group A and 21 months (range 4-39) in group B. The per patient analysis revealed a significant benefit of personalized predictive dosimetry in terms of better overall response at 3 months (80% vs. 33.3%, p = 0.007) and at 6 months (77.8% vs. 22.2%, p = 0.06). This trend was found in the analysis by nodule with a response rate according to mRECIST of 87.5% for personalized dosimetry versus 68.4% for standard dosimetry at 3 months, p = 0.24. Only one grade 3 biological toxicity (hyperbilirubinemia) was noted in group A. The comparison between the administered activity and the recommended activity recalculated a posteriori using Simplicit90Y® showed that the vast majority of patients who progressed (83.33%) received less activity than that recommended by the personalized approach or an inadequate distribution of the administered activity. CONCLUSIONS: Our study aligns to recent literature and confirms that the use of personalized dosimetry allows a better selection of HCC patients who can benefit from SIRT, and consequently, improves the effectiveness of this treatment.

Comparison of PMT-based TF64 and SiPM-based Vereos PET/CT systems for 90 Y imaging and dosimetry optimization: A quantitative study.

BACKGROUND: Selective internal radiotherapy based on transarterial radioembolization (TARE) with yttrium-90 (90 Y) microspheres is an established treatment for primary or metastatic liver disease. PURPOSE: The objective of this work is to optimize the dosimetry of patients treated with 90 Y TARE, using positron emission tomography (PET) images. METHODS: The NEMA 2012 PET phantom was filled with nearly 3.9 GBq of 90 Y activity and acquired at days 0, 3, 5, 7, and 9 on a classic time-of-flight PET/computed tomography (CT) scanner (Philips TF64) and on a silicon photomultiplier (SiPM)-based PET/CT scanner (Philips Vereos). Acquisitions were carried on following the guidelines proposed in a previously published multicentric trial and images were reconstructed by varying and combining the available parameters. Comparisons were performed to identify the best set(s) of parameters leading to the most accurate 90 Y-PET image(s), in terms of activity distribution. Then, for both scanners, the best images were analyzed with Simplicit90 Y, a personalized dosimetry software using multicompartmental Medical Internal Radiation Dose model. The comparison between measured and true doses allowed to identify the image granting the most consistent dose estimations and, therefore, to designate the set of parameters to be applied on patients' data for the reconstruction of optimized clinical images. Posttreatment dosimetry of four patients was then realized with Simplicit90 Y using optimized imaging datasets. RESULTS: Based on activity distribution comparisons and dose estimations over phantom and patients data, the SiPM-based PET/CT system appeared more suitable than the photomultiplier tube-based TF64 for 90 Y-PET imaging. With the SiPM-based PET/CT system, reconstructed images with a 2-mm voxel size combined with the application of the point spread function correction led to the most accurate results for quantitative 90 Y measures. CONCLUSIONS: For the SiPM-based PET/CT scanner, an optimized set of reconstruction parameters has been identified and applied on patients' data in order to generate the most accurate image to be used for an improved personalized 90 Y-PET dosimetry, ensuring a reliable evaluation of the delivered doses.

Register-based information on thyroid diseases in Europe: lessons and results from the EUthyroid collaboration.

Objective: Registers of diagnoses and treatments exist in different forms in the European countries and are potential sources to answer important research questions. Prevalence and incidence of thyroid diseases are highly dependent on iodine intake and, thus, iodine deficiency disease prevention programs. We aimed to collect European register data on thyroid outcomes to compare the rates between countries/regions with different iodine status and prevention programs. Design: Register-based cross-sectional study. Methods: National register data on thyroid diagnoses and treatments were requested from 23 European countries/regions. The provided data were critically assessed for suitability for comparison between countries/regions. Sex- and age-standardized rates were calculated. Results: Register data on ≥1 thyroid diagnoses or treatments were available from 22 countries/regions. After critical assessment, data on medication, surgery, and cancer were found suitable for comparison between 9, 10, and 13 countries/regions, respectively. Higher rates of antithyroid medication and thyroid surgery for benign disease and lower rates of thyroid hormone therapy were found for countries with iodine insufficiency before approx. 2001, and no relationship was observed with recent iodine intake or prevention programs. Conclusions: The collation of register data on thyroid outcomes from European countries is impeded by a high degree of heterogeneity in the availability and quality of data between countries. Nevertheless, a relationship between historic iodine intake and rates of treatments for hyper- and hypothyroid disorders is indicated. This study illustrates both the challenges and the potential for the application of register data of thyroid outcomes across Europe.

