Dysfunction In Adult Patients Research Articles

ОСНОВНЫЕ ПРИЧИНЫ И ФАКТОРЫ РИСКА РАЗВИТИЯ ОЛЬФАКТОРНОЙ ДИСФУНКЦИИ У ВЗРОСЛЫХ ПАЦИЕНТОВ

Pathology of smell is an interdisciplinary problem. Olfactory disorders are polyetiological and occur in a wide variety of diseases. However, with these complaints, patients first turn to otolaryngologists. The article describes the etiopathogenetic mechanisms of olfactory disorders, identifying the following main causes and risk factors for the development of olfactory dysfunction in adult patients: diseases of the nose and paranasal sinuses; acute respiratory viral diseases; head and nose injuries; consequences of surgical treatment in the nasal cavity and paranasal sinuses, intracranial operations; diseases of the nervous system; diseases of the endocrine system and internal organs; intoxication; taking medications; smoking; alcohol and drug addiction, age over 65 years, metabolic disorders. The mechanism of disturbance of the olfactory function is determined by the level of damage to the olfactory analyzer and is conductive, sensorineural, central and mixed. Chronic diseases of the nose and paranasal sinuses are the most common cause of olfactory dysfunction. Timely detection of olfactory disorders is fundamentally important for early diagnosis of the diseases that cause them. Determining the causes and risk factors of olfactory disorders is an important task, as it helps determine treatment tactics for patients.

The association of self-reported awake bruxism and sleep bruxism with temporomandibular pain and dysfunction in adult patients with temporomandibular disorders.

To investigate the association of the severity of temporomandibular disorders (TMD) pain and dysfunction with the frequency of self-reported awake bruxism (AB), sleep bruxism (SB), and stress in an adult TMD-patient population. This cross-sectional study included 237 TMD patients based on the Diagnostic Criteria for TMD. Age, sex, frequency of self-reported AB and SB, and stress were included as independent variables. TMD pain and TMD dysfunction were included as dependent variables in regression analyses. Univariate and multivariable linear regression analyses were used to predict TMD pain and TMD dysfunction in two separate models. Finally, network analysis was performed to investigate the associations between all variables. In the univariate analyses, TMD pain was significantly associated with self-reported AB-frequent (unstandardized coefficient (B) = 3.196, 95%CI 1.198-5.195, p = 0.002). TMD dysfunction was significantly associated with AB-frequent (B = 2.208, 95%CI 0.177-4.238, p = 0.033) and SB-sometimes (B = 1.698, 95%CI 0.001-3.394, p = 0.050). In the multivariable analyses, TMD pain was significantly associated with TMD dysfunction (B = 0.370, p < 0.001), stress (B=0.102, p < 0.001). TMD dysfunction was significantly associated with TMD pain (B = 0.410, p < 0.001) only. Network analysis showed that TMD pain is a bridge factor between AB, stress, and TMD dysfunction. TMD pain is directly associated with AB, stress, and TMD dysfunction, while TMD dysfunction is only associated with TMD pain. Reducing pain may improve pain-related dysfunction, and the management of AB and stress may improve TMD pain and dysfunction, and vice versa.

Endothelial Dysfunction in Adult Patients of Sickle Cell Disease

Sickle cell disease is one of the most common hemoglobinopathy worldwide. It is an autosomal recessive genetic disorder caused by replacement of adenine to thymine nucleotide in the beta chain of hemoglobin results in replacement of valine for glutamic acid at 6th position. This substitution results in formation of sickle hemoglobin (HbS) which in turn leads to a reduced lifespan of red blood cells (RBC). In hypoxic conditions, HbS has a tendency to aggregate and form fibrillar structure called tactoid within the red cells

The association between myocardial ischemia and myocardial dysfunction in adult patients with systemic right ventricle – A single centre multimodality study

