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Summary: Objective: Monitoring the influence of cautious iodine fortification (IF) on the incidence rate of overt thyrotoxicosis in Denmark with formerly frequent multinodular toxic goitre. Design: A 21‐year (1997‐2017) prospective population‐based study identified all new cases of overt biochemical thyrotoxicosis in two open cohorts: a Western cohort with moderate iodine deficiency (ID) and an Eastern cohort with mild ID (total n = 533 969 by 1 January 1997). A diagnostic algorithm was applied to all thyroid function tests performed within the study areas. Mandatory IF of salt was initiated in mid‐2000 (13 ppm). This study is a part of DanThyr. Results: The standardized incidence rate (SIR) of thyrotoxicosis at baseline (1997‐1998) was 128.5/100.000/year in the cohort with moderate ID and 80.1 in the cohort with mild ID. SIR increased markedly in both cohorts during the initial years of IF (moderate/mild ID: +39/+52% in 2000‐2001/2004‐2005) and subsequently decreased to baseline level (mild ID) or below (moderate ID) by 2008. The decline was due to a marked decrease in the incidence rate among elderly subjects and a moderate decrease among the middle aged. The follow‐up period for the mildly iodine deficient cohort was restricted to 2008. A continuous decline in SIR was observed for the remainder of the study period in the area with moderate ID (33% below baseline in 2016‐2017). Conclusion: The rise in thyrotoxicosis incidence with cautious mandatory IF returned to baseline level after 7‐8 years and levelled out at 33% below baseline in the population with previously moderate ID after 16‐17 years. [ABSTRACT FROM AUTHOR]

Objective Thyroid core needle biopsy (CNB) is increasingly being used as a tool for evaluating thyroid nodules; thus, standardization of its diagnostic terminology is called for. We aimed to analyse the pathologic reporting system of thyroid CNB based on the recently proposed protocol by the Korean Endocrine Pathology Thyroid Core Needle Biopsy Study Group and evaluate its usefulness. Design/Methods A total of 1998 consecutive cases of thyroid CNBs were reviewed and divided into six categories according to the protocol. Malignancy rate in each category and the diagnostic performance of thyroid CNB were calculated using 705 resected cases. Results Thyroid CNB yielded 132 nondiagnostic (6.6%), 791 benign (39.6%), 328 indeterminate (16.4%), 227 follicular neoplasm (11.4%), 69 suspicious for malignancy (3.5%) and 451 malignant lesions (22.6%). In resected specimens, all of the cases designated as suspicious for malignancy and malignant categories in CNB were proven to be true malignant lesions. Lesions diagnosed with follicular neoplasm in CNB were identified as malignant lesions in 57.0%. Malignancy rate was significantly higher in indeterminate lesions with nuclear atypia compared to those with architectural atypia (80.0% vs 28.2%). When CNB diagnoses of indeterminate lesions or higher categories were considered positive, the sensitivity and positive predictive value for final malignant diagnoses were 99.2% and 81.3%, respectively. Conclusions CNB is an accurate method of evaluating thyroid nodules and can serve as an alternative to fine needle aspiration when it is used and reported according to standardized diagnostic categories. [ABSTRACT FROM AUTHOR]

Objective The accurate diagnosis of thyroid nodules is important for making management decisions. The purpose of this study was to evaluate the feasibility of core-needle biopsy with BRAFV600E mutation analysis (CNB + BRAFV600E) and to compare the clinical usefulness of CNB + BRAFV600E and fine-needle aspiration with BRAFV600E mutation analysis (FNA + BRAFV600E) in the diagnosis of thyroid malignancy. Design, patients and measurements The results of BRAFV600E mutation analyses of 820 nodules from 820 patients (153 men, 667 women; mean age, 51·1 years), who underwent CNB + BRAFV600E ( n = 256) or FNA + BRAFV600E ( n = 564) between January 2011 and March 2012 were retrospectively evaluated. The feasibility of CNB + BRAFV600E was assessed by comparing its rate of detection of BRAFV600E mutations and positive predictive value with those of FNA + BRAFV600E. The clinical usefulness of CNB + BRAFV600E was determined by comparing rates of inconclusive results, the additional value of BRAFV600E mutation analysis, diagnostic surgery and diagnostic performance with those of FNA + BRAFV600E. Results CNB + BRAFV600E and FNA + BRAFV600E had similar rates of BRAFV600E mutation detection (66·3% vs 64·4%, P = 0·883) and positive predictive value (100·0% vs 96·6%, P = 0·135). CNB + BRAFV600E had a significantly higher diagnostic accuracy rate (95·7% vs 85·9%, P < 0·001), and significantly lower rates of inconclusive results (8·2% vs 51·8%, P < 0·001), and diagnostic surgery (8·9% vs 22·3%, P = 0·006), than FNA + BRAFV600E. Conclusions The greater diagnostic performance of CNB + BRAFV600E and its lower rate of inconclusive results than FNA + BRAFV600E suggest that CNB + BRAFV600E can reduce rates of preventable diagnostic surgery. [ABSTRACT FROM AUTHOR]