18F-Fluorocholine PET/CT Is More Sensitive Than 11C-Methionine PET/CT for the Localization of Hyperfunctioning Parathyroid Tissue in Primary Hyperparathyroidism.

Preoperative molecular imaging is paramount to direct surgery in primary hyperparathyroidism (pHPT). We investigated the diagnostic performance of 18F-fluorocholine (18F-FCH) PET/CT compared with 11C-methionine (11C-MET) PET/CT for localization of hyperfunctioning parathyroid tissue in patients with pHPT and negative or inconclusive 99mTc-sestaMIBI (99mTc-MIBI) SPECT findings. Methods: Fifty-eight patients with biochemical evidence of pHPT and negative or inconclusive 99mTc-MIBI SPECT findings were referred for presurgical detection and localization of hyperfunctioning parathyroid tissue by 11C-MET and 18F-FCH PET/CT. The PET/CT results were classified into 3 categories (positive, inconclusive, or negative) based on the nodular aspect of tracer uptake and the visualization of corresponding nodules on CT. The PET/CT results were correlated with the surgical and histopathologic findings, which were used as the gold standard. Results: Fifty-three patients were included for analysis. 18F-FCH PET/CT was positive in 39 patients (74%), inconclusive in 5 (9%), and negative in 9 (17%), compared with 25 (47%), 12 (23%), and 16 (30%), respectively, for 11C-MET PET/CT. 18F-FCH localized 11 additional foci (6 positive and 5 inconclusive), compared with 11C-MET. Twenty-six patients (sex ratio, 10/16 M/F) underwent surgery, with resection of 31 lesions (22 adenomas, 6 hyperplastic glands, and 3 carcinomas) and 1 normal gland. At follow-up, 21 patients (81%) were considered cured after surgery, whereas 3 patients (12%) had persistence of hypercalcemia. With inconclusive cases being considered negative, 18F-FCH PET/CT correctly localized 26 lesions in 24 of 26 patients (92%), compared with 16 lesions in 15 of 26 patients (58%) localized by 11C-MET PET/CT. Per-patient-based sensitivity and positive predictive value were 96% and 96%, respectively, for 18F-FCH and 60% and 94%, respectively, for 11C-MET (P < 0.0001). Per-lesion-based sensitivity and positive predictive value were 84% and 90%, respectively, for 18F-FCH and 52% and 94%, respectively, for 11C-MET (P < 0.0001). Conclusion: In the presence of biochemical evidence of pHPT with negative or inconclusive 99mTc-MIBI SPECT findings, 18F-FCH PET/CT performs better than 11C-MET PET/CT for the detection of pathologic parathyroid tissue, allowing localization of parathyroid adenoma or hyperplasia in 96% of patients.

Iron Deficiency Is a Risk Factor for Thyroid Dysfunction During Pregnancy: A Population-Based Study in Belgium.

Background: Iron deficiency affects thyroid hormone synthesis by impairing the activity of the heme-dependent thyroid peroxidase. The prevalence of iron deficiency is elevated particularly in pregnant women. This study aimed to investigate the effects of iron status on thyroid function in a nationally representative sample of mildly iodine-deficient pregnant women. Methods: The study population comprised a sample of pregnant women in Belgium during the first and third trimesters of pregnancy (n = 1241). Women were selected according to a multistage proportional-to-size stratified and clustered sampling design. Urine and blood samples were collected, and a questionnaire was completed face to face with the study nurse. Concentrations of free thyroxine (fT4), total thyroxine (T4), free triiodothyronine, thyrotropin (TSH), thyroglobulin (Tg), thyroid peroxidase antibodies, Tg antibodies, hemoglobin, serum ferritin (SF), soluble transferrin receptor, urinary iodine concentrations (UICs) were measured and body iron stores (BIS) were calculated. Results: Median UICs were 117 and 132 µg/L in the first and third trimesters of pregnancy, respectively (p < 0.05). The frequency of SF <15 µg/L was 6.2% in the first trimester and 39.6% in the third trimester of pregnancy (p < 0.05). UIC was a significant predictor of serum Tg concentrations (p < 0.01) but not of thyroid hormone or TSH concentrations. The frequency of fT4

