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Abstract Nephrocalcinosis is a complex disease with a multitude of triggering factors. An association with congenital hypothyroidism has been described in the literature, but the mechanisms leading to its development remain unclear. A 7‐month‐old infant presented with muscular hypotonia and signs of malnutrition was diagnosed with congenital hypothyroidism, nephrocalcinosis of unclear origin, and multiple kidney stones. Urine analysis revealed the presence of calcium oxalate crystals and slightly elevated oxaluria without hypercalciuria. Targeted exome sequencing found no variants in the four causative genes of primary oxaluria, namely AGXT, CBX5, GRHPR, and HOGA1. The clinical outcome was favorable with thyroid hormone and potassium citrate treatment. Ultrasound follow‐up showed progressive improvement of nephrocalcinosis. The low level of urinary oxalate and the prevalence of dihydrate calcium oxalate crystals spoke against primary or secondary oxaluria. Recent evidence from mitochondrial research shows that thyroid hormone T3 enhances mitochondrial calcium levels by stimulating calcium uptake by the mitochondrial calcium uniporter. A reduced calcium uptake and metabolism in mitochondria might represent an explanation for cytoplasmic calcium accumulation in tubular cells, subsequently precipitating nephrocalcinosis in the absence of thyroid hormone. Even if the pathophysiological mechanisms are not yet fully understood, recent evidence is supportive of a causal relationship between hypothyroidism and nephrocalcinosis, a sometimes overlooked association.

Background: Although attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, its aetiology remains unclear. We aimed to establish a relationship between ADHD diagnosis and serum levels of glucose, free thyroxine (FT4), and thyroid stimulating hormone (TSH) in primary school aged boys. Methods: In a cross-sectional study, we enrolled 133 participants aged 6.5–12.5 years, 67 of whom met DSM-5 criteria for ADHD and 66 healthy age-matched boys. The ADHDT test (ADHDT) was used to assess ADHD symptoms and the Wechsler Intelligence Scale for Children – Revised was used to exclude participants with cognitive deficits. The ADHD participants were tested using the Iowa Conners' Teacher Rating Scale. Results: The ADHD participants had lower glucose levels, higher TSH values, and significantly lower FT4 values than the control group. The multiple logistic regression analysis showed that TSH is a parameter that is 2.7% more likely to occur in the ADHD group. We found a significant correlation between the TSH level and the symptoms of hyperactivity (r = 0.318, p = 0.009) and impulsivity (r = 0.275, p = 0.024) as well as between the glucose level and the symptoms of hyperactivity (r = 0.312, p = 0.010). Conclusions: Certain ADHD symptoms may correlate with certain hormonal patterns. Our results suggest that the likelihood of suffering from ADHD was lower when FT4 levels were elevated. One biochemical parameter that was significantly and independently associated with the diagnosis of ADHD was the serum TSH level. Trial registration: On June 26, 2018, at its VI session in 2018, the Ethics Committee of the Institute for Mental Health in Belgrade, Serbia, has considered and unanimously approved the conduct of the research, under the number 1704/1. [ABSTRACT FROM AUTHOR]

Background: Nephrotic syndrome (NS) is the commonest glomerular disease among children. It is characterized by heavy proteinuria and is a risk factor for hypothyroidism in the affected children. Hypothyroidism is of concern because it affects the physical and intellectual development of children and adolescents. This study sought to establish the prevalence and factors associated with hypothyroidism among children and adolescents with NS. Methods: A cross-sectional design was used to study 70 children and adolescents aged 1–19 years diagnosed with nephrotic syndrome and being followed up in the kidney clinic in Mulago National Referral Hospital. Questionnaires were used to collect patients' socio-demographics and clinical information. A blood sample was taken for analysis for thyroid stimulating hormone (TSH) and free thyroxine (FT4), renal function tests and serum albumin. Hypothyroidism included both overt and subclinical forms. Overt hypothyroidism was defined as TSH level > 10 mU/L and FT4 < 10pmol/L, or FT4 < 10pmol/l with normal TSH, or TSH < 0.5mU/l. Sub-clinical hypothyroidism was defined as TSH ranging between 5 and10 mU/L with normal age appropriate FT4 levels. Urine samples were collected and taken for a dipstick examination. The data was analyzed using STATA version 14. The Bayesian Logistic regression analysis approach was used to estimate odds ratios (OR) and their associated 95% credible intervals. All predictor variables with p value < 0.05 at frequentist statistical analysis were considered significant. Results: The mean age (standard deviation) of participants was 9 years (3.8). There were more males; 36 of 70 (51.4%). The prevalence of hypothyroidism was 23% (16/70 participants). Of the 16 children with hypothyroidism, 3 (18.7%) had overt hypothyroidism while 13 had subclinical hypothyroidism. Only low serum albumin was found to be strongly associated with hypothyroidism; Bayesian OR 132.57 (CI 9.13–567.10) with a frequentist OR of 37 and a p value of 0.001. Conclusion: The prevalence of hypothyroidism among children and adolescent with nephrotic syndrome attending Mulago Hospital paediatric kidney clinic was 23%. Hypoalbuminemia was found to be associated with hypothyroidism. Therefore, children and adolescents that have severely low levels of serum albumin should be screened for hypothyroidism and linked to endocrinologists for care. [ABSTRACT FROM AUTHOR]

Aim: To weight the prognostic value of thyroid hormones in catastrophic acute‐on‐chronic liver failure (ACLF). Methods: A retrospective cohort (n = 635) and two prospective cohorts (n = 353, and 198) were enrolled in this study. The performance of a novel developed prognostic score was assessed from aspects of reliability, discrimination, and clinical net benefit. Results: Thyroid‐stimulating hormone (TSH) was identified to have the most potential as a prognostic predictor for hepatitis B virus‐related ACLF among thyroid hormones. The novel score (modified chronic liver failure–organ failure score [mCLIF‐OFs]) was developed with weighted TSH and other scored organs in the CLIF‐OFs using the retrospective cohort (n = 635). The predicted risk and observed probabilities of death were comparable across the deciles of mCLIF‐OFs (Hosmer–Lemeshow χ2 = 4.28, p = 0.83; Brier scaled = 11.9). The C‐index of mCLIF‐OFs (0.885 [0.883–0.887]) for 30‐day mortality was significantly higher than that of the CLIF‐OFs, chronic liver failure–sequential organ failure assessment score (CLIF‐SOFAs), CLIF‐C ACLFs, Model of End‐stage Liver Disease (MELD), and Child–Pugh (all p < 0.001). The absolute improvements of prediction error rates of the mCLIF‐OFs compared to the above five scores were from 19.0% to 61.1%. After the analysis of probability density function, the mCLIF‐OFs showed the least overlapping coefficients (27.9%) among the above prognostic scores. Additionally, the mCLIF‐OFs showed greater net benefit than the above five prognostic scores over a wide range of risk threshold of death. Similar results were validated in two prospective ACLF cohorts with HBV and non‐HBV etiologies. Conclusion: Weighted TSH portended the outcome of ACLF patients, which could be treated as a "damaged organ" of the hypothalamic–pituitary–thyroid axis. The novel mCLIF‐OFs is a reliable prognostic score with better discrimination power and clinical net benefit than CLIF‐OFs, CLIF‐SOFAs, CLIF‐C ACLFs, MELD, and Child–Pugh. [ABSTRACT FROM AUTHOR]

