Long-Term Outcome of Patients with TPO Mutations.
Ontology highlight
ABSTRACT: Introduction
Thyroid peroxidase (TPO) deficiency is the most common enzymatic defect causing congenital hypothyroidism (CH). We aimed to characterize the long-term outcome of patients with TPO deficiency.Methods
Clinical and genetic data were collected retrospectively.Results
Thirty-three patients with primary CH caused by TPO deficiency were enrolled. The follow-up period was up to 43 years. Over time, 20 patients (61%) developed MNG. Eight patients (24%) underwent thyroidectomy: one of them had minimal invasive follicular thyroid carcinoma. No association was found between elevated lifetime TSH levels and the development of goiter over the years.Conclusions
This cohort represents the largest long-term follow up of patients with TPO deficiency. Our results indicate that elevated TSH alone cannot explain the high rate of goiter occurrence in patients with TPO deficiency, suggesting additional factors in goiter development. The high rate of MNG development and the risk for thyroid carcinoma indicate a need for long-term follow up with annual ultrasound scans.
SUBMITTER: Tobias L
PROVIDER: S-EPMC8432017 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundLoss-of-function mutations in the thyrotropin receptor (TSHR) gene lead to resistance to TSH (RTSH) presenting with either congenital hypothyroidism (CH) or subclinical hypothyroidism (SCH). Despite several reports of patients with TSHR mutations, data on the long-term outcome of this condition are limited, and no consensus exists on the need for hormone replacement therapy. The aim of the present study was to assess the long-term outcome in children and adolescents with RTSH due to TSHR mutations.MethodsThe TSHR gene was sequenced in 94 subjects (aged 3 days-21 years) with either nonautoimmune SCH or CH with RTSH.ResultsTwenty-seven subjects (29%) carried mutations in TSHR. Fifteen infants were identified by neonatal screening, and the other 79 patients were detected in the process of testing for various other conditions or because of family occurrence of thyroid test abnormalities. Six different mutations were identified: c.484C>G (p.P162A), c.202C>T (p.P68S), c.790C>T (p.P264S), c.269A>C (p.Q90P), c.1957C>G (p.L653V), and c.1347C>T (p.R450C). Twelve subjects were homozygous, three were compound heterozygous, and 12 were heterozygous. Mean serum TSH levels at diagnosis and at last visit were significantly higher in patients with TSHR mutations than in those without mutations (29.04 vs. 14.15, p=0.002; 31.73 vs. 6.19, p<0.0001, respectively). Homozygous patients had a more severe phenotype (TSH 53.6 vs. 9.24, p<0.0001). Mean serum free thyroxine (fT4) levels at the last visit were significantly lower than at the first visit in the homozygous individuals (p=0.05) for a follow-up period of as long as 11 years. Heterozygous subjects had only mild hyperthyrotropinemia with stable TSH levels. However, homozygous subjects showed a trend toward increased TSH and decreased fT4 with time.ConclusionSCH in heterozygotes with TSHR mutations is a stable compensated condition with an appropriately adjusted set point for pituitary-thyroid feedback that does not require replacement therapy. However, homozygous subjects, with incompletely compensated SCH, show reduced fT4 levels over time and may require levothyroxine treatment. Replacement therapy should be considered on an individual basis, and long-term follow up is recommended.
| S-EPMC4361004 | biostudies-literature
Project description:Acute epiglottitis is a potentially life threatening disease, with a growing incidence in the adult population. Its long-term outcome after Intensive Care Unit (ICU) hospitalization has rarely been studied.Thirty-four adult patients admitted for acute epiglottitis were included in this retrospective multicentric study. The mean age was 44 ± 12 years (sex ratio: 5.8). Sixteen patients (47%) had a history of smoking while 8 (24%) had no previous medical history. The average time of disease progression before ICU was 2.6 ± 3.6 days. The main reasons for hospitalization were continuous monitoring (17 cases, 50%) and acute respiratory distress (10 cases, 29%). Microbiological documentation could be made in 9 cases (26%), with Streptococcus spp. present in 7 cases (21%). Organ failure at ICU admission occurred in 8 cases (24%). Thirteen patients (38%) required respiratory assistance during ICU stay; 9 (26%) required surgery. Two patients (6%) died following hypoxemic cardiac arrest. Five patients (15%) had sequelae at 1 year. Patients requiring respiratory assistance had a longer duration of symptoms and more frequent anti inflammatory use before ICU admission and sequelae at 1 year (p < 0.05 versus non-ventilated patients). After logistic regression analysis, only exposure to anti-inflammatory drugs before admission was independently associated with airway intervention (OR, 4.96; 95% CI, 1.06-23.16).The profile of the cases consisted of young smoking men with little comorbidity. Streptococcus spp. infection represented the main etiology. Outcome was favorable if early respiratory tract protection could be performed in good conditions. Morbidity and sequelae were greater in patients requiring airway intervention.