Decision-Analytic Modeling Studies in Prevention and Treatment of Iodine Deficiency and Thyroid Disorders: A Systematic Overview.

Background: Prevention and treatment of iodine deficiency-related diseases remain an important public health challenge. Iodine deficiency can have severe health consequences, such as cretinism, goiter, or other thyroid disorders, and it has economic implications. Our aim was to give an overview of studies applying decision-analytic modeling to evaluate the effectiveness and/or cost-effectiveness of iodine deficiency-related prevention strategies or treatments related to thyroid disorders. Methods: We performed a systematic literature search in PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online), EMBASE (Excerpta Medica Database), Tuft's Cost-Effectiveness Analysis Registry, and National Health System Economic Evaluation Database (NHS EED) to identify studies published between 1985 and 2018 comparing different prevention or treatment strategies for iodine deficiency and thyroid disorders by applying a mathematical decision-analytic model. Studies were required to evaluate patient-relevant health outcomes (e.g., remaining life years, quality-adjusted life years [QALYs]). Results: Overall, we found 3950 studies. After removal of duplicates, abstract/title, and full-text screening, 17 studies were included. Eleven studies evaluated screening programs (mainly newborns and pregnant women), five studies focused on treatment approaches (Graves' disease, toxic thyroid adenoma), and one study was about primary prevention (consequences of iodine supplementation on offspring). Most of the studies were conducted within the U.S. health care context (n = 7). Seven studies were based on a Markov state-transition model, nine studies on a decision tree model, and in one study, an initial decision tree and a long-term Markov state-transition model were combined. The analytic time horizon ranged from 1 year to lifetime. QALYs were evaluated as health outcome measure in 15 of the included studies. In all studies, a cost-effectiveness analysis was performed. None of the models reported a formal model validation. In most cases, the authors of the modeling studies concluded that screening is potentially cost-effective or even cost-saving. The recommendations for treatment approaches were rather heterogeneous and depending on the specific research question, population, and setting. Conclusions: Overall, we predominantly identified decision-analytic modeling studies evaluating specific screening programs or treatment approaches; however, there was no model evaluating primary prevention programs on a population basis. Conclusions deriving from these studies, for example, that prevention is cost-saving, need to be carefully interpreted as they rely on many assumptions.

Unilateral Adrenalectomy Could Be a Valid Option for Primary Nodular Adrenal Disease: Evidence From Twins.

Primary pigmented nodular adrenal disease (PPNAD) accounts for <1% of ACTH-independent Cushing syndrome. We describe the case of twin female patients with PPNAD who both had sustainable disease control after unilateral adrenalectomy, which corroborates current evidence in favor of unilateral adrenalectomy for a subset of patients with PPNAD. Patient A presented with a 10-kg weight gain over the past year and facial plethora. Diagnostic evaluation revealed abolition of normal cortisol rhythm with suppressed ACTH levels, normal adrenal CT and MRI imaging and a slightly left-predominant adrenal uptake on 131I iodomethyl norcholesterol scintigraphy coupled with single-photon emission CT/CT. PPNAD was confirmed after genetic testing revealed a known pathogenic PRKA1A mutation (c.709 (-7-2) del6). At that time, her twin sister (patient B) was asymptomatic. Patient A underwent successful unilateral adrenalectomy and histology confirmed PPNAD. Two years after initial onset of symptoms in patient A, patient B was seen for the same subtle symptoms of progressive weight gain. Diagnostic test results were identical, revealing the same clinical features and mutational status as patient A. Patient B also underwent unilateral adrenalectomy with a favorable outcome. Follow-up 3 years after surgery for patient A and 18 months for patient B showed sustained disease control without recurrence and uncompromised quality of life, with no adrenal insufficiency having occurred. Unilateral adrenalectomy can be a successful therapeutic approach for patients with PPNAD with a mild phenotype without the risk and the inconvenience of subsequent adrenal insufficiency, which alters quality of life.

