scholarly journals Predictors of transient congenital primary hypothyroidism: data from the German registry for congenital hypothyroidism (AQUAPE “HypoDok”)

2021 ◽  
Author(s):  
Nicola Matejek ◽  
Sascha R. Tittel ◽  
Holger Haberland ◽  
Tilman Rohrer ◽  
Eva-Maria Busemann ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Congenital Hypothyroidism ◽  
Neonatal Screening ◽  
Roc Analysis ◽  
Operating Characteristic ◽  
Primary Hypothyroidism ◽  
Treatment Withdrawal ◽  
Associated Malformations ◽  
German Registry ◽  
Higher Sensitivity

AbstractNeonatal screening for congenital primary hypothyroidism (CH) may not distinguish between transient (TCH) and permanent dysfunction (PCH), causing potential overtreatment and concerns in affected families. To specify the indication for interruption of therapy, we analysed the German registry “HypoDok” for infants with CH, which oversees 1625 patients from 49 participating centres in Germany and Austria from 1997 until today. A total of 357 patients with a thyroid gland in loco typico were identified and retrospectively grouped according to cessation (TCH, n = 24) or continuation (PCH, n = 333) of l-thyroxine (l-T4) treatment at 2 years of age. The receiver operating characteristic (ROC) analysis was performed to identify cutoffs predicting TCH by screening TSH concentrations and l-T4 dosages. Gestational ages, birth weights and prevalence of associated malformations were comparable in both groups. The cutoff screening TSH concentration was 73 mU/L. The cutoff daily l-T4 dosage at 1 year was 3.1 μg/kg (90% sensitivity, 63% specificity; 36 μg/day) and at 2 years of age 2.95 μg/kg (91% sensitivity, 59% specificity; 40 μg/day). At 2 years of age, specificity (71%) increased when both of these parameters were considered together.Conclusion: The decision to continue or cease l-T4 treatment at 2 years of age in CH patients diagnosed in neonatal screening may be based on their screening TSH concentrations and individual l-T4 dosages at 1 and 2 years of age. Thus, TCH and PCH may be distinguished; overtreatment avoided; and affected families reassured. What is Known:• The course of congenital primary hypothyroidism may be transient, causing potential overtreatment.• The dose ofl-thyroxine at 1 or 2 years of age may predict a transient course of primary congenital hypothyroidism. What is New:• TSH screening concentration andl-thyroxine dosages at 1 and 2 years of age represent reliable predictors for transient congenital primary hypothyroidism with higher sensitivity and specificity when considered together in order to select eligible patients who qualify for treatment withdrawal.

scholarly journals Predictors of Transient Congenital Primary Hypothyroidism: Data from the German Registry for Congenital Hypothyroidism (AQUAPE "HypoDok")

2021 ◽  
Author(s):  
Nicola Matejek ◽  
Sascha R. Tittel ◽  
Holger Haberland ◽  
Tilman Rohrer ◽  
Eva-Maria Busemann ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Receiver Operating Characteristic ◽  
Congenital Hypothyroidism ◽  
Neonatal Screening ◽  
Roc Analysis ◽  
Operating Characteristic ◽  
Primary Hypothyroidism ◽  
Associated Malformations ◽  
German Registry ◽  
Receiver Operating

Abstract Neonatal screening for congenital primary hypothyroidism (CH) may not distinguish between transient (TCH) and permanent dysfunction (PCH), causing potential overtreatment and concerns in affected families. To specify the indication for interruption of therapy we analysed the German registry "HypoDok" for infants with CH, which oversees 1,625 patients from 49 participating centres in Germany and Austria from 1997 until today. 357 Patients with a thyroid gland in loco typico were identified and retrospectively grouped according to cessation (TCH n=24) or continuation (PCH n=333) of L-Thyroxine (L-T4) treatment at 2 years of age. The receiver operating characteristic (ROC) analysis was performed to identify cut-offs predicting TCH by screening TSH concentrations and L-T4 dosages. Gestational ages, birth weights and prevalence of associated malformations were comparable in both groups. The cut-off screening TSH concentration was 73 mU/L. The cut-off daily L-T4 dosage at 1 year was 3.1 µg/kg (90% sensitivity, 63% specificity; 36 µg/d) and at 2 years of age 2.95 µg/kg (91% sensitivity, 59% specificity; 40 µg/d). At 2 years of age, specificity (71%) increased when these both parameters were considered together. Conclusion: The decision to continue or cease L-T4 treatment at 2 years of age in CH patients diagnosed in neonatal screening may be based on their screening TSH concentrations and individual L-T4 dosages at 1 and 2 years of age. Thus, TCH and PCH may be distinguished; overtreatment avoided, and affected families reassured.