| S-EPMC4422676 | biostudies-other
Project description:Introduction: Evidence of sex-related differences in patients with pacemakers regarding comorbidities is insufficiently investigated. The aim of this study was to determine the relationship of cardiovascular comorbidities and sex category with properties of pacemaker implantation, pacemaker follow-up, and long-term survival. Methods: This retrospective, single-center cohort study consisted of 6,362 pacemaker-patients (39.7% female) enrolled between May 2000 and April 2015. Functional pacemaker parameters were registered at regular pacemaker controls. Survival status and cause of death were analyzed in relation to comorbidities, implanted pacing devices, and echocardiography. Survival analyses were plotted for a 10-year follow-up. Results: Patients with hypertension or hyperlipidemia had higher rates of implantations due to sick sinus syndrome (28.6 vs. 25.5% without hypertension, P < 0.001; 30.7 vs. 25.7% without hyperlipidemia, P < 0.001), while endocarditis was associated with higher rates of implantations due to AV block (46.7 vs. 33.4%, P < 0.001). Patients with valvular heart disease had higher rates of pacemaker implantation due to bradycardic atrial fibrillation (24.9 vs. 21.0% without valvular heart disease, P < 0.001). Ventricular pacing threshold increased in both sexes during the follow-up and was higher in women in the final follow-up (0.94 vs. 0.91 V in men, P = 0.002). During the 10-years follow-up, 6.1% of women and 8.6% of men underwent lead replacement (P = 0.054). Device and lead replacement rates were increased if the comorbidities coronary artery disease, heart failure, hypertension, hyperlipidemia, valvular heart disease, previous stroke/TIA, atrial arrhythmias, chronic kidney disease, or endocarditis were present. Diabetes and previous CABG increase the rates of device replacement, but not the rate of lead replacement. Severe tricuspid regurgitation after implantation of pacemaker was present in more men than women (14.4 vs. 6.1%, P < 0.001). In a multivariate COX regression, the following variables were associated with independent decrease of 10-year survival: hypertension (HR 1.34, 95% CI 1.09-1.64), chronic kidney disease (HR 1.83, 95% CI 1.53-2.19), tricuspid regurgitation after pacemaker implantation (HR 1.48, 95% CI 1.26-1.74). Survival was independently increased in female sex (HR 0.83, 95% CI 0.70-0.99) and hyperlipidemia (HR 0.81, 95% CI 0.67-0.97). Conclusions: Cardiovascular comorbidities influenced significantly pacemaker implantations and long-term outcome. Trial Registration: ClinicalTrials.gov Unique identifier: NCT03388281.
| S-EPMC7536343 | biostudies-literature
Project description:BackgroundInfantile hypercalcaemia (IH) is a vitamin D3 metabolism disorder. The molecular basis for IH is biallelic mutations in the CYP24A1 or SLC34A1 gene. These changes lead to catabolism disorders (CYP24A1 mutations) or excessive generation of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] (SLC34A1 mutations). The incidence rate of IH in children and the risk level for developing end-stage renal disease (ESRD) are still unknown. The aim of this study was to analyse the long-term outcome of adolescents and young adults who suffered from IH in infancy.DesignForty-two children (23 girls; average age 10.7 ± 6.3 years) and 26 adults (14 women; average age 24.2 ± 4.4 years) with a personal history of hypercalcaemia with elevated 1,25(OH)2D3 levels were included in the analysis. In all patients, a genetic analysis of possible IH mutations was conducted, as well as laboratory tests and renal ultrasonography.ResultsIH was confirmed in 20 studied patients (10 females). CYP24A1 mutations were found in 16 patients (8 females) and SLC34A1 in 4 patients (2 females). The long-term outcome was assessed in 18 patients with an average age of 23.8 years (age range 2-34). The average glomerular filtration rate (GFR) was 72 mL/min/1.73 m2 (range 15-105). Two patients with a CYP24A1 mutation developed ESRD and underwent renal transplantation. A GFR <90 mL/min/1.73 m2 was found in 14 patients (77%), whereas a GFR <60 mL/min/1.73 m2 was seen in 5 patients (28%), including 2 adults after renal transplantation. Three of 18 patients still had serum calcium levels >2.6 mmol/L. A renal ultrasound revealed nephrocalcinosis in 16 of 18 (88%) patients, however, mild hypercalciuria was detected in only one subject.ConclusionsSubjects who suffered from IH have a greater risk of progressive chronic kidney disease and nephrocalcinosis. This indicates that all survivors of IH should be closely monitored, with early implementation of preventive measures, e.g. inhibition of active metabolites of vitamin D3 synthesis.