Objective The prognosis of Graves' disease (GD) varies among patients. However, the immune pathogenesis of refractory GD is still unknown. The aim of this study was to explore the cytokine expression profile associated with refractory GD. Methods Preliminary cytokine protein microarray screening was performed to detect differentially expressed cytokines in the plasma of four patients with refractory GD and four patients with stable GD. Some differentially expressed cytokines were then validated in plasma by enzyme-linked immunosorbent assay (ELISA) and in peripheral blood mononuclear cells (PBMCs) by quantitative real-time polymerase chain reaction (qRT-PCR) on another independent set of samples. Results We found that 21 cytokines were differentially expressed between patients with intractable GD and those in remission, including 18 upregulated and 3 downregulated cytokines with a fold change >1·30 and <0·77, respectively. Intractability-related elevation of three cytokines (IL-4, IL-6 and IL-10) was validated by ELISA in plasma on another GD cohort with 30 patients in recurrence and 14 in remission ( t-test, P = 0·035, 0·033 and 0·041, respectively). Furthermore, mRNA expression of IL-4, IL-6 and IL-10 in PBMCs, detected by qRT-PCR, was significantly elevated in patients with refractory GD compared with those in remission ( P = 0·039, 0·047 and 0·042, respectively). Conclusion The severity of GD is associated with the aberrant expression and secretion of several cytokines that may serve as potential biomarkers and predictors for disease prognosis. Targeting these cytokines or their receptors may also lead to a novel therapeutic intervention for GD. [ABSTRACT FROM AUTHOR]

Objective Antibodies against thyroglobulin, thyroid peroxidase and the TSH receptor are accepted as pathophysiological and diagnostic biomarkers in autoimmune thyroid disease ( AITD). In contrast, the prevalence, aetiology and clinical relevance of autoantibodies against the human sodium-iodine symporter ( NISAb) and pendrin (PenAb) remain unclear. The objectives of the study were to investigate the presence of NISAb and PenAb in Danish twins, with and without AITD, to study whether the published variations in NISAb and PenAb frequencies were related to differences in methodology or study populations, and to evaluate whether the presence of NISAb or PenAb most likely results from genetic or nongenetic factors. Methods Sera from 93 patients with AITD and 230 healthy controls were evaluated for NISAb and PenAb using radioligand binding assays ( RBA). Results Patients with AITD had a higher prevalence than the controls: NISAb: 17% vs 0% ( P < 0·001) and PenAb: 11% vs 0% ( P < 0·001). Subdividing according to cause of AITD yielded similar results: 20% (11/56) of patients with Graves' disease ( GD) and 14% (5/37) of patients with Hashimoto's thyroiditis ( HT) had NISAb, ( P < 0·05, vs control population). Seven of 56 (13%) patients with GD and three of 37 (8%) patients with HT had PenAb ( P < 0·05 vs control population). No twin pairs were concordant for NISAb or PenAb, not even among twin pairs concordant for AITD. Conclusions In accord with studies using the same RBAs, the frequency of NISAb and PenAb was low in Danish patients with AITD and absent in healthy individuals, suggesting that differences between studies rely on assay differences. The skewed distribution of NISAb and PenAb within AITD concordant twin pairs suggests that NISAb and PenAb are likely attributable to the effects of environmental factors acting in genetic susceptible individuals. [ABSTRACT FROM AUTHOR]