scholarly journals Primary congenital hypothyroidism: defects in iodine pathways

2003 ◽  
pp. 247-256 ◽  
Author(s):  
JJ de Vijlder
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Congenital Hypothyroidism ◽  
Primary Hypothyroidism ◽  
Special Importance ◽  
Hormone Production ◽  
Central Hypothyroidism ◽  
Hormone Synthesis ◽  
Diagnosis And Classification ◽  
The Central Nervous System

The thyroid gland is the only source of thyroid hormone production. Thyroid hormone is essential for growth and development, and is of special importance for the development of the central nervous system. It was for that reason that neonatal screening on congenital hypothyroidism was introduced and is now performed in many countries. Defects in thyroid hormone production are caused by several disorders in hormone synthesis and in the development of the thyroid gland (primary hypothyroidism) or of the pituitary gland and hypothalamus (central hypothyroidism).This paper describes defects in the synthesis of thyroid hormone caused by disorders in the synthesis or iodination of thyroglobulin, leakage of iodinated proteins by a stimulated thyroid gland and the presence of abnormal iodoproteins, mainly iodinated albumin, in the thyroid gland and blood circulation. Circulating thyroglobulin and abnormal iodoproteins, as well as the breakdown products of these iodoproteins excreted in urine, are used for etiological diagnosis and classification. Moreover, our finding of an enzyme that catalyses the dehalogenation of iodotyrosines, which is important for iodine recycling and required for economical use of iodine, is also referred to.

Cognitive and Behavioral Complications of Congenital Hypothyroidism

2010 ◽  
Author(s):  
Ruth D. Nass
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Brain Development ◽  
Congenital Hypothyroidism ◽  
Behavioral Problems ◽  
Thyroid Stimulating Hormone ◽  
Primary Hypothyroidism ◽  
Normal Brain ◽  
Gene Encoding ◽  
Hormone Synthesis

Congenital hypothyroidism (CH) affects approximately 1 in 3,500 newborns. There is a female preponderance. In areas of iodine insufficiency, the incidence is higher, since iodine is a key element in the synthesis of thyroid hormone. Approximately 85% of CH cases are sporadic, whereas 15% are hereditary. Thyroid hormone is essential for normal pre- and postnatal brain development. The importance of in utero thyroid hormone status is demonstrated by the fact that maternal hypothyroidism during pregnancy is known to result in cognitive and motor deficits in the offspring (Forrest 2004; Zoeller and Rovet 2004). Congenital hypothyroidism is already expressed in fetal life; maternal T4, transferred via the placenta, is not sufficient for normal brain development (Forrest 2004; Haddow et al. 1999; Opazo et al. 2008; Pop and Vulsma 2005). Prior to newborn screening, CH that went undiagnosed and untreated for more than 3 months was associated with permanent and significant mental retardation, as well as behavioral problems. Outcome is now significantly better. Children with CH have normal intelligence, although subtle and specific cognitive and behavioral problems occur. Congenital hypothyroidism can be caused by primary hypothyroidism, due to a defect of the thyroid gland, or by central hypothyroidism secondary to defective hypothalamic or pituitary regulation of thyroid hormone. Several types of primary thyroid abnormalities may occur. Thyroid dysgenesis is the result of a missing, ectopic, or hypoplastic gland. Proteins that are crucial for normal thyroid gland development include the thyroid transcription factors PAX8, TTF1, TTF2, FOXE1 and the thyroid stimulating hormone (TSH) receptor gene. Thyroid dyshormonogenesis is generally due to an autosomal recessive genetic defect in any of many stages of thyroid hormone synthesis, secretion and transport (Moreno and Visser 2007). One in 50,000 children has autosomal dominant thyroid hormone resistance (RTH) due to a mutation in the gene encoding for the TRb thyroid receptors (Hauser et al. 1993; Weiss et al. 1993). Iodine deficiency can also cause CH (endemic cretinism) (DeLange et al. 2000). Gaudino and colleagues (2005) determined the etiology of CH in 49 non-athyroid cases.