Is there still a role for thyroid scintigraphy in the workup of a thyroid nodule in the era of fine needle aspiration cytology and molecular testing?

Thyroid scintigraphy is now rarely used in the work-up of a thyroid nodule except in the presence of a low TSH value. Therefore, autonomously functioning thyroid nodules (AFTNs) with a normal TSH value are diagnosed only in the rare medical centers that continue to use thyroid scan systematically in the presence of a thyroid nodule. In this review, we discuss the prevalence of AFTN with a normal TSH level and the possible consequences of performing fine needle aspiration cytology (FNAC) in an undiagnosed AFTN. We also discuss the risk of malignant AFTN which may be higher than previously stated.

Neonatal thyroid-stimulating hormone level is influenced by neonatal, maternal, and pregnancy factors.

The percentage of newborns with a neonatal whole blood thyroid-stimulating hormone (TSH) greater than 5 mIU/L has been used as an indicator of iodine deficiency at the population level. However, TSH levels in newborns may be influenced by many factors other than iodine status. The objective of this study was to identify neonatal, maternal, and pregnancy-related determinants of neonatal TSH levels in a retrospective cohort study. The study sample included 313 Belgian mothers and their 4- to 5-year-old children. The children had a neonatal TSH concentration between 0 and 15 mIU/L at neonatal screening, and blood samples were collected 3 to 5 days after birth. Children with suspected congenital hypothyroidism (neonatal TSH level >15 mIU/L), prematurely born (i.e., <37 weeks), or with a low birth weight (i.e., <2500 g) were excluded. Information about maternal and birth-related determinants was collected from the neonatal screening center via a self-administered questionnaire filled in by the mother together with the child's health booklet. Higher TSH levels were found in spring and winter compared to summer and autumn (P = .011). Higher TSH levels were associated with lifetime smoking behavior (up to child birth) in the mother (P = .005), lower weight gain during pregnancy (P = .014), and longer pregnancies (P = .003). This study showed that several neonatal, maternal, and pregnancy-related determinants are influencing neonatal TSH level.

Thiamazole Pretreatment Lowers the (131)I Activity Needed to Cure Hyperthyroidism in Patients With Nodular Goiter.

CONTEXT: Relatively low radioiodine uptake (RAIU) represents a common obstacle for radioiodine ((131)I) therapy in patients with multinodular goiter complicated by hyperthyroidism. OBJECTIVE: To evaluate whether thiamazole (MTZ) pretreatment can increase (131)I therapeutic efficacy. DESIGN AND SETTING: Twenty-two patients with multinodular goiter, subclinical hyperthyroidism, and RAIU < 50% were randomized to receive either a low-iodine diet (LID; n = 10) or MTZ 30 mg/d (n = 12) for 42 days. Thyroid function and 24-hour RAIU were measured before and after treatment. Thyroid volume was evaluated by either magnetic resonance imaging or single photon emission computed tomography. RESULTS: Mean 24-hour RAIU increased significantly from 32 ± 10% to 63 ± 18% in the MTZ group (P < .001). Consequently, there was a 31% decrease in the calculated median therapeutic (131)I activity after MTZ (P < .05). No significant changes in 24-hour RAIU were observed after diet. In the MTZ group, median serum TSH levels increased significantly by 9% and mean serum free T4 and free T3 concentrations decreased by 22% and 15%, respectively, whereas no changes in thyroid function were observed in the LID group. Thyroid volume did not significantly change in either of the two groups. At 12 months after radioiodine treatment, median serum TSH was within the normal range in both groups. CONCLUSIONS: MTZ treatment before (131)I therapy resulted in an average 2-fold increase in thyroid RAIU and enhanced the efficiency of radioiodine therapy assessed at 12 months. MTZ pretreatment is therefore a safe, easily accessible alternative to recombinant human TSH stimulation and a more effective option than LID.