Background 22q11·2 deletion syndrome (22q11·2 DS) is a relatively common yet under-recognized genetic syndrome that may present with endocrine features. We aimed to address the factors that contribute to the high prevalence of hypocalcaemia. Methods We investigated hypocalcaemia in a well-characterized sample of 138 adults with 22q11·2 DS (65 m, 73 F; mean age 34·2, SD 11·8, years) using laboratory studies and lifelong medical records. Logistic regression modelling was used to identify features associated with lifetime prevalence of hypocalcaemia. Results Of the total sample, 111 (80·4%) had a lifetime history of hypocalcaemia. Eleven (84·6%) of 13 subjects with neonatal hypocalcaemia had documented recurrence of hypocalcaemia. Lifetime history of hypocalcaemia was associated with lifetime prevalence of hypoparathyroidism ( P < 0·0001) and hypothyroidism ( P = 0·04), as statistically independent factors. Hypomagnesaemia was associated with concurrent hypocalcaemic measurements, especially in the presence of concurrent hypoparathyroidism ( P = 0·02). Conclusions The results suggest that, in addition to the major effect of hypoparathyroidism, hypothyroidism may play a role in hypocalcaemia in 22q11·2 DS and that there is a high recurrence rate of neonatal hypocalcaemia. Hypomagnesaemia may contribute to hypocalcaemia by further suppressing parathyroid hormone ( PTH). Although further studies are needed, the findings support regular lifelong follow-up of calcium, magnesium, PTH and TSH levels in patients with 22q11·2 DS. At any age, hypocalcaemia with hypoparathyroidism and/or hypothyroidism may suggest a diagnosis of 22q11·2 DS. [ABSTRACT FROM AUTHOR]

Objective The use of age-specific reference ranges for TSH is advocated, but the impact of this on laboratory diagnosis of thyroid dysfunction is unclear. Our aims were to determine age-specific TSH reference ranges and to examine interassay differences in performance. Design We analysed TSH results from 223 045 consecutive samples assayed over 1 year by a single pathology provider using the Siemens Centaur assay. We excluded patients with evidence of thyroid disease to derive a reference population of 148 938 individuals and analysed results in the 5-year age bands. We reassayed 120 samples using three other methods ( Architect, Roche and Immulite) to assess precision and bias. Results The 2·5th percentile for TSH was consistent across age groups (approximately 0·5 m U/l), whereas the 97·5th percentile increased from age 40 upwards, with the reference range upper limit being 3·75 m U/l at age 40 and 5·0 m U/l at age 90. In most age bands, the use of age-specific upper limits reclassified only 0·1-1·9% of participants as normal or abnormal compared with a common cut-off of 4·0 m U/l; in participants aged 85 years or more, reclassification rates were higher (2·1-4·7%). The four TSH assays showed good agreement at low-normal TSH concentrations (<2 m U/l), but at concentrations of 4·0 m U/l, there were intermethod differences of approximately 1 m U/l. Conclusion The use of age-specific reference ranges for TSH has only minor effects on thyroid status, except in the very old. At high-normal TSH concentrations, between-method differences in performance have a comparable impact to that of age and may affect clinical decision-making. [ABSTRACT FROM AUTHOR]

There is much concern expressed in the literature regarding the lack of predictive power of the thyroid fine needle aspiration/biopsy ( TFNAB) approach to defining the nature of clinically detected thyroid nodules. This has been exacerbated in the past decade or more by the routine use of ultrasonography ( US) in examining the thyroid as well as the introduction of molecular testing in the realm of thyroid pathology. Some have even gone so far as to suggest replacing the TFNAB with molecular signature testing to reduce the degree of uncertainty for a specific cytological diagnosis. This review addresses those concerns with a re-emphasis on understanding the basic keys to successfully evaluating a patient with a thyroid nodule by routine TFNAB examination. These keys include bringing to bear an experienced group of physicians in an integrated team approach, a sharpened focus on the TFNAB cytological categories and a grounded understanding of the predictive ability of molecular testing in a given patient when the cytological interpretation creates too much uncertainty in the minds of the patients and clinicians in attempting to reach a decision on how to manage a thyroid nodule. With this practical approach in mind, the false-negative and false-positive rates of 'negative (benign)' and 'positive (malignant)' thyroid aspirates should be no more than 1%; and the prevalence of an 'indeterminate' aspirate - the area in TFNAB attracting the most attention for improvement with novel biomarkers - should be 10% or less. Thus, physicians should be capable of managing at least 90% of patients undergoing TFNAB in a confident manner without further testing beyond the routine, future re-examination of the patient's nodule to re-assess for any change in its nature or its impact on the patient's quality of life. The other 10% can then be considered for molecular testing in a manner tailored to those individuals truly in need of a more sophisticated - and expensive - approach to the characterization of their thyroid nodules. As the era of US has matured - just as with the era of serum PSA testing for prostate cancer in men - we have experienced a paradigm shift: Given the incidence of thyroid nodules in the U.S. adult population in comparison with the risk of dying of thyroid malignancy, the main role of TFNAB is to reduce the need for surgical intervention. [ABSTRACT FROM AUTHOR]