Primary hypothyroidism, the most common form of hypothyroidism, requires effective patient understanding and management for successful long-term treatment. This study aimed to investigate the influence of patient knowledge, attitude, practice (KAP), depression, and medication adherence on treatment response in primary hypothyroidism. A cross-sectional observational study was conducted at Al Hassan Metabolism, Endocrine, and Diabetes Center (HMEDC) in Iraq between September 2022 and March 2023. We enrolled 111 patients with signs and symptoms of primary hypothyroidism over 6 months. A validated questionnaire assessed patient knowledge, attitude, practice (KAP), depression, and medication adherence. Thyroid-stimulating hormone (TSH) levels were measured to assess treatment response. Data were analyzed using SPSS v26, with categorical variables presented as percentages. The student's t-test was used to assess statistical significance, with P - valuess below 0.05 considered significant and P - values below 0.01 considered highly significant. The mean age of patients was 45 ± 11.9 years. Approximately 34% of patients had insufficient knowledge, and 30% indicated a positive attitude towards their treatment. A total of 35% of patients had excellent practice. There was no statistically significant association between KAP and age or gender. There was a significant positive correlation between higher levels of education and improved KAP scores. A total of 44.1% of participants reported moderate depression, and 58% demonstrated adherence to levothyroxine (LT4) treatment. Despite good adherence, the combination of fair knowledge and moderate-to-severe depression resulted in suboptimal outcomes for replacement treatment. [ABSTRACT FROM AUTHOR]

Background: Hypothyroidism is common postlaryngectomy and is associated with laryngectomy‐specific complications. The objective of this study is to determine the incidence and predictors of hypothyroidism postlaryngectomy and its associated complications. Methods: Systematic review, data extraction, and meta‐analyses were performed following the PRISMA protocol. Six databases were searched for studies reporting on postlaryngectomy thyroid status with incidence, risk factors, management, or complications. Results: Fifty‐one studies with 6333 patients were included. The pooled incidence of postlaryngectomy hypothyroidism is 49% (CI 42%–57%). Subgroup analysis showed postlaryngectomy hypothyroidism rates significantly correlated with hemithyroidectomy and radiotherapy. Patients who underwent laryngectomy, hemithyroidectomy, and radiotherapy had a 65% (CI 59%–71%) rate of hypothyroidism; laryngectomy and hemithyroidectomy 46% (CI 33%–60%); laryngectomy and radiotherapy 26% (CI 19%–35%); and laryngectomy alone 11% (CI 4%–27%) (p < 0.001). Conclusions: Laryngectomized patients with partial thyroidectomy or radiation therapy are at significant risk of postoperative hypothyroidism. Evidence‐based protocols for early detection and (prophylactic) treatment should be established. [ABSTRACT FROM AUTHOR]

This article discusses a study that examines the potential link between hypothyroidism and survival in pancreatic cancer patients. The researchers found that hypothyroidism was present in a significant percentage of patients with pancreatic ductal adenocarcinoma (PDAC), and it was associated with worse overall survival. The study suggests that further research is needed to better understand the relationship between hypothyroidism and survival in PDAC patients. [Extracted from the article]

Alagille Syndrome (ALGS) is a complex genetic disorder characterized by cholestasis, congenital cardiac anomalies, and butterfly vertebrae. The variable phenotypic expression of ALGS can lead to challenges in accurately diagnosing affected infants, potentially resulting in misdiagnoses or underdiagnoses. This study highlights novel JAG1 gene mutations in two cases of ALGS. The first case with a novel p.Pro325Leufs*87 variant was diagnosed at 2 months of age and exhibited a favorable prognosis and an unexpected manifestation of congenital hypothyroidism. Before the age of 2, the second patient was incorrectly diagnosed with liver structural abnormalities, necessitating extensive treatment. In addition, he exhibited delays in language acquisition that may have been a result of SNAP25 haploinsufficiency. The identification of ALGS remains challenging, highlighting the importance of early detection and genetic testing for effective patient management. The variant p.Pro325Leufs*87 is distinct from reported variants linked to congenital hypothyroidism in ALGS patients, thereby further confirming the clinical and genetic complexity of ALGS. This emphasizes the critical need for individualized and innovative approaches to diagnosis and medical interventions, uniquely intended to address the complexity of this syndrome. [ABSTRACT FROM AUTHOR]

Background: Following rubella virus control, the most important cause of congenital infections is human cytomegalovirus (HCMV). Congenital CMV (cCMV) may happen both in primary and non-primary maternal infections. The present study aimed to screen cCMV in symptomatic newborns suspected of congenital rubella syndrome (CRS) in Iran. Methods: Out of 1629 collected infants' serum samples suspected of CRS but negative for rubella IgM, 524 samples were selected regarding cCMV complications. These samples were divided into two age groups: 1- one month and younger, 2- older than 1 month up to one year. Anti-HCMV IgM detection was performed on these serums. Then HCMV IgG avidity assay and HCMV DNA detection were carried out on all samples with positive and borderline results in IgM detection. Results: Herein, 3.67% of symptomatic infants aged one month and younger had positive and borderline HCMV IgM, 12.5% of which had a low avidity index (AI). HCMV IgM detection rate among symptomatic infants older than one month to one year was 14.5%. Identified genotypes in this study were gB-1(63.63%), gB2 (18.18%), and gB3 (18.18%), respectively. Conclusions: This comprehensive study was performed on serum samples of symptomatic infants clinically suspected of cCMV from all over Iran. There was a good correlation between serology findings and PCR. [ABSTRACT FROM AUTHOR]

Thyroid hormones have vital roles in development, growth and energy metabolism. Within the past two decades, disturbances in thyroid hormone action have been implicated in ageing and the development of age-related diseases. This Review will consider results from biomedical studies that have identified the importance of precise temporospatial regulation of thyroid hormone action for local tissue maintenance and repair. Age-related disturbances in the maintenance of tissue homeostasis are thought to be important drivers of age-related disease. In most iodine-proficient human populations without thyroid disease, the mean, median and 97.5 centile for circulating concentrations of thyroid-stimulating hormone are progressively higher in adults over 80 years of age compared with middle-aged (50–59 years) and younger (20–29 years) adults. This trend has been shown to extend into advanced ages (over 100 years). Here, potential causes and consequences of the altered thyroid status observed in old age and its association with longevity will be discussed. In about 5–20% of adults at least 65 years of age, thyroid-stimulating hormone concentrations are elevated but circulating concentrations of thyroid hormone are within the population reference range, a condition referred to as subclinical hypothyroidism. Results from randomized clinical trials that have tested the clinical benefit of thyroid hormone replacement therapy in older adults with mild subclinical hypothyroidism will be discussed, as well as the implications of these findings for screening and treatment of subclinical hypothyroidism in older adults. Thyroid hormones have key functions throughout the body. However, thyroid function declines with age and thyroid diseases increase in prevalence. This Review outlines our current knowledge about how thyroid function changes with age and the implications for patient care. Key points: In line with the emerging role of thyroid hormone action in tissue maintenance and repair, studying local control of thyroid hormone in ageing is an area urgently in need of research. The mechanisms contributing to altered thyroid status in old age are probably heterogeneous and comprise selective survival, transient age-related changes and persistent age-related changes. Increased circulating levels of thyroid-stimulating hormone and/or reduced circulating levels of thyroid hormone is a heritable phenotype associated with exceptional longevity. Subclinical hypothyroidism is a frequent diagnosis among older adults; in randomized clinical trials, levothyroxine therapy provided no apparent clinical benefits in older adults with mild subclinical hypothyroidism. Older adults form a heterogeneous group, so future research should explore strategies for safe screening, initiation, continuation and/or discontinuation of treatment of subclinical hypothyroidism in specific subgroups of older adults. [ABSTRACT FROM AUTHOR]