BackgroundThe exact interaction of factors leading to myocardial dysfunction and fibrosis of the systemic right ventricle (SRV) is not completely understood. Myocardial ischemia and injury associated with a supply-demand mismatch of the pressure overloaded SRV are thought to play an important role, however studies confirming this are lacking. MethodsAdult SRV patients were included in this single centre cohort study. All patients underwent a comprehensive diagnostic and imaging workup. A two-day stress-rest SPECT was performed to assess myocardial perfusion. SRV ischemia was defined as decreased segmental tracer uptake during exercise with significant improvement at rest. Contrast enhanced cardiac magnetic resonance imaging (CMR) was also performed in a subgroup of patients without contraindication, to assess focal myocardial fibrosis. Differences between patients with and without SRV ischemia were assessed. ResultsTwenty-three SRV patients (15 with transposition of the great arteries after atrial switch procedure and 8 with congenitally corrected transposition of the great arteries; 5 (22%) females; mean age 38 ± 11 years) were included. Seven (30%) patients had SRV ischemia on SPECT. Late gadolinium enhancement on CMR was more common in patients with SRV ischemia (p = 0.002). However, there was no association between SRV ischemia and different echocardiographic or CMR parameters of SRV systolic function, laboratory markers (high-sensitivity troponin I and NT-proBNP) and exercise capacity. ConclusionsOur multimodality study showed that SRV ischemia in adult SRV patients was associated with more focal myocardial fibrosis, but not with functional or imaging markers of SRV function.

The Rate of Eustachian Tube Dysfunction in Adult Patients With Chronic Inflammatory Middle Ear Disease Is Low.

To assess the rate of dilatory (chronic obstructive) eustachian tube dysfunction (ETD) in adult patients scheduled for surgery for chronic inflammatory middle ear disease. We included adult patients with chronic inflammatory middle ear disease (chronic suppurative otitis media, adhesive otitis media [middle ear atelectasis], cholesteatoma). We excluded patients with pathologies that do not stem from ETD (e.g., noninflammatory chronic middle ear disease [e.g., otosclerosis], tumors, solely external auditory canal conditions), patients scheduled for implantable electronic hearing devices independent of disease, patients with otitis media with effusion and scheduled paracentesis or ventilation tubes only, patients with previous radiotherapy or previous balloon eustachian tuboplasty, and children and patients unable to complete questionnaires. We evaluated ETD with Valsalva maneuver and in case of negative or unclear Valsalva with the eustachian tube score (ETS). A negative Valsalva maneuver and an ETS score of 5 or lower were used to define dilatory (chronic obstructive) ETD. Rate of ETD in the included patients. From a total of 482 consecutive patients, 350 patients had positive Valsalva maneuver or ETS score higher than 5. From the 193 patients with negative or unclear Valsalva maneuver, 77 patients had an ETS score of 5 or lower, and 55 rejected further diagnostics with ETS. Based on a large cohort of adult patients with chronic inflammatory middle ear disease scheduled for middle ear surgery, the majority (82%) seems to have no dilatory (chronic obstructive) ETD that can be detected with current routine clinical methods and tubomanometry. Common pathophysiological explanations should be questioned critically, especially in the context of communication with patients.

Left ventricular global longitudinal strain can detect subclinical left ventricular systolic dysfunction in adult patients with primary nephrotic syndrome.

It has been shown that there is an increased risk of cardiovascular events such as heart failure and death in nephrotic syndrome. Left ventricle global longitudinal strain (LVGLS) is a more sensitive measure of assessing myocardial dysfunction and is more reproducible than left ventricle ejection fraction (LVEF%). LVGLS can detectsubclinical deterioration in the left ventricle early. In this study, we aimed to investigate LVGLS in Primary Nephrotic Syndrome (PNS) patients with normal LVEF%. Patients with histopathologically confirmed PNS were evaluated for this prospective single-center study. Patients with similar age and gender characteristics without nephrotic syndrome were included as the control group. LVGLS measurements were performed by 2D speckle tracking echocardiography. A total of 171 patients, 57 with PNS and 114 in the control group, were included in the study. The mean age was 38±12 years in the study population, and 95(56%) of the patients were women. LVEF% was 60.2±4.2 in the PNS group and 61.1±3.2 in the control group, and there was no significant difference between the two groups (p=0.111). LVGLS was found to be significantly lower in the PNS group (-19.3±2.3% vs.-20.8±1.5 %, p<0.001). A significant relationship was observed between PNS and LVGLS in the multivariable linear regression analysis (β= 4.428, CI 95% =0.57?1.48, p<0.001). A significant relationship was observed between PNS and LVGLS, and LVGLS was found to be lower in PNS patients. In patients with PNS, subclinical left ventricular systolic dysfunction may be detected in the early period by measuring LVGLS.

