Purpose
Graves’ orbitopathy (GO) is a specific inflammatory disorder of the orbit characterized by a highly heterogeneous clinical phenotype. The role of thyrotropin receptor antibodies (TSH-R-Ab) ...has been widely researched, however there is still no evidence that these antibodies have a direct pathogenic role in this pathology. The aim of this study was to examine their relation to the individual clinical features of GO.
Methods
Ninety-one consecutive patients with GO were recruited. Total antibody concentration (TSH-R binding inhibitory immunoglobulins, TBII) and their functional activity (stimulating TSH-R-Ab, TSAb) were measured using binding immunoassay and cell-based bioassay, respectively.
Results
Both TSAb and TBII levels were significantly associated to the clinical parameters of GO activity. TSAb was a more sensitive serological marker compared to TBII pertaining to eyelid retraction and edema, proptosis, extra-orbital muscle disorders, diplopia, irritable eye symptoms, and photophobia. TSAb, but not TBII, was a significant predictive marker of conjunctival redness, chemosis, caruncle/plica inflammation, eye irritation, and orbital pain, (odds ratio: 3.096, p = 0.016; 5.833, p = 0.009; 6.443, p = 0.020; 3.167, p = 0.045; 2.893, p = 0.032; versus 2.187, p = 0.093; 2.775, p = 0.081; 3.824, p = 0.055; 0.952, p = 0.930; 2.226, p = 0.099, respectively). Neither TSAb nor TBII correlated with the level of proptosis (ρ = 0.259, p = 0.090, and ρ = 0.254, p = 0.104, respectively), however rising TSAb levels were strongly associated to the level of proptosis.
Conclusions
TSH-R-Ab were significantly associated with GO’s phenotype. Especially TSAb, as a sensitive and predictive serological biomarker, can improve diagnosis and management of GO.
Purpose
Thyrotropin receptor autoantibodies (TSH-R-Ab) are heterogeneous in their biological function and play a significant role in the pathophysiology of both Graves’ disease and Graves’ ...orbitopathy (GO). The clinical significance and utility of determining functional TSH-R-Ab in a Serbian collective were evaluated.
Methods
91 consecutive patients with GO were included in this study. Total TSH-R-Ab concentration, referred to as TSH-R binding inhibitory immunoglobulins (TBII) was detected using a competitive-binding immunoassay. Stimulating and blocking TSH-R-Ab (TSAb and TBAb) were measured with cell-based bioassays.
Results
Stimulating TSAb activity and TBII positivity were detected in 85 of 91 (93.4%) and 65 of 91 (71.4%) patients with GO (
P
< 0.001). Blocking TBAb activity was observed in only one patient who expressed dual stimulating and blocking TSH-R-Ab activity. The sensitivity rates for differentiating between clinically active versus inactive and mild versus moderate-to-severe GO were 100% and 100% for TSAb, respectively. In contrast, these were 82% and 87% only for TBII. Seven of eight (87.5%) and one of eight (12.5%) euthyroid patients with GO were TSAb and TBII positive, respectively (
P
< 0.031). TSAb serum levels significantly predicted GO activity compared to TBII (odds ratio, OR, 95%CI: 3.908, 95%CI 1.615–9.457,
P
= 0.003; versus 2.133, 0.904–5.032,
P
= 0.084, univariate analysis; and OR 4.341, 95%CI 1.609–11.707,
P
= 0.004; versus 2.337, 0.889–6.145,
P
= 0.085 multivariate analysis).
Conclusion
Stimulating TSAb are highly prevalent in patients with GO and show superior clinical characteristics and predictive potential compared to the traditionally used TBII.
Purpose
The aim of this study was to assess the impact of repurposing health care facilities in response to COVID-19 on the access of patients with thyroid disease to health care.
Methods
This study ...consisted of a web-based survey. The survey was anonymous and consisted of forty questions.
Results
This survey included 206 respondents. 91.3% of the respondents had health insurance through the Republic Fund of Health Insurance, 9.7% had private or both health insurances, and 3.4% did not have any health insurance. A significant proportion of respondents (60.4%) had to switch from public to private health care to reach a physician and 73.8% had to switch from public to private laboratories. For the 91.9%, this was perceived as a financial burden. Before the pandemic, 83.1% of respondents reported regular follow-up by physicians, which decreased to 44.9% during the pandemic (
p
< 0.01). 76.3% of the respondents regarded that their thyroid disease was managed optimally before the pandemic, while this figure declined to only 48% during the pandemic (
p
< 0.01).
Conclusions
The COVID-19 pandemic disrupted the medical care of thyroid patients in Serbia. For the patients treated in the public health care system, access to general practice was hindered, while access to specialist care was disrupted. It led to a switch from public to private health care, which was perceived as a financial burden for almost all the respondents. However, private health care proved to be an important safety net when the public system was overwhelmed.
Purpose
Patients with Graves’ orbitopathy can present with asymmetric disease. The aim of this study was to identify clinical characteristics that distinguish asymmetric from unilateral and symmetric ...Graves’ orbitopathy.
Methods
This was a multi-centre study of new referrals to 13 European Group on Graves’ Orbitopathy (EUGOGO) tertiary centres. New patients presenting over a 4 month period with a diagnosis of Graves’ orbitopathy were included. Patient demographics were collected and a clinical examination was performed based on a previously published protocol. Patients were categorized as having asymmetric, symmetric, and unilateral Graves’ orbitopathy. The distribution of clinical characteristics among the three groups was documented.
Results
The asymmetric group (
n
= 83), was older than the symmetric (
n
= 157) group mean age 50.9 years (SD 13.9) vs 45.8 (SD 13.5),
p
= 0.019, had a lower female to male ratio than the symmetric and unilateral (
n
= 29) groups (1.6 vs 5.0 vs 8.7,
p
< 0.001), had more active disease than the symmetric and unilateral groups mean linical Activity Score 3.0 (SD 1.6) vs 1.7 (SD 1.7),
p
< 0.001 vs 1.3 (SD 1.4),
p
< 0.001 and significantly more severe disease than the symmetric and unilateral groups, as measured by the Total Eye Score mean 8.8 (SD 6.6) vs 5.3 (SD 4.4),
p
< 0.001, vs 2.7 (SD 2.1),
p
< 0.001.
Conclusion
Older age, lower female to male ratio, more severe, and more active disease cluster around asymmetric Graves’ orbitopathy. Asymmetry appears to be a marker of more severe and more active disease than other presentations. This simple clinical parameter present at first presentation to tertiary centres may be valuable to clinicians who manage such patients.
This paper tries to present morphological productivity of compound nouns in a corpus comprised of news, literary, academic and TV registers using an onomasiological approach, namely, the productivity ...at the level of word-formation rules. The productivity at the aforementioned level is the union of the productivity at the level of word-formation types and morphological types. By using manual, descriptive, analytic and statistical methods, we came to 571 examples of compound nouns that fell into 10 different conceptual categories (Agent, Action, Result, Object, Location, Instrument, Substance, Time, Quantity, State), i.e. clusters. Each cluster offered pieces of information on the interaction of different concepts within different word-formation types together with the morphological aspect through different morphological types, which was the aim of the paper. The results proved our initial hypothesis that the interaction of different elements is of the utmost significance for better understanding of compounding. The interaction of two concepts dominated all clusters while the combination of two stems, especially two nouns, dominated morphological types.
Mutations in CRLF1 cause familial achalasia Busch, A.; Žarković, M.; Lowe, C. ...
Clinical genetics,
July 2017, 2017-Jul, 2017-07-00, 20170701, Letnik:
92, Številka:
1
Journal Article
Recenzirano
We here report a family from Libya with three siblings suffering from early onset achalasia born to healthy parents. We analyzed roughly 5000 disease‐associated genes by a next‐generation sequencing ...(NGS) approach. In the analyzed sibling we identified two heterozygous variants in CRLF1 (cytokine receptor‐like factor 1). Mutations in CRLF1 have been associated with autosomal recessive Crisponi or cold‐induced sweating syndrome type 1 (CS/CISS1), which among other symptoms also manifests with early onset feeding difficulties. Segregation analysis revealed compound heterozygosity for all affected siblings, while the unaffected mother carried the c.713dupC (p.Pro239Alafs*91) and the unaffected father carried the c.178T>A (p.Cys60Ser) variant. The c.713dupC variant has already been reported in affected CS/CISS1 patients, the pathogenicity of the c.178T>A variant was unclear. As reported previously for pathogenic CRLF1 variants, cytokine receptor‐like factor 1 protein secretion from cells transfected with the c.178T>A variant was severely impaired. From these results we conclude that one should consider a CRLF1‐related disorder in early onset achalasia even if other CS/CISS1 related symptoms are missing.
It is well known that glucocorticoids induce insulin resistance, but the exact time scale in humans is not well known. The aim of the study was to determine the time scale of effects of pharmacologic ...doses of glucocorticoids on insulin sensitivity. Subjects were treated with repeated methylprednisolone infusions and oral prednisone for Graves’ orbitopathy. Insulin sensitivity was determined using euglycemic hyper-insulinemic clamp (EHGC) before, during the first glucocorticoid infusion and after 2 months of treatment. EHGC started 2 h after the start of the glucocorticoid infusion, and lasted for 2 h. In another group of patients, insulin sensitivity was determined by short insulin tolerance test (SITT) before and during the first glucocorticoid infusion. SITT started 15 min after the start of the glucocorticoid infusion and lasted for 15 min. Ten subjects were included in each protocol. All were euthyroid during the study period. Four hours after the start of the glucocorticoid infusion significant reduction of insulin sensitivity was observed, which did not change for a further 2 months of glucocorticoid treatment before 7.82 (95% confidence interval (CI) 5.35–10.29), first infusion, 4.93 (95% CI 2.99–6.87), after 2 months 5.36 (95%CI 3.91–6.81) mg/kg/min. No significant change in insulin sensitivity occurred during the first 30 min of glucocorticoid infusion before 139.7 (95%CI 94.1–185.3), during 146.7 (95%CI 106.3–187.1) μmol/l/min. In humans, glucocorti-coid-induced insulin resistance develops quickly, in about 4 h, and does not change during further glucocorticoid treatment.
This paper studies the morphological productivity of adjective-forming prefixes at the level of word-formation rules. The productivity at the aforementioned level is the union of the productivity at ...the level of word-formation types and morphological types. The aim of the paper is to offer pieces of information on the interaction of different concepts within different word-formation types together with the morphological aspect through different morphological types. We find 267 examples of adjectives and analyse 31 prefixes interacting with various simple or complex adjectives in the corpus comprised of news, literary, academic and TV registers. After analytic, descriptive and statistical methods, we conclude that they fall into 5 different conceptual categories, i.e., wordformation type clusters (Quality, Location, Quantity, Time and State). The majority of clusters show that the stem is determining the conceptual category while prefixes refine it. The highest productivity rates are recorded with such word-formation types. The only exceptions are Quantity and Time where the conceptual category depends on the prefixes and stems equally. The results from the morphological analyses show that most of the prefixes are inserting additional semantic pieces of information, usually recording the highest PR and not changing the conceptual category of the stem and appearing within one or multiple clusters, with exceptions for Quantity and Time.
The aim of the study was to evaluate thyroid-stimulating hormone (TSH) concentration in a reference group and to compare it with the TSH in subjects with high probability of thyroid dysfunction. The ...study population consisted of 852 subjects. The reference group consisting of 316 subjects was obtained by the exclusion of the subjects having thyroid disease, taking thyroid influencing drugs, having increased thyroid peroxidase (TPO) antibodies, or having abnormal thyroid ultrasound. 42 high probability of thyroid dysfunction subjects were defined by the association of increased TPO antibody concentration, changed echogenicity, and changed echosonographic structure of thyroid parenchyma. In the reference group TSH reference range was 0.45 mU/l (95% CI 0.39-0.56 mU/l) to 3.43 mU/l (95% CI 3.10-4.22 mU/l). To distinguish reference and high probability of thyroid dysfunction group a TSH threshold was calculated. At a threshold value of 3.09 mU/l (95% CI 2.93-3.38 mU/l), specificity was 95% and sensitivity 38.1%. Using 2 different approaches to find upper limit of the TSH reference range we obtained similar results. Using reference group only a value of 3.43 mU/l was obtained. Using both reference group and subjects with the high probability of thyroid dysfunction we obtained 95% CI for the upper reference limit between 2.93 and 3.38 mU/l. Based on these premises, it could be argued that conservative estimate of the TSH upper reference range should be 3.4 mU/l for both sexes.
Graves' orbitopathy (GO) is an autoimmune condition, which is associated with poor clinical outcomes including impaired quality of life and socio-economic status. Current evidence suggests that the ...incidence of GO in Europe may be declining, however data on the prevalence of this disease are sparse. Several clinical variants of GO exist, including euthyroid GO, recently listed as a rare disease in Europe (ORPHA466682). The objective was to estimate the prevalence of GO and its clinical variants in Europe, based on available literature, and to consider whether they may potentially qualify as rare. Recent published data on the incidence of GO and Graves' hyperthyroidism in Europe were used to estimate the prevalence of GO. The position statement was developed by a series of reviews of drafts and electronic discussions by members of the European Group on Graves' Orbitopathy. The prevalence of GO in Europe is about 10/10,000 persons. The prevalence of other clinical variants is also low: hypothyroid GO 0.02-1.10/10,000; GO associated with dermopathy 0.15/10,000; GO associated with acropachy 0.03/10,000; asymmetrical GO 1.00-5.00/10,000; unilateral GO 0.50-1.50/10,000.
GO has a prevalence that is clearly above the threshold for rarity in Europe. However, each of its clinical variants have a low prevalence and could potentially qualify for being considered as a rare condition, providing that future research establishes that they have a distinct pathophysiology. EUGOGO considers this area of academic activity a priority.
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