Introduction: Altered levels of thyroid hormones can impact various body systems, including the nervous system. Hypothyroidism may disrupt nerve conduction due to pathophysiological changes associated with hormone deficiency. The tribal population, characterized by distinct lifestyles and dietary habits, may experience unique influences on their growth and development. Aim: This study aimed to compare nerve conduction in newly diagnosed and untreated tribal women affected by hypothyroidism with euthyroid tribal women. Method: A cross-sectional study was conducted in southern Odisha, India, spanning from April 2020 to January 2021. Forty-five newly diagnosed hypothyroid tribal women were enlisted from the outpatient department of general medicine as the case group. Additionally, 45 age-matched apparently healthy euthyroid tribal women were included as the control group. The subjects' height and weight were measured by an expert clinician. Nerve conduction (motor and sensory) study on both extremities (left and right side) were conducted for all participants in the human physiology laboratory. Results: The mean age of participants was 48.13±12.12 years in the case group and 47.18±12.2 years in the control group. In hypothyroid tribal women, a significant decrease in conduction velocity was observed in the majority of motor nerves (right median [p = .03], left median [p = .02], left ulnar [p = .04], right posterior tibial [p = .001], left posterior tibial [p = .0001]) and sensory nerves (right median [p =.005], right ulnar [p = .02], right sural [p = .001], and left sural [p = .02]). Conclusion: In newly diagnosed cases of hypothyroidism in tribal women, there is a risk of neuropathy that impacts both motor and sensory neurons. Therefore, it is crucial to initiate early diagnosis and immediate treatment to prevent additional neurological damage. [ABSTRACT FROM AUTHOR]

Objective: Patients with Graves' disease often engage in shared decision‐making to select an individualised treatment regimen from multiple options. Radioactive iodine (RAI) is one of the treatment choices for their condition, aims to improve quality of life and well‐being. Likewise, dissatisfaction with treatment outcomes can result in decision regret. We employed validated questionnaires to assess the prospective quality of life, decision regret and relative factors involved in decision‐making of patients with late hypothyroidism after RAI therapy. Methods: A questionnaire survey was conducted among patients in hypothyroidism status for more than 1 year after RAI therapy. Disease‐specific and generic QoL were assessed using the short form of thyroid‐related patient‐reported outcome (ThyPRO‐39) questionnaire. Patient satisfaction regarding their decision to undergo RAI was assessed using the Decision Regret Scale (DRS) and patients were asked about the importance of relative factors in decision‐making. Results: Of 254 patients who responded to the survey, the mean age of patients was 45.3 years (range: 18–78 years) and the median time from RAI therapy to survey was 4 years (range: 1–30 years). Patients' median and mean DRS score were 34.4 and 38.8 (range: 0–100), respectively. A total of 100 (39.4%) patients express absent‐to‐mild regret (score: 0–25), 154 (60.6%) patients express moderate‐to‐severe regret (score: >25). The mean score of the absent‐to‐mild regret group were significantly higher than those of the moderate‐to‐severe regret group on most ThyPRO‐39 scales. A statistically significant positive correlation was observed between DRS score and most ThyPRO‐39 scale score. There was a significant positive association between higher DRS score and longer time intervals after RAI treatment, a brief duration of hyperthyroidism, and the significance of long‐time outpatient follow‐up. More decision regret was negatively associated Iodine‐free diet, ineffectiveness of ATD, fear of surgery. Conclusion: Impairment of quality of life was positively correlated with decision regret in patients with late‐hypothyroidism after radioiodine therapy. Patients with insufficient information support before decision‐making are more likely to have higher decision regret after treatment. Our findings suggest that health providers should fully communicate with patients and provide information support in multiple dimensions during the shared‐decision‐making process. [ABSTRACT FROM AUTHOR]

Background: Neonate screening is a preventative measure that can contribute to early diagnosis of treatable diseases. Hypothyroidism in neonates is among the common preventable factors leading to intellectual disability. This study aims to describe the prevalence and experience with four-step screening to diagnose congenital hypothyroidism. Methods: The statistical population of this cross-sectional study included 392 preterm neonates (gestational ages less than 36 weeks and 6 days) in 2018-2019 from the health centers covered by Shahid Beheshti University of Medical Sciences (Tehran, Iran) who had been referred for screening. Neonates were screened in the first 3-6 days after birth and then on days 14, 42, and 72. In neonates with TSH serum levels of 10 mU/L, TSH-T4 was measured. Next, the physician decided on the medication based on the results. Results: At the primary screening of the neonates average TSH level was 2.08 ± 2.4 mU/L. Thirty-three neonates (8.4%) indicated disrupted screening results. The secondary screening of 388 neonates (98.97%) revealed an average TSH serum level of 1.9 ± 1.96 mU/L, and 19 (5.9%) indicated TSH serum levels higher than 5 (mU/L). The third screening test was performed on 382 (97.44%) of the neonates. The average TSH level was 1.3 ± 2.4 mU/L, 340 (85.96%) indicated normal levels, and 42 (11.47%) had unfavorable results. Finally, the fourth screening test was performed on 373 (95.15%) neonates. The mean TSH level was 2.21 ± 1.9 mU/L, which revealed 24 (6.12%) unfavorable test results. The percentage of hypothyroidism in neonates was 5.6% (23 cases). In this study, the prevalence of hypothyroidism was 4.33% (17 cases) in girls and 1.53% (6 cases) in boys. Conclusion: The results of this study revealed the high incidence rate of congenital hypothyroidism among preterm neonates. Therefore, preventing congenital hypothyroidism misdiagnosis requires a series of screening tests. Also, findings indicated that the results of screening tests for preterm neonates with prolonged GAs and higher birth weights are more accurate and reliable. [ABSTRACT FROM AUTHOR]

Background: Nonthyroidal illness syndrome (NTIS) can result in thyroid function test alterations that mimic hypothyroidism. The duration of NTIS‐induced changes in dogs is not well‐described. Objectives: Document alterations in thyroid function tests during NTIS and recovery, and the time necessary for their resolution. Animals: From 103 dogs sampled, 25 euthyroid dogs with acute, resolvable illness having a low serum total thyroxine (TT4) concentration on admission were analyzed. Methods: Prospective observational study. Serum TT4 concentration was measured in 103 dogs within 4 hours of admission. If below the reference interval (RI), subsequent serum samples were obtained every 24 hours from admission until discharge (acute phase) and at 2 weeks and 4 weeks after discharge (recovery phase). Serum samples were submitted for batch measurement of serum TT4, free thyroxine (fT4), total 3,5,3′‐triiodothyronine (TT3), and thyroid‐stimulating hormone (TSH) concentrations. Results: In the cohort of dogs analyzed, serum TT4, TT3, and fT4 concentrations were below the RI in 100%, 80%, and 16% at admission; 20%, 80%, and 0% at discharge; 4%, 8%, and 0% at 2 weeks; and 0%, 0%, and 0% at 4 weeks, respectively. Serum TSH concentration was within the RI in 100% at admission and discharge, and above the RI in 4% and 12% at 2 weeks and 4 weeks, respectively. Conclusions and Clinical Importance: Naturally occurring NTIS in dogs induces alterations in thyroid function tests during acute illness and recovery. Measurement of serum TT4 concentration 2 to 4 weeks after discharge or serum fT4 concentration by ED during illness is recommended for accurate assessment of thyroid function in acutely ill dogs. [ABSTRACT FROM AUTHOR]

Aim: To study prevalence and spectrum of behavioural problems in adolescents attending paediatrics OPD and IPD tertiary care Hospital. Material and Methods: This observational descriptive study conducted at tertiary care hospital. Seventy three adolescents were enrolled after taking informed consent from parents of all children and children in case of age above 18 years. First of all Binet Kamat Test (BKT) was administered by trained psychologists for IQ assessment to rule out Intellectual Disability. Blood Samples were drawn after taking all aseptic precautions and was sent for nutritional deficiency and endocrinal evaluation with testing for complete blood count, serum vitamin B12, serum folate levels and TSH levels. Results: A higher prevalence of the behavioural problem and nutritional disorder including the anemia, Vitamin B12, folic acid, BMI, and thyroid disease among the adolescents. The presence of somatic problem (31.4%) and the anxiety problem (28.6%) was the most common pattern among the behavioural problems. Conclusion: A higher prevalence of the behavioural problem and nutritional disorder including the anemia, Vitamin B12, folic acid, BMI, and thyroid disease among the adolescents. The presence of somatic problem (31.4%) and the anxiety problem (28.6%) was the most common pattern among the behavioural problems. [ABSTRACT FROM AUTHOR]