Perioperative right ventricular dysfunction in adult patients undergoing non-complex cardiac surgery: diagnosis and management

Even though there is no precise consensus on definition of the right ventricular dysfunction and the right ventricular failure, their reported incidence after cardiac surgery ranges from 0.04% to 2.9%. Right ventricular dysfunction is clinically important because it has been consistently shown to have a negative impact on the perioperative outcomes. In this article we explore current evidence on perioperative diagnosis and management of adult patients with right ventricular dysfunction who are undergoing non-complex cardiac surgery. We propose criteria for the right ventricular dysfunction, describe its pathophysiological mechanisms, diagnostic and therapeutic options as well as current challenges. The function of the right ventricle is determined by preload, afterload, contractility, ventricular interdependence, and heart rhythm. These five factors should all be assessed in a particular patient. Right ventricular dysfunction is not always easy to confirm. Transthoracic and transesophageal echocardiography are the mainstay of diagnosis. Also, clinical and laboratory findings should be considered especially when the patient approaches the extreme of right ventricular dysfunction spectrum—right ventricular failure. Right ventricular failure should be anticipated, and management focused on its prevention and treatment of the underlying cause. The clinical aim is to optimise the volume status, minimise the right ventricular afterload, optimise right ventricular free wall and interventricular septum performance, and to maximise the left heart pressure work. If the patient does not respond to conservative therapy, mechanical support should be promptly considered.

Incidence, risk factors and prognostic effect of imaging left ventricular diastolic dysfunction in patients with COVID-19: protocol for a systematic review

IntroductionRecent reports linked acute COVID-19 infection in critical patients to cardiac structure and function abnormalities. The left ventricular (LV) diastolic dysfunction could result in obvious adverse prognostic impacts. The aim...

Novel molecular biomarkers of cancer therapy-induced cardiotoxicity in adult population: a scoping review.

AimCancer treatments are associated with cardiotoxic events that predispose to cardiac pathology and compromise the survival of patients, making necessary the identification of new molecular biomarkers to detect cardiotoxicity. This scoping review aims to identify the available evidence on novel molecular biomarkers associated with cardiotoxicity in the adult population undergoing cancer therapy.Methods and resultsThe databases Medline, Web of Science, Scopus, and Embase were screened for the identification of published studies until 23 August 2020, searching for novel molecular biomarkers reported in cancer therapy‐related cardiac dysfunction in adult patients. A total of 42 studies that met the eligibility criteria were included. Fourteen studies reported 44 new protein biomarkers, 18 studies reported 57 new single nucleotide polymorphism biomarkers, and 11 studies reported 171 new gene expression profiles associated with cardiotoxicity. Data were extracted for 272 novel molecular biomarkers reported and evaluated in 7084 cancer patients, of which only 13 were identified in more than one study (MPO, sST2, GDF‐15, TGF‐B1, rs1056892, rs1883112, rs4673, rs13058338, rs1695, miR‐1, miR‐25‐3p, miR‐34a‐5p, and miR‐423‐5p), showing values for area under the curve > 0.73 (range 0.74–0.85), odds ratio 0.26–7.17, and hazard ratio 1.28–1.80.ConclusionsMultiple studies presented a significant number of novel molecular biomarkers as promising predictors for risk assessment of cardiac dysfunction related to cancer therapy, but the characteristics of the studies carried out and the determinations applied do not allow suggesting the clinical use of these molecular biomarkers in the assessment of cancer therapy‐induced cardiotoxicity.

Predictors of preoperative cognitive dysfunction in adults with Moyamoya disease: a preliminary research