Summary Objective C-type natriuretic peptide (CNP) and thyroid hormone (TH) are essential for normal skeletal growth. Plasma CNP peptides correlate with growth velocity, but the relationship between thyroid status and CNP production is unknown. This study examined the impact of restoring normal TH levels on CNP and height velocity (HV) in children with acquired hypo- and hyperthyroidism. Design We performed a prospective, observational study in prepubertal children with acquired hypothyroidism ( n = 15) and hyperthyroidism ( n = 12). Measurements Blood levels of CNP, amino-terminal proCNP (NTproCNP), bone-specific alkaline phosphatase (BSAP), IGF-I and TH levels were measured before and during the first 6 months of standard treatment for hypo- and hyperthyroidism, and correlations were determined. Results At baseline, HV, CNP, NTproCNP and BSAP were significantly higher in hyper- than in hypothyroid subjects. Changes in TH after treatment were closely coupled to change in CNP and NTproCNP in hyperthyroid, but not in hypothyroid, children. In addition, a positive association of HV with CNP peptides was found during treatment of hyperthyroidism. Normalizing TH did not correlate with changes in BSAP or IGF-I in either group. Conclusions Plasma CNP peptides are higher in children with hyperthyroidism than in those with hypothyroidism at diagnosis and, in hyperthyroid children, change concordantly with TH and HV during treatment. Differential responses of CNP in the two groups suggest CNP production is dependent on growth plate activity and not a direct effect of TH on CNP gene expression. Our findings suggest novel mechanisms underlying changes in skeletal response during treatment in children with acquired thyroid disease. [ABSTRACT FROM AUTHOR]

Summary Objective ShearWave™ Elastography (SWE) is real-time, quantitative and user-independent technique, recently introduced in the diagnostic work-up of thyroid nodules. Hashimoto's thyroiditis (HT), characterized by variable degrees of lymphocytic infiltration and fibrosis, might affect shear wave propagation. The aim of this study was to assess the feasibility of SWE in cytologically benign thyroid nodules within both Hashimoto's and nonautoimmune thyroid glands. The effect of autoimmunity on the gland stiffness was also evaluated. Design longitudinal study in a single centre. Patients SWE was performed in 75 patients with a benign thyroid nodule at cytology: 33 with Hashimoto's thyroiditis (HT group) and 42 with uni- or multi-nodular goitre, negative for thyroid autoimmunity (non-HT group). Results The elasticity index (EI) of the extra-nodular tissue was greater, though not statistically significant, in the HT than in the non-HT group (24·0 ± 10·5 kPa vs 20·8 ± 10·4 kPa; P = 0·206). However, the EI of extra-nodular tissue was related to the TPOAb titre in the HT group ( P = 0·02) and was significantly higher in patients with HT receiving L-thyroxine than in the euthyroid subjects ( P = 0·02). The EI of thyroid nodules was similar in HT and non-HT groups. In both groups, the stiffness of nodules was significantly higher than that of the embedding tissue. Conclusions Our data indicate that SWE correctly defines the elasticity of thyroid nodules independently from the coexistence of autoimmune thyroiditis, always being able to differentiate nodular tissue from the surrounding parenchyma. In HT, the stiffness of extra-nodular tissue increases in relation to both the thyroid antibody titre and the degree of impairment of thyroid function. [ABSTRACT FROM AUTHOR]

UK national guidelines recommend the measurement of TSH receptor antibodies (TRAb) in certain clinical scenarios. A commercial third-generation TRAb autoantibody M22-biotin ELISA assay was introduced in May 2008 in our centre. To evaluate the diagnostic performance of a TRAb assay in a retrospective and subsequently a prospective cohort in a UK centre. A retrospective review of patients with thyroid disease followed by a prospective observational study in consecutive patients with newly found suppressed serum thyrotrophin (TSH). Medical records of 200 consecutive patients with thyroid disorders who had TRAb measured since the introduction of the assay. In a prospective study 44 patients with newly identified hyperthyroidism (TSH < 0·02 mIU/l) had sera assayed for TRAb prior to their clinic appointment at which a final diagnosis was sought. In the retrospective cohort, the manufacturer's cut-off point of TRAb ≥0·4 U/l resulted in a positive predictive value (PPV) of 95%, sensitivity 85%, specificity 94% and negative predictive value (NVP) 79% to diagnose Graves' disease using defined criteria. Receiver operating characteristic (ROC) analysis determined an optimal cut-off point of TRAb ≥3·5 U/l with a 100% specificity to exclude patients without Graves' disease at the cost though of a lower sensitivity (43%). In the prospective study, the sensitivity, PPV, specificity and NPV were all 96% using the ≥0·4 U/l cut-off. When combining hyperthyroid patients from both cohorts the assay sensitivity and specificity at ≥0·4 U/l cut-off were 95% and 92% respectively. A positive TRAb result increased the probability of Graves' disease for a particular patient by 25-35% and only six (2·5%) patients had a diagnosis of hyperthyroidism of uncertain aetiology after TRAb testing. The assay studied specifically identifies patients with Graves' disease. It is a reliable tool in the initial clinical assessment to determine the aetiology of hyperthyroidism and has the potential for cost-savings. [ABSTRACT FROM AUTHOR]

