Serum thyrotropin concentration in children with isolated thyroid nodules.

OBJECTIVE: To investigate the correlation between serum thyroid-stimulating hormone (TSH) concentration and nodule nature in pediatric patients with thyroid nodules, with the aim of identifying a marker able to differentiate benign and malignant nodules. STUDY DESIGN: This was a retrospective analysis of serum TSH concentrations in a multicentric case series of 125 pediatric patients with benign and malignant thyroid nodules. RESULTS: Of the 125 patients, 99 had benign thyroid nodules and 26 had differentiated thyroid cancer (24 papillary and 2 follicular). Final diagnosis was based on surgery in 57 cases and on a benign cytology plus clinical follow-up in 68 cases. Serum TSH concentration was significantly higher in patients with thyroid cancer compared with those with benign nodules (3.23 ± 1.59 mU/L vs 1.64 ± 0.99 mU/L; P < .001). Binary logistic regression analysis revealed that serum TSH was the sole predictor of malignancy (P < .001). Dividing the patient cohort into 5 groups based on serum TSH quintiles (TSH cutoffs 0.40, 1.00, 1.50, 1.80, and 2.80 mU/L), we observed that cancer prevalence increased in parallel with serum TSH (P < .001), with respective rates of 0%, 4%, 16%, 32%, and 52% in the 5 quintile groups. CONCLUSION: Because cases with malignant nodules are most likely seen in the upper normal serum TSH range (ie, >2.8 mU/L), serum TSH concentration can serve as a predictor of thyroid cancer in pediatric patients with thyroid nodules and can inform the decision of when to submit patients to further investigation by cytology

Congenital Hypothyroidism: A 2020-2021 Consensus Guidelines Update-An ENDO-European Reference Network Initiative Endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology

Background An ENDO-ERN initiative was launched which was endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology with 22 participants from the ENDO-ERN and the two societies. The aim was to update the practice guidelines for the diagnosis and management of congenital hypothyroidism (CH). A systematic literature search was conducted to identify key articles on neonatal screening, diagnosis and management of primary and central congenital hypothyroidism. The evidence-based guidelines were graded with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, describing both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. Summary The recommendations include the various neonatal screening approaches for CH as well as the etiology (also genetics), diagnostics, treatment and prognosis of both primary and central CH. When CH is diagnosed, the expert panel recommends the immediate start of correctly dosed levothyroxine treatment and frequent follow-up including laboratory testing to keep thyroid hormone levels in their target ranges, timely assessment of the need to continue treatment, attention for neurodevelopment and neurosensory functions and, if necessary, consulting other health professionals, and education of the child and family about CH. Harmonisation of diagnostics, treatment and follow-up will optimise patient outcomes. Lastly, all individuals with CH are entitled to a well-planned transition of care from pediatrics to adult medicine. Conclusions This consensus guidelines update should be used to further optimize detection, diagnosis, treatment and follow-up of children with all forms of CH in the light of the most recent evidence. It should be helpful in convincing health authorities of the benefits of neonatal screening for CH. Further epidemiological and experimental studies are needed to understand the increased incidence of this conditio

Genetic polymorphisms and susceptibility to lung disease

Susceptibility to infection by bacterium such as Bacillus anthracis has a genetic basis in mice and may also have a genetic basis in humans. In the limited human cases of inhalation anthrax, studies suggest that not all individuals exposed to anthrax spores were infected, but rather, individuals with underlying lung disease, particularly asthma, sarcoidosis and tuberculosis, might be more susceptible. In this study, we determined if polymorphisms in genes important in innate immunity are associated with increased susceptibility to infectious and non-infectious lung diseases, particularly tuberculosis and sarcoidosis, respectively, and therefore might be a risk factor for inhalation anthrax. Examination of 45 non-synonymous polymorphisms in ten genes: p47phox (NCF1), p67phox (NCF2), p40phox (NCF4), p22phox (CYBA), gp91phox (CYBB), DUOX1, DUOX2, TLR2, TLR9 and alpha 1-antitrypsin (AAT) in a cohort of 95 lung disease individuals and 95 control individuals did not show an association of these polymorphisms with increased susceptibility to lung disease

Fertility in adult females with congenital hypothyroidism (CH) diagnosed by neonatal screening

Background: CH interferes with human reproductive physiology, reduces the likelihood of pregnancy and adversely affects pregnancy and perinatal outcome. However, in subjects with early treated CH, a normal pubertal development has been reported. There are no systematic studies about fertility and pregnancy outcome in affected adults. Objective and hypotheses: Fertility and pregnancy evalutation in CH adult females. Methods: Gynecologic history was evaluated in a semistructurated questionnaire carried out by expert clinicians. The results were compared with data derived from national register of births. 155 girls with permanent CH between 1978 and 1994, in 4 italian regions, were recalled. 69 (44.6%) subjects (mean age 22.1 ± 4.4 yrs; 25 (36%) athyreosis, 32 ectopic gland (47%), 12 (17%) in situ gland) agreed to participate our study. Results: 9 pts reported 10 pregnancies (15%),3 of which terminated by abortion (1 miscarriage: 6° week of GA in 28.4 yrs pt with ectopic thyroid gland; 2 elective abortion: 4° week of GA in 20.2 yrs pt with hypoplasia, 6° week of GA in 21.3 yrs pt with athyreosis). The abortion rate was 1.45% for miscarriage (0.54% in control population), 2.9% for elective abortion (0.86% in control population).In the fullterm pregnancies the mean increase of L-T4 dose needed in each trimester was 15% (10%-20%), 15%(10%-20%) and 20%(10%-30%) respectively. TSH values >2.5 mU/L were found in 7/7 cases in the 1st trimester, in 4/7 in the 2nd, in 4/7 in the 3th. All newborn showed normal results at neonatal screening and at thyroid ultrasound. The table shows the data of live births subdivided according to maternal age

Congenital hypothyroidism due to defects of thyroid development and mild increase of TSH at screening: data from the Italian National Registry of infants with congenital hypothyroidism.

CONTEXT: Over the years lower TSH cutoffs have been adopted in some screening programs for congenital hypothyroidism (CH) worldwide. This has resulted in a progressive increase in detecting additional mild forms of the disease, essentially with normally located and shaped thyroid. However, the question of whether such additional mild CH cases can benefit from detection by newborn screening and early thyroid hormone treatment is still open. OBJECTIVE: The aim of this study was to estimate the frequency of cases with mild increase of TSH at screening in the Italian population of babies with permanent CH and to characterize these babies in terms of diagnosis classification and neonatal features. METHODS: Data recorded in the Italian National Registry of infants with CH were analyzed. RESULTS: Between 2000 and 2006, 17 of the 25 Italian screening centers adopted a TSH cutoff at screening of <15.0 μU/mL. It was found that 21.6% of babies with permanent CH had TSH at screening of 15.0 μU/mL or less, whereas this percentage was 54% in infants with transient hypothyroidism. Among the babies with permanent CH and mild increase of TSH at screening (≤15 μU/mL), 19.6% had thyroid dysgenesis with serum TSH levels at confirmation of the diagnosis ranging from 9.9 to 708 μU/mL. These babies would have been missed at screening if the cutoff had been higher. CONCLUSIONS: Lowering TSH cutoff in our country has enabled us to detect additional cases of permanent CH, a number of which had defects of thyroid development and severe hypothyroidism at confirmation of the diagnosis