Nonthyroidal Illness Research Articles

The Impact of Nutritional Support in Low T3 Syndrome

The Impact of Nutritional Support in Low T3 Syndrome

Characteristics of euthyroid sick syndrome in patients with breast cancer

Purpose. Determination of thyroid hormones (TH) and cortisol levels in blood in patients with breast cancer (BC) without previously detected endocrine pathology in the anamnesis.Patients and methods. Twenty-five primary luminal A breast cancer patients before and aſter surgical removal of the tumour and 25 breast cancer patients with secondary metastatic brain lesions were examined. The levels of total and free forms of TH (T4, FT4, T3 FT3) and cortisol were determined in serum by RIA method.Results. Before treatment in all patients with breast cancer the level of T3 was decreased 1.3 times and FT3 was increased 1.3 times (p < 0.05) against the background of normal TTH content. In 80 % of patients, blood cortisol concentration was 2 times higher than normal, and in 16 % of patients, T4 level was 1.8 times higher than normal (p < 0.05). Aſter tumour removal, FT3 levels in all patients and cortisol levels in 40 % of patients did not differ from normal. T4 content in 40 % of patients, and T3 and TTH in 28 % of women were above normal. A distinctive feature of patients with brain metastases of breast cancer was low T4 and cortisol levels in 36 % of patients against the background of low T3 levels.Conclusions. Euthyroid sick syndrome was detected in all patients with BC: low serum T3 levels against the background of normal serum levels of TTH. Patients with primary BC were characterized by high concentrations of FT3 and cortisol, which could promote proliferation of malignant cells and decrease antitumour immunity. The condition of 1/3 of patients with brain metastases was aggravated by low levels of T4 and cortisol which could indicate the depletion of the main regulatory systems and an unfavorable disease prognosis.

Induced types 2 and 3 deiodinase in the muscle of critically ill patients correlates with endoplasmic reticulum and mitochondria alterations: Implications to nonthyroidal illness syndrome pathophysiology

Induced types 2 and 3 deiodinase in the muscle of critically ill patients correlates with endoplasmic reticulum and mitochondria alterations: Implications to nonthyroidal illness syndrome pathophysiology

Types 2 and 3 deiodinase are induced in blood cells of critical ill patients: Implications to nonthyroidal illness syndrome pathophysiology

Types 2 and 3 deiodinase are induced in blood cells of critical ill patients: Implications to nonthyroidal illness syndrome pathophysiology

Endocrinological Involvement in Children and Adolescents Affected by COVID-19: A Narrative Review.

Since the advent of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, an increased incidence of several endocrinological anomalies in acute-phase and/or long-term complications has been described. The aim of this review is to provide a broad overview of the available literature regarding changes in the worldwide epidemiology of endocrinological involvement in children since December 2019 and to report the evidence supporting its association with coronavirus disease 2019 (COVID-19). Although little is known regarding the involvement of endocrine organs during COVID-19 in children, the current evidence in adults and epidemiological studies on the pediatric population suggest the presence of a causal association between the virus and endocrinopathies. Untreated transient thyroid dysfunction, sick euthyroid syndrome, nonthyroidal illness syndrome, and hypothalamic-pituitary-adrenal (HPA) axis and central precocious puberty have been observed in children in acute infection and/or during multisystem inflammatory syndrome development. Furthermore, a higher frequency of ketoacidosis at onset in children with a new diagnosis of type 1 diabetes is reported in the literature. Although the direct association between COVID-19 and endocrinological involvement has not been confirmed yet, data on the development of different endocrinopathies in children, both during acute infection and as a result of its long-term complications, have been reported. This information is of primary importance to guide the management of patients with previous or current COVID-19.

Prognostic role of euthyroid sick syndrome in MIS-C: results from a single-center observational study.