Aim: Our aim was to assess undiagnosed congenital heart defects (CHD) after newborns' hospital discharge in patients with a murmur or CHD suspicion, to find out the signs that predict CHDs and to estimate the costs of the examinations. Methods: We reviewed retrospective medical records of patients (n = 490) referred for the evaluation of CHD suspicion during 2017–2018. Results: The median age of the patients was 2.5 (IQR 0.5–7.4) years. Sixty‐three (13%) patients had an abnormal echocardiography. Neither ductal‐dependent nor cyanotic CHDs were found. Cardiac interventions were performed for 14 out of 63 (22%) patients. Clinical signs indicating CHDs were murmur grade ≥3 (10/11 [91%] vs. 53/479 [11%], p < 0.001) and harsh murmur (15/44 [34%] vs. 48/446 [11%], p < 0.001). Abnormal electrocardiography did not indicate CHD (8/40 [20%] vs. 55/447 [12%], p = 0.165). The total cost of the examinations was 259 700€. The share of the cost of studies assessed as benign was 59%. Conclusion: Only a few CHDs were found after newborn hospital discharge among patients who received foetal and newborn screening and were examined due to CHD suspicion. The high number of benign murmurs in children leads to many referrals, resulting in unnecessary healthcare costs. [ABSTRACT FROM AUTHOR]

Objective:To evaluate quality indicators of the Neonatal Screening Referral Service of the state of Mato Grosso (NSRS-MT) from 2005 to 2019. Methods: Cross-sectional, retrospective, exploratory, descriptive, and observational study from 2005 to 2019. The following parameters were analyzed: age of newborns at the first collection, time between sample collection and arrival at the laboratory, time between the arrival and release of results and time between requesting the second sample and arrival at the NSRS. The population coverage of the program and the incidence of each clinical situation screened were also analyzed. Results: NSRS-MT coverage was analyzed and recorded as 76%. The incidence was analyzed for congenital hypothyroidism (CH) 1:1867, phenylketonuria (PKU) 1:33,311, sickle cell disease (SCD) 1:2004, cystic fibrosis (CF) 1:12,663, congenital adrenal hyperplasia (CAH) 1:15,843, and biotinidase deficiency (DB) 1:25,349. The median age (days) at the first consultation was: 44 for HC, 22 for PKU, 60 for DF, 52 for FC, 79 for HAC and 79 for DB. The mean time between exam collection and delivery to the NSRS was 8.4 days; between the arrival and release of results, 9 days; and for the return of recalls, 59 days. Conclusions: Regarding the coverage of the target population and collection at the ideal age, the NSRS-MT presents values below the national average. However, regarding the mean age at the time of the first consultation, the state’s performance is better than the national. [ABSTRACT FROM AUTHOR]

Background & Objective: Selective high-risk screening of children suspected of having inherited metabolic disorders was conducted jointly by Chemical Pathology section and the Pediatric Department of Indus Hospital and Health Network- (IHHN) from October 2020-March 2022. Tandem mass spectrometry (MS) for newborn screening was recently introduced in a local laboratory. We did a selective high screening of children for metabolic disorders by using MS for neonates and other relevant tests for older children in our hospital. The present study was undertaken to get an estimate of the number of metabolic cases screened and identified after inclusion of an extended workup. Methods: This is a retrospective chart review of children who were selectively screened for IMDs. Patients' records with ages ranging from birth to fourteen years of age were retrieved from the electronic records department of IHHN from October 2020 to March 2022. Records were searched for demographic data, history, signs, symptoms, and lab investigations. All relevant information was recorded on a pre-designed questionnaire. Results: A total of 178 children were screened for inherited metabolic disorders. Majority of the children screened were less than one month of age 96 (54%). Consanguinity was noted in 74 (41.5%) children. Most common symptoms observed were failure to thrive in 77 children (43%), hypoglycemia in 45 children (25%), and feeding difficulty in 36 children (20%). Inherited metabolic disorders were confirmed in 12 children out of which five had congenital adrenal hyperplasia, four had cystic fibrosis and three children had congenital hypothyroidism. Conclusion: In the present study, we were able to screen several children after inclusion of an extended metabolic workup. However, confirmation of many disorders like fatty acid oxidation defects, disorders of carbohydrate metabolism, and sphingolipidosis could not be done due to lack of confirmatory tests. We recommend that confirmatory tests of these disorders be included in local labs. [ABSTRACT FROM AUTHOR]

Substantial change in climate over the years in South Asia is directly affecting the diet and health of the population. It is important to analyze the aftermath of this change and its impact on the thyroid status. In recent years, a complex interplay of the changing climate with the environmental, geographical and dietary factors has contributed to the continued prevalence of hypothyroidism in Pakistani women. To study the influence of various factors which might be aggravating hypothyroidism in the female population of Pakistan, a thorough search of literature was conducted of various databases including Google Scholar and PubMed. Google as a search engine was also explored. This included both interventional and observational studies, published in English, from the year 1950 onwards uptil June 2023. It also included WHO website and local news clips about the awareness campaigns on iodine deficiency over the past years. All studies conducted on females to diagnose hypothyroidism, with both positive and negative outcomes were included in this study. The factors contributing to hypothyroidism among the female population in Pakistan encompass the effects of climate change, both direct and indirect, topographical factor, indiscriminate use of hazardous pesticides, presence of chemical contaminants in food and water, and a lack of awareness among the public and healthcare professionals about the condition’s symptoms and management. [ABSTRACT FROM AUTHOR]

Copyright of Revista Médica de Rosario is the property of Circulo Medico de Rosario and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Karbala Journal of Pharmaceutical Sciences is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose Emotional stress is a precipitating factor for Graves disease (GD). However, the influence of stress relief on the course of GD is unknown. Here, we present a series of patients diagnosed with stress-induced GD in whom stress relief alone led to remission of GD. Cases We report on 11 patients in whom hyperthyroid symptoms started just after severe emotional stress. All patients had suppressed thyroid-stimulating hormone (TSH) levels and elevated free thyroxine (FT4; 22.2–49.5 pmol/L) and TSH-receptor antibody (TRAb; 0.57–40 U/L) levels and were subsequently diagnosed with stress-induced GD. However, all patients declined antithyroid drug treatment. Surprisingly, clinical and biochemical remission was observed in 9 out of 11 patients after 1 to 3 and 2 to 7 months of self-reported stress relief, respectively. Five patients showed long-lasting remission (median follow-up 2.3 years). In 4 patients, remission was initially achieved, but GD relapsed 1 to 4 years afterwards. In 2 patients, treatment with antithyroid drugs was initiated because of rapidly increasing FT4 levels. Baseline FT4 and TRAb levels tended to be higher in patients who did not achieve remission. Furthermore, patients without long-lasting remission were more frequently known to have prior thyroid disease. Conclusion We report on a series of patients with stress-induced GD in whom stress relief alone led to remission of GD (thus without antithyroid drugs). This may indicate that clinicians could consider stopping antithyroid drug treatment or at least shortening the treatment period after stress relief in patients with stress-induced GD. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to examine the features of critical congenital heart disease (CCHD). Methods: The study was planned as a retrospective cohort study. Data for the study were obtained through national data collection systems and 2018–2020 CCHD cohort was established. In this study, we divided the patients into two groups: Group 1 included seven primary target diseases of the newborn CCHD screening program and Group 2 included secondary target diseases. Results: There were 9884 CCHD cases, with a prevalence of 27.8 per 10,000 live births. Of the cases 44.4% were in Group 1 (12.3 per 10,000) and 54.8% were in Group 2 (15.2 per 10,000). Of all cases 55.5% were male and the female/male ratio was 1/1.2. While 21.8% of the cases were premature, 23.0% were babies with low birth weight (LBW), 4.8% were born from multiple pregnancies. The highest prevalence of CCHD was found in LBW (84.8 per 10,000), premature infants (57.8 per 10,000) (p < 0.001). The fatality rate in the cohort was 16.6% in the neonatal period, 31.6% in the first year of life respectively. The mean estimated survival time in the birth cohort was 40.0 months (95% CI: 39.5–40.6). The mean survival time for Group 1 diseases was 33.4 months (95% CI: 32.5–34.2), while it was 45.4 months (95% CI: 44.7–46.0) for Group 2 diseases (p < 0.001). Preterm birth, LBW, maternal age and region were evaluated as factors associated with mortality risk. Conclusion: This study showed that CCHDs are common in Turkey and mortality rates are high. There are regional differences in CCHD both prevalence and survival. Improving prenatal diagnosis rates and expanding neonatal CCHD screening are of key importance. [ABSTRACT FROM AUTHOR]