| S-EPMC8311581 | biostudies-literature
Project description:Heart failure (HF) is a leading cause of mortality and hospitalization in the elderly. However, data are scarce about their response to device treatment such as cardiac resynchronization therapy (CRT). We aimed to evaluate the age-related differences in the effectiveness of CRT, procedure-related complications, and long-term outcome. Between 2000 and 2020, 2656 patients undergoing CRT implantation were registered and analyzed retrospectively. Patients were divided into 3 groups according to their age: group I, < 65; group II, 65-75; and group III, > 75 years. The primary endpoint was the echocardiographic response defined as a relative increase > 15% in left ventricular ejection fraction (LVEF) within 6 months, and the secondary endpoint was the composite of all-cause mortality, heart transplantation, or left ventricular assist device implantation. Procedure-related complications were also assessed. After implantation, LVEF showed significant improvement both in the total cohort [28% (IQR 24/33) vs. 35% (IQR 28/40); p < 0.01)] and in each subgroup (27% vs. 34%; p < 0.01, 29% vs. 35%; p < 0.01, 30% vs. 35%; p < 0.01). Response rate was similar in the 3 groups (64% vs. 62% vs. 56%; p = 0.41). During the follow-up, 1574 (59%) patients died. Kaplan-Meier curves revealed a significantly lower survival rate in the older groups (log-rank p < 0.001). The cumulative complication rates were similar among the three age groups (27% vs. 28% vs. 24%; p = 0.15). Our results demonstrate that CRT is as effective and safe therapy in the elderly as for young ones. The present data suggest that patients with appropriate indications benefit from CRT in the long term, regardless of age.
| S-EPMC10651580 | biostudies-literature
Project description:ObjectiveTo investigate the long-term outcome of patients with spinal cord infarct (SCI) and identify prognostic predictors.MethodsWe reviewed 115 patients with SCI treated between 1990 and 2007. Severity of impairment was defined using the American Spinal Injury Association (ASIA) scoring. Functional outcome endpoints were ambulatory status, need for bladder catheterization, and pain.ResultsMean age was 64 years; 72 (62.6%) patients were men. A total of 45% of infarcts were perioperative (69% aortic surgeries). A total of 68% reached maximal deficit within 1 hour (mean = 5 hours). Impairment at nadir was ASIA A 23%, B 26%, C 14%, and D 37%. A total of 75/93 (81%) patients studied with MRI had cord signal abnormality. At nadir, 81% required wheelchair, 86% required catheterization, and 32% had pain. At last follow-up (mean = 3 years), 23% had died. Among survivors, 42% required a wheelchair, 54% required catheterization, and 29% had pain upon last follow-up. Of 74 patients using a wheelchair at hospital dismissal, 41% were walking by final follow-up. Of 83 patients catheterized at dismissal, 33% were catheter-free at last follow-up. Older age (p < 0.0001), increased severity of impairment at nadir (p = 0.02), and peripheral vascular disease (p = 0.003) were independent risk factors for mortality. Severe impairment (ASIA A/B) at nadir predicted wheelchair use (p < 0.0001) and bladder catheterization (p < 0.0001) at last follow-up.ConclusionsGradual improvement in not uncommon after spinal cord infarction and it may continue long after hospital dismissal. While severe impairment at nadir is the strongest predictor of poor functional outcome, meaningful recovery is also possible in a substantial minority of these patients.