Euthyroid sick syndrome (ESS) is characterized by low serum levels of free triiodothyronine (fT3) with normal or low levels of thyroid stimulating hormone (TSH) and free thyroxine (fT4) and is reported in different acute clinical situations, such as sepsis, diabetic ketoacidosis and after cardiac surgery. Our aim was to evaluate the predicting role of ESS for disease severity in patients with Multisystem Inflammatory Syndrome in children (MIS-C). A single-centre observational study on consecutive patients with MIS-C. Before treatment clinical, and laboratory data were collected and, in a subset of patients, thyroid function tests were repeated 4 weeks later. Variables distribution was analyzed by Mann-Whitney U-test and correlations between different parameters were calculated by Spearman's Rho coefficient. Forty-two patients were included and 36 (85.7%) presented ESS. fT3 values were significantly lower in patients requiring intensive care, a strong direct correlation was shown between fT3 and Hb, platelet count and ejection fraction values. A significant inverse correlation was retrieved between fT3 levels and C-reactive protein, brain natriuretic peptide, IL-2 soluble receptor and S-100 protein. Subjects with severe myocardial depression (EF < 45%) had lower fT3 values than subjects with higher EF. The thyroid function tests spontaneously normalized in all subjects who repeated measurement 4 weeks after admission. ESS is a frequent and transient condition in acute phase of MIS-C. A severe reduction of fT3 must be considered as important prognostic factor for severe disease course, with subsequent relevant clinical impact in the management of these patients.

Spectrum of Thyroid Dysfunction in Patients with Chronic Kidney Disease in Benin City, Nigeria.

There is an indication of abrupt rise in chronic kidney disease (CKD) in Nigeria and thyroid function involvement has not been sufficiently evaluated. This study determined thyroid gland function among subjects with CKD in Benin City, Nigeria. A total of 184 randomized CKD patients attending specialist clinic and 80 healthy control subjects were recruited for this study. A well-structured questionnaire was used to obtain data on socio-demography. Blood specimens were collected and used for the determination of thyroid function parameters; thyroid stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (fT3), thyroxine (T4), free thyroxine (fT4), thyroid peroxidase antibody (TPO-Abs), thyroid globulin antibody (Tg-Abs) and Deiodinase enzyme Type 1 (D1). SPINA GD and SPINA GT were calculated using Michaelis-Menten model. The CKD was classified into stages using Modification of Drug in Renal Disease (MDRD) formula. Thyroid dysfunctions observed were clinical hyperthyroidism 1 (0.54%), non-thyroidal illness 78 (42.4%), clinical hypothyroidism 11 (6.0%), sub-clinical hyperthyroidism 3 (1.60%), and sub-clinical hypothyroidism 11 (6.0%), while euthyroid were 80 (43.5%). SPINA GD of CKD patients (33.85 ± 10.94) was not significantly different when compared with controls (24.85 ± 1.57), whereas, SPINA GT was significantly higher (p < 0.01) among CKD patients (3.74 ± 0.31) than controls (2.68 ± 0.11). Autoimmune thyroid disease demonstrated by positive Tg-Abs and TPO-Abs were observed among approximately 7.9% of CKD patients. Serum TPO-Abs concentration increased with CKD progression. Thyroid dysfunction is involved in the pathogenesis of CKD patients. The etiologies are multifactorial and immunological mechanisms of autoimmune thyroid disease may be a contributing factor.

WPŁYW INFEKCJI SARS-CoV-2 NA FUNKCJĘ TARCZYCY – PATOMECHANIZM I IMPLIKACJE KLINICZNE

The SARS-CoV-2 virus is the pathogenic agent of the COVID-19 disease, which pandemic had caused 6.8 million deaths worldwide by February 2023. In the course of the disease, involvement of the thyroid gland is observed. The pathomechanism of damage to the thyroid gland is bidirectional – direct cytotoxicity of the virus and the indirect effect of a cytokine storm. Circulating pro-inflammatory cytokines lead to deiodinase activity dysregulation, resulting in changes in plasma concentrations of TSH, fT3, and fT4. These hormone abnormalities are observed in about 16% of patients during COVID-19 and may also result from the treatment itself – systemic corticosteroids. Dysregulation of the immune system also leads to autoinflammatory thyroid diseases. It seems crucial to monitor thyroid hormones to detect subclinical forms of thyroiditis early. This paper presents the prevalence and potential pathomechanism of thyroid disorders observed during SARS-CoV-2 infection – subacute thyroiditis, low T3 syndrome, Graves-Basedow disease, and Hashimoto’s disease.