The diagnostic and referral workflow for children with neuromuscular disorders is evolving, particularly as newborn screening programs are expanding in tandem with novel therapeutic developments. However, for the children who present with symptoms and signs of potential neuromuscular disorders, anatomic localization, guided initially by careful history and physical examination, continues to be the cardinal initial step in the diagnostic evaluation. It is important to consider whether the localization is more likely to be in the lower motor neuron, peripheral nerve, neuromuscular junction, or muscle. After that, disease etiologies can be divided broadly into inherited versus acquired categories. Considerations of localization and etiologies will help generate a differential diagnosis, which in turn will guide diagnostic testing. Once a diagnosis is made, it is important to be aware of current treatment options, as a number of new therapies for some of these disorders have been approved in recent years. Families are also increasingly interested in clinical research, which may include natural history studies and interventional clinical trials. Such research has proliferated for rare neuromuscular diseases, leading to exciting advances in diagnostic and therapeutic technologies, promising dramatic changes in the landscape of these disorders in the years to come. [ABSTRACT FROM AUTHOR]

Thyroid dysfunction stands as the most prevalent endocrine disorder in individuals with Down syndrome, particularly showcasing both clinical and subclinical hypothyroidism. TSH and FT4 blood values serve as common diagnostic and treatment adjustment markers. In Down syndrome (DS), hormone values may deviate from those observed in the general population, which may lead to overdiagnosis and consequent iatrogenesis of subclinical hypothyroidism. The objective of this study was to analyze the appropriateness of the replacement therapeutic approach by identifying the TSH and FT4 values that can be considered normal in these patients. Methods: A cross-sectional study was conducted in 503 subjects with DS of both sexes and without age limit drawn from the Health Program for individuals with DS in Valencia (Spain) from February 1993 to November 2021. The exclusion criteria included hyperthyroidism, nodules, tumors, or individuals under treatment with drugs influencing iodine metabolism. The normality of data distribution was assessed using the Shapiro–Wilk test. Outliers were detected using the Reed's criterion. Hormone values were estimated using quantile regression models for the 2.5th and 97.5th percentiles. Results: The normal values identified were 0.88–11.25 mIU/L for TSH and 0.71–1.63 ng/dL for FT4. The Wald test indicated no significant differences in the reference intervals based on age or sex. Conclusion: The establishment of these values, which, in people with DS, can be considered unique, is of great importance, allowing a watchful waiting attitude to be maintained before starting replacement therapy that is unnecessarily or adjusting medication in diagnosed cases. [ABSTRACT FROM AUTHOR]

One concern for Salvadoran and other Latin American public health researchers across the nineteenth and twentieth centuries was the purported link between goiter (bocio) and cretinism (cretinismo). Goiter is empirical medical condition that is inseparable from scenes of social and political inequality, neocolonialism, development, and war, however effectively the tools that measured it often obfuscated these factors. This article draws on more than a century of goiter research and representation in popular culture to argue that goiter research was part of broader health discourse that focused on poor and rural women and girls in an attempt to improve the productive and reproductive potential of El Salvador. It discusses how goiter research positioned El Salvador as a site of knowledge production for global health. It also proposes that goiter is best understood as a disability and uses insights from critical disability studies to understand how certain groups of people were constructed as problem populations. Over time, understandings of goiter shifted and new explanations came to the fore, but the lingering association of goiter with inheritable disability proved difficult to shake. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a novel disease caused by the SARS-CoV-2 virus and has emerged as a deadly pandemic affecting countries all over the world. Here we share our experience of managing adults with chronic kidney disease (CKD) and concomitant COVID-19 infection jointly managed by pediatric and adult nephrology teams. This retrospective study was done on patient admissions (>18 years) between 20th June- 30th October 2020 with previously diagnosed CKD and hospitalised with COVID-19 infection. The demographic details, underlying comorbidities, clinical presentation, medications, laboratory, radiological profile and outcomes were studied. A total of 213 adults (62% males) with CKD were admitted during this period with a median (IQR) age of 52 (42, 60) years; 75 (35.2%) had associated diabetes mellitus, 83.1% hypertension, 5.2% hypothyroidism and 7% coronary artery disease. 165 (77.5%) were on maintenance haemodialysis (MHD), and 72.8% had arteriovenous fistula as vascular access at presentation. Most (84.5%) patients were symptomatic for COVID-19, and about 2/3 diarrhoea had moderate to severe disease. Oxygen therapy was needed in 62.9%, and medications used were hydroxychloroquine in 84.5%, azithromycin in 21.6%, ivermectin in 82.6%, steroids in 63.8% and Low molecular weight heparin in 59.2%. A further comparison of patients with CKD5D and CKDND revealed similar parameters except for a higher incidence of diarrhoea, acute kidney injury (AKI) and a shorter period to RTPCR negativity (12.5 vs 15 days; P = 0.038) in CKDND. The overall mortality was 24.4%, with similar mortality rates in both groups (P = 0.709) and 20.7% needed ICU transfer. Adults with CKD especially on haemodialysis, are prone to more severe COVID-19 infection and take a longer time for viral clearance (>2 weeks); the mortality too is higher in these patients. [ABSTRACT FROM AUTHOR]

Neonatal diabetes and congenital hypothyroidism (CH) syndrome is a rare condition caused by homozygous or compound heterozygous mutations in the GLIS3 gene. Small for gestational age, congenital glaucoma, polycystic kidney disease, cholestatic hepatic fibrosis, pancreatic exocrine insufficiency, developmental delay, dysmorphic facial features, sensorineural deafness, osteopenia, and skeletal anomalies are other accompanying phenotypic features in the 22 cases described so far. We present a male patient with neonatal diabetes, CH, congenital glaucoma, developmental delay, and facial dysmorphism. During the patient's 17-year follow-up, no signs of exocrine pancreatic insufficiency, liver and kidney diseases, deafness, osteopenia, and bone fracture were observed. A homozygous exon 10-11 deletion was detected in the GLIS3 gene. We report one of the oldest surviving GLIS3 mutation case with main findings of neonatal diabetes and CH syndrome to contribute to the characterization of the genotypic and phenotypic spectra of the syndrome. [ABSTRACT FROM AUTHOR]

Background and Objective: Newborn screening (NBS) aims towards early detection of congenital disorders or prevention of intellectual and physical defects and life-threatening illness. Three disorders namely congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH) and glucose-6-phosphate dehydrogenase deficiency (G-6-PDD) were selected for a preliminary study for NBS. The study aimed to establish NBS in the Indian scenario that could lay a framework for future such initiatives. Methods: A screening programme was conducted at a tertiary care hospital for 1 year. All the neonates born at All India Institute of Medical Sciences (AIIMS), Patna, were screened for their blood levels of glucose-6-phosphate dehydrogenase (G-6-PD), 17-hydroxyprogesterone (17-OHP) and thyroid-stimulating hormone (TSH). Heel-prick blood samples were collected within 48–72 h of birth, and the level of these parameters was accessed by enzyme immunoassay (EIA). Results: A total of 492 neonates were born from January 2020 to December 2020, of which 369 newborns were screened for CAH, CH and G-6-PDD. Of 369 neonates, one case (male) had an increased level of TSH, six cases (all males) had an increased level of 17-OHP and no case was found with G-6-PDD. Interpretation and Conclusions: Preliminary data on the prevalence of various genetic disorders revealed that CAH is the most prevalent disorder followed by CH in the population of Bihar. More efforts need to be undertaken to create awareness and to make screening a successful programme in India. A cost-effective nationwide screening programme is highly recommended for the detection of such cases at the earliest to avoid their future complication. [ABSTRACT FROM AUTHOR]