scholarly journals Fully Automated Colorimetric Analysis of the Optic Nerve Aided by Deep Learning and Its Association with Perimetry and OCT for the Study of Glaucoma

2021 ◽  
Vol 10 (15) ◽  
pp. 3231
Author(s):  
Marta Gonzalez-Hernandez ◽  
Daniel Gonzalez-Hernandez ◽  
Daniel Perez-Barbudo ◽  
Paloma Rodriguez-Esteve ◽  
Nisamar Betancor-Caro ◽  
...  
Keyword(s):  
Distribution Function ◽  
Deep Learning ◽  
Optic Nerve ◽  
Roc Analysis ◽  
Operating Characteristic ◽  
Learning Models ◽  
Colorimetric Analysis ◽  
Cirrus Oct ◽  
And Function ◽  
Usual Pattern

Background: Laguna-ONhE is an application for the colorimetric analysis of optic nerve images, which topographically assesses the cup and the presence of haemoglobin. Its latest version has been fully automated with five deep learning models. In this paper, perimetry in combination with Laguna-ONhE or Cirrus-OCT was evaluated. Methods: The morphology and perfusion estimated by Laguna ONhE were compiled into a “Globin Distribution Function” (GDF). Visual field irregularity was measured with the usual pattern standard deviation (PSD) and the threshold coefficient of variation (TCV), which analyses its harmony without taking into account age-corrected values. In total, 477 normal eyes, 235 confirmed, and 98 suspected glaucoma cases were examined with Cirrus-OCT and different fundus cameras and perimeters. Results: The best Receiver Operating Characteristic (ROC) analysis results for confirmed and suspected glaucoma were obtained with the combination of GDF and TCV (AUC: 0.995 and 0.935, respectively. Sensitivities: 94.5% and 45.9%, respectively, for 99% specificity). The best combination of OCT and perimetry was obtained with the vertical cup/disc ratio and PSD (AUC: 0.988 and 0.847, respectively. Sensitivities: 84.7% and 18.4%, respectively, for 99% specificity). Conclusion: Using Laguna ONhE, morphology, perfusion, and function can be mutually enhanced with the methods described for the purpose of glaucoma assessment, providing early sensitivity.

scholarly journals Quantitative Assessment of the Echogenicity of a Breast Tumor Predicts the Response to Neoadjuvant Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3546
Author(s):  
Katarzyna Sylwia Dobruch-Sobczak ◽  
Hanna Piotrzkowska-Wróblewska ◽  
Piotr Karwat ◽  
Ziemowit Klimonda ◽  
Ewa Markiewicz-Grodzicka ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Treatment Response ◽  
Roc Analysis ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Quantitative Measure ◽  
Malignant Cell ◽  
Breast Cancer Patients ◽  
The Third ◽  
Leibler Divergence

The aim of the study was to improve monitoring the treatment response in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). The IRB approved this prospective study. Ultrasound examinations were performed prior to treatment and 7 days after four consecutive NAC cycles. Residual malignant cell (RMC) measurement at surgery was the standard of reference. Alteration in B-mode ultrasound (tumor echogenicity and volume) and the Kullback-Leibler divergence (kld), as a quantitative measure of amplitude difference, were used. Correlations of these parameters with RMC were assessed and Receiver Operating Characteristic curve (ROC) analysis was performed. Thirty-nine patients (mean age 57 y.) with 50 tumors were included. There was a significant correlation between RMC and changes in quantitative parameters (KLD) after the second, third and fourth course of NAC, and alteration in echogenicity after the third and fourth course. Multivariate analysis of the echogenicity and KLD after the third NAC course revealed a sensitivity of 91%, specificity of 92%, PPV = 77%, NPV = 97%, accuracy = 91%, and AUC of 0.92 for non-responding tumors (RMC ≥ 70%). In conclusion, monitoring the echogenicity and KLD parameters made it possible to accurately predict the treatment response from the second course of NAC.