Diagnosis and management of thyroid disorders and thyroid hormone supplementation in adult horses and foals.

Equine thyroid disorders pose a diagnostic challenge in clinical practice because of the effects of nonthyroidal factors on the hypothalamic-pituitary-thyroid axis, and the horse's ability to tolerate wide fluctuations in thyroid hormone concentrations and survive without a thyroid gland. While benign thyroid tumours are common in older horses, other disorders like primary hypothyroidism or hyperthyroidism in adult horses and congenital hypothyroidism in foals are rare. There is a common misunderstanding regarding hypothyroidism in adult horses, especially when associated with the clinical profile of obesity, lethargy, and poor performance observed in dogs and humans. Low blood thyroid hormone concentrations are often detected in horses as a secondary response to metabolic and disease states, including with the nonthyroidal illness syndrome; however, it is important to note that low thyroid hormone concentrations in these cases do not necessarily indicate hypothyroidism. Assessing equine thyroid function involves measuring thyroid hormone concentrations, including total and free fractions of thyroxine (T4) and triiodothyronine (T3); however, interpreting these results can be challenging due to the pulsatile secretion of thyroid hormones and the many factors that can affect their concentrations. Dynamic testing, such as the thyrotropin-releasing hormone stimulation test, can help assess the thyroid gland response to stimulation. Although true hypothyroidism is extremely rare, thyroid hormone supplementation is commonly used in equine practice to help manage obesity and poor performance. This review focuses on thyroid gland pathophysiology in adult horses and foals, interpretation of blood thyroid hormone concentrations, and evaluation of horses with thyroid disorders. It also discusses the use of T4 supplementation in equine practice.

Investigating the Predictive Value of Thyroid Hormone Levels for Stroke Prognosis.

Given the expansion of life expectancy, the aging of the population, and the anticipated rise in the number of stroke survivors in Europe with severe neurological consequences in the coming decades, stroke is becoming the most prevalent cause of functional disability. Therefore, the prognosis for a stroke must be timely and precise. Two databases (MEDLINE and Scopus) were searched to identify all relevant studies published between 1 January 2005 and 31 December 2022 that investigated the relationship between thyroid hormone levels and acute stroke severity, mortality, and post-hospital prognosis. Only full-text English-language articles were included. This review includes Thirty articles that were traced and incorporated into the present review. Emerging data regarding the potential predictive value of thyroid hormone levels suggests there may be a correlation between low T3 syndrome, subclinical hypothyroidism, and poor stroke outcome, especially in certain age groups. These findings may prove useful for rehabilitation and therapy planning in clinical practice. Serum thyroid hormone concentration measurement is a non-invasive, relatively harmless, and secure screening test that may be useful for this purpose.

Critically ill patients: Histopathological evidence of thyroid dysfunction

PurposeCritical illness is characterized by severe biphasic physical and metabolic stress as result of systemic inflammatory response syndrome and/or multiple organ dysfunction syndrome, and is frequently associated with non-thyroidal illness. Purpose of this study is to better understand the cytomorphological basis of NTI by performing histopathological examinations of thyroid gland on autopsies of patients who died from critical illness. MethodsHistopathological examination of thyroid gland of 58 critically ill patients was performed in our hospital. The cases included 24 cases of burn injury, 24 cases of traumatic brain injury, and 10 cases of cerebral stroke. Thyroid samples obtained during autopsy were preserved in formol saline and stained with hematoxylin and eosin. The sections were visualized under light microscopy. ResultsOut of 58 cases examined, 21 patients showed normal thyroid findings, and rest of the cases had unusual thyroid findings in the histopathological study. The principal finding was distortion of thyroid follicular architecture. Other findings include mononuclear cell infiltration, clumping of thyroglobulin, and exhaustion of thyroid follicles. ConclusionCritical illness produces metabolically damaging effects on thyroid gland, which functionally corresponds to a state of low T3 syndrome. These changes are more pronounced in BI and cerebral stroke than in TBI.