ObjectiveTo explore potential risk factors of preoperative cognitive dysfunction in adult patients with moyamoya disease (MMD) and discuss significance of moyamoya vessels.MethodsThe author reviewed adult MMD patients harboring no parenchymal infarction or hemorrhage underwent a standardized neuropsychological assessment test battery from December 2018 to May 2019. The authors defined patients with cognitive dysfunction as cognitive impairment shown on 3 or more neuropsychological tests. According to the presence of cerebral angiography, arterial stenosis, moyamoya vessels, and compensatory arteries were conducted. Univariate and multivariate analyses were performed to identify predictors for cognitive dysfunction before surgery. Subgroup analyses by onset type and Suzuki stage were carried out to identify specific predictors for preoperative cognitive dysfunction.ResultsIn total, 29 of 92 (31.52%) patients had cognitive dysfunction. Multivariate analysis showed that moyamoya vessels generating from left hemisphere was recognized as independent predictor for cognitive dysfunction (P = 0.025, OR [95%CI], 0.085 [0.012–0.874]). For patients in left ICA-moyamoya subgroup, 19 of 45 (42.22%) cases with sparse moyamoya vessels had cognitive dysfunction (P = 0.031), while 22 (91.67%) of patients with dense moyamoya vessels had normal cognition (P = 0.004). Moyamoya vessels arising from ophthalmic artery had no significant association with cognitive dysfunction (P = 0.111). Multivariate analysis found that moyamoya vessels originating from left ICA was recognized as independent predictors for preoperative cognitive dysfunction (P = 0.048, OR [95%CI], 0.394 [0.132–0.926]).ConclusionsMoyamoya vessels arising from left hemisphere was a risk factor for the preoperative cognitive dysfunction in adult patients with MMD, with the denser moyamoya vessels, the less cognitive dysfunction. The current study offers a new perspective of moyamoya vessels and supporting data for choosing MMD candidates on cerebral revascularization.

Evaluation of Thyroid Dysfunction in Adult Patients of Celiac Disease

OBJECTIVES: &#x0D; To assess free thyroxine (fT4), thyroid stimulating hormone (TSH), and anti thyroid peroxidase antibodies (anti TPO abs) in adult Celiac disease patients and non-celiac controls and to find out any statistically significant difference in their corresponding means between the two groups.&#x0D; METHODOLOGY:&#x0D; The study design was analytical cross sectional. Sixty adult patients of celiac disease (CD) and 30 apparently healthy non-celiac adults were included in the study. CD patients had earlier been diagnosed by elevated levels of serological evidence of elevated (greater than 15X ULN) anti tissue transglutaminase (TTG) (IgA class) antibodies. CD was ruled out in the control group by normal levels of the antibodies. TSH, fT4 and anti TPO abs were obtained from all individuals of CD patient and control groups. &#x0D; RESULTS:&#x0D; Mean age of Celiac disease in patients was 23.85±5.43 years. Mean age of individuals in the control group was 24.26±5.55 years. Statistically significant difference in mean TSH and anti-TPO abs levels between the CD patient group and control group (p values of 0.03 and 0.038, respectively) was present. No statistically significant difference was seen between mean fT4 of patients and control group (p=0.74). Subclinical and overt hypothyroidism was present in 10% and 5% of CD patients, while anti TPO abs was positive in 16.6% of CD patients.&#x0D; CONCLUSION:&#x0D; There is a considerably high prevalence of subclinical and overt hypothyroidism as well as serological evidence of thyroid dysfunction in adult patients of CD.

HIGH NORMAL BLOOD PRESSURE CAN CAUSE DECLINE OF ATTENTION FUNCTION AMONG ELDERLY OUT-PATIENTS WITH DIABETES: SHIP-FD 5-YEAR FOLLOW-UP STUDY

Objective: We evaluated which degree of increased BP would cause diminished attention function, one of the higher-order brain functions, among patients with diabetes. Design and method: We conducted a baseline survey regarding cognitive/physical function in diabetic out-patients in 2014 and its follow-up study in 2019. The decline of attention function was defined by the delta of the performance time of trail making test part A (TMT-A) at baseline and follow-up. Delta TMT-A was categorized into three levels; under 0 second as “not decline” (ND), 0–10 seconds as “slight decline” (SD), and 10 and over as “moderate decline” (MD). Office blood pressure level was categorized into normal, high-normal, elevated, grade I hypertension, and grade II and III hypertension according to JSH2019. Multinomial logistic regression analyses were performed adjusting for sex, age, HbA1c and usage of antihypertensives at baseline survey to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) of the decline of attention function by BP levels. Results: Among 157 participants (mean age: 65.0 years, 63.7% men) whose delta TMT-A was assessed, proportions of SD and MD were 23% and 20% in normal (n = 35), 23% and 51% in high-normal (n = 35), 24% and 36% in elevated (n = 42), 34% and 28% in grade I (n = 32), and 54% and 31% in grade II and III hypertension (n = 13). After excluded participants with TMT-A at baseline &gt;=117.5 seconds or with missing values of co-variates, 142 remained for further analyses. Multivariate adjusted ORs (95% CIs) of MD, referring normal, were 8.60 (2.07–35.6) by high normal, 3.67 (0.99–13.5) by elevated, 2.78 (0.67–11.6) by grade I, and 6.95 (0.90–53.7) by grade II and III. Any significant increase in SD risk by BP categories was not observed. Even after adjusting TMT-A time and MMSE at baseline, results were similar. After stratified by age, this relationship was observed only in participants aged 65-year and older. Conclusions: The present study indicated that high-normal BP might promote the lowering of attention function in elderly patients with diabetes. Further study with a longer follow-up period is needed to assess the effect of BP on attention dysfunction in adult patients.