Introduction Neonatal hyperthyrotropinaemia (HT), defined by elevated TSH and normal T4, is either transient or persistent. The eventual outcome of neonatal HT is unpredictable and the management of HT patients is controversial. We assessed perinatal parameters and diagnostic measures that may distinguish between transient and persistent HT, compared with congenital hypothyroidism (CH). We also aimed to recommend optimal treatment in these forms of thyroid impairment. Design and patients A multi-centre, retrospective study was conducted in six paediatric endocrinology units. Forty-three HT patients and 83 CH patients were included in the study. Measurements We evaluated differences in birth weight (BW), gestational age (GA), modes of diagnosis, screening and confirmatory T4 and TSH levels, thyroid imaging results and optimal thyroxine doses between HT and CH and between the two forms of HT. Results Newborns with HT had lower BW and GA than those with CH. Transient ( n = 18) and persistent HT ( n = 25) patients were indistinguishable by most parameters, but those with persistent HT had a higher prevalence of abnormal thyroid imaging (69% vs 8%; P = 0·005). During treatment, 79% and 55% of transient and persistent HT patients respectively experienced elevated levels of free T4. Although most HT patients were reevaluated after 2·5 years, six transient HT patients stopped therapy and showed full recovery within the first year of life. Conclusions We recommend obtaining thyroid imaging to distinguish between the two forms of HT. Adherence to recommended doses of thyroxine and probably early cessation of therapy in transient HT can prevent iatrogenic hyperthyroidism in these patients. [ABSTRACT FROM AUTHOR]

Background and objectives The value and practice of thyroid radionuclide imaging in the diagnosis and management of hyperthyroidism is unsettled. Our objectives were to determine the influence of thyroid uptake and scintigraphy on the diagnosis of hyperthyroidism and the prediction of outcome following radioiodine therapy. Patients and design We reviewed records and scintigraphic studies on 881 hyperthyroid patients carried out between 2000 and 2007. The agreement between the clinical and scintigraphic diagnosis was evaluated by kappa statistics. We determined the relationship between 4-h 123I uptake and the outcome of 131I treatment in 626 patients. A multiple logistic regression model was used to determine variables influencing treatment outcome in 1 year. Results The diagnostic categories were Graves’ disease (GD, n = 383), toxic multinodular goitre ( n = 253), solitary toxic nodule ( n = 164) and Graves’ disease coexisting with nodules ( n = 81). The mean age of the patients was 58 ± 17, (M:F 160:721). There was good agreement between clinical and scintigraph diagnosis ( K = 0·60, 95% CI 0·57–0·64, P < 0·001); and they were correctly matched in 74%; mismatched in 6% and indeterminate in 20% of patients. Treatment outcome was not associated with scintigraph diagnosis ( P = 0·98) or radioiodine uptake at 4 h ( P = 0·2). The use of antithyroid medications before treatment predicted treatment failure (odds ratio 2·0, 95% CI 1·2–3·6, P = 0·01). Conclusion Thyroid scintigraphy and uptake studies did not influence diagnosis or treatment outcomes in most cases of hyperthyroidism. Our findings in this retrospective study do not justify their routine use. Selective scanning will reduce cost and exposure to radioisotopes without compromising diagnostic accuracy or treatment outcomes. [ABSTRACT FROM AUTHOR]