The diurnal change of thyroid-stimulating hormone and the effect of this change on thyroid functions in patients with chronic kidney disease.

Thyroid-stimulating hormone (TSH) has a pulsatile and circadian rhythm in healthy individuals. We aimed to evaluate the diurnal changes of free thyroid hormones and serum TSH levels in patients with end-stage renal failure (ESRF) whose thyroidal functions are at normal ranges. Thirty hemodialysis patients with chronic renal failure and without a known thyroidal disease who are over 18 and 35 healthy individuals were included. The serum TSH, free T3, and free T4 levels were examined among the patient and control group which were taken at 8:00 a.m., 4:00 p.m., and 0:00 a.m. Twenty-two (73.3%) patients were male, and the mean age of the patient group was 64 (sd = 14.45 years). Seventeen (48.6%) of the control group were female, and the mean age was 31.9 (sd = 6.4 years). Serum free T3 levels, measured at three different time points (8:00 a.m., 4:00 p.m., and 0:00 a.m.), were significantly lower in the patient group than in the control group and serum free T4 levels were measured at three different time points (8:00 am, 4:00 p.m., and 0:00 a.m.) were significantly higher in the patient group than in the control group. Serum TSH levels were higher in the patient group than in the control group at 08:00, and were lower at 24:00 (p < 0.001). The nocturnal increase of serum TSH level under 0.525 suggested diurnal rhythm disruption with 83% sensitivity and 87% specificity. The nocturnal serum TSH increase is not seen in ESRF patients who did not have a thyroid disease. We think that not observing a nocturnal TSH increase could be an early indication of the sick euthyroid syndrome.

Thyroid Dysfunction at Different Stages of Chronic Kidney Disease: A Cross-Sectional Study at a Rural Teaching College in Central India.

Background The high prevalence of thyroid dysfunction in patients with chronic kidney disease (CKD) indicates a major correlation between the progression of CKD and thyroid dysfunction. In this study, we highlighted thyroid dysfunction and its relation to the severity and different stages of CKDs. Materials and methods From October 2018 to September 2020, 200 cases with CKD, admitted under the Department of Medicine at a rural teaching hospital in central India, were selected for the study. The collected data was analyzed and correlated using the Chi-square test, and the parameters suggested the presence or absence of low T3 syndrome, low T4 syndrome, and primary hypothyroidism. Results Out of 200 patients enrolled, 181 (91.5%) had thyroid abnormalities. Among these patients, the presence of low T3 syndrome was 57%, low T4 syndrome was 23%, and primary hypothyroidism was 10.5%. It was reported that as the CKD stages advanced, TSH levels increased with a statistically significant difference (p=0.04). Conclusions As kidney function progressively deteriorated, specifically in stage five, the chances of occurrence of hypothyroidism increased.

Low T3 syndrome as a predictor of poor prognosis in peripheral T-cell lymphomas.

The purpose of the study was to evaluate the prognostic value of low T3 syndrome in peripheral T-cell lymphomas (PTCLs). One hundred and seventy-four patients of newly diagnosed PTCLs were enrolled in the study. We performed statistical analysis based on the clinical data collected. Thirty-Six (20.69%) patients had low T3 syndrome at first admission. Results suggested that the patients with higher score of ECOG PS, International Prognostic Index (IPI) and Prognostic Index for T-cell lymphoma (PIT), bone marrow involvement and lower level of albumin tended to develop low T3 syndrome. The median progression-free survival (PFS) and overall survival (OS) were 10months and 36months, respectively, for all patients. Pre-existing low T3 syndrome was in correlation with worse PFS and OS. Patients with low T3 syndrome showed worse PFS (4months vs 13months, P = 0.0001) and OS (7months vs 83months, P < 0.0001) than patients without low T3 syndrome. IPI and PIT, respectively, combined with low T3 syndrome improved the ability to predict OS and PFS of PTCLs. The study indicated that low T3 syndrome may be a good candidate for predicting prognosis of peripheral T-cell lymphomas.