Beyond gait and balance: urinary and bowel dysfunction in X-linked adrenoleukodystrophy

ObjectiveTo characterize the prevalence, onset, and burden of urinary and bowel dysfunction in adult patients with adrenoleukodystrophy (ALD) and to evaluate any sex differences in symptom presentation.MethodsIn this retrospective and prospective study, we performed medical record review (n = 103), analyzed the results of clinically indicated urodynamic testing (n = 11), and developed and distributed a symptom and quality of life (QOL) survey (n = 59).ResultsUrinary and bowel symptoms are highly prevalent in both males (75.0%) and females (78.8%) in this population, most commonly urinary urgency, often leading to incontinence. Time to onset of first urinary or bowel symptom occurs approximately a decade earlier in males. Seventy-two percent of symptomatic patients report a limitation to QOL. Urodynamic evaluation provides evidence of three distinct mechanisms underlying lower urinary tract dysfunction: involuntary detrusor contractions (indicating uncontrolled neuronal stimulation with or without leakage), motor underactivity of the bladder, and asynergy between detrusor contraction and sphincter relaxation.ConclusionsBeyond gait and balance difficulties, urinary and bowel symptoms are common in adults with ALD and impair QOL. Males are affected at a younger age but both sexes experience a higher symptom burden with age. As this population also experiences gait and balance impairment, patients with ALD are more vulnerable to urinary urgency leading to incontinence. Urodynamic evaluation may help better elucidate the pathophysiologic mechanisms underlying neurogenic lower urinary tract dysfunction, which can allow more targeted treatment.

Usefulness of echocardiographic tissue doppler imaging in diastolic dysfunction

Background: Heart failure is a complex clinical syndrome arising from any structural or functional cardiac condition that impairs left ventricular (LV) filling or ejection. The present study was conducted to assess usefulness of echocardiography in left ventricular diastolic dysfunction in adult patients with diabetes mellitus and hypertension. Materials & Methods: 56 patients with diastolic dysfunction of both genders were subjected to Echocardiography performed with convex transducer of Aplio & Ge. Grading of left ventricular systolic and left ventricular diastolic dysfunction was done. Results: Out of 56 patients, males were 34 and females were 22. Left ventricular diastolic dysfunction was found in 30 and left ventricular systolic dysfunction in 26 subjects. In LVDD, 16 were diabetics and 14 were non- diabetic. In LVSD, 12 were diabetics and 16 were non- diabetics. Grading in LVDD found to be 0 seen in 2 in diabetics, 1 seen in 2 and 4, 2 seen in 5 and 6, 3 in 7 and 4 subjects with non- diabetes and diabetes respectively. In LVSD, grading found to be 0 seen in 2 and 0, 1 seen in 6 and 3, 2 seen in 5 and 7, 3 in 3 and 2 subjects with non- diabetes and diabetes respectively. The difference was significant (P

Blood-brain barrier leakage in systemic lupus erythematosus is associated with gray matter loss and cognitive impairment

ObjectivesTo examine the association between blood-brain barrier (BBB) integrity, brain volume and cognitive dysfunction in adult patients with systemic lupus erythematosus (SLE).MethodsA total of 65 ambulatory patients with SLE and...

Hormonal dysfunction in adult patients affected with inherited metabolic disorders.