TSH measurement is not an appropriate screening test for autonomous functioning thyroid nodules: a retrospective study of 368 patients.

OBJECTIVE: Based on the assumption that normal TSH concentration rules out the presence of autonomous functioning thyroid nodules (AFTNs), clinical guidelines on the management of thyroid nodules only recommend a thyroid scan if TSH concentration is subnormal. However, the proportion of AFTN presenting with a normal TSH is unknown. Our objective is therefore to determine the proportion of AFTNs with a normal TSH level to ascertain whether a normal TSH really rules out an AFTN. DESIGN: Retrospective study on 368 patients with an AFTN. METHODS: Thyroid scans with a diagnosis of AFTN were reviewed retrospectively by one of us (R Moreno-Reyes), blinded to the clinical data. The diagnosis of solitary AFTN was confirmed in 368 patients. Among them, we selected 217 patients based on the absence of another thyroid nodule >10 mm, the absence of medical conditions able to interfere with thyroid function, and the completeness of the data. RESULTS: The proportion of AFTNs with normal TSH was 49%. This proportion increased to 71% in patients for whom thyroid scan was performed in the workup of a thyroid nodule. CONCLUSIONS: Our data suggest that serum TSH is not an effective screening tool to diagnose AFTNs. Using 'TSH-only' screening, as recommended by the majority of guidelines, the diagnosis of AFTN would have been missed in 71% of our patients in the workup of a thyroid nodule. Thyroid scan remains the gold standard for detecting AFTN and should be considered before performing fine-needle aspiration cytology (FNAC), as the reliability of FNAC in an unsuspected AFTN remains unclear.

Iron status and its determinants in a nationally representative sample of pregnant women.

Iron-deficiency anemia is associated with adverse neonatal health outcomes. Iron status and its determinants were assessed in a representative sample of Belgian pregnant women. Blood samples were collected and a questionnaire was completed face-to-face. Hemoglobin (Hb) and mean cell volume were measured using a Beckman Coulter Hematology Analyzer and serum ferritin (SF) and transferrin receptor (sTfr) concentrations by immunoassay. In total, 55 obstetric clinics and 1,311 pregnant women were included. Approximately 40% of third-trimester and 6% of first-trimester women had SF levels less than 15 µg/L. Approximately 21% of third-trimester and 4% of first-trimester women had anemia (Hb <110 g/L). Of the third-trimester women, 23% were iron-deficient nonanemic (SF <15 µg/L and Hb ≥110 g/L), 16% had iron-deficiency anemia (SF <15 µg/L and Hb <110 g/L), and approximately 7% had tissue iron deficiency (sTfr >8.5 mg/L). The median body iron stores were 8.1 mg/kg among first-trimester women, but only 3.6 mg/kg among third-trimester women. SF levels were significantly positively associated with age and education level, and were higher among nulliparous women and lower among North-African women. sTfr concentrations were significantly negatively associated with age and were lower among smokers, nulliparous women, and women who planned their pregnancy. Despite the fact that two thirds of Belgian pregnant women took iron-containing supplements, iron deficiency and iron-deficiency anemia were frequent in third-trimester women. The World Health Organization regards this as a moderate public health problem. National iron supplementation guidelines are needed in Belgium to optimize iron status during pregnancy.

Corticosteroid therapy, vitamin D status, and inflammatory cytokine profile in the HIV-tuberculosis immune reconstitution inflammatory syndrome.