Context: Subtle cognitive impairments have been described in children with congenital hypothyroidism (CH) detected by neonatal screening (NS), even with early and adequate treatment. Patients with CH may present with brain cortical thickness (CT) abnormalities, which may be associated with neurocognitive impairments. Objective: This work aimed to evaluate the CT in adolescents with CH detected by the NS Program (Paraná, Brazil), and to correlate possible abnormalities with cognitive level and variables of neurocognitive prognosis. Methods: A review was conducted of medical records followed by psychometric evaluation of adolescents with CH. Brain magnetic resonance imaging with analysis of 33 brain areas of each hemisphere was performed in 41 patients (29 girls) and in a control group of 20 healthy adolescents. CT values were correlated with Full-scale Intelligence Quotient (FSIQ) scores, age at start of treatment, pretreatment thyroxine levels, and maternal schooling. Results: No significant difference in CT between patients and controls were found. However, there was a trend toward thinning in the right lateral orbitofrontal cortex among patients and in the right postcentral gyrus cortex among controls. CT correlated significantly with FSIQ scores and with age at start of treatment in 1 area, and with hypothyroidism severity in 5 brain areas. Maternal schooling level did not correlate with CT but was significantly correlated with FSIQ. Cognitive level was within average in 44.7% of patients (13.2% had intellectual deficiency). Conclusion: There was a trend toward morphometric alterations in the cerebral cortex of adolescents with CH compared with healthy controls. The correlations between CT and variables of neurocognitive prognosis emphasize the influence of hypothyroidism on cortical development. Socioeconomic status exerts a limiting factor on cognitive outcome. [ABSTRACT FROM AUTHOR]

Context: The link between congenital hypothyroidism (CH) and neurodevelopment is suggested, yet studies applying quantifiable measures are lacking. Moreover, socioeconomic disparities and subtle variation in timing of approach make the relationship difficult to detect. Objective: To evaluate associations between CH and abnormalities in neurodevelopment and growth and determine the critical period for intervention. Methods: We utilized a nationwide database to conduct a longitudinal analysis of 919 707 children. Exposure to CH was identified using claims-based data. The primary outcome of interest was suspected neurodevelopmental disorder, as measured using the Korean Ages & Stages Questionnaires (K-ASQ) administered annually from 9 to 72 months of age. Secondary outcomes were height and BMI z-scores. After randomly matching cases and controls at a 1:10 ratio, we employed inverse probability of treatment weighting and generalized estimating equation models for our analyses. We conducted subgroup analysis based on the age of treatment initiation. Results: The prevalence of CH in our population was 0.05% (n = 408). Relative to the control group, the CH group had higher risk of suspected neurodevelopmental disorders (propensity score-weighted odds ratio: 4.52; 95% CI: 2.91, 7.02), and significantly increased risk in each of the 5 K-ASQ domains. No time interactions were noted at any rounds for the outcomes according to when the neurodevelopmental assessment was conducted (all P for interaction >.05). The CH group also had higher risk for low height-for-age z-score, but not for elevated BMI-for-age z-score. In subgroup analysis, delayed medication for CH correlated with worse neurodevelopmental outcomes. Conclusion: The CH group had worse neurodevelopmental outcomes and reduced height-for-age z-score. Outcomes were worse when onset of treatment was increasingly delayed. [ABSTRACT FROM AUTHOR]

Context: Patients with congenital hypothyroidism (CH) are affected more often than the general population by other chronic diseases and neurological difficulties. Objective: The aim of this nationwide population-based register study was to investigate the incidence of congenital malformations, comorbidities, and the use of prescribed drugs in patients with primary CH. Methods: The study cohort and matched controls were identified from national population-based registers in Finland. All diagnoses from birth until the end of 2018 were collected from the Care Register, and subject-specific prescription drug purchases were identified from The Prescription Register from birth until the end of 2017. Results: Diagnoses of neonatal and chronic diseases were collected for 438 full-term patients and 835 controls (median follow-up time 11.6 years; range, 0-23 years). Newborns with CH were more often found to have neonatal jaundice (11.2% and 2.0%; P< .001), hypoglycemia (8.9% and 2.8%; P< .001), metabolic acidemia (3.2% and 1.1%; P = .007), and respiratory distress (3.9% and 1.3%; P< .003) as compared to their matched controls. Congenital malformations were diagnosed in 66 of 438 (15.1%) CH patients and in 62 of 835 (7.4%) controls (P < .001). The most commonly affected extrathyroidal systems were the circulatory and musculoskeletal systems. The cumulative incidence of hearing loss and specific developmental disorders was higher among CH patients than controls. The use of antidepressant and antipsychotic drugs was similar in CH patients and their controls. Conclusion: CH patients have more neonatal morbidity and congenital malformations than their matched controls. The cumulative incidence of neurological disorders is higher in CH patients. However, our results do not support the existence of severe psychiatric comorbidity. [ABSTRACT FROM AUTHOR]

One of the main challenges of newborn screening programs, which screen for inherited metabolic disorders, is cutting down on false positives (FPs) in order to avoid family stresses, additional analyses, and unnecessary costs. False positives are partly caused by an insubstantial number of robust biomarkers in evaluations. Another challenge is how to distinguish between diseases which share the same primary marker and for which secondary biomarkers are just as highly desirable. Focusing on pathologies that involve butyrylcarnitine (C4) elevation, such as short-chain acylCoA dehydrogenase deficiency (SCADD) and isobutyrylCoA dehydrogenase deficiency (IBDD), we investigated the acylcarnitine profile of 121 newborns with a C4 increase to discover secondary markers to achieve two goals: reduce the FP rate and discriminate between the two rare diseases. Analyses were carried out using tandem mass spectrometry with whole blood samples spotted on filter paper. Seven new biomarkers (C4/C0, C4/C5, C4/C5DC\C6OH, C4/C6, C4/C8, C4/C14:1, C4/C16:1) were identified using a non-parametric ANOVA analysis. Then, the corresponding cut-off values were found and applied to the screening program. The seven new ratios were shown to be robust (p < 0.001 and p < 0.01, 0.0937 < ε2 < 0.231) in discriminating between FP and IBDD patients, FP and SCADD patients, or SCADD and IBDD patients. Our results suggest that the new ratios are optimal indicators for identifying true positives, distinguishing between two rare diseases that share the same primary biomarker, improving the predictive positive value (PPV) and reducing the false positive rate (FPR). [ABSTRACT FROM AUTHOR]

The phenotypic variability associated with pathogenic variants in Lysine Acetyltransferase 6B (KAT6B, a.k.a. MORF, MYST4) results in several interrelated syndromes including Say-Barber-Biesecker-Young-Simpson Syndrome and Genitopatellar Syndrome. Here we present 20 new cases representing 10 novel KAT6B variants. These patients exhibit a range of clinical phenotypes including intellectual disability, mobility and language difficulties, craniofacial dysmorphology, and skeletal anomalies. Given the range of features previously described for KAT6B-related syndromes, we have identified additional phenotypes including concern for keratoconus, sensitivity to light or noise, recurring infections, and fractures in greater numbers than previously reported. We surveyed clinicians to qualitatively assess the ways families engage with genetic counselors upon diagnosis. We found that 56% (10/18) of individuals receive diagnoses before the age of 2 years (median age = 1.96 years), making it challenging to address future complications with limited accessible information and vast phenotypic severity. We used CRISPR to introduce truncating variants into the KAT6B gene in model cell lines and performed chromatin accessibility and transcriptome sequencing to identify key dysregulated pathways. This study expands the clinical spectrum and addresses the challenges to management and genetic counseling for patients with KAT6B-related disorders.