Objectives Radioactive iodine (131I) therapy is increasingly viewed as a safe and effective treatment for paediatric and adolescent hyperthyroidism. Our objective was to estimate treatment response and its predictors and describe current referral practices for 131I therapy. Design Retrospective study. Patients One hundred and thirty-one children 30 days–21 years old with laboratory evidence of hyperthyroidism, seen in an academic paediatric and adolescent endocrinology practice. Measurements Rate of referral, indications for 131I, predictors of poor treatment response. Results Thirty-eight of 102 patients with persistent hyperthyroidism (37%) received 131I (160 μCi/g thyroid tissue/131I uptake), as did an additional 10 patients initially evaluated by adult thyroidologists. Primary indications were intolerance to (29%) or poor control on (19%) antithyroid drugs, patient preference (50%) and unknown (2%). Of 48 patients treated with 131I, 89% and 11% became hypothyroid after one and two 131I doses, respectively. The goal of 131I therapy was attainment of hypothyroidism. ‘Poor treatment response’ (seen in 27%) was defined as requirement for a second 131I dose or failure to achieve hypothyroidism after 6 months. Predictors of poor treatment response included: previous use of antithyroid drugs (37% vs. 0%, P = 0·02), ophthalmopathy (58% vs. 8%, P = 0·002), and an interval of ≥12 months from diagnosis to 131I (50% vs. 10%, P = 0·003). A very elevated free T4 tended to be more prevalent in those with poor response. Conclusions In children and adolescents with hyperthyroidism, high rates of success after 131I are achievable. Use of antithyroid drugs, pre-existing eye disease and prolonged time to 131I may confer relative resistance to 131I. [ABSTRACT FROM AUTHOR]

Objective It is claimed that second generation thyrotropin-binding inhibitory immunoglobulin (TBII) assays have a very high sensitivity for the diagnosis of Graves’ hyperthyroidism (GH). However, studies evaluating the accuracy of TBII have been retrospective in nature and/or GH had not been diagnosed independently of TBII. The aim of the present study, therefore, was to prospectively evaluate the frequency and characteristics of TBII-seronegative patients in a population of untreated GH diagnosed independent of serum TBII. Design Prospective multicentre observational study. Patients A total of 259 consecutive untreated patients with a first episode of GH, diagnosed independent of serum TBII. TBII levels were measured by second generation assay and correlated to thyroid function, clinical characteristics and exposure to environmental factors. Results Serum TBII was positive in 245 (94·6%) patients and negative (< 2 IU/l) in 14 (5·4%) patients. TBII-seronegative patients had lower fT4 (median 42·5 vs. 53·9 pmol/l, P = 0·02), T3 (median 3·55 vs. 4·90 nmol/l, P < 0·01) and fT3-index (median 4·30 vs. 6·27, P < 0·01) compared to TBII-seropositive patients. None of the TBII-seronegative patients had TSH-receptor activating mutations, Graves’ orbitopathy or pretibial myxedema. Serum TBII was positively correlated to free T3 (fT3)-index and free T4 (fT4)-index (P < 0·01), goitre size (P < 0·01) and the prevalence of Graves’ orbitopathy (P < 0·01). There were no significant differences between TBII-seropositive and TBII-seronegative patients in environmental factors. Conclusion The prevalence of TBII-seronegativity in untreated patients with GH is 5·4% using a second generation assay. TBII-seronegative patients have biochemically less severe thyrotoxicosis and no Graves’ orbitopathy. TBII-seronegative and TBII-seropositive patients apparently belong to the same population of GH, albeit the severity of the autoimmune attack is less in TBII-seronegative patients. [ABSTRACT FROM AUTHOR]

Objective To evaluate the prevalence and significance of focal thyroid lesions identified by 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in patients with nonthyroidal head and neck cancers (HNC). Patients and measurements Patients with histologically identified HNC who underwent FDG-PET and computed tomography (CT) were reviewed retrospectively. We evaluated the prevalence of patients with focal thyroid FDG uptake and the risk of malignancy and proper management in these patients. Results Of 689 HNC patients, 19 (2·8%) had focal thyroid FDG uptake. Of the 12 patients with a histological diagnosis by surgery or needle biopsy, 5 (41·7%) had carcinomas, 4 papillary and 1 follicular, whereas the others had benign thyroid lesions. The maximum standardized uptake value on PET was not sufficient to discriminate between malignant and benign thyroid lesions (8·4 ± 13·2 vs. 4·2 ± 4·0; P > 0·4). The identification of incidental thyroid diseases helped guide patient counselling and combined surgery with HNC and thyroidectomy. Conclusion Focal thyroid lesions incidentally found on FDG-PET in patents with nonthyroidal HNC have a high probability of malignancy. These lesions deserve further diagnostic examination before HNC treatment to ensure adequate therapy for incidental thyroid cancers. [ABSTRACT FROM AUTHOR]