BACKGROUND: Tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) in patients coinfected with human immunodeficiency virus (HIV) and tuberculosis starting antiretroviral therapy (ART) is associated with hypercytokinemia. As adjunctive corticosteroid therapy and vitamin D have immunomodulatory properties, we investigated the relationship between cytokine/chemokine profiles, corticosteroid use, and vitamin D deficiency in TB-IRIS patients. METHODS: Plasma from 39 TB-IRIS and 42 non-IRIS patients was collected during a prospective study of HIV-associated tuberculosis patients starting ART. In total, 26% of patients received corticosteroid (CTC) therapy pre-ART for severe tuberculosis. Concentrations of total 25-hydroxyvitamin D (25(OH)D) and 14 cytokines/chemokines were determined at ART initiation and 2 weeks later. RESULTS: Patients prescribed concurrent CTC had lower interferon γ (IFN-γ), IP-10, tumor necrosis factor (TNF), interleukin (IL)-6, IL-8, IL-10, IL-12p40, and IL-18 pre-ART (P ≤ .02). TB-IRIS presented at 12 days (median) of ART, irrespective of CTC use. In patients who developed TB-IRIS (not on CTC) IL-6, IL-8, IL-12p40, IL-18, IP-10, and TNF increased during 2 weeks (P ≤ .04) of ART. Vitamin D deficiency (total 25(OH)D <75 nmol/L) was highly prevalent (89%) at baseline. Although vitamin D deficiency at either baseline or 2 weeks was not associated with TB-IRIS, in those not on CTC the median 25(OH)D decreased during 2 weeks (P = .004) of ART. Severe vitamin D deficiency (total 25(OH)D <25 nmol/L) was associated with higher baseline TNF, IL-6, and IL-8 irrespective of IRIS status. CONCLUSIONS: CTC modifies the inflammatory profile of those who develop TB-IRIS. The association between severe vitamin D deficiency and elevated proinflammatory cytokines support a study of vitamin D supplementation in HIV-TB co-infected patients starting ART.

Does a small difference in iodine status among children in two regions of Belgium translate into a different prevalence of thyroid nodular diseases in adults?

PURPOSE: To explore whether there are regional differences in iodine status and in prevalence of thyroid diseases in the two main regions of Belgium. METHODS: A national survey of iodine status among children was performed in 1998. The raw data of this survey were reanalyzed to explore regional differences. The total number of thyroidectomies, carried out for multinodular goiter or solitary nodules, was obtained from the Minimal Clinical Summary hospital discharge database. Percentage of people with thyroid diseases going to the general practitioner or the specialist was assessed by means of data about the number of adults using anti-thyroid medications. Food consumption patterns were explored using national food consumption data. RESULTS: In Flanders, median urinary iodine concentration (UIC) was higher than in Wallonia, 84 µg/L (n = 1,316) and 78 µg/L (n = 1,268), respectively (p < 0.001). There were no differences in goiter prevalence and thyroid volume between the regions among children. Data from the food consumption survey showed a significant higher consumption of seafood in Flanders compared to Wallonia. Further, it was observed that the number of thyroidectomies, carried out for MNG or solitary nodules, and the use of anti-thyroid medication were significantly higher in Wallonia than in Flanders. CONCLUSION: Iodine status in children was found slightly different in both regions of the country. This finding is in agreement with a higher incidence of thyroidectomies and more extensive use of anti-thyroid medications in the adult population in the region with the lowest iodine excretion.

Projected reduction in healthcare costs in Belgium after optimization of iodine intake: impact on costs related to thyroid nodular disease.

BACKGROUND: Several surveys in the last 50 years have repeatedly indicated that Belgium is affected by mild iodine deficiency. Within the framework of the national food and health plan in Belgium, a selective, progressive, and monitored strategy was proposed in 2009 to optimize iodine intake. The objective of the present study was to perform a health economic evaluation of the consequences of inadequate iodine intake in Belgium, focusing on undisputed and measurable health outcomes such as thyroid nodular disease and its associated morbidity (hyperthyroidism). METHODS: For the estimation of direct, indirect, medical, and nonmedical costs related to thyroid nodular diseases in Belgium, data from the Federal Public Service of Public Health, Food Chain Safety and Environment, the National Institute for Disease and Disability Insurance (RIZIV/INAMI), the Information Network about the prescription of reimbursable medicines (FARMANET), Intercontinental Marketing Services, and expert opinions were used. These costs translate into savings after implementation of the iodization program and are defined as costs due to thyroid nodular disease throughout the article. Costs related to the iodization program are referred to as program costs. Only figures dating from before the start of the intervention were exploited. Only adult and elderly people (≥18 years) were taken into account in this study because thyroid nodular diseases predominantly affect this age group. RESULTS: The yearly costs due to thyroid nodular diseases caused by mild iodine deficiency in the Belgian adult population are ∼€38 million. It is expected that the iodization program will result in additional costs of ∼€54,000 per year and decrease the prevalence of thyroid nodular diseases by 38% after a 4-5-year period. The net savings after establishment of the program are therefore estimated to be at least €14 million a year. CONCLUSIONS: Optimization of iodine intake in Belgium should be quite cost effective, if only considering its impact on nodular thyroid disease. There are likely added benefits relating to more optimal thyroid hormone influenced brain development that are more difficult to estimate but may be even more important.