Thyroid hormone (TH) is indispensable for brain development in utero and during the first 2–3 years of life, and the negative effects of TH deficiency on brain development are irreversible. Detection of TH deficiency early in life by neonat al screening allows early treatment, thereby preventing brain damage. Inborn shortage of TH, also named congenital hypothyroidism (CH), can be the result of defective thyroid gland development or TH synthesis (primary or thyroidal CH (CH-T)). Primary CH is characterized by low blood TH and elevated thyroi d-stimulating hormone (TSH) concentrations. Less frequently, CH is due to insufficient stimulation of the thyroid gland because of disturbed hypothalamic or pituitary function (central CH). Central CH is characterized by low TH concentrations, while TSH is normal, lo w or slightly elevated. Most newborn screening (NBS) programs for CH are primarily TSH based and thereby do not detect central CH. Only a few NBS programs worldwide aim to detect both forms of CH by different strategies. In the Netherlands, we have a uni que T4–TSH–thyroxine-binding globulin (TBG) NBS algorithm for CH, which enables the detection of primary and central CH. Although the necessity of central CH detection by NBS is still under debate, it has been shown that most central CH patients have moderate-to-severe hyp othyroidism instead of mild and that early detection of central CH by NBS probably improves its clinical outcome and clinical care for central CH patients with multiple pituitary hormone deficiency. We are therefore convinced that detection of central CH by NBS is of utmost importance.

Background Congenital hypothyroidism (CH) is the most common congenital endocrine disorder in childhood and is one of the most preventable causes of intellectual disability (ID). Late initiation of thyroid hormone substitution therapy has a negative impact on intellectual abilities in CH patients. Objective To compare Intelligence Quotient (IQ) between children with CH who underwent early treatment among the children without CH. Methods We performed online literature searches of ScienceDirect, Pubmed, Cochrane Library, and Google Scholar. We included clinical studies that examined IQ scores in patients with early-treated CH and without CH. Review Manager 5.4 was used to perform the meta-analysis. Results Twelve studies comparing pediatric patients with and without CH were included in this meta-analysis, for a total of 808 patients. Based on data analysis, IQ levels of verbal IQ [mean difference (MD) -9.05; (95%CI -14.51 to -3.59); (P

Background and Objectives: Congenital thyroid dyshormonogenesis is caused by alterations in the synthesis of thyroid hormones in a newborn. Additionally, 10 to 20% of these cases are hereditary, caused by defects in proteins involved in hormonal synthesis. One of the most common causes is mutations in the thyroid peroxidase (TPO) enzyme gene, an autosomal recessive disease. We aimed to detect mutations of the TPO gene in 12 Chilean patients with congenital hypothyroidism due to dyshormonogenesis (CHD) and to characterize these patients clinically and molecularly. Materials and Methods: Twelve patients under 20 years of age with CHD, controlled at San Juan de Dios Hospital in Santiago, Chile, were selected according to the inclusion criteria: elevated neonatal TSH, persistent hypothyroidism, and thyroid normotopic by imaging study. Those with deafness, Down syndrome, and central or transient congenital hypothyroidism were excluded. Blood samples were taken for DNA extraction, and the 17 exons and exon–intron junctions of the TPO gene were amplified by PCR. The PCR products were sequenced by Sanger. Results: Two possibly pathogenic mutations of the TPO gene were detected: c.2242G>A (p.Val748Met) and c.1103C>T (p.Pro368Leu). These mutations were detected in 2 of 12 patients (16.6%): 1 was compound heterozygous c.1103C>T/c.2242G>A, and the other was heterozygous for c.2242G>A. In the diagnostic confirmation test, both patients presented diffuse hyper-uptake goiter on thyroid scintigraphy and high TSH in venous blood (>190 uIU/mL). Conclusions: The frequency of patients with possibly pathogenic mutations in TPO with CHD was 16.6%. Its study would allow for genetic counseling to be offered to the families of affected patients.

A higher incidence of primary congenital hypothyroidism (CH) has been related to increased sensitivity in neonatal screening tests. The benefit of treatment in mild cases remains a topic of debate. We evaluated the impact of reducing the blood-spot TSH cut-off (b-TSH) from 10 (Group 2) to 6 mIU/L (Group 1) in a public neonatal screening program. During the study period, 40% of 123 newborns with CH (n = 162,729; incidence = 1:1323) had b-TSH between 6 and 10 mIU/L. Group 1 patients had fewer clinical signs (p = 0.02), lower serum TSH (p < 0.01), and higher free T4 (p < 0.01) compared to those in Group 2 at diagnosis. Reducing the b-TSH cut-off from 10 to 6 mIU/L increased screening sensitivity, allowing a third of diagnoses, mainly mild cases, not being missed. However, when evaluating the performances of b-TSH cut-offs (6, 7, 8, 9, and 10 mIU/L), the lower values were associated with low positive predictive values (PPVs) and unacceptable increased recall rates (0.57%) for a public health care program. A proposed strategy is to adopt a higher b-TSH cut-off in the first sample and a lower one in the subsequent samples from the same child, which yields a greater number of diagnoses with an acceptable PPV.

Infants of mothers with Graves’ disease (GD) may develop central hypothyroidism (CH) due to exposure of the foetal hypothalamic-pituitary-thyroid axis to higher-than-normal thyroid hormone concentrations, primary hypothyroidism (PH) due to transplacental passage of maternal thyroid stimulating hormone receptor antibody (TRAb), antithyroid drugs (ATD) or thyroid dysgenesis secondary to maternal uncontrolled hyperthyroidism. We describe two infants with PH and four infants with CH born to mothers with poorly controlled Graves' disease. All infants required levothyroxine and had normal developmental milestones. While national guideline consensus for high thyroid stimulating hormone (TSH) on neonatal screening is well-established, thyroid function tests (TFTs) should be serially monitored in infants with low TSH on screening, as not all mothers with Graves’ disease are diagnosed antenatally.

The iodine supply of pregnant and lactating women is crucial for the health of the fetus and newborn, especially for the proper function of the thyroid gland. Inadequate iodine saturation can lead to serious consequences, including permanent health damage to the child. In the Czech Republic, we use neonatal TSH obtained within the Nationwide Newborn Screening Program for Congenital Hypothyroidism to monitor the iodine supply of newborns. The monitoring results were favorable until recently (until 2018 in Bohemia and until 2022 in Moravia); however, in recent years, there has been an increase in the percentage of newborns with elevated TSH, indicating a deepening iodine deficiency in this vulnerable population. One of the reasons may be inadequate iodine supplementation of pregnant women beyond the normal dietary intake (i.e., 150–200 µg of iodine per day) and a decrease in the consumption of dairy, eggs and iodized salt. The Czech Republic must now focus again on this at-risk population regarding the deepening iodine deficiency. It is important to focus primarily on educational activities and ensure adequate iodine supplementation during pregnancy. [ABSTRACT FROM AUTHOR]

The aim of this short article is to summarize the results and basic performance metrics of newborn laboratory screening from a 13-year period in the Czech Republic. The total cumulative prevalence of all 18 screened diseases was 1 : 1081. The highest prevalence was in congenital hypothyroidism 1 : 2894; phenylketonuria 1 : 4 960; cystic fibrosis 1 : 6309; biotinidase deficiency 1 : 9253; congenital adrenal hyperplasia 1 : 12 190 and medium-chain fatty acid acyl-CoA dehydrogenase deficiency 1 : 22 833. The other screened diseases showed a prevalence of about 1 : 100 000 or less. [ABSTRACT FROM AUTHOR]

Ectopic thyroid, the presence of thyroid tissue in locations other than the normal anterior neck region between the second and fourth tracheal cartilages, is the most common form of thyroid dysgenesis. A 32-year-old female patient sought medical attention at the Otolaryngology Department with a foreign body sensation in her throat. To ensure an accurate diagnosis, hereby, the authors conducted a comprehensive diagnostic work-up, which included Technetium-99 (Tc-99m) scanning. Remarkably, the scanning results revealed radiotracer uptake in the base of the tongue while indicating an absence of uptake in the thyroid bed. By shedding light on present captivating case, the present report offers valuable insights into the usage of Technetium imaging in diagnosing doubtful Lingual Thyroid (LT) cases. [ABSTRACT FROM AUTHOR]

An editorial is presented on Monocarboxylate transporter 8 (MCT8) deficiency, a rare neurodevelopmental disorder caused by mutations in the SLC16A2 gene. Topics include the challenges in clinical management, the potential benefits of T3-analogue Triac in treating MCT8 deficiency, and the need for international collaboration to improve diagnosis and therapeutic options.