Inherited metabolic disorders (IMDs ) are a rare and diverse group of metabolic conditions mainly caused by enzyme deficiencies, and in some of these, hormonal dysfunction is a relatively common complication. It may present in childhood and subsequently hormonal replacement is required throughout their life. Endocrinopathies can be a presenting symptom of an IMD in adulthood, which should be suspected when associated with multiorgan involvement (neurological, musculoskeletal or liver, etc.). A single IMD can affect any gland with hypogonadism, adrenal insufficiency, diabetes mellitus and thyroid dysfunction being the most common. In some cases, however, it is diagnosed later in their adult life as a secondary complication of previous therapies such as chemotherapy used during Haematopoietic Stem Cell Transplantation (HSCT) in childhood.The mechanisms of endocrine dysfunction in this group of conditions are not well understood. Regardless, patients require ongoing clinical support from the endocrine, metabolic, bone metabolism and fertility specialists throughout their life.Hormonal profiling should be part of the routine blood test panel to diagnose asymptomatic endocrine disorders with delayed manifestations. It is also worth considering screening for common hormonal dysfunction when patients exhibit atypical non-IMD related symptoms. In some adult-onset cases presenting with multiple endocrinopathies, the diagnosis of an IMD should be suspected.Given that new therapies are in development (e.g. gene therapies, stem cell therapies, pharmacological chaperone and substrate reduction therapies), clinicians should be aware of their potential long-term effect on the endocrine system.

Risk factors for renal dysfunction in adult patients with short bowel syndrome

Risk factors for renal dysfunction in adult patients with short bowel syndrome

Amiodarone-associated thyroid dysfunction in adult patients with congenital heart disease: a nationwide health insurance data analysis including &amp;gt;50.000 individuals

Abstract Background Arrhythmias are common in adult patients with congenital heart disease (ACHD). Amiodarone is widely used as an antiarrhythmic agent. Thyroid dysfunction represents a serious complication of amiodarone treatment. Systematic data on the prevalence of thyroid dysfunction, risk factors for complications and treatment options are lacking. Purpose Based on data from one of the largest German Health Insurance Companies (BARMER GEK, approx. 9 million members), we performed a retrospective analysis investigating the rate of thyroid complications under active amiodarone therapy in ACHD patients and a comparison group of cardiac patients without congenital heart disease on amiodarone between 2005 and 2018. Result Overall, 910 ACHD (34% female; median age 66 y; CHD complexity mild, moderate, severe in 64.6%, 23.6%,11.8%, respectively) and 49,782 non-ACHD patients (37% female, median age 73.4 y) received prescriptions for amiodarone without documented pre-existing thyroid disease or use of thyroid medication. Over a treatment period of 184,770 patient-years, 10,874 incidents of thyroid dysfunction occurred in the non-ACHD and 201 in the ACHD cohort, corresponding to an event-rate of 6% and 5.3% per patient year, respectively. Overall, 23.5% of the ACHD patients developed thyroid dysfunction (56.71% hypothyroidism, 43.3% hyperthyroidism). Risk factors for developing thyroid dysfunction on time dependent Cox-analysis were female gender (hazard ratio [HR] 1.44, 95% CI: 1.39–1.50; p&amp;lt;0.001), lower patient age (HR: 0.96 per 10 years, 95% CI: 0.94–0.98, p&amp;lt;0.001) renal dysfunction (HR 1.24, 95% CI: 1.19–1.29, p&amp;lt;0.001), history of alcohol abuse (HR 1.17, 95% CI: 1.07–1.27, p,0.001) and smoking (HR 1.12, 95% CI: 1.06–1.19, p&amp;lt;0.001). Congenital heart disease itself was not associated with a higher risk of thyroid dysfunction (HR 0.96, 95% CI: 0.83–1.10, p=0.53). Within the ACHD group, patients with complex disease had a significantly higher risk of thyroid dysfunction (HR 1.5, 95% CI: 1.00–2.25, p=0.049) compared to patients with simple diagnoses. Once thyroid disease occurred, 48.5% of patients were continued on amiodarone therapy, 12.8% of patients underwent an electrophysiologic procedure and only 2.1% of patients received class I antiarrhythmics. Specific thyroid therapy included thyroxine (62.6% of hypothyroid patients) or thiamazole (22.6% of hyperthyroid patients). Only 2.3% of patients required surgery or radiotherapy within 6 months after thyroid dysfunction. Conclusion Amiodarone-associated thyroid dysfunction is a frequent complication in ACHD patients. Overall, one in 4 ACHD patients on amiodarone developed thyroid dysfunction in our study. In itself, ACHD does not seem to increase the risk of thyroid dysfunction. However, female gender, complexity of disease, younger age and renal dysfunction emerged as independent risk factors. When amiodarone therapy can not be avoided, close follow-up and regular thyroid function tests are recommended. Funding Acknowledgement Type of funding source: None

Lower urinary tract dysfunction in adult patients with mitochondrial disease.