A potential role of endogenous progesterone in modulation of GH, prolactin and thyrotrophin secretion during normal menstrual cycle.

OBJECTIVE: Previous studies investigating the fluctuations of endocrine secretion across the menstrual cycle yielded inconsistent results. Our objective was to evaluate during the menstrual cycle the potential role of endogenous oestradiol and progesterone in the regulation of hormones primarily controlled by the circadian clock and/or the sleep-wake cycle. SUBJECTS AND DESIGN: Ten normally cycling young lean women were investigated once during follicular and once during luteal phase. Sleep was polygraphically recorded, and blood samples were obtained at 20-min intervals for 24 h. RESULTS: Sleep variables and diurnal melatonin and cortisol profiles (hormones primarily controlled by the circadian clock) were similar in both conditions. The TSH evening rise (a circadian marker) was similar in both conditions, but the sleep-related nocturnal TSH decrease occurred earlier during the luteal phase (P = 0.03) and tended to correlate positively with progesterone levels (r(s) = -0.64, P < 0.06). Daytime GH secretion and afternoon/evening PRL secretion (hormones primarily controlled by the sleep-wake homeostasis) were increased in the luteal phase compared with those of the follicular phase (GH: P = 0.04; PRL: P = 0.01). The increase in 24-h GH secretion was associated with higher progesterone levels (r(s) = 0.78, P = 0.02). In luteal phase, the evening PRL rise was associated with higher progesterone (r(s) = 0.70, P = 0.04) and oestradiol (r(s) = 0.72, P = 0.03) levels. CONCLUSION: The present data indicate that in normally cycling young women, daytime GH and PRL secretions are increased in luteal phase. These data also suggest that endogenous progesterone could play a modulation role on pituitary hormone secretion, stimulating GH and PRL release and enhancing the inhibitory action of sleep on TSH secretion.

Vitamin D deficiency and hyperparathyroidism in relation to ethnicity: a cross-sectional survey in healthy adults.

BACKGROUND: The study of vitamin D status at population level gained relevance since vitamin D deficiency was recently suggested to trigger chronic disease. AIM OF THE STUDY: We aimed to describe vitamin D status, its association with bone and mineral metabolism and risk factors for deficiency in adults over 40 years in Belgium. METHODS: We conducted a cross-sectional survey in a stratified random sample of 401 subjects aged between 40 and 60 years living in Brussels, and drawn from 4 different ethnic backgrounds: autochthonous Belgian, Moroccan, Turkish and Congolese. 25-Hydroxyvitamin D (25OHD), parathyroid hormone (PTH), osteocalcin, C-telopeptide and bone mineral density was measured. RESULTS: Three-hundred and six subjects (77%) showed 25OHD concentrations below 50 nmol/l,135 (34%) below 25 nmol/l and 18 (5%) below 12.5 nmol/l. The proportion of subjects with vitamin D deficiency was four times greater amongst those of Moroccan or Turkish descent compared with those of Congolese or Belgian descent. Moroccan subjects showed a significant higher PTH and bone marker concentrations compared to Belgian. Ethnicity, season and sex were independently associated with vitamin D deficiency in multivariate analysis. CONCLUSION: The prevalence of vitamin D deficiency is very high amongst the adult population of Brussels but immigrants are at greater risk. Given the established link between population health and adequate vitamin D status, a policy of vitamin D supplementation should be considered in these risk groups.