| S-EPMC3466672 | biostudies-literature
Project description:Although the effect of being overweight on the long- and short-term outcome of THA remains unclear, the majority of orthopaedic surgeons believe being overweight negatively influences the longevity of a hip implant. We asked whether complications and long-term survival of cemented THA differed in overweight patients (body mass index [BMI] > 25 kg/m2) and obese patients (BMI > 30 kg/m2) compared with normal-weight patients (BMI < 25 kg/m2). We retrospectively analyzed 411 consecutive patients (489 THAs) treated with cemented THA between 1974 and 1993. Except for cardiovascular comorbidity, we observed no differences in demographics among these weight groups. We found no differences in the number of intraoperative or postoperative complications. The survival rates for the three BMI groups were similar. The 10-year survival for any revision was 94.9% (95% confidence interval, 91.6%-98.2%), 90.4% (95% confidence interval, 85.6%-95.2%), and 91% (95% confidence interval, 81.2%-100%) for normal-weight, overweight, and obese patients, respectively. Cox regression analysis showed BMI and weight had no major influence on survival rates. The differences in mean Harris hip score at final followup were 4.8 between normal-weight and overweight patients and 7.1 between normal-weight and obese patients. Being overweight and obesity had no influence on perioperative complication rates in this cohort and did not negatively influence the long-term survival of cemented THA.
| S-EPMC2311471 | biostudies-other
Project description:ObjectiveThis study aims to identify the demographic, clinical, and therapeutic characteristics of four patients with hemimasticatory spasm (HMS) seen in our outpatient department over a period of 20 years.MethodsWe performed a retrospective chart review of four patients with HMS who visited outpatient services in the Department of Neurology from 2001 to 2020.ResultsThe follow-up for all patients ranged from 2 years to 9 years. Three patients had facial or bucco-oral morphea. Two patients maintained long-term improvements in symptoms after being treated with botulinum toxin for 4-7 years, while one patient reported improvement in symptoms with treatment of carbamazepine that subsequently remitted after pregnancy.ConclusionThis report highlights the long-term outcome of HMS in our patients. Our patients reported a significant reduction or complete resolution of symptoms after treatment, and eventually, two patients were asymptomatic while off treatment.
| S-EPMC9171317 | biostudies-literature
Project description:ObjectivesTo determine the long-term (> 6 mo) functional status of PICU patients with significant new functional morbidities at hospital discharge.DesignLongitudinal cohort followed-up using structured chart reviews of electronic health records.SettingElectronic health records of former PICU patients at seven sites.PatientsRandomly selected patients from the Trichotomous Outcome Prediction in Critical Care study discharged from the hospital with new functional status morbidity who had sufficient electronic health record data to determine functional status.InterventionsNone.Measurements and main resultsLong-term functional status was measured with the Functional Status Scale and categorized by comparison to hospital discharge Functional Status Scale. Improvement or new morbidity was based on a change in Functional Status Scale of greater than or equal to 2 in a single domain. Overall, 56% (n = 71) improved, 15% (n = 19) did not change, 9% (n = 11) developed a new morbidity, and 21% (n = 26) died. The shortest median follow-up time from PICU discharge was 1.4 years for those who died and the longest was 4.0 years for those improved. Functional status at baseline (pre-acute illness) was different among the outcome groups with those that improved having the highest frequency of baseline normal status or only mild dysfunction. Of the long-term survivors with improvement, 82% (n = 58) improved to normal status or mild dysfunction, 11% (n = 8) improved to moderate dysfunction, and 7% (n = 5) improved to severe dysfunction. Trauma patients improved and cancer patients died more frequently than other diagnoses. The long-term outcome groups were not associated with hospital discharge functional status.ConclusionsA majority of PICU survivors discharged with significant new functional morbidity with follow-up after 6 or more months improved, many to normal status or only mild dysfunction, while 29% died or developed new morbidity. Of the long-term survivors, 70% had significant improvement after a median follow-up time of 4.0 years.
| S-EPMC7790876 | biostudies-literature
Project description:SCID is a fatal syndrome caused by mutations in at least 13 different genes. It is characterized by the absence of T cells. Immune reconstitution can be achieved through nonablative related donor BMT. However, the first transplant may not provide sufficient immunity. In these cases, booster transplants may be helpful. A prospective/retrospective study was conducted of 49 SCID patients (28.7% of 171 SCIDs transplanted over 30 years) who had received booster transplants to define the long-term outcome, factors contributing to a need for a booster and factors that predicted success. Of the 49 patients, 31 (63%) are alive for up to 28 years. Age at initial transplantation was found to have a significant effect on outcome (mean of 194 days old for patients currently alive, versus a mean of 273 days old for those now deceased, P=0.0401). Persistent viral infection was present in most deceased booster patients. In several patients, the use of two parents as sequential donors resulted in striking T-and B-cell immune reconstitution. A majority of the patients alive today have normal or adequate T-cell function and are healthy. Nonablative booster BMT can be lifesaving for SCID.
| S-EPMC3737279 | biostudies-literature