Mitochondrial diseases present with a spectrum of clinical features, usually with multiorgan involvement and are often characterized by a loss of smooth muscle function. Hence, we hypothesized that mitochondrial dysfunction may contribute to lower urinary tract (LUT) dysfunction. We performed a prospective cohort study at a single, quaternary, mitochondrial disease referral center, enrolling consecutive adult patients with genetically confirmed mitochondrial disease. Data regarding baseline characteristics and disease burden were gathered. LUT dysfunction was assessed using the International Consultation on Incontinence Modular Questionnaire-Lower Urinary Tract Symptoms (ICIQ-LUTS) questionnaire, bladder voiding efficiency (BVE), and bladder diaries. Patients with one or more features of LUT dysfunction were offered urodynamic testing. A total of 109 patients were included. Twenty-six percent of patients manifested at least one feature of LUT dysfunction, which was objectively confirmed in all 14 patients who consented to urodynamic investigation. Disease burden, defined by the Newcastle Mitochondrial Disease Adult Scale (NMDAS), demonstrated a linear relationship with ICIQ-LUTS severity (P = .01), with a statistically significant relationship between NMDAS-gastrointestinal scores and LUTS scores (P < .001). Limitations include mutational heterogeneity across the patient cohort. This is the largest study exploring LUT in patients with mitochondrial disease and supports previous smaller studies suggesting LUT dysfunction is underrecognized in patients with mitochondrial disease and impacts considerably on their quality of life. We propose a clinical guideline for identifying mitochondrial disease patients at risk of LUT dysfunction.

SUN-414 Tyrosine Kinase Inhibitors Induced Thyroid Dysfunction: An Experience from a Tertiary Care Hospital

Tyrosine kinase inhibitors (TKI) belong to a new class of molecular multi-targeted anticancer therapy which targets different growth factor receptors and hence attenuates cancer cell survival and growth. TKI-induced thyroid dysfunction is recognized as a common adverse effect of treatment., but the onset of thyroid dysfunction is variable. This study analysed correlation between initiation of TKIs and the onset of thyroid dysfunction in non-thyroid cancers patients without any background thyroid dysfunction.METHODS:This was a retrospective cohort study to evaluate thyroid dysfunction in adult patients (n=227, M:F=153:74) with non-thyroidal cancers treated with TKIs. Patients having pre-existing thyroid disease including euthyroid goitres were excluded. Demographic, clinical, and cancer treatment data were collected. Thyroid function tests (TFTs) were done prior to initiation, at 2 months, 6 months and at 1 year. TFTs were classified as euthyroid (thyrotropin [TSH] normal), subclinical (SCH; TSH 5-10 mIU/L, or higher TSH if free thyroxine normal), or overt hypothyroidism (OH; TSH >10 mIU/L, low free thyroxine, or requiring replacement).RESULTS:Of the 227 patients in the study, OH occurred in 57 patients (25.1%)(M:F = 19:38) and SCH occurred in 89 patients (39.2%) (M:F=39:50) with TKI therapy at the end of 12 months. 37 patients (M:F=13:24) developed OH in first 6 months after initiation of TKIs. Female patients were more likely to have OH in the first 6-month period following TKIs irrespective of type of TKI or the cancers. SCH was also more common after 2 months in female patients (n=23) (M:F=6:17) but the conversion of SCH to OH was more common in male patients at the end of 12 months. The symptoms were variable and most the patients did have any thyroid specific symptoms. After adjustment for age, sex, cancer type, cancer stage, performance status, and type of TKI, OH remained significantly associated with survival at 1-year (hazard ratio=0.461; p<0.0001), whereas SCH did not (hazard ratio=0.591; p=0.165). Analysis of hypothyroid patients (SCH and OH) with TSH >5 and <10 mIU/L stratified by hormone replacement status showed improved survival associated with hormone replacement, although 1 year follow-up is too short to comment on overall survival rates.CONCLUSIONS:New onset hypothyroidism, both OH and SCH is common in non-thyroidal cancer patients treated with TKI. SCH is more common after 2 months and OH after 6 months following TKI initiation. Female sex is more predisposed to develop thyroid dysfunction irrespective of underlying cancer or type of TKI used but male patients progressed to OH at the end of 12 months.