Thyroid hormones modifications among COVID-19 patients undergoing pulmonary rehabilitation.

Patients with severe COVID-19 often experience long-lasting disabilities that can improve after pulmonary rehabilitation. Moreover patients with severe COVID-19 display thyroid function alterations due to a non-thyroidal illness syndrome (NTIS). The aim of our study was to evaluate thyroid function parameters among patients hospitalized for COVID-19 who were eligible or not to respiratory rehabilitation and their modifications during follow-up. Post-COVID-19 patients referred to a Respiratory Rehabilitation Unit were evaluated. Outpatients, not candidate for rehabilitation, were enrolled as Control group. Patients who had completed a 4-week-rehabilitation program were enrolled as Rehabilitation Group. All patients were evaluated at T0 (4 weeks after the discharge home in Control Group and after completion of rehabilitation in Rehabilitation Group) and at T1 (3 months after T0). The final study group included 39 patients (20 in the Rehabilitation group and 19 in the Control group). Patients in the Rehabilitation Group had more frequently received invasive or non-invasive ventilation, had a longer length-of-stay in referring hospitals, had a higher number of comorbidities and displayed a worse performance at 6-minute-walking-test (6MWT) and Short-Physical-Performance-Battery-test (SPPB). FT3 values were lower at T0 in the Rehabilitation Group, while TSH and FT4 values were similar in the two groups. While no significant modifications in thyroid-function-parameters were observed in the Control Group, a significant increase in FT3 value was observed in the Rehabilitation Group at T1. Participants of both groups had improved the results of 6MWT at T1, while SPPB values improved only in the Rehabilitation Group. COVID-19 patients after pulmonary rehabilitation experience an increase in FT3 values during follow-up, paralleled with an amelioration of functional capabilities.

Transient low T3 syndrome in patients with COVID-19: a new window for prediction of disease severity.

To investigate the relationship of low T3 syndrome with disease severity in patients with COVID-19. The clinical data of 145 patients with COVID-19 were retrospectively collected, and patients were divided into a low T3 group and a normal T3 group. Logistic regression models were used to assess predictive performance of FT3. Receiver operating characteristic (ROC) analysis was used to evaluate the use of low T3 syndrome in predicting critical disease. Kaplan-Meier analysis was used to analyze the impact of low T3 syndrome on mortality. The prevalence of low T3 level among COVID-19 patients was 34.48%. The low T3 group was older, and had lower levels of hemoglobin, lymphocytes, prealbumin, and albumin, but higher levels of white blood cells, neutrophils, CRP, ESR, and D-dimer (all p<0.05). The low T3 group had greater prevalences of critical disease and mortality (all p <0.05). Multivariate logistic regression analysis showed that the Lymphocytes, free T3 (FT3), and D-dimer were independent risk factors for disease severity in patients with COVID-19. ROC analysis showed that FT3, lymphocyte count, and D-dimer, and all three parameters together provided reliable predictions of critical disease. Kaplan-Meier analysis showed the low T3 group had increased mortality (p<0.001). Six patients in the low T3 group and one patient in the normal T3 group died. All 42 patients whose T3 levels were measured after recovery had normal levels after discharge. Patients with COVID-19 may have transient low T3 syndrome at admission, and this may be useful for predicting critical illness.