To investigate whether previous hyperthyroidism is a cause of permanent secondary osteoporosis.In this cross-sectional study, 164 women with untreated or previously treated overt and symptomatic hyperthyroidism were examined 0–31 years after the initial episode of hyperthyroidism and its treatment, and were compared with a control group of 79 age-matched women without previous history of hyperthyroidism. Subjects with current or previous metabolic bone disease, any antiresorptive treatment for osteoporosis or treatments and habits known to affect bone metabolism were excluded.The age of the first manifestation of the disease, the age at the measurement of bone mineral density (BMD) at the spine and femoral neck and the interval between diagnosis and treatment of hyperthyroidism and BMD measurement were recorded and the Z-scores and T-scores of BMD were analysed.Untreated hyperthyroidism and hyperthyroidism up to 3 years after its diagnosis and treatment were associated with decreased BMD. Three or more years after the first episode of the disease the mean Z-score at both skeletal sites was near zero and not different from the controls. The age at which hyperthyroidism was manifested for the first time had no effect on the final outcome. Women affected at a young age (13–30 years) had a more pronounced loss of BMD when examined untreated or early (< 3 years) after diagnosis, but a BMD significantly above zero if examined later (> 3 years). Older women (aged 51–70 years) showed a similar pattern, although the differences were not significant. Middle-aged subjects (31–50 years) had the smallest loss of BMD during the first 3 years. Analysis of T-scores of former hyperthyroid women aged≥ 51 years showed no significantly different relative risk (RR) for osteoporosis in comparison with the controls. However, the study was not powered enough to give meaningful RR results.Overt symptomatic hyperthyroidism is associated with decreased BMD during the first 3 years after diagnosis and treatment of the disease. After this interval, former hyperthyroid women have a Z-score near zero and not different from women without a history of the disease, apparently because of recovery of the bone density lost early during the course of the disease. Symptomatic hyperthyroidism does not seem to be a cause of long-lasting osteoporosis, and the age of the patient during the first episode is irrelevant. [ABSTRACT FROM AUTHOR]

INTRODUCTION The rates of sensitivity and specificity of fine needle aspiration biopsy (FNAB) for the diagnosis of thyroid malignancy differ considerably among various reported series. These values are influenced by three factors: (a) whether only clearly positive and negative results are considered, or whether the commonly encountered 10–20% of indeterminate/suspicious ones are included; (b) whether adenomas are considered as neoplasms in one group with carcinomas; and (c) whether only histologically proven cases are used in calculations or whether patients with benign clinical follow-up are included. AIM The aim of the study was to evaluate the sensitivity and specificity of FNABs performed at this institution in the last 7 years from the clinical point of view, considering only benign vs. suspicious/malignant FNAB results (indicating surgery), and benign (including adenomas) vs. malignant definitive histology. STUDY DESIGN Retrospective study comparing pre-operative FNAB results with definitive histological examination after operation. PATIENTS A total of 2492 FNABs were performed in 2100 patients (1875 women and 225 men); their ages ranged from 9 to 85 years, with a median of 46 years. Clinical diagnosis was multinodular goitre in 1330, single nodule in 591, Hashimoto's thyroiditis in 147 and subacute thyroiditis in 32 cases. In 148 instances, the nodule was cystic. A history of previous treatment for carcinoma of the thyroid was present in 12 patients. Five hundred and thirty-six patients subsequently underwent thyroid surgery. STATISTICS The values of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy were calculated. RESULTS The sensitivity was 86%, specificity 74%, PPV 34%, NPV 97% and diagnostic accuracy 75%. CONCLUSIONS The specificity and positive predictive value are low when fine needle aspiration biopsy results are divided into two categories only (these being indication for... [ABSTRACT FROM AUTHOR]

