Does the Thymus Index Predict COVID-19 Severity?

BACKGROUND: The COVID-19 (coronavirus disease 2019) pandemic is a global health emergency that is straining health care resources. Identifying patients likely to experience severe illness would allow more targeted use of resources. This study aimed to investigate the association between the thymus index (TI) on thorax computed tomography (CT) and prognosis in patients with COVID-19. METHODS: A multicenter, cross-sectional, retrospective study was conducted between March 17 and June 30, 2020, in patients with confirmed COVID-19. The patients' clinical history and laboratory data were collected after receiving a signed consent form. Four experienced radiologists who were blinded to each other and patient data performed image evaluation. The appearance of the thymus was assessed in each patient using 2 published systems, including the TI and thymic morphology. Exclusion criteria were lack of initial diagnostic thoracic CT, previous sternotomy, pregnancy, and inappropriate images for thymic evaluation. A total of 2588 patients with confirmed COVID-19 and 1231 of these with appropriate thoracic CT imaging were included. Multivariable analysis was performed to predict the risk of severe disease and mortality. RESULTS: The median age was 45 (interquartile range, 33-58) years; 52.2% were male. Two hundred forty-nine (20.2%) patients had severe disease, and 60 (4.9%) patients died. Thymus index was significantly associated with mortality and severe disease (odds ratios, 0.289 [95% confidence interval, 0.141-0.588; P = 0.001]; and 0.266 [95% confidence interval, 0.075-0.932; P = 0.038]), respectively. Perithymic lymphadenopathy on CT imaging had a significantly strong association with grades of TI in patients with severe disease and death ( V = 0.413 P = 0.017; and V = 0.261 P = 0.002, respectively). A morphologically assessable thymus increased the probability of survival by 17-fold and the absence of severe disease by 12-fold. CONCLUSION: Assessment of the thymus in patients with COVID-19 may provide useful prognostic data for both disease severity and mortality.

Congenital Hypothyroidism: Space-Time Clustering of Thyroid Dysgenesis Indicates a Role for Environmental Factors in Disease Etiology.

Background: The etiology of most cases of congenital hypothyroidism (CHT) due to thyroid dysgenesis (DG) is unknown. If transient environmental factors can impact on thyroid gland development, then clustering of cases in time and/or space may occur, and this would be more likely in thyroid DG than dyshormonogenesis (DHG). Methods: The newborn screening program for CHT in Scotland is linked to a central database that includes case details such as postcode. The etiology of CHT is investigated in many cases of CHT using scintigraphy and/or ultrasonography. We looked for evidence of a change in CHT incidence with year of birth and according to season of the year. We then undertook space-time clustering analysis (using a method based on K-functions, with nearest neighbor thresholds) of CHT in Scotland between 1979 and 2015. We also looked for evidence of overall changes associated with sex and area-based birth density. Results: Of 531 cases with CHT during the study period, 290 cases had been categorized as DG (n = 229) or DHG (n = 61) following more detailed investigation. The incidence of CHT increased with year of birth and was in part linked to changing methodology, but there was no seasonality. There was no evidence of overall space-time clustering (p = 0.06), but there was evidence of clustering in babies with DG (p = 0.007). This picture appeared to be most closely linked to underlying thyroid gland hypoplasia rather than thyroid gland agenesis or ectopia. There was significant space-time clustering for both males and females, but clustering was restricted to lesser birth density areas. There was also evidence of clustering for unknown cases (p < 0.001). Clustering of these cases was restricted to females but was present for cases from both greater and lesser birth density areas. There was no evidence of clustering in cases of DHG. Conclusions: These data suggest that an unidentified environmental factor or factors may be involved in the etiology of thyroid DG in Scotland. The variation in CHT incidence observed internationally may reflect environmental as well as genetic factors.

Heterogeneous tissue in the thyroid fossa on ultrasound in infants with proven thyroid ectopia on isotope scan--a diagnostic trap.

BACKGROUND: Thyroid imaging is of proven help in establishing a diagnosis of congenital hypothyroidism in infants. US often shows tissue in the thyroid fossa when radionuclide scintigraphy reveals only ectopic uptake. OBJECTIVE: Our hypothesis was that the use of US alone could lead to the mistaken diagnosis of normal or dysplastic thyroid in cases of scintigraphy-proven thyroid ectopia. MATERIALS AND METHODS: We undertook a detailed retrospective review and analysis of imaging and concurrent biochemistry in infants with thyroid ectopia, confirmed by radionuclide scintigraphy. RESULTS: Eighteen infants had thyroid ectopia; ten of the original US reports had suggested that cervical thyroid tissue was present. Review showed bilateral tissue in the thyroid fossa in all that was non-thyroidal in nature since, apart from showing no radionuclide uptake, it exhibited some or all of the following typical features: hyperechogenicity, heterogeneity, small size, poor vascularity, and anechoic and/or hypoechoic cysts. Also, extension of the tissue both around and behind the large cervical blood vessels was a universal finding. CONCLUSION: Considerable experience is required to interpret neonatal thyroid US. We caution against diagnosing a dysplastic/hypoplastic thyroid gland in situ on the basis of US alone, particularly if the tissue exhibits any of the non-thyroidal features described.

Audit of initial management of congenital hypothyroidism in the United Kingdom--comparison of UK practice with European and UK guidelines.

BACKGROUND: Prompt and adequate management of newly diagnosed congenital hypothyroidism (CH) has been shown to optimise intellectual outcome. METHODS: A questionnaire survey of the British Society for Paediatric Endocrinology and Diabetes (BSPED) membership was undertaken, examining current clinical practice in neonatal CH. Results were compared with published management guidelines from Europe and the UK. RESULTS: The response rate was 86%. The majority were largely compliant with both guidelines. 43% review newly referred infants on the day of notification. However, 26% treat severe CH with < 10 microg/kg/day thyroxine and nearly 20% do not follow up until at least 14 days after initiating treatment, in contrast to both guidelines. Despite a new liquid T4 preparation being licensed, respondents preferred tablet T4. CONCLUSION: Rapidity of assessment and adequate follow up of suspected CH is critical to outcome. Existing European and UK guidelines should be reviewed and expanded to incorporate new evidence, together with increased advice on preparation and administration of T4.

Permanent congenital hypothyroidism with blood spot thyroid stimulating hormone <10†mU/L.

BACKGROUND: The UK recommended lower threshold for neonatal blood spot thyroid stimulating hormone (TSH) screening for congenital hypothyroidism (CHT) is 10.0 mU/L. Some laboratories use lower thresholds. This will lead to referral of mildly or unaffected infants but some will require thyroxine therapy. METHODS: Laboratory referrals with a first or repeat capillary TSH between 8.0 and <10.0 mU/L were identified (January 2004 to March 2014). The outcome of these cases was examined. RESULTS: 26 infants had one or more blood spot TSH values between 8.0 and 9.99 mU/L; 65% had transient elevated neonatal TSH while one is awaiting diagnostic challenge. The remaining eight (31%) have permanent CHT; three with dyshormonogenesis, two with thyroid ectopia and the others met the criteria for definite CHT. Two out of three with dyshormonogenesis presented with decompensated hypothyroidism. CONCLUSIONS: Infants with permanent and occasionally severe CHT may have a screening TSH below the UK recommended lower cut-off.