SARS-CoV-2 infection and thyroid dysfunction in children

The problem of thyroid dysfunction related to SARS-CoV-2 infection remains unclear in children. Therefore, the study aimed to reveal the interrelationship between thyroid dysfunction and COVID-19 severity­ as well as to determine optimal cut-off values for screening for thyroid disorders in children. A total number of 90 children aged from 1 month to 17 years were involved in the study. Patients with known thyroid disease were not recruited for the research. A thyroid panel was assessed for all participants that included: free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH) and anti-thyroid peroxidase (ATPO) antibodies. Statistical analysis was done using the computer software Statistica 13.0. Research has revealed euthyroid sick syndrome (ESS) in 14.10% of SARS-CoV-2 infected children more often among patients with severe COVID-19 and multisystem inflammatory syndrome (33.33%) compared to mild COVID-19 course (6.67%) and moderate disease severity (8.89%) (P &lt; 0.05). Significant correlation relationships were revealed for next values – FT3 and erythrocyte sedimentation rate (ESR) (rs = -0.22; P &lt; 0.05); FT3 and C-reactive protein (CRP) (rs = -0.33; P &lt; 0.05); FT3 and procalcitonin (rs = -0.43; P &lt; 0.05). The next cut-off values for ESS determination were revealed: ESR 18.5 mm/h (AUC 0.803); CRP 11.5 mg/l (AUC 0.763); ferritin 84.8 ng/ml (AUC 0.733). Results suggest that pediatricians should pay attention to the endocrine disruptions by COVID-19 in children. Keywords: COVID-19, euthyroid sick syndrome in children, inflammatory markers

Non-thyroidal illness syndrome and the prognosis of heart failure: a systematic review and meta-analysis

Heart failure (HF) is a complex and multifactorial syndrome caused by impaired heart function. The high morbidity and mortality of HF cause a heavy burden of illness worldwide. Non-thyroidal illness syndrome (NTIS) refers to aberrant serum thyroid parameters in patients without past thyroid disease. Observational studies have indicated that NTIS is associated with a higher risk of all-cause mortality in HF. This meta-analysis aimed to investigate the association between NTIS and HF prognosis. Medline, Embase, Web of Science, and the Cochrane database were searched for any studies reporting an association between NTIS and HF prognosis from inception to July 1st 2022. A meta-analysis was then performed. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS). The heterogeneity of the results was assessed with I2 and Cochran's Q statistics. Sensitivity analysis and publication bias analysis were also conducted. A total of 626 studies were retrieved, and 18 studies were finally included in the meta-analysis. The results showed that NTIS in HF patients was significantly associated with an increased risk of all-cause mortality and major cardiovascular events (MACE), but not with in-hospital mortality. The stability of the data was validated by the sensitivity analysis. There was no indication of a publication bias in the pooled results for all-cause mortality and MACE. This meta-analysis showed that NTIS was associated with a worse outcome in HF patients. However, the association between NTIS and in-hospital mortality of HF patients requires further investigation.

The severity of valvular heart disease in euthyroid individuals is associated with thyroid hormone levels but not with TSH levels.

Abnormal thyroid function is a metabolic disorder and can lead to several complications, including cardiovascular diseases. In this study, we aimed to examine the relationship between clinical traits and outcomes and the thyroid hormone level of euthyroid individuals with valvular heart disease (VHD). The thyroid function was evaluated in 526 euthyroid VHD patients and 155 healthy control people. As well as clinical indicators were collected and analyzed. No difference in TSH levels (p>0.05) was recorded; however, fT3, TT3, and TT4 levels were lower in the euthyroid VHD patients than in healthy control(4.3 vs 4.63; 1.37 vs 1.48; 97.7 vs 102.09, respectively, all p<0.05), while the fT4 level was higher (12.91 vs 12.35, p<0.05). Moreover, all showed a continuous trend with the change of NYHA grade which does not consist of the incidence of euthyroid sick syndrome(ESS). Further analysis showed that for every 10-fold increase in BNP, fT4 increases by 83%, fT3 decreases by 30%, and TT3 decreases by 12% after being adjusted for other influencing factors. Meanwhile, adjusted fT4 was correlated with multiple worse clinical indicators, which were influenced by age. Thyroid hormones are widely regulated in VHD patients even with acceptable cardiac function, except for TSH level. And the adjusted fT4 is related to worse clinical indicators and outcomes which are only recorded in patients under 53 years old.

Endocrinology for the hepatologist.

Endocrinology for the hepatologist.