OBJECTIVESThe surface phenotypes of intrathyroidal lymphocytes have been studied in various thyroid diseases. In most of the previous reports, intrathyroidal lymphocytes were obtained by surgical operation. We evaluated the usefulness of surface phenotype study of intrathyroidal lymphocytes obtained by fine needle aspiration in the diagnosis of Graves' disease, chronic thyroiditis, and malignant lymphoma of the thyroid. PATIENTS AND DESIGNEighty-seven untreated patients including 24 with Graves' disease, 59 with chronic thyroiditis, and 4 with malignant lymphoma of the thyroid, and 2 treated patients with malignant lymphoma of the thyroid were studied. Surface phenotypes of the peripheral lymphocytes and the intrathyroidal lymphocytes obtained by fine needle aspiration were analyzed using a FACScan and the monoclonal antibodies: anti-Leu5b/CD2, Leu4/CD3, Leu3a/CD4, Leu2a/CD8, and Leu12/CD19. Percentages of cells positive for each monoclonal antibody were calculated. In one case with malignant lymphoma, monoclonal antibodies to surface-immunoglobulin markers were also studied. RESULTSIn peripheral lymphocytes, the percentage of positive cells in each phenotype was almost normal in each disease. In intrathyroidal lymphocytes, the percentage of CD19 positive cells was increased, and the percentage of CD2 and CD3 positive cells was reduced compared to those of peripheral lymphocytes in each disease. The percentage of intrathyroidal CD19 positive cells was remarkably high in malignant lymphoma, constituting more than 70% of cells. In Graves' disease, a relative decrease in the percentage of intrathyroidal CD4 positive cells and an increase in CD8 positive cells compared to peripheral lymphocytes were observed. In 2 treated patients with malignant lymphoma of the thyroid, the intrathyroidal CD19 positive cells almost disappeared in a patient shortly after successful treatment, and reappeared to constitute 76% of cells in a patient in relapse. In one case with... [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the acute transient thyroid swelling as a complication of the thyroid fine-needle aspiration biopsy (FNAB) for the diagnosis and management of thyroid nodules.

The author discusses the study conducted on the management of hypothyroid pregnant women in Tayside, Scotland using comprehensive databases. The author is particular over the wide variation of thyroid tests conducted in women despite the availability of local and international guidelines. The author expresses disappointments over the publications of high-profile international guidelines that showed suboptimal management of hypothyroidism among pregnant women.

In this article the author discusses diagnosis and treatment of central hypothyroidism (CH), which is a rare cause of hypothyroidism with varied clinical symptoms. He explores the study by Koulouri and colleagues which suggests that the levels of free thyroxine (FT4) about 16 picomoles per liter (pmol/l) may show an appropriate target in treated patients with CH. He notes that levothyroxine (LT4) replacement therapy might be optimal by fulfilling the associated conditions.

The article presents a commentary on the diagnosis and treatment of hyperthyroidism and the role played by radioiodine uptake measurement and thyroid scintigraphy in it. It refers to the paper "The utility of radioiodine uptake and thyroid scintigraphy in the diagnosis and management of hyperthyroidism," by O.E. Okosieme and colleagues published within the issue, which clarifies whether radioiodine uptake measurement and thyroid scintigraphy fulfil these promises in routine practice.

A letter to the editor is presented regarding the association of HLA DQ4-DR8 haplotype with papillary thyroid carcinomas in female patients.

OBJECTIVE: Transient elevation of serum free T4 (gestational transient hyperthyroxinaemia; GTH) occurs occasionally during normal pregnancy, especially in early gestation. However, the frequency of GTH and its clinical features remain unclear to date. The aim of this study was to determine the occurrence rate of GTH and the relation between serum levels of hCG, free T4 (fT4), and TSH in a large number of pregnant women. DESIGN: The four criteria of GTH were as follows: (1) no past history of thyroid disease, (2) negative tests for MCHA and TGHA, (3) no multiple pregnancies or trophoblastic disease and (4) transient hyperthyroxinaemia at less than 16 weeks of gestation. Thyroid function and hCG levels in 23 163 pregnant women were evaluated by mass sreening. If individual fT4 levels were more than the upper limit, blood re-sampling and the clinical and laboratory analysis of thyroid function were performed to exclude women with thyroid disease. The concentrations of hCG, fT4, and TSH in women with GTH and normal pregnant controls (n = 218) were compared. Regression analysis was performed for the comparison between hCG, fT4, and TSH levels in women with GTH. MEASUREMENTS: Blood samples were obtained using dried blood spots. Blood levels of fT4 was measured by radioimmunoassay, TSH and hCG were measured by fluoroimmunoassay. Anti-microsome antibody (MCHA) and anti-thyroglobulin antibody (TGHA) were measured by indirect agglutination reaction. RESULTS: GTH was observed in 66 of 23 163 women. The overall occurrence rate of GTH was 0.285%. In 22 of the 66 GTH women, serum TSH was undetectable. Using regression analyses, the concentration of fT4 was correlated with hCG levels in women with GTH (P < 0.05, r = 0.269), whereas the concentration of TSH was not correlated with hCG or fT4 level. The concentrations (M ± SD) of fT4, TSH, and hCG in women with GTH were 42.5 ± 12.3 pmol/l, 0.20 ± 0.31 mU/l and 190.2 ± 98.8 × 10[sup 3] IU/l, whereas... [ABSTRACT FROM AUTHOR]