INTRODUCTION: Congenital hypothyroidism results from insufficient secretion of thyroid hormones, which are related to the maturation of the central nervous system, being the main cause of preventable intellectual disability in childhood. The diagnosis can be suspected from the neonatal screening test, revealing its importance, since most cases are asymptomatic or oligosymptomatic at birth with nonspecific manifestations, as well as the classic manifestations become evident only later, causing neurological damage. OBJECTIVE: describe a clinical case of a patient diagnosed with congenital hypothyroidism on the sixth day of life, screened through the neonatal screening test, with subsequent laboratory confirmation, highlighting points of diagnosis, treatment and clinical follow-up, avoiding the progression of late diagnosis. CASE REPORT: male patient, born through normal delivery without complications, who developed asymptomatic hypoglycemia at the first hours of life, treatment resistant. The patient presented alterations compatible with congenital hypothyroidism in the neonatal screening test, with subsequent confirmation through laboratory tests. Thyroglobulin replacement was started on the seventh day of life, with progressive improvement in hypoglycemia and favorable clinical evolution throughout the first months of life. CONCLUSION: Congenital hypothyroidism is the main cause of preventable intellectual disability in childhood, it must be diagnosed as early as possible, demonstrating the importance of neonatal screening tools. After the institution of appropriate treatment and clinical follow-up, the evolution is favorable, avoiding the drastic progression of late diagnosis.

BACKGROUND Hemodynamic instability and myocardial dysfunction are major factors preventing the transplantation of hearts from organ donors after brain death. Intravenous levothyroxine is widely used in donor care, on the basis of observational data suggesting that more organs may be transplanted from donors who receive hormonal supplementation. METHODS In this trial involving 15 organ-procurement organizations in the United States, we randomly assigned hemodynamically unstable potential heart donors within 24 hours after declaration ofdeath according to neurologic criteria to open-label infusion of intravenous levothyroxine (30 Bg per hour for a minimum of 12 hours) or saline placebo. The primary outcome was transplantation of the donor heart; graft survival at 30 days after transplantation was a prespecified recipient safety outcome. Secondary outcomes included weaning from vasopressor therapy, donor Neurejection fraction, and number of organs transplanted per donor. RESULTS A total of 838 brain-dead donors were enrolled; 419 were assigned to receive levothyroxine and 419 to receive saline. Hearts were transplanted from 230 donors (54.9°6) in the levothyroxine group and 223 (53.2°6) in the saline group (adjusted risk ratio, 1.01; 95% confidence interval [CI], 0.97 to 1.07; P=0.57). Graft survival at 30 days occurred in 224 hearts (97.4°6) transplanted from donors assigned to receive levothyroxine and 213 hearts (95.5%) transplanted from donors assigned to receive saline (difference, 1.9 percentage points; 95% CI, -2.3 to 6.0; P<0.001 for noninferiority at a margin of 6 percentage points). There were no substantial between-group differences in weaning from vasopressor therapy, ejection fraction on echocardiography, or organs transplanted per donor, but more cases of severe hypertension and tachycardia occurred in the levothyroxine group than in the saline group. CONCLUSIONS In hemodynamically unstable brain-dead potential heart donors, intravenous levothyroxine infusion did not result in significantly more hearts being transplanted than saline infusion. (Funded by Mid-America Transplant and others; ClinicalTrials .gov number, NCT04415658.) [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate various therapeutic approaches, identify potential predictive factors for the recurrence and development of hypothyroidism, and examine specific clinical and laboratory characteristics of patients with subacute thyroiditis (SAT) due to SARS-CoV-2 infection. Methods: We retrospectively analyzed the medical records of 226 patients with confirmed SAT diagnosed from January 2020 to November 2022. Results: The mean age was 48.01 ± 0.75 years, and the F/M ratio was 2.3/1. At the end of the follow-up period, 69 patients (32.1%) had developed hypothyroidism. Treatment duration was significantly shorter with nonsteroidal anti-inflammatory drugs (NSAIDs) (17.40 ± 2.56 days), while time-to-symptom relief was shorter with glucocorticoids (CGs). Recurrence was observed only in those treated with corticosteroid preparations (14.1%). C-reactive protein levels at treatment discontinuation were higher in patients who experienced SAT recurrence, while the coexistence of Hashimoto's thyroiditis was a significant predictive factor for the development of hypothyroidism. The TSH value at the time of treatment withdrawal >4.12 μIU/mL showed optimal sensitivity and specificity for the prediction of permanent hypothyroidism. Regarding COVID-19, 34 patients (15%) experienced related SAT, with similar clinical manifestations of the disease but a higher BMI and shorter time-to-symptom relief. Conclusion: In conclusion, GCs administration alleviated acute symptoms earlier during the onset of SAT, whereas NSAIDs had a shorter treatment duration, and both regimens could not prevent the development of delayed hypothyroidism. The clinical characteristics of SAT due to COVID-19 infections were similar to those of typical SAT disease. [ABSTRACT FROM AUTHOR]

Background: Subclinical hypothyroidism is diagnosed when serum thyroid stimulating hormone levels are higher whilst free thyroxine levels remain within their respective reference ranges. These reference ranges are uniformly applied in all adults, despite serum thyroid stimulating hormone levels naturally increasing with age. Research has found that mildly elevated thyroid stimulating hormone levels may be associated with some benefits in ageing patients, including reduced mortality and better cardiorespiratory fitness. Levothyroxine is typically prescribed to patients with hypothyroidism, but no conclusive evidence exists on whether levothyroxine therapy is beneficial or detrimental in older subclinical hypothyroid patients. Despite this, prescriptions for levothyroxine are increasing year-on-year. This study aims to determine if receiving levothyroxine affects the cardiovascular and bone health outcomes of subclinical patients in primary care aged 50 years and over. Methods: This project includes a retrospective cohort analysis and a target trial emulation study using electronic patient records collected between 2006 and 2021 and recorded in The Health Improvement Network database. The primary outcome of this study is to compare the cardiovascular outcomes of subclinical hypothyroid patients aged over 50 years treated with levothyroxine compared to those untreated. Secondary outcomes are bone health and all-cause mortality outcomes. Descriptive and inferential statistics will both be employed to analyse the data. Secondary analysis will explore confounding factors, including age, sex, smoking status, body mass index, co-morbidities, and levothyroxine dosage. Discussion: There needs to be a greater understanding of the potential risks of the current treatment for older patients with subclinical hypothyroidism in a primary care setting. We will investigate the clinical importance of this issue and whether older subclinical hypothyroid patients have poorer outcomes when treated. Clarifying this concern may help address the healthcare resource implications of ageing patients being misclassified as having mild hypothyroidism, as these patients are more likely to repeat their blood tests. This could reduce prescription wastage and improve patient outcomes and quality of life in the ageing population. Trial registration: Not applicable. [ABSTRACT FROM AUTHOR]