scholarly journals Urinary Metabolomics Study of Patients with Bicuspid Aortic Valve Disease

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4220
Author(s):  
Massimo Chessa ◽  
Mario Panebianco ◽  
Sara Corbu ◽  
Milena Lussu ◽  
Angelica Dessì ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Metabolic Pathways ◽  
Congenital Heart ◽  
Roc Analysis ◽  
Operating Characteristic ◽  
Molecular Fingerprint ◽  
Metabolomics Study ◽  
Cardiovascular Anomalies ◽  
Potential Use

Bicuspid aortic valve (BAV) is the most common congenital heart defect responsible for valvular and aortic complications in affected patients. Causes and mechanisms of this pathology are still elusive and thus the lack of early detection biomarkers leads to challenges in its diagnosis and prevention of associated cardiovascular anomalies. The aim of this study was to explore the potential use of urine Nuclear Magnetic Resonance (NMR) metabolomics to evaluate a molecular fingerprint of BAV. Both multivariate and univariate statistical analyses were performed to compare the urinary metabolome of 20 patients with BAV with that of 24 matched controls. Orthogonal partial least squared discriminant analysis (OPLS-DA) showed statistically significant discrimination between cases and controls, suggesting seven metabolites (3-hydroxybutyrate, alanine, betaine, creatine, glycine, hippurate, and taurine) as potential biomarkers. Among these, glycine, hippurate and taurine individually displayed medium sensitivity and specificity by receiver operating characteristic (ROC) analysis. Pathway analysis indicated two metabolic pathways likely perturbed in BAV subjects. Possible contributions of gut microbiota activity and energy imbalance are also discussed. These results constitute encouraging preliminary findings in favor of the use of urine-based metabolomics for early diagnosis of BAV.

Pubertal development and adult height in patients with congenital hypothyroidism detected by neonatal screening in southern Brazil

2020 ◽  
Vol 33 (11) ◽  
pp. 1449-1455
Author(s):  
Suzana Nesi-França ◽  
Rodrigo B. Silveira ◽  
Juliana Cristina R. Rojas Ramos ◽  
Adriane A. Cardoso-Demartini ◽  
Monica N. Lima Cat ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Neonatal Screening ◽  
Adult Height ◽  
Screening Program ◽  
Pubertal Development ◽  
Z Score ◽  
Normal Range ◽  
Adequate Treatment ◽  
Increased Risk ◽  
Puberty Onset

AbstractObjectivesAdequate treatment of congenital hypothyroidism (CH) is required for normal growth and sexual development. To evaluate pubertal development in patients with permanent CH detected by a statewide Neonatal Screening Program of Paraná and, secondly, to evaluate adult height (AH) in a subgroup of patients.MethodsClinical, laboratory, and auxological data obtained from medical records of 174 patients (123 girls).ResultsMedian chronological age (CA) at treatment initiation was 24 days, and mean initial levothyroxine dose was 11.7 ± 1.9 μg/kg/day; mean CA at puberty onset was 11.5 ± 1.3 years (boys) and 9.7 ± 1.2 years (girls); mean CA in girls who underwent menarche (n=81) was 12.1 ± 1.1 years. Thyroid-stimulating hormone (TSH) values above the normal range were observed in 36.4% of the boys and 32.7% of the girls on puberty onset, and in 44.6% around menarche. Among 15 boys and 66 girls who had reached the AH, the median height z-score value was significantly greater than the target height (TH) z-score value in boys (p=0.01) and in girls (p<0.001). Boys with normal TSH values at puberty onset had greater mean AH z-score compared with boys with TSH values above the normal range (p=0.04).ConclusionsIn this group, pubertal development in girls with CH was not different from that reported in healthy girls in the general Brazilian population. Boys with higher TSH at puberty onset may have an increased risk of not reaching their potential height compared with those with normal TSH during this period. In a subgroup who attained AH, the median AH z-score was greater than the median